Toxins

23 pages, 2353 KB

Open AccessArticle

Chemical, Biological, and Ecological Evidence for Aerobic Deoxynivalenol Detoxification in Agronomic Soil-Derived Bacterial Communities

by Natalia Martínez-Reyes, Rosa E. Cardoza, Estela Melcón-Fernández, Rafael Balaña-Fouce, Lea Brückner, Rocío Montes-Ruiz, Benedikt Cramer, Hans-Ulrich Humpf, Pedro A. Casquero and Santiago Gutiérrez

Toxins 2026, 18(6), 273; https://doi.org/10.3390/toxins18060273 - 22 Jun 2026

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Abstract

Deoxynivalenol (DON) is a prevalent trichothecene mycotoxin in cereals that poses food and feed safety risks while causing important economic losses. Microbial biotransformation offers a selective, mild strategy for DON detoxification. Here, we screened aerobic soil-derived bacterial communities from diverse agricultural environments, using [...] Read more.

Deoxynivalenol (DON) is a prevalent trichothecene mycotoxin in cereals that poses food and feed safety risks while causing important economic losses. Microbial biotransformation offers a selective, mild strategy for DON detoxification. Here, we screened aerobic soil-derived bacterial communities from diverse agricultural environments, using DON as the sole carbon source for this mycotoxin depletion. More than half of the tested enrichment samples showed a reduced DON signal, as observed by HPLC-UV. To assess the biological relevance, culture extracts were tested for cytotoxicity in HepG2 cells. Z13, a soil sample that depleted DON but produced no other detectable metabolites, showed reduced cytotoxicity, comparable to the negative control. In contrast, samples that depleted DON but produced 3-keto-DON remained toxic. High-resolution LC-MS analysis indicated the formation of metabolites putatively identified as 3-keto-DON in enrichment cultures and 3-epi-DON in a Devosia strain culture. Community composition was profiled with 16S rRNA gene amplicon sequencing, which showed that Z13 presented a remarkable drop in diversity upon microbial cultivation, and included genera such as Devosia, Nocardioides, and Pseudomonas. Together, these results provide integrated chemical, biological, and ecological evidence for aerobic DON biotransformation in soil-derived communities, identify pathway products, and highlight practical constraints related to community dependence and storage sensitivity. Full article

(This article belongs to the Special Issue Biosynthesis and Detoxification of Mycotoxins)

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12 pages, 649 KB

Open AccessArticle

Botulinum Toxin Treatment for Uncommon Phenotypes of Laryngeal Adductor Breathing Dystonia

by Domenico Antonio Restivo, Angelo Alito, Demetrio Milardi, Mario Stampanoni Bassi, Sara Lanza, Angelo Quartarone and Rosario Marchese-Ragona

Toxins 2026, 18(6), 272; https://doi.org/10.3390/toxins18060272 - 20 Jun 2026

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Abstract

Laryngeal adductor breathing dystonia (LABD) is a rare form of focal, task-specific respiratory dystonia affecting the laryngeal muscles of unknown aetiology. Unlike classical laryngeal dystonia (spasmodic dysphonia), LABD is not primarily characterised by impaired speech, but rather by dysfunction of respiratory laryngeal control. [...] Read more.

Laryngeal adductor breathing dystonia (LABD) is a rare form of focal, task-specific respiratory dystonia affecting the laryngeal muscles of unknown aetiology. Unlike classical laryngeal dystonia (spasmodic dysphonia), LABD is not primarily characterised by impaired speech, but rather by dysfunction of respiratory laryngeal control. The hallmark pathophysiological alteration consists of involuntary, action-induced adductor spasms of the laryngeal muscles during respiration, particularly during inspiration. LABD must be distinguished from inducible laryngeal obstruction (ILO), a broader, heterogeneous condition encompassing episodic, stimulus-triggered supraglottic or glottic closure, associated with asthma, reflux, or psychological triggers, that is generally not task-specific and lacks the neurological substrate characteristic of dystonia. In contrast, LABD is a persistent, effort-dependent, neurologically driven dystonia, demonstrable by paradoxical adductor spasms on fibreoptic laryngoscopy during normal inspiration and confirmed electromyographically by paradoxical thyroarytenoid muscle activation instead of the expected inspiratory relaxation. Traditional treatments, including respiratory retraining, speech therapy, biofeedback, psychotherapy, benzodiazepines, dopamine-blocking agents, and anticholinergic drugs, have proved largely ineffective. Tracheostomy may be required in cases of severe respiratory compromise. Botulinum toxin type A (BoNT/A) injections have been reported to successfully reduce inspiratory stridor in selected patients. Here, we present three cases of LABD displaying distinct phenotypes, in which typical features were associated with involvement of extra-laryngeal cranial districts, further expanding the known phenotypic spectrum of this condition. Full article

