Toxins

25 pages, 1487 KB

Open AccessArticle

Brazilian Bothrops and Crotalus Snake Venoms as a Source of Antiprotozoal Agents: Unlocking Toxins for Therapeutic Development

by Tulio Custódio Reis, Ana Clara Lunardi Yagi, Eloise T. Filardi, Marcela Romanazzi, Michele Ferreira da Silva Mela, Rui S. Ferreira Júnior, Felipe A. Cerni, Márcia A. S. Graminha and Manuela B. Pucca

Toxins 2026, 18(9), 405; https://doi.org/10.3390/toxins18090405 - 21 Sep 2026

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Abstract

Leishmaniasis and Chagas disease are neglected tropical diseases that continue to pose significant public health challenges, highlighting the need for new therapeutic strategies. Brazilian snake venoms represent a valuable and underexplored source of bioactive molecules with diverse pharmacological activities and promising therapeutic potential. [...] Read more.

Leishmaniasis and Chagas disease are neglected tropical diseases that continue to pose significant public health challenges, highlighting the need for new therapeutic strategies. Brazilian snake venoms represent a valuable and underexplored source of bioactive molecules with diverse pharmacological activities and promising therapeutic potential. In this context, the present study aimed to investigate the in vitro antiprotozoal potential of venoms from Bothrops and Crotalus species, including Bothrops jararacussu, Bothrops pauloensis, Bothrops alternatus, Bothrops leucurus, Bothrops atrox, Bothrops jararaca, Crotalus durissus terrificus, and Crotalus durissus ruruima, metalloprotease (MTL)- and crotoxin (CTX)-enriched, against Leishmania spp. and Trypanosoma cruzi. Crude venom protein profiles were analyzed by SDS-PAGE, and cytotoxicity was assessed in differentiated C2C12 myotubes and murine peritoneal macrophages. Antiprotozoal activity was evaluated against extracellular parasite forms, including promastigotes of Leishmania amazonensis and Leishmania infantum and epimastigotes of T. cruzi. Venoms exhibiting the highest selectivity indices (SIs), calculated using murine macrophage cytotoxicity data, were further tested against intracellular amastigotes of L. amazonensis. Among the tested samples, B. jararacussu venom showed activity against promastigotes of both L. amazonensis (IC₅₀ = 2.9 µg mL⁻¹) and L. infantum (IC₅₀ = 2.8 µg mL⁻¹), as well as in epimastigotes of T. cruzi (IC₅₀ = 15.5 µg mL⁻¹). The MTLand CTX pools from C. d. ruruima venom exhibited the highest activity against promastigotes of L. amazonensis, with IC₅₀ values of 1.6 and 3.8 µg mL⁻¹, respectively. Against intracellular amastigotes, MTL and CTX showed IC₅₀ values of 4.1 and 2.5 µg mL⁻¹, respectively, with selectivity indices (SIs) of 73.1 and 120, respectively. Overall, these findings provide preliminary evidence for the antiparasitic potential of snake venom-derived molecules, supporting further characterization and in vivo evaluation. Full article

(This article belongs to the Special Issue Venom Peptides as Precision Therapeutics: From Discovery to Clinical Translation)

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4 pages, 171 KB

Open AccessEditorial

Botulinum Toxin Therapy for Diseases in the Oral and Maxillofacial Regions: Current Evidence and Future Perspectives

by Kazuya Yoshida

Toxins 2026, 18(9), 404; https://doi.org/10.3390/toxins18090404 - 21 Sep 2026

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Abstract

Botulinum neurotoxin (BoNT) therapy has developed from a treatment primarily used for neurological disorders into a versatile therapeutic modality applied across a broad range of medical and dental conditions [...] Full article

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

42 pages, 708 KB

Open AccessArticle

Why the Same Dose of Botulinum Toxin A Is Less Predictable in Small Muscles: A Discrete Threshold Model

by Andrea Felice Armenti and Francesco Armenti

Toxins 2026, 18(9), 403; https://doi.org/10.3390/toxins18090403 - 21 Sep 2026

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Abstract

Pharmacodynamic models of botulinum toxin type A map a mean concentration onto a smooth dose–response curve, yet the outcome is binary and arises from a finite population of near-threshold motor units. We analyse a discrete model in which N units are silenced once [...] Read more.

Pharmacodynamic models of botulinum toxin type A map a mean concentration onto a smooth dose–response curve, yet the outcome is binary and arises from a finite population of near-threshold motor units. We analyse a discrete model in which N units are silenced once local SNAP-25 cleavage exceeds a unit-specific threshold, and a functional block of neuromuscular transmission follows once the silenced fraction exceeds a collective threshold. Whether that collective threshold is a fraction of the population or a fixed count changes the location of the dose–response curve and not its steepness: under a fraction, potency is invariant to unit number at fixed dose–concentration gain, and the transition contracts in absolute dose where fixed-count architectures require it to widen. The width contracts as

N^{- 1 / 2}

, an exponent that is prior and not claimed here. One consequence needs no measurement: a quantal terminal response caps the silenced fraction below unity, so any fixed count fails above a target size it determines, whereas the toxin block targets differ by orders of magnitude. A second reinterprets existing data, flat cohort dose–response curves being what a near-step individual response predicts once convolved with between-subject dispersion. Outcome is accordingly less repeatable in the smallest targets. No parameter is fitted. Full article

(This article belongs to the Section Bacterial Toxins)

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26 pages, 2350 KB

Open AccessSystematic Review

From Neurophysiological Mechanisms to Rehabilitation After Botulinum Toxin Type A in Post-Stroke Spasticity

by Bart Eeckhaut, Steven Truijen, Parham Haghshenas, Antriana Roussou, Petros Taflampas and Wim Saeys

Toxins 2026, 18(9), 402; https://doi.org/10.3390/toxins18090402 - 20 Sep 2026

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Abstract

Background: Botulinum toxin type A (BoNT-A) is globally recognized as a standard treatment for post-stroke spasticity (PSS), although its secondary mechanisms remain underinvestigated. The objective of this study was to investigate the neurophysiological mechanisms underlying BoNT-A treatment in PSS and explore their implications [...] Read more.

Background: Botulinum toxin type A (BoNT-A) is globally recognized as a standard treatment for post-stroke spasticity (PSS), although its secondary mechanisms remain underinvestigated. The objective of this study was to investigate the neurophysiological mechanisms underlying BoNT-A treatment in PSS and explore their implications for mechanism-based rehabilitation. Methods: A systematic review and meta-analysis (PROSPERO registration number ID: CRD420261352230) of 39 studies involving 760 patients was conducted on 18 August 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, Scopus, and Embase were systematically searched using the PICO framework. Where possible, quantitative data were pooled according to predefined neurophysiological constructs, including passive stretch-evoked activity, voluntary activation of the injected muscle, compound muscle action potential (CMAP), reciprocal motor control, normalized Hmax/Mmax, and specific spinal inhibitory mechanisms. Results: Quantitative synthesis demonstrated construct-specific neurophysiological changes following BoNT-A treatment. Passive stretch-evoked activity showed the largest pooled effect (Hedges’ g = 0.80, 95% CI 0.35–1.24), followed by CMAP amplitude (g = 0.69, 95% CI 0.23–1.14) and reciprocal motor control (g = 0.52, 95% CI 0.23–0.81). Effects on voluntary activation of the injected muscle (g = 0.31, 95% CI −0.38 to 1.00) and normalized Hmax/Mmax (g = 0.22, 95% CI −0.74 to 1.17) were smaller and more heterogeneous. Reciprocal and recurrent inhibition were each represented by single-study estimates, while supraspinal outcomes were synthesized narratively due to methodological heterogeneity. Conclusions: The findings support a predominantly peripheral mechanism of BoNT-A while suggesting possible secondary changes within spinal and supraspinal motor control pathways. However, the certainty of evidence was low to very low. These neurophysiological effects provide a rationale for individualized, mechanism-based rehabilitation during the post-injection therapeutic window, although higher-quality evidence is required to confirm this framework. Full article

(This article belongs to the Special Issue Botulinum Toxin Application in Post-Stroke Rehabilitation)

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38 pages, 53975 KB

Open AccessArticle

Clinical and Pathological Findings in Coastal Birds Affected by Domoic Acid Toxicity

by Corinne M. Gibble, Melissa A. Miller, Raphael M. Kudela, Angelina Reed, Kevin Keel and Rebecca S. Duerr

Toxins 2026, 18(9), 401; https://doi.org/10.3390/toxins18090401 - 20 Sep 2026

Viewed by 1083

Abstract

In 2017, an unusually large number of live stranded and dead marine birds were found in California, coincident with a large bloom of the diatom Pseudo-nitzschia that produced the toxin domoic acid (DA). The most abundant bird species affected by this large die-off [...] Read more.

In 2017, an unusually large number of live stranded and dead marine birds were found in California, coincident with a large bloom of the diatom Pseudo-nitzschia that produced the toxin domoic acid (DA). The most abundant bird species affected by this large die-off and stranding event were Pacific Loons (Gavia pacifica) and Red-throated Loons (Gavia stellata). International Bird Rescue (IBR; San Pedro, CA) received 117 live loons with suspected DA toxicosis. Many birds that survived the first few days in rehabilitation quickly re-attained suitable health metrics; however, 68 loons (58.1%) died or were considered unreleasable due to ongoing abnormal behavior or injuries that necessitated humane euthanasia. In this descriptive study, both live stranded euthanized birds and dead stranded birds were examined to characterize and better understand the effects of DA toxicosis in the avian brain and body. Utilizing a suite of diagnostics, our analysis revealed novel pathological patterns that divided these birds into three groups: those suspected of having acute, subacute, and chronic DA toxicosis. Domoic Acid was found in all groups, and the severity of the microscopic lesions appeared to correspond with the amount of time each bird survived post-stranding. Our investigation is the first known account identifying the pathological progression from acute to chronic DA toxicosis in birds. Full article

(This article belongs to the Special Issue Unveiling the Toxic Effects of Harmful Algal Blooms: 2nd Edition)

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12 pages, 558 KB

Open AccessArticle

Early Onset of AbobotulinumtoxinA Effects in Post-Stroke Upper Limb Spasticity: A Prospective Observational Pilot Study

by Riccardo Marvulli, Serena Caforio Montesardo, Chiara Moccia, Marisa Megna and Maurizio Ranieri

Toxins 2026, 18(9), 400; https://doi.org/10.3390/toxins18090400 - 18 Sep 2026

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Abstract

Upper limb spasticity is a common complication of stroke that negatively affects motor function, range of motion, and quality of life. Although abobotulinumtoxinA is widely used for the treatment of focal post-stroke spasticity, evidence regarding its early onset of action remains limited. This [...] Read more.

Upper limb spasticity is a common complication of stroke that negatively affects motor function, range of motion, and quality of life. Although abobotulinumtoxinA is widely used for the treatment of focal post-stroke spasticity, evidence regarding its early onset of action remains limited. This prospective observational pilot study investigated the early clinical, functional, and neurophysiological effects of abobotulinumtoxinA in 20 adults with post-stroke upper limb spasticity. Patients received ultrasound-guided injections into the biceps brachii and flexor digitorum superficialis muscles and were evaluated at baseline, 24 h, 5 days, 7 days, 14 days, and 30 days after treatment. Outcome measures included the Modified Ashworth Scale (MAS), passive range of motion (ROM), caregiver-reported hand function assessed using a visual analog scale (VAS), and compound muscle action potential (cMAP) recordings. No significant changes were observed at 24 h. A significant reduction in spasticity was detected at the day-5 assessment, accompanied by significant improvements in ROM and functional outcomes. Neurophysiological assessment demonstrated significant reductions in cMAP amplitudes at the day-5 assessment, indicating early neuromuscular transmission blockade. Clinical improvements were also first detected at day-5 assessment and were maintained at subsequent evaluations through day 30. These findings indicate that clinically meaningful effects of abobotulinumtoxinA were detectable by the first scheduled assessment at day 5 after injection. Given the absence of intermediate assessments between 24 h and day 5, the exact timing of treatment onset cannot be determined. A multimodal assessment approach may help characterize early treatment-related changes and provide useful information for future studies investigating the timing of adjunctive rehabilitation interventions. Full article

(This article belongs to the Section Bacterial Toxins)

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13 pages, 1044 KB

Open AccessSystematic Review

Adjunctive Use of Botulinum Toxin in Orthognathic Surgery: A Systematic Review of Current Evidence and Clinical Perspectives

by Audra Janovskienė, Justina Stučinskaitė-Maračinskienė, Žygimantas Petronis, Jan Pavel Rokicki, Dainius Razukevičius and Loreta Pilipaitytė

Toxins 2026, 18(9), 399; https://doi.org/10.3390/toxins18090399 - 18 Sep 2026

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Abstract

Background: Botulinum toxin type A (BoNT-A) has been proposed as an adjunct to orthognathic surgery because its temporary neuromuscular effects may reduce muscular loading during postoperative healing and potentially influence fixation stability, skeletal relapse, and postoperative recovery. This systematic review aimed to evaluate [...] Read more.

Background: Botulinum toxin type A (BoNT-A) has been proposed as an adjunct to orthognathic surgery because its temporary neuromuscular effects may reduce muscular loading during postoperative healing and potentially influence fixation stability, skeletal relapse, and postoperative recovery. This systematic review aimed to evaluate the available clinical evidence regarding the adjunctive use of BoNT-A in orthognathic surgery. Methods: A systematic literature search was conducted in PubMed, the Cochrane Library, and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies directly comparing orthognathic surgery with and without adjunctive BoNT-A administration and reporting outcomes related to mechanical stability, skeletal stability, or postoperative recovery were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool for randomized controlled trials and ROBINS-I for the non-randomized study. Results: Three studies met the eligibility criteria, comprising two randomized controlled trials and one retrospective comparative study. Considerable heterogeneity was observed in surgical procedures, targeted muscles, BoNT-A doses, timing of administration, and evaluated outcomes. Individual studies reported associations between BoNT-A administration and a lower incidence of fixation plate fracture, reduced anteroposterior skeletal relapse at the Pogonion, or lower preanalgesic pain scores and postoperative opioid consumption. However, these findings were derived from different studies evaluating distinct interventions and outcomes and were not consistently demonstrated across comparable outcome measures. Conclusions: BoNT-A may represent a promising adjunct to orthognathic surgery, with potential benefits for fixation-related mechanical stability, selected parameters of skeletal relapse, and postoperative pain management. However, the limited number of studies, methodological limitations, and substantial clinical heterogeneity preclude definitive conclusions. Further well-designed randomized controlled trials with standardized injection protocols and longer follow-up are required before routine clinical use can be recommended. Full article

(This article belongs to the Special Issue Botulinum Toxin for the Pain Management in Musculoskeletal and Temporomandibular Disorders)

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15 pages, 1629 KB

Open AccessArticle

Goal Attainment and Outcome Evaluation for Upper and Lower Limb Spasticity: A Real-Life Cohort Analysis in a Community-Based Outreach Service

by Aideen Steed, Heather Williams, Jessie Alfonso, Denise Hancock and Stephen A. Ashford

Toxins 2026, 18(9), 398; https://doi.org/10.3390/toxins18090398 - 18 Sep 2026

Cited by 1 | Viewed by 508

Abstract

Botulinum toxin type A (BoNT-A) is an established treatment for spasticity. Goal Attainment Scaling (GAS), alongside standardized measures such as Arm Activity Measure (ArmA) and Leg Activity Measure (LegA), enables evaluation of patient-centered outcomes. This real-world cohort study evaluated goal attainment and standardized [...] Read more.