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15 pages, 4156 KB

Open AccessArticle

Enhancing Neuronal Networks with Rhinella schneideri Skin Secretion Molecules: Implications for Neurodegenerative Disorders

by Giovanna Arruda Caires, Isabela Souza Pereira, Carlos DeOcesano-Pereira, Daniel Carvalho Pimenta, Irina Kerkis, Juliana Mozer Sciani and Hugo Vigerelli

Toxins 2026, 18(6), 271; https://doi.org/10.3390/toxins18060271 - 20 Jun 2026

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Abstract

Neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases, are hallmarked by the progressive degeneration of neuronal networks. Given the lack of disease-modifying cures, current therapies are limited to symptomatic relief. Here, we investigated the neurotrophic potential of the skin secretion (SS) from Rhinella schneideri [...] Read more.

Neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases, are hallmarked by the progressive degeneration of neuronal networks. Given the lack of disease-modifying cures, current therapies are limited to symptomatic relief. Here, we investigated the neurotrophic potential of the skin secretion (SS) from Rhinella schneideri, its polar fraction (PF) and nonpolar (NPF) fraction, and respective subfractions on the morphology of neuron-like cells. Following initial H₂O-CH₂CL₂ partitioning, PF and NPF subfractions were isolated via RP-HPLC. Chemical characterization using LC-MS-IT-TOF identified eight distinct molecules, notably bufotenine and marinobufagin. Cytotoxicity screening established safe working concentrations (100–250 ng/mL for SS/PF; 250–500 ng/mL for NPF and subfractions) for downstream morphological evaluations using High Content Screening (HCS). The subfraction polar 5 (SfP5) elicited a robust neurotrophic response, significantly enhancing all assessed morphometric parameters: total neurite outgrowth (+72%), branching points (+120%), maximum process length (+60%), and total number of processes (+35%). Our data show that Rhinella schneideri SS contains molecules that improve in vitro neuronal networks, serving as a promising source for preliminary screening of neuroprotective effects. Full article

(This article belongs to the Section Animal Venoms)

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6 pages, 1140 KB

Open AccessCase Report

Dangerous Measures: A Case Report and Review of Motoro Ray Envenomation

by Philip Dwek, Omer Jamal, Shaleesa Clarke, Kiran Wadhawan and Andrea K. Boggild

Toxins 2026, 18(6), 270; https://doi.org/10.3390/toxins18060270 - 19 Jun 2026

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Abstract

Aquatic envenomations may cause severe tissue injury, neurologic morbidity, and even mortality among those whose leisure and/or occupational activities expose them to marine and freshwater animals. The Motoro ray, or Potamotrygon motoro (also known as an ocellate river stingray) is endemic to freshwater [...] Read more.

Aquatic envenomations may cause severe tissue injury, neurologic morbidity, and even mortality among those whose leisure and/or occupational activities expose them to marine and freshwater animals. The Motoro ray, or Potamotrygon motoro (also known as an ocellate river stingray) is endemic to freshwater tributaries throughout Brazil, and is a frequent source of severe envenoming of local fisherman and those residing near waterways. Local wound management including immersion in warm water, wound cleaning and debridement, as well as antibiotics are mainstays of treatment, as are local anesthetics (e.g., nerve blocks) and systemic opioid analgesics; however, high-quality evidence supporting such interventions is lacking. We present a case of a Canadian who was envenomed by his pet Motoro ray, and describe his clinical presentation and evolution of symptoms over the subsequent months. With the ever-increasing trade of exotic wildlife, clinicians, public health authorities, and those within the broader wildlife regulatory ecosystem should be attuned for unanticipated adverse consequences, such as those described herein. We further situate this case within the existing published literature around this particular species of ray, which is not typically considered an ornamental fish. Full article

(This article belongs to the Special Issue Venoms of Aquatic Organisms: Biochemistry, Evolution, and Future Perspectives)

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11 pages, 2170 KB

Open AccessArticle

The Impact of OnabotulinumtoxinA on Oral Pain Medication Prescription Fills and Low-Value Care in Patients with Cervical Dystonia in the United States: A Retrospective Claims Analysis

by Christopher Rhyne, Annaliza Dominguez, Ning Cheng, Shivaji Manthena, Krutika Parikh and Bahman Jabbari

Toxins 2026, 18(6), 269; https://doi.org/10.3390/toxins18060269 - 17 Jun 2026

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Abstract

(1) Background: While evidence supporting the use of onabotulinumtoxinA in patients with cervical dystonia (CD) is well-established, more evidence is needed to understand if onabotulinumtoxinA treatment can reduce reliance on addictive medication. (2) Methods: This retrospective study used claims data to evaluate the [...] Read more.