Botulinum toxin type A (BoNT-A) is an established treatment for spasticity. Goal Attainment Scaling (GAS), alongside standardized measures such as Arm Activity Measure (ArmA) and Leg Activity Measure (LegA), enables evaluation of patient-centered outcomes. This real-world cohort study evaluated goal attainment and standardized measure functional changes following BoNT-A for arm and/or leg spasticity, evaluated using GAS as well as passive function subscales of ArmA (ArmA-PF) and LegA (LegA-PF), and active function subscales (ArmA-AF; LegA-AF). Inclusion in the analysis was based on documented baseline and post-intervention GAS scores following BoNT-A therapy (n = 390). Across 855 treatment cycles, 1258 goals were set and categorized, of which 150 (11.9%) were related to active function and 705 (56.0%) to passive function. The mean GAS T-score improved from 36.2 to 49.4 (change 13.1, p < 0.001), with significant gains observed for both passive (change 13.7, p < 0.001) and active goals (change 12.6, p < 0.001). Passive function improved significantly on ArmA-PF (change 2.5) and LegA-PF (change 2.1), while significant changes in ArmA-AF and LegA-AF were not seen. In conclusion, goal-directed spasticity management incorporating BoNT-A resulted in improvements in goal attainment, which corresponded to a clinically meaningful change in passive function measured by ArmA-PF and LegA-PF, but not for active function. Passive function was the most common treatment priority. Findings provide real-world evidence to support community-based spasticity services and the use of structured goal setting, ArmA and LegA application, in routine practice. Full article

(This article belongs to the Special Issue Physical and Pharmacological Combination Therapy Incorporating Botulinum Toxins)

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24 pages, 10827 KB

Open AccessArticle

Multi-Omics and Functional Analysis of Salmonella ArtAB Toxin Activity Reveals Transcriptomic Remodeling and Epithelial Barrier Dysfunction

by Noah M. Souza, Alexander O. Hale, Richard S. Beard, Jr. and Juliette K. Tinker

Toxins 2026, 18(9), 397; https://doi.org/10.3390/toxins18090397 - 17 Sep 2026

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Abstract

AB₅ toxins are important virulence factors produced by Gram-negative bacteria and have been identified in many non-typhoidal Salmonella (NTS) serovars; however, their effects on host cell signaling and epithelial barrier function remain poorly understood. This study characterized the molecular and functional effects [...] Read more.

AB₅ toxins are important virulence factors produced by Gram-negative bacteria and have been identified in many non-typhoidal Salmonella (NTS) serovars; however, their effects on host cell signaling and epithelial barrier function remain poorly understood. This study characterized the molecular and functional effects of purified ArtAB toxin and its binding subunit, ArtB, from multidrug-resistant Salmonella Typhimurium definitive type 104 (DT104). Equimolar concentrations of ArtAB (10 µg/mL) and ArtB (7.25 µg/mL) were evaluated in Chinese hamster ovary (CHO-K1) cells using cytotoxicity assays, quantitative proteomics, and mRNA sequencing, while barrier function was assessed in C2BBe1 human intestinal epithelial cells using electric cell-substrate impedance sensing (ECIS). In CHO-K1 cells, both proteins exhibited minimal cell death. ArtB elicited pronounced proteomic changes associated with endoplasmic reticulum (ER) homeostasis, vesicular trafficking, and lysosomal processing, but limited transcriptional responses. ArtAB instead altered host transcriptional programs associated with cell growth, inflammatory signaling, and cytoskeletal organization. Unlike ArtB, ArtAB significantly reduced barrier function in C2BBe1 cells. Together, these findings show that ArtAB remodels host cell signaling without overt cytotoxicity in CHO-K1 cells and produces a distinct functional effect in C2BBe1 cells. Although obtained in different cellular models, these results provide insight into the potential role of ArtAB in NTS pathogenesis. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Online Conference on Toxins (2025))

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26 pages, 2475 KB

Open AccessReview

Hyperspectral Imaging for Mycotoxin Monitoring in Food: A Comprehensive Review of Technologies, Algorithms, and Applications

by Guangyao Ying, Maofa Zeng, Liang Hong, Zhaokui Li, Jun Li and Huili Xia

Toxins 2026, 18(9), 396; https://doi.org/10.3390/toxins18090396 - 16 Sep 2026

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Abstract

Mycotoxin contamination represents one of the most pressing food safety challenges worldwide, with millions of tons of agricultural commodities affected annually. Conventional detection methods, while accurate, are labor-intensive, destructive, and unsuitable for large-scale screening. Hyperspectral imaging (HSI) has emerged as a transformative non-destructive [...] Read more.

Mycotoxin contamination represents one of the most pressing food safety challenges worldwide, with millions of tons of agricultural commodities affected annually. Conventional detection methods, while accurate, are labor-intensive, destructive, and unsuitable for large-scale screening. Hyperspectral imaging (HSI) has emerged as a transformative non-destructive analytical technique capable of simultaneously capturing spatial and spectral information across hundreds of contiguous wavelengths. This review critically evaluates the current state of HSI technology for mycotoxin detection in food products, covering the physical principles underlying spectral–mycotoxin interactions, systematic applications across major mycotoxin classes (aflatoxins, deoxynivalenol, ochratoxin A, fumonisins, and zearalenone), and the integration of machine learning and deep learning algorithms for spectral data analysis. The review reveals that while Vis-NIR (400–1000 nm) and SWIR (1000–2500 nm) HSI systems have achieved classification accuracies exceeding 90% for several mycotoxin–matrix combinations, fundamental challenges persist in model transferability, direct quantification at regulatory thresholds, and scalability for industrial deployment. Recent advances in transformer architectures, transfer learning, interpretable deep learning, and portable multispectral systems demonstrate encouraging progress toward practical implementation. This review concludes by identifying critical research gaps and proposing strategic directions for translating HSI-based mycotoxin detection from laboratory proof-of-concept to routine industrial application. Full article

(This article belongs to the Special Issue Challenges of Mycotoxins in Food Chains: Occurrence, Detection and Control)

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36 pages, 2826 KB

Open AccessReview

Multiclass Cyanotoxins in Aquatic Environments: Occurrence, Impacts and Detection Techniques

by Galina Nugumanova

Toxins 2026, 18(9), 395; https://doi.org/10.3390/toxins18090395 - 14 Sep 2026

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Abstract

Cyanobacterial harmful algal blooms (cyanoHABs) typically involve the release of a wide spectrum of toxic metabolites produced by different cyanobacteria, which can cause adverse health effects in animals and humans. At the same time, many cyanobacteria are capable of producing more than one [...] Read more.

Cyanobacterial harmful algal blooms (cyanoHABs) typically involve the release of a wide spectrum of toxic metabolites produced by different cyanobacteria, which can cause adverse health effects in animals and humans. At the same time, many cyanobacteria are capable of producing more than one toxin simultaneously. As a result, the multiclass toxins released into aquatic environments can exert complex and combined effects on various ecosystem components. This review aims to provide an overview of the occurrence and effects of different cyanotoxins in aquatic systems and current analytical methods of their simultaneous detection. The main classes of cyanotoxins have been considered in this review. The occurrences, properties, and environmental and health impacts of these toxins are described. The main methods for cyanobacterial toxin analysis are covered. A comprehensive review and analysis of liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection and sample preparation approaches used to identify various classes of cyanotoxins is provided, together with a practical decision tree for analytical workflow selection according to toxin class and sample matrix, highlighting key trends and outlining directions for further research in this area. Full article

(This article belongs to the Special Issue Advances in Detecting, Monitoring, Predicting, Managing and Controlling Harmful Algal Blooms)

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17 pages, 4474 KB

Open AccessArticle

Composition and In Vitro Activity–Cytotoxicity Profiles of Vespa basalis Venom: Combined Proteomic, Metabolomic, and Molecular-Weight-Fractionated Analyses

by Yong-Hua Wu, Zheng-Xu Zhong, Yan Li, Jing-An Wang, Zheng-Wen Ou, Hou-Jin Li and Wen-Jian Lan

Toxins 2026, 18(9), 394; https://doi.org/10.3390/toxins18090394 - 12 Sep 2026

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Abstract

Vespa basalis Smith venom (VBsV) causes painful and potentially severe systemic reactions, yet the relationships among its composition, bioactivity, and cytotoxicity remain poorly understood. Proteomic and metabolomic profiling was combined with ultrafiltration and gel filtration to characterize VBsV and obtain >3 kDa, operationally [...] Read more.

Vespa basalis Smith venom (VBsV) causes painful and potentially severe systemic reactions, yet the relationships among its composition, bioactivity, and cytotoxicity remain poorly understood. Proteomic and metabolomic profiling was combined with ultrafiltration and gel filtration to characterize VBsV and obtain >3 kDa, operationally defined 700–3000 Da, and <700 Da fractions. The effect on LPS-induced NO production was evaluated by nitric oxide (NO) release in LPS-stimulated RAW264.7 cells, and cytotoxicity was assessed in tumor and THLE-2 liver cells. Five venom allergen proteins were identified, including two phospholipase A1 isoforms, hyaluronidase A, antigen 5, and venom dipeptidyl peptidase IV. Targeted profiling also detected several neurotransmitters and energy metabolites, including 5-hydroxytryptamine, L-glutamate, histamine, γ-aminobutyric acid, inosine, and adenosine. The 700–3000 Da fraction exhibited the strongest NO-suppressive and tumor-cell-viability effects among the tested fractions. The 700–3000 Da fraction suppressed NO release (IC₅₀, approximately 23 μg/mL) and reduced tumor-cell viability, while minimally affecting THLE-2 cells at 10–80 μg/mL; by contrast, the >3 kDa fraction showed greater THLE-2 cytotoxicity. These findings identify the 700–3000 Da fraction as a priority for direct compositional characterization and isolation of the responsible molecules. Full article

(This article belongs to the Special Issue Advances in Composition and Pharmacological Properties of Toxins Derived from Venoms)

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18 pages, 4215 KB

Open AccessReview

α-Latrotoxin and Pain: A Nociceptor Perspective on Latrodectism

by Bazbek Davletov, Alexandr Ignatchenko, Aisha Zhantleuova and Rashid A. Giniatullin

Toxins 2026, 18(9), 393; https://doi.org/10.3390/toxins18090393 - 10 Sep 2026

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Abstract

Alpha-latrotoxin (α-LTX) is the principal vertebrate-specific neurotoxin in widow spider (Latrodectus) venom and a powerful presynaptic secretagogue. Although its receptors, pore-forming activity and stimulation of neurotransmitter release have been studied extensively in central and motor neurons, its relationship to the severe, [...] Read more.

Alpha-latrotoxin (α-LTX) is the principal vertebrate-specific neurotoxin in widow spider (Latrodectus) venom and a powerful presynaptic secretagogue. Although its receptors, pore-forming activity and stimulation of neurotransmitter release have been studied extensively in central and motor neurons, its relationship to the severe, persistent pain of latrodectism remains poorly understood. This focused review re-examines α-LTX from a nociceptive perspective. The available evidence supports a model in which α-LTX binds adhesion G protein-coupled receptor L1 (ADGRL1; latrophilin-1) and neurexin-1α on susceptible sensory neurons; inserts a large cation-permeable pore; and promotes membrane depolarisation, calcium entry and release of pain-associated neuropeptides. The transcript-level gene expression of α-LTX receptor genes in dorsal root ganglion neurons and evidence of toxin-evoked neuropeptide release provide a molecular basis for direct nociceptor activation, although functional validation in defined nociceptor subclasses remains necessary. A comparison with the nociceptive ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) highlights their convergence on calcium-dependent sensory excitation, while distinguishing α-LTX from toxins that modulate endogenous channels. We propose that the pain of latrodectism is a composite state in which direct nociceptor activation complements muscle spasm and tissue-derived signalling, positioning α-LTX as a distinctive probe of pain pathways. Full article

(This article belongs to the Special Issue Venom and Neurology: From Molecular Mechanism to Clinical Medicine)

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31 pages, 14987 KB

Open AccessReview

Predictive Artificial Intelligence Models for Mycotoxin Surveillance and Mitigation in Poultry Production Systems

by Padmini Vaka, Laharika Kappari, Gokul V. Selvaraj, Ramesh K. Selvaraj, Todd J. Applegate and Revathi Shanmugasundaram

Toxins 2026, 18(9), 392; https://doi.org/10.3390/toxins18090392 - 10 Sep 2026

Viewed by 552

Abstract

Mycotoxins are widespread contaminants in animal feeds and continue to pose serious threats to animal welfare, production efficiency, food security, and sustainable economic growth worldwide. Chickens are highly susceptible to multiple mycotoxins, such as aflatoxins (AFLs), deoxynivalenol (DON), fumonisins (FBs), zearalenone (ZEA), ochratoxin [...] Read more.

Mycotoxins are widespread contaminants in animal feeds and continue to pose serious threats to animal welfare, production efficiency, food security, and sustainable economic growth worldwide. Chickens are highly susceptible to multiple mycotoxins, such as aflatoxins (AFLs), deoxynivalenol (DON), fumonisins (FBs), zearalenone (ZEA), ochratoxin A (OTA), and T-2 toxin. Exposure to these toxins can damage intestinal integrity, compromise immune functions, impair nutrient absorption, and ultimately reduce production efficiency even at subclinical concentrations. Conventional mycotoxin detection methods, such as enzyme-linked immunosorbent assays (ELISA) and chromatographic techniques, provide accurate quantification but remain expensive, labor-intensive, time-consuming, and inefficient for large-scale screening, particularly when masked mycotoxins are present. The frequent co-occurrence of multiple mycotoxins further complicates risk assessment and effective management. Emerging analytical technologies, including hyperspectral imaging, biosensors, Internet of Things (IoT)-based platforms, and machine-learning algorithms, offer promising advancements for rapid detection and predictive risk forecasting. This review summarizes the toxicological impacts of major mycotoxins on poultry, outlines critical challenges in detection and prevention, and evaluates current artificial intelligence (AI) and machine learning (ML) approaches for mycotoxin identification, prediction, and management. A systematic literature search conducted across PubMed, ScienceDirect and Google Scholar identified 176 unique studies published between 2010 and 2026. Key knowledge gaps include limited availability of high-quality datasets and source code, inconsistent model interpretability, and poor reproducibility across production environments. By integrating conventional toxicology with data-driven approaches, this review highlights how predictive modeling can strengthen mycotoxin surveillance and support proactive mitigation strategies in modern poultry production systems. Full article

(This article belongs to the Special Issue Mycotoxin Contamination in Animal Feed: Toxicity and Effects)

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10 pages, 1575 KB

Open AccessCommunication

Ultrasound Detected Myokymia Is Associated with Increased Duration of Hospitalization and Healthcare Cost After Rattlesnake Bite in Arizona

by Farshad Mazda Shirazi, Srikar R. Adhikari, Vance G. Nielsen and Geoffrey Thomas Smelski

Toxins 2026, 18(9), 391; https://doi.org/10.3390/toxins18090391 - 10 Sep 2026

Viewed by 386

Abstract

Neurotoxic envenomation by rattlesnakes has been of great concern throughout the Americas and in Arizona. In addition to clinical weakness, patients sometimes display myokymia, a disordered fasciculation of skeletal muscle, which is mediated by Mojave toxin. As neurotoxic venoms have been associated with [...] Read more.