(1) Background: While evidence supporting the use of onabotulinumtoxinA in patients with cervical dystonia (CD) is well-established, more evidence is needed to understand if onabotulinumtoxinA treatment can reduce reliance on addictive medication. (2) Methods: This retrospective study used claims data to evaluate the impact of onabotulinumtoxinA treatment on opioid, benzodiazepine (BZD), and skeletal muscle relaxant (SMR) prescription fills among patients diagnosed with CD with prior use of these medications. Among the 564 eligible patients, three non-mutually exclusive cohorts were identified based on medication use data: opioid (n = 306), BZD (n = 271), and SMR (n = 371). The follow-up period continued for 12 months after onabotulinumtoxinA treatment initiation. (3) Results: Among patients with >1 opioid fill at baseline, 30.4% had no opioid fills in the 12-month period following onabotulinumtoxinA initiation. The opioid cohort had significantly reduced mean opioid prescription fills per patient (17.0%; p < 0.0001) in the follow-up period compared with baseline. A 30.0% decrease was observed in the mean morphine milligram equivalent (MME)/day after onabotulinumtoxinA initiation (p < 0.0001). Similar trends of decreased BZD and SMR prescription fills were observed. (4) Conclusions: Following initiation of onabotulinumtoxinA treatment, patients living with CD who had prior opioid, BZD, or SMR use had significant reductions in respective prescription fills for opioids, BZDs, and SMRs. Full article

(This article belongs to the Section Bacterial Toxins)

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17 pages, 3585 KB

Open AccessArticle

Broad-Spectrum Antiviral and Antibacterial Activity of the Scorpion Venom Peptide HP1090

by Ariel J. Asuzano, Lia-Raluca Olari, Nourice Jaber, Verena Vogel, Marina S. Fam, Armando A. Rodríguez Alfonso, Nico Preising, Ludger Ständker, Barbara Spellerberg, Hans-Georg Breitinger, Ulrike Breitinger and Jan Münch

Toxins 2026, 18(6), 268; https://doi.org/10.3390/toxins18060268 - 16 Jun 2026

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Abstract

HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited [...] Read more.

HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited dose-dependent virucidal activity against multiple enveloped viruses, including herpes simplex virus type 1 and 2 (HSV-1, HSV-2), human immunodeficiency virus type 1 (HIV-1), and Zika virus (ZIKV), with IC₅₀ values ranging from 14.7 to 56.1 µg/mL. No activity was observed against the non-enveloped human rhinovirus 14 (HRV14), suggesting strict dependence on a viral lipid envelope. Consistent with a membrane-targeting mechanism, HP1090 induced rapid and concentration-dependent permeabilization of virus-like liposomes. HP1090 also displayed antibacterial activity against selected clinically relevant pathogens in agar-based growth inhibition assays. However, antibacterial effects required substantially higher concentrations (>125 µg/mL) and varied between bacterial species, with some strains showing little or no susceptibility. Membrane permeabilization assays in Listeria monocytogenes demonstrated disruption of bacterial membrane integrity as a contributing mechanism. No cytotoxicity was observed on mammalian cell lines at effective antiviral concentrations. Together, these findings establish HP1090 as a membrane-active venom peptide and, by linking envelope-dependent viral inactivation with bacterial membrane permeabilization, support a shared biophysical mode of action relevant to the development of membrane-targeting anti-infectives. Full article

(This article belongs to the Section Animal Venoms)

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29 pages, 1226 KB

Open AccessReview

Biophysical and Biochemical Assays for Screening Small Molecule Inhibitors Targeting Toxin–Ribosome Interactions

by Eric J. Bryan, Vishal Vijayanand, Xiao-Ping Li, John E. McLaughlin, Michael Pierce, Arkajyoti Dutta and Nilgun E. Tumer

Toxins 2026, 18(6), 267; https://doi.org/10.3390/toxins18060267 - 16 Jun 2026

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Abstract

Ribosome-inactivating proteins are a class of toxins that target eukaryotic ribosomes, inhibit protein synthesis, and ultimately induce cell death. Several of these toxins pose significant clinical and public health threats. Among these, ricin, derived from the castor bean plant (Ricinus communis), [...] Read more.