Neurotoxic envenomation by rattlesnakes has been of great concern throughout the Americas and in Arizona. In addition to clinical weakness, patients sometimes display myokymia, a disordered fasciculation of skeletal muscle, which is mediated by Mojave toxin. As neurotoxic venoms have been associated with increased release of creatine kinase (CK) activity and concordant increases in length of stay (LOS) in the hospital, it was retrospectively determined if point-of-care ultrasound detected myokymia at the bite site was associated with increased CK activity, LOS, and healthcare cost compared to rattlesnake envenomations not associated with myokymia. The Arizona Poison and Drug Information Center patient database was queried for patients with point-of-care ultrasound exam results at or near the bite site from 2017 to 2021. Using point-of-care ultrasound to detect subclinical myokymia, thirty-seven patients that met inclusion criteria were determined to have myokymia (n = 16) and/or not display it (n = 21). Patients with myokymia had twice the CK activities, double the LOS, and two-fold the healthcare costs of patients without myokymia detected. These findings serve as a rationale for future investigations to link ultrasound detected myokymia with patient outcomes. Full article

(This article belongs to the Section Animal Venoms)

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55 pages, 7867 KB

Open AccessReview

Twenty-Five Years of Human Urinary Biomonitoring of Mycotoxins: Analytical Advances and Applications in Risk Assessment

by Oana Mîrza, Denisia Pașca, Lara Manyes, Anamaria Cozma-Petruț, Roxana Banc, Simona Codruța Hegheș, Lorena Filip and Béla Kiss

Toxins 2026, 18(9), 390; https://doi.org/10.3390/toxins18090390 - 9 Sep 2026

Viewed by 454

Abstract

Mycotoxins are secondary fungal metabolites that have continuously attracted research interest, both for their potential negative effects on animal and human health and for the economic losses they entail. Studies assessing exposure to mycotoxins have become increasingly widespread. The aim of this study [...] Read more.

Mycotoxins are secondary fungal metabolites that have continuously attracted research interest, both for their potential negative effects on animal and human health and for the economic losses they entail. Studies assessing exposure to mycotoxins have become increasingly widespread. The aim of this study was to provide a comprehensive description of mycotoxins and to evaluate the evolution of research on monitoring mycotoxin exposure using human urine samples, concerning analytical techniques and occurrence. Studies published in English over the last 25 years from four databases (Web of Science, PubMed, Science Direct, Scopus) were analyzed. Evaluating 73 original articles, a constant interest in the analysis of ochratoxin A in human urine samples could be observed (maximum level 148 ng/mL), a fact also justified by its demonstrated toxicity. The most commonly used analytical technique to evaluate mycotoxin presence in human urine was liquid chromatography coupled with high-performance detectors. The limitations of the review include the large period covered and the lack of mycotoxin concentrations expressed in ng biomarker/mL urine in some articles. Finally, an overview of how mycotoxin levels in human urine can be applied to mycotoxin exposure risk assessment was included. Full article

(This article belongs to the Special Issue Biomonitoring and Human Exposure on Mycotoxins: One Health)

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17 pages, 710 KB

Open AccessReview

From Venom to Kidney Injury: A Critical Review of Daboia siamensis Envenoming

by Ren-Chieh Wu and Kuang-Ting Yeh

Toxins 2026, 18(9), 389; https://doi.org/10.3390/toxins18090389 - 9 Sep 2026

Viewed by 431

Abstract

Acute kidney injury (AKI) is a severe complication of Eastern Russell’s viper (Daboia siamensis) envenoming, but species-specific mechanisms, treatment effects, and long-term outcomes remain uncertain. This review addressed four questions: the human renal evidence specific to D. siamensis; venom and [...] Read more.

Acute kidney injury (AKI) is a severe complication of Eastern Russell’s viper (Daboia siamensis) envenoming, but species-specific mechanisms, treatment effects, and long-term outcomes remain uncertain. This review addressed four questions: the human renal evidence specific to D. siamensis; venom and host pathways contributing to AKI; conclusions supported for antivenom timing and thrombotic microangiopathy (TMA); and quantifiable long-term kidney risk. PubMed and OpenAlex were searched from inception through 3 August 2026. Species-authenticated human evidence was separated from mixed-species or D. russelii studies and from venom-analytical and experimental evidence. Referral cohorts show AKI and dialysis burdens, but heterogeneous ascertainment, definitions, and care preclude pooled incidence. Proteomic and experimental studies support interacting coagulopathic, endothelial, hemodynamic, pigment, inflammatory, and direct renal pathways; no human study quantifies their relative contribution, and no D. siamensis study localizes specific venom antigens within renal tissue. Observational data support prompt use of indicated, regionally appropriate antivenom but do not validate a universal two-hour renal-protection threshold. TMA and long-term outcome evidence remain largely indirect. Serial renal and coagulation surveillance is warranted irrespective of whether injury is direct or indirect. Prospective, species-authenticated studies linking venom kinetics and toxin profiles to standardized renal phenotypes and follow-up are required. Full article

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14 pages, 416 KB

Open AccessReview

Bacterial Superantigen-Mediated Toxic Shock: Hyperinflammatory Trajectories and Extracorporeal Immunomodulation in Streptococcal Toxic Shock Syndrome

by Kuo-Hao Lo, Kuo-Cheng Lu, Yen-Hung Liu and Yi-Chou Hou

Toxins 2026, 18(9), 388; https://doi.org/10.3390/toxins18090388 - 8 Sep 2026

Viewed by 456

Abstract

Streptococcal toxic shock syndrome (STSS) is a fulminant manifestation of invasive group A Streptococcus infection characterized by superantigen-driven hyperinflammation, refractory shock, and rapidly progressive multiorgan dysfunction. Despite antimicrobial therapy, source control, intravenous immunoglobulin, and intensive organ support, some patients deteriorate rapidly, prompting interest [...] Read more.

Streptococcal toxic shock syndrome (STSS) is a fulminant manifestation of invasive group A Streptococcus infection characterized by superantigen-driven hyperinflammation, refractory shock, and rapidly progressive multiorgan dysfunction. Despite antimicrobial therapy, source control, intravenous immunoglobulin, and intensive organ support, some patients deteriorate rapidly, prompting interest in extracorporeal immunomodulation. This narrative review examines the biological rationale and clinical experience of hemoadsorption in STSS, supported by an illustrative case and comparison with published reports. Our patient developed vasopressor-dependent shock, acute kidney injury, thrombocytopenia, hepatic and myocardial injury, hyperlactatemia, and metabolic acidosis within 48 h. CytoSorb was integrated with continuous venovenous hemofiltration during ongoing deterioration, followed by hemodynamic and organ recovery; however, concurrent therapies preclude attribution of benefit to hemoadsorption. Published cases show a similar pattern, with extracorporeal escalation initiated during refractory shock and accumulating organ dysfunction rather than at a predefined biomarker threshold. Although experimental and observational evidence supports the biological activity of hemoadsorption, clinical evidence remains insufficient to establish a survival benefit. Current evidence does not support routine hemoadsorption for STSS. A rapidly progressive, multidimensional hyperinflammatory trajectory may instead provide a framework for future studies of patient selection and treatment timing. Full article

(This article belongs to the Collection Staphylococcus aureus Toxins)

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3 pages, 162 KB

Open AccessEditorial

The Role of Uremic Toxins in Comorbidities of Chronic Kidney Disease

by Suguru Yamamoto

Toxins 2026, 18(9), 387; https://doi.org/10.3390/toxins18090387 - 7 Sep 2026

Viewed by 358

Abstract

The number of patients with chronic kidney disease (CKD) has increased worldwide [...] Full article

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

15 pages, 530 KB

Open AccessArticle

Evaluation of the Efficacy of an Aflatoxin Binder in Holstein Dairy Cows in Perú Under Field Conditions

by Ivonne Salazar-Rodríguez, Iván López, Patricia Glorio-Paulet, Isabel Cristina Molina-Botero, Arturo Gerardo Valdivia-Flores and Carlos Gómez-Bravo

Toxins 2026, 18(9), 386; https://doi.org/10.3390/toxins18090386 - 7 Sep 2026

Viewed by 387

Abstract

The strategy of adding mycotoxin binders (MTBs) to feed lactating cows to reduce the absorption of aflatoxins (AFs) in the gastrointestinal tract and reduce milk contamination by hydroxylated AF compounds, especially AFM1, to below the maximum contaminant level (MCL) has become widespread. However, [...] Read more.

The strategy of adding mycotoxin binders (MTBs) to feed lactating cows to reduce the absorption of aflatoxins (AFs) in the gastrointestinal tract and reduce milk contamination by hydroxylated AF compounds, especially AFM1, to below the maximum contaminant level (MCL) has become widespread. However, the indiscriminate use of MTBs is very common. The objective of the study was to determine, under field conditions, the efficacy of an MTB in reducing AFM1 contamination in cow’s milk. Feed and raw milk were evaluated on-farm using lateral flow immunochromatography devices. In a 2 × 2 Latin square design, in two separate test periods, two diets were administered consecutively to each of twelve Holstein cows (multiparous, 220 ± 20 lactation days): 1: Basal diet naturally contaminated (120 AFB1 µg/d); 2: Basal diet plus an MTB (calcium carbonate and yeast fragments; 150 g/d). MTB intake effectively reduced the mean concentration, daily excretion, and percentage transfer rate of AFM1 in milk (0.724 ± 0.045 to 0.479 ± 0.055 µg/kg, p < 0.01; 15.6 ± 1.7 to 9.7 ± 1.5 µg/d, p < 0.05; and 13.0 ± 1.4 to 8.1 ± 1.3%, p < 0.05, respectively). These results highlight the need to evaluate, under field conditions, the effectiveness of MTBs as part of a mycotoxin contamination control program on dairy farms. Full article

(This article belongs to the Special Issue Aflatoxins: Contamination, Analysis and Control)

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19 pages, 19231 KB

Open AccessArticle

On the Application of Respirometric System on Hazelnut Samples to Predict Aflatoxin Production

by Francesca Bosco, Chiara Mollea, Gabriele Baldissone, Micaela Demichela and Davide Fissore

Toxins 2026, 18(9), 385; https://doi.org/10.3390/toxins18090385 - 6 Sep 2026

Viewed by 334

Abstract

In the present work, the correlation between the respirometric activity and the aflatoxin synthesis of the hazelnut microbiota has been investigated. Microcosms containing a monolayer of hazelnuts were maintained at controlled conditions in terms of temperature and humidity. To monitor microbial growth, CO [...] Read more.

In the present work, the correlation between the respirometric activity and the aflatoxin synthesis of the hazelnut microbiota has been investigated. Microcosms containing a monolayer of hazelnuts were maintained at controlled conditions in terms of temperature and humidity. To monitor microbial growth, CO₂ was evaluated along with the specific O₂ uptake rate, RO₂, measured by a respirometric sensor, usually applied in the evaluation of soil microbial activity. The respiratory quotient (RQ) was calculated and a linear relationship between RQ and produced aflatoxins was obtained. Depending on incubation time, four main clusters of RQ values were identified: for higher incubation time (15–40 days) RQ was lower than 2 and an aflatoxin amount of 0.31–0.35 μg/kg was observed. CO₂, O₂, and aflatoxin data have been used to develop an autoregressive model and excellent agreement between measurements and estimations was obtained. In most cases, an error lower than 1% on the estimated value of the mycotoxin amount revealed the accuracy of the evaluation of the RQ. The present work represents the first attempt to develop an effective method, fast and low-cost, for the in-line monitoring of mycotoxin contamination. Full article

(This article belongs to the Section Mycotoxins)

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19 pages, 8725 KB

Open AccessArticle

Integrated Fermentation, Microbiome and Metabolomic Profiles Reveal Rumen Lipotoxicity Induced by the Masked Mycotoxin Zearalenone-14-Glucoside

by Zixin Wang, Mingzhu Chen, Jialei Liu, Tao Wang, Zhe Sun and Xiaolu Jin

Toxins 2026, 18(9), 384; https://doi.org/10.3390/toxins18090384 - 6 Sep 2026

Viewed by 274

Abstract

The ubiquitous presence of modified mycotoxins such as zearalenone-14-glucoside (ZEN-14G) in agricultural resources presents a critical challenge to livestock safety, specifically regarding their capacity to disrupt lipid metabolism and fermentation in the rumen. This study aimed to evaluate the dose- and time-dependent direct [...] Read more.

The ubiquitous presence of modified mycotoxins such as zearalenone-14-glucoside (ZEN-14G) in agricultural resources presents a critical challenge to livestock safety, specifically regarding their capacity to disrupt lipid metabolism and fermentation in the rumen. This study aimed to evaluate the dose- and time-dependent direct effects of ZEN-14G on rumen fermentation characteristics, nutrient disappearance, and mycotoxin biotransformation under controlled in vitro conditions, and to explore the associated microbial and metabolic responses. An in vitro batch fermentation system was established with three ZEN-14G doses, namely control (CON), low dosage (GL), and high dosage (GH), across three time points (6, 12, and 24 h). Basic fermentation parameters, fat disappearance rates, and ZEN-14G metabolites were quantified, while 16S rRNA gene sequencing and untargeted metabolomics were conducted specifically on 24 h endpoint samples from the CON and GH groups to investigate downstream mechanistic disruptions. The results showed that while baseline pH homeostasis remained unaffected across groups, ZEN-14G dose-dependently inhibited fat disappearance, with the GH group exhibiting a significant reduction throughout fermentation. Targeted quantification confirmed that ZEN-14G was predominantly deglucosylated to free ZEN and reduced to α/β-ZEL. Endpoint multi-omics revealed that although overall α/β-diversity was maintained at 24 h, ZEN-14G induced fine-scale strain-level replacement (12% shared ASVs), marked by the depletion of the key lipolytic bacterium Prevotella sp. R79. Untargeted metabolomics showed marked disruptions in sphingolipid metabolism and linoleic acid oxidation, where the accumulation of cytotoxic oxidized fatty acids (12,13-EpOME) and membrane turnover markers (sphingosine) positively correlated with enriched Bacillota. In summary, under macroscopic acid–base homeostasis, masked ZEN-14G directly impairs ruminal lipid metabolism, alters microbial community structure at the strain level, and perturbs cell membrane lipid turnover strictly within an in vitro system. These findings establish a key mechanistic baseline for masked mycotoxin biotransformation in the rumen, highlighting the necessity for future in vivo feeding trials to fully evaluate their systemic risk profile in ruminants. Full article

(This article belongs to the Section Mycotoxins)

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52 pages, 611 KB

Open AccessReview

Global Occurrence, Co-Contamination Patterns, and Toxic Effects of Mycotoxins in Fish Feed: A Multi-Species Perspective Review

by Queenta Ngum Nji and Patrick Berka Njobeh

Toxins 2026, 18(9), 383; https://doi.org/10.3390/toxins18090383 - 6 Sep 2026

Viewed by 296

Abstract

Aquaculture has become the fastest-growing food-production sector worldwide, with increasing reliance on plant-based feed ingredients such as maize, soybean, wheat, rice, and oilseed meals. Although these ingredients reduce dependence on fishmeal, they are highly susceptible to fungal contamination and subsequent mycotoxin production. Global [...] Read more.

Aquaculture has become the fastest-growing food-production sector worldwide, with increasing reliance on plant-based feed ingredients such as maize, soybean, wheat, rice, and oilseed meals. Although these ingredients reduce dependence on fishmeal, they are highly susceptible to fungal contamination and subsequent mycotoxin production. Global surveys reveal widespread contamination of aquafeeds with major regulated mycotoxins, including aflatoxins, fumonisins, deoxynivalenol, zearalenone, ochratoxin A, and T-2 toxin, alongside emerging toxins such as enniatins, beauvericins, and sterigmatocystin metabolites. Aflatoxin B₁ is the most prevalent and toxic mycotoxin, with contamination prevalence often exceeding 80–100% in Africa and Asia with contamination levels surpassing 400 µg/kg in some regions of these continents. Fumonisins, deoxynivalenol, and zearalenone are also commonly detected, with fumonisins levels occasionally exceeding 7000 µg/kg. Mycotoxins induce diverse toxic effects in fish, including growth suppression, hepatotoxicity, nephrotoxicity, immunosuppression, oxidative stress, reproductive dysfunction, and mortality. Collectively, these findings highlight the urgent need for improved surveillance, feed management, and harmonized regulations addressing multi-mycotoxin exposure to safeguard aquaculture productivity, fish, and public health. This review synthesizes current knowledge on the global mycotoxin contamination patterns, analytical detection methods in fish feed and processed seafood as well as the toxicological effects of mycotoxins, with emphasis on species-specific responses and food safety implications. Full article

(This article belongs to the Special Issue Mycotoxin Occurrence, Toxicology, and Effects on Animals, Animal Feeds and Detoxification Methods)

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19 pages, 12142 KB

Open AccessArticle

Transcriptomic and Metabolomic Analyses of the Mechanisms Underlying Zearalenone Removal by Lactobacillus paracasei

by Min Gan, Peirong Chen, Rui Zeng, Fuhua Wang and Yarong Zhao

Toxins 2026, 18(9), 382; https://doi.org/10.3390/toxins18090382 - 4 Sep 2026

Viewed by 247

Abstract

Zearalenone (ZEN) is a mycotoxin produced by Fusarium species that is harmful to agricultural crops. Therefore, the prevention and control of ZEN contamination is an important concern for food safety. Lactobacillus paracasei 85 is a well-recognized probiotic with considerable potential for mycotoxin biocontrol [...] Read more.

Zearalenone (ZEN) is a mycotoxin produced by Fusarium species that is harmful to agricultural crops. Therefore, the prevention and control of ZEN contamination is an important concern for food safety. Lactobacillus paracasei 85 is a well-recognized probiotic with considerable potential for mycotoxin biocontrol owing to its diverse probiotic properties and antimicrobial activity. Based on its reported potential, we aimed to evaluate its ability to degrade ZEN using degradation assays under optimal conditions. Transcriptome sequencing, untargeted metabolomics, and integrated bioinformatics analyses were conducted to explore the molecular mechanisms underlying ZEN removal. Transcriptomic analysis showed that the strain activated central carbon and secondary metabolism during ZEN removal, and all seven differentially expressed genes closely related to carbohydrate metabolism were downregulated. Metabolomic analysis revealed that lipid and amino acid metabolism, in addition to carbohydrate metabolism, played important roles in ZEN removal. Correlation analysis between carbohydrate metabolism-related genes and their metabolites revealed that these genes were significantly associated with four metabolites: myo-inositol, guanosine, glycolic acid, and trehalose. As key nodes in the carbohydrate metabolism pathway, changes in the expression of these four metabolites and their interactions with genes may represent key regulatory factors responsible for the overall downregulation of carbohydrate metabolism. Full article

(This article belongs to the Topic Mycotoxins: Contamination, Prevention and Control, Toxic Mechanisms and Detoxification Strategies)

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20 pages, 1255 KB

Open AccessArticle

Mycotoxin Notifications in the European Rapid Alert System for Food and Feed (RASFF): Temporal Trends and Implications for Food Safety and Exposure

by Sandra Juárez-García, Ana Isabel Fernández-Díez, Rafael Mora-Medina, Nahúm Ayala-Soldado, Antonio Lora-Benitez, Rosario Moyano-Salvago and Ana María Molina-López

Toxins 2026, 18(9), 381; https://doi.org/10.3390/toxins18090381 - 4 Sep 2026

Viewed by 670

Abstract

Mycotoxin contamination in food and feed remains a major public health concern because of its potential toxicological impact and its global economic implications. Aflatoxins and ochratoxin A are of particular concern due to their carcinogenic, hepatotoxic, and nephrotoxic effects, highlighting the need for [...] Read more.

Mycotoxin contamination in food and feed remains a major public health concern because of its potential toxicological impact and its global economic implications. Aflatoxins and ochratoxin A are of particular concern due to their carcinogenic, hepatotoxic, and nephrotoxic effects, highlighting the need for effective surveillance systems to reduce dietary exposure in the population. This study analyzes 2479 mycotoxin-related notifications concerning both food and feed reported through the iRASFF system during the period 2020–2024, with the aim of characterizing temporal notification trends, identifying the most affected food products and geographical regions, and evaluating the evolution of control strategies implemented by competent authorities. The results did not show a statistically significant long-term increasing trend in the number of mycotoxin notifications, although interannual fluctuations may reflect both changes in contamination patterns and improvements in detection and reporting systems. Products originating outside the European Union accounted for 90.44% of notifications and showed a significantly higher mean number of notifications than products originating within the European Union. Turkey (24%) and the United States (14%) were the most frequently reported countries of origin at a global level. Aflatoxins were the most frequently detected mycotoxins in food (84%), followed by ochratoxin A (15%), mainly affecting nuts, cereals, fruits, vegetables and herbs and spices. These findings demonstrate that mycotoxins continue to represent a persistent challenge for European food safety. Strengthening surveillance systems, enhancing international cooperation, and adapting control strategies to emerging environmental and trade-related factors are essential to minimize consumer exposure, particularly to compounds with genotoxic and carcinogenic potential, and to improve risk management within the food supply chain. Full article

(This article belongs to the Special Issue Mycotoxins Along the Food Chain: Detection, Contamination and Control)

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23 pages, 2229 KB

Open AccessArticle

Toxic Plants Potentially Impacting the Health Status of Livestock in St. Kitts—A Surveillance Study

by Andras-Laszlo Nagy, Francesca Caloni, Regina Tose Kemper, Sofia Gonzalez Lleras, Heather Beigh, Christian DeJean, Maurice Matthew and Georgios Paraschou

Toxins 2026, 18(9), 380; https://doi.org/10.3390/toxins18090380 - 3 Sep 2026

Viewed by 302

Abstract

Tropical regions are characterized by exceptional biodiversity, including extremely diverse flora. Many plants produce chemical compounds that function as defense mechanisms, some of which are toxic to mammals, including livestock species. However, documentation of toxic plants in the Caribbean region remains limited. The [...] Read more.

Tropical regions are characterized by exceptional biodiversity, including extremely diverse flora. Many plants produce chemical compounds that function as defense mechanisms, some of which are toxic to mammals, including livestock species. However, documentation of toxic plants in the Caribbean region remains limited. The present study aimed to identify toxic and potentially toxic plant species affecting livestock on the island of Saint Christopher (St. Kitts) through surveys of a representative number of farms across all nine parishes. An extensive literature review was performed in order to characterize the local flora and to identify plant species with known or suspected toxic potential. Farm visits were conducted using a structured surveillance questionnaire developed by the authors. During these visits, representative photographs of commonly encountered toxic plants were taken. The identified plant species were classified according to the chemical nature of their active ingredient, and their main clinical effects were described. Ten plant species (Abrus precatorius, Senna occidentalis, Catharanthus roseus, Crotalaria retusa, Datura stramonium, Manihot esculenta, Mimosa pudica, Nerium oleander, Nicotiana tabacum and Ricinus communis) were found to be widespread throughout the island and have been documented in the literature as toxic to livestock. By knowing the distribution of these species, high-risk areas and pastures can be identified, thereby supporting targeted prevention and more effective management of future plant-associated toxicosis outbreaks. Full article

(This article belongs to the Special Issue Toxicity of Plant Natural Products and Their Applications)

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13 pages, 532 KB

Open AccessArticle

OnabotulinumtoxinA Improves Sleep Quality in Patients with Chronic Migraine: A Prospective Real-World Study

by Giovanna Viticchi, Lorenzo Falsetti, Marco Bartolini, Sergio Salvemini, Gioacchino De Vanna, Eleonora Beccacece, Najdi Tanuzi and Mauro Silvestrini

Toxins 2026, 18(9), 379; https://doi.org/10.3390/toxins18090379 - 3 Sep 2026

Viewed by 377

Abstract

Sleep disturbances are highly prevalent in patients with chronic migraine (CM) and are increasingly recognized as major contributors to disease burden and headache chronification. Growing evidence suggests that dysregulation of calcitonin gene-related peptide (CGRP) signaling and central sensitization may represent common biological mechanisms [...] Read more.

Sleep disturbances are highly prevalent in patients with chronic migraine (CM) and are increasingly recognized as major contributors to disease burden and headache chronification. Growing evidence suggests that dysregulation of calcitonin gene-related peptide (CGRP) signaling and central sensitization may represent common biological mechanisms linking migraine and sleep impairment. OnabotulinumtoxinA (OBT-A), an established preventive treatment for CM, inhibits the release of CGRP and other nociceptive mediators from trigeminal sensory neurons, thereby reducing peripheral and central sensitization. However, its effects on sleep quality remain incompletely characterized. The aim of this prospective real-world observational pilot study was to evaluate the impact of OBT-A treatment on sleep quality in patients with CM. Consecutive patients initiating OBT-A therapy at a tertiary headache center were enrolled and assessed at baseline (before the first OBT-A treatment cycle) and after three months, immediately before the second scheduled administration, using the Pittsburgh Sleep Quality Index (PSQI), alongside measures of migraine frequency, acute medication use, migraine-related disability, and headache impact. Fifteen patients completed follow-up evaluations. OBT-A treatment was associated with significant improvements across all clinical outcomes. Median monthly migraine days decreased from 18 to 10 (adjusted p = 0.006), while acute medication use, MIDAS scores, and HIT-6 scores were significantly reduced. Sleep quality improved markedly, with median PSQI scores decreasing from 10 to 6 (adjusted p = 0.006). Eleven of 15 patients (73.3%) achieved a ≥3-point reduction in PSQI, and the proportion of participants with pathological sleep quality (PSQI > 5) decreased from 86.7% to 53.3%. Although this categorical improvement did not reach statistical significance (exact p = 0.063), likely due to the limited sample size, it may nonetheless suggest a beneficial effect on sleep quality, although the lack of statistical significance warrants cautious interpretation. These findings provide preliminary real-world evidence that OBT-A treatment is associated with improved subjective sleep quality in patients with chronic migraine. Improvements in sleep quality occurred alongside reductions in migraine frequency, acute medication use, disability, and headache impact. Given the observational and uncontrolled design of the study, it remains unclear whether sleep improvement reflects a direct effect of OBT-A or occurs secondarily to improvements in migraine-related outcomes. Larger prospective controlled studies are needed to clarify the mechanisms underlying sleep improvement and its relationship with treatment response. Full article

(This article belongs to the Special Issue Application of Botulinum Neurotoxin in Headache or Facial Pain Disorders)

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14 pages, 11843 KB

Open AccessCommunication

Dystonia 3×3: A Training Guideline for Beginners in Botulinum Neurotoxin Treatment of Cervical Dystonia

by Sebastian Paus, Andreas Funke, Jürgen Hamacher, Bernhard Haslinger, Jan Heckelmann, Chi Wang Ip, Wolfgang H. Jost, Anatol Kivi, Stephan Klebe, John-Ih Lee, Ebba Lohmann, Frederic Mack, Axel Schramm, Andrea Stenner, Pawel Tacik, Uwe Walter and David T. Weise

Toxins 2026, 18(9), 378; https://doi.org/10.3390/toxins18090378 - 2 Sep 2026

Viewed by 541

Abstract

Cervical dystonia (CD) is a hyperkinetic movement disorder characterized by involuntary muscle contractions leading to abnormal postures of the head and neck. The injection of botulinum neurotoxin type A (BoNT-A) into the muscles involved is the treatment of choice for CD. BoNT-A therapy [...] Read more.

Cervical dystonia (CD) is a hyperkinetic movement disorder characterized by involuntary muscle contractions leading to abnormal postures of the head and neck. The injection of botulinum neurotoxin type A (BoNT-A) into the muscles involved is the treatment of choice for CD. BoNT-A therapy of CD requires appropriate training, which has not been standardized in Germany. To address the key challenges in BoNT-A education, an expert panel developed a simplified step-by-step treatment guideline for beginners, adapted from the established Col-Cap-Concept (“Dystonia 3×3”). Based on expert consensus, recommendations were developed for the core clinical elements of BoNT-A treatment in CD—recognition of the movement pattern, identification of target muscles, development of an injection plan, ultrasound-guided injection, and dosing, taking into account the target audience of the guideline. As such, Dystonia 3×3 provides a user-friendly beginner’s guidebook, enhancing accessibility and standardization of CD treatment training. Further research is required to evaluate its clinical efficacy and suitability for training. Full article

(This article belongs to the Section Bacterial Toxins)

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25 pages, 2855 KB

Open AccessArticle

Analysis of 113 Mycotoxins and Plant Toxins in Wheat, Soy and Pea Protein Concentrates from the German Market Reveals, i.a., a High Prevalence of Alterperylenol in Wheat Gluten

by Ahmed H. El-Khatib, Arnold Bahlmann, Christoph Hutzler and Stefan Weigel

Toxins 2026, 18(9), 377; https://doi.org/10.3390/toxins18090377 - 2 Sep 2026

Viewed by 424

Abstract

Wheat, soy and pea protein isolates used for the production of plant-based meat alternatives were analyzed for 87 mycotoxins and 26 plant toxins by means of a validated QuEChERS-based LC-MS/MS multi-method. For wheat gluten, the results revealed the presence of Alternaria toxins, deoxynivalenol, [...] Read more.

Wheat, soy and pea protein isolates used for the production of plant-based meat alternatives were analyzed for 87 mycotoxins and 26 plant toxins by means of a validated QuEChERS-based LC-MS/MS multi-method. For wheat gluten, the results revealed the presence of Alternaria toxins, deoxynivalenol, enniatins, ergot alkaloids and ochratoxin A (OTA). For soy protein, beauvericin, enniatin B and OTA were the most frequently detected mycotoxins, while for pea protein, OTA was the most frequently detected mycotoxin. From plant toxins, the tropane alkaloids atropine and scopolamine were detected in wheat gluten and soy protein. The emerging Alternaria toxin alterperylenol was reported for the first time in wheat gluten (85% of samples). OTA was present at high levels in all three matrices (exceeding the EU maximum level in one wheat gluten sample). Ergot alkaloids were found in 95% of wheat gluten samples, but none exceeded the ML. The highest co-occurrence of different toxins was observed in wheat gluten (median: 22, max: 27 toxins/sample), followed by soy protein (median: five, max: nine toxins/sample) and pea protein (median: one, max: five toxins/sample). Full article

(This article belongs to the Section Mycotoxins)

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28 pages, 2057 KB

Open AccessReview

Phytotoxins Produced by Diplodia and Other Fungal Species Involved in Oak (Quercus) Diseases

by Antonio Evidente

Toxins 2026, 18(9), 376; https://doi.org/10.3390/toxins18090376 - 31 Aug 2026

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Abstract

Forests are an indispensable resource for human existence in the different regions of the world. Forests are often concentrated in a few parts and vary in size. The most important and extensive green reserve on Earth is the Amazon rainforest. Unfortunately, the forests [...] Read more.

Forests are an indispensable resource for human existence in the different regions of the world. Forests are often concentrated in a few parts and vary in size. The most important and extensive green reserve on Earth is the Amazon rainforest. Unfortunately, the forests are continually suffering massive losses due to abiotic stresses and deforestation to obtain other arable lands and microbial diseases, particularly those caused by pathogenic fungi. Pathogenic fungi play an important role in inducing oak decline, which is one of the most relevant forest diseases globally. The pathogens also affect disease development and its global distribution. In this review, the phytotoxins produced by fungal pathogens of different oak species in various world regions are described in depth. In particular, the isolation, the chemistry and biology of phytotoxins synthesized by oak pathogenic fungi are reported, and their role in pathogenesis is also discussed. For some phytotoxins, the enantioselective synthesis, the structure–biological activity relationships, and their utilization in agro-industry and medical applications are also discussed. In addition, for the Diplodia species, the comparison between their secondary metabolite profile and taxonomy with those of fungal pathogens of other close forest plants is discussed. Thus, fungal diseases of numerous oak trees and the serious damages they cause to the forest heritage are described, as well as the chemical and biological properties and results of some of the structure–activity relationship (SAR) studies of the phytotoxins involved. In addition, for the Diplodia species both phylogenetically closely related and unrelated, comparison between their secondary metabolite profile with those of pathogens of other close forest plants, in combination with traditional taxonomic characteristics, has helped to better understand the pathogenic process relationships within the same fungal f the pathogenic process within the same fungal family. Full article

(This article belongs to the Special Issue Phytotoxin Produced by Fungi Pathogen for Forest Plants)

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Toxins, Volume 18, Issue 9 (September 2026) – 48 articles

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