Ribosome-inactivating proteins are a class of toxins that target eukaryotic ribosomes, inhibit protein synthesis, and ultimately induce cell death. Several of these toxins pose significant clinical and public health threats. Among these, ricin, derived from the castor bean plant (Ricinus communis), is a highly potent biotoxin with recognized bioterrorism potential. Other ribosome-inactivating proteins, including Shiga toxin produced by pathogenic Shigella and Escherichia coli, as well as mucoricin from Mucorales fungi, contribute to disease severity and can lead to life-threatening complications. Despite these risks, no approved therapeutics are currently available. The development of effective inhibitors depends on robust and well-defined strategies to identify and validate small molecules that disrupt toxin–ribosome interactions. Efforts to target the catalytic active site have met with limited success, largely due to its broad, shallow, and highly polar architecture, which is not conducive to high-affinity binding by drug-like molecules. In contrast, the ribosome-binding interface represents a more tractable target, as it is essential for toxin recruitment and offers more structurally defined and druggable features. Inhibitors targeting this interface can also exert allosteric effects by disrupting long-range conformational coupling between the ribosome-binding region and the active site, thereby attenuating catalytic activity without directly engaging the catalytic pocket. In this review, we compile and evaluate biophysical and biochemical assays for the discovery and characterization of small-molecule inhibitors that target toxin–ribosome interactions. We examine in vitro binding approaches, including surface plasmon resonance-based fragment screening and fluorescence anisotropy assays for ranking inhibitory activity. We further review biochemical and molecular assays that assess ribosome protection from toxin-mediated depurination, along with complementary cell-based assays that evaluate functional rescue in cellular systems. Collectively, this review consolidates current screening methodologies and highlights opportunities to refine assay strategies, thereby supporting the advancement of targeted therapeutics. Full article

(This article belongs to the Special Issue Advances in Ricin and Shiga Toxin Inhibitors)

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14 pages, 2037 KB

Open AccessArticle

Development of an Innovative Galleria mellonella Model for Ricin Poisoning

by Annabelle Garnier, Emilie Tessier, Arnaud Avril and Clémence Rougeaux

Toxins 2026, 18(6), 266; https://doi.org/10.3390/toxins18060266 - 12 Jun 2026

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Abstract

Ricin is considered a chemical and biological weapon. It is found in the seeds of a plant, Ricinus communis. There are different isoforms of ricin with different levels of toxicity, depending on the R. communis plant. There is no current prophylaxis and [...] Read more.

Ricin is considered a chemical and biological weapon. It is found in the seeds of a plant, Ricinus communis. There are different isoforms of ricin with different levels of toxicity, depending on the R. communis plant. There is no current prophylaxis and specific treatment for ricin poisoning is recent. Assessing potential countermeasures against this toxin still relies on testing on vertebrate animal models. Galleria mellonella larva, already used for the testing of bacteria, viruses, and fungi, represents an alternative model that is more ethical, inexpensive, and easier to use. In this study, we demonstrated for the first time the sensitivity of G. mellonella larvae to different cultivars of ricin. We observed mortality and a reduction in health index scoring over the days of testing. The health index scoring was based on the survival, the melanization, the mobility, and the capacity of larvae to produce a cocoon or not. Mortality was cultivar- and dose-dependent. Mortality of G. mellonella larvae was reduced when they were treated with a monoclonal antibody and concomitantly injected with ricin. Thus, G. mellonella represents a rapid and simple model of ricin poisoning, and, more particularly, a relevant model to test new therapeutics against ricin. Full article

(This article belongs to the Section Plant Toxins)

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10 pages, 228 KB

Open AccessArticle

Long-Term Risk of Stroke After Snake Envenomation: A Nationwide Population-Based Cohort Study in Korea

by JeongMi Moon, ByeongJo Chun, EuJene Jung, DongKi Kim and YeonJi Seong

Toxins 2026, 18(6), 265; https://doi.org/10.3390/toxins18060265 - 12 Jun 2026

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Abstract

Snake envenomation causes acute cerebrovascular complications, but its long-term effect on stroke risk remains unclear. This study suggests that snake envenomation may be associated with long-term stroke risk. Using the Korean National Health Insurance Service database, we conducted a nationwide population-based cohort study [...] Read more.

Snake envenomation causes acute cerebrovascular complications, but its long-term effect on stroke risk remains unclear. This study suggests that snake envenomation may be associated with long-term stroke risk. Using the Korean National Health Insurance Service database, we conducted a nationwide population-based cohort study to evaluate the long-term risk of stroke following snake envenomation. A total of 764 adult patients diagnosed with snake envenomation and treated with antivenom were identified and matched with 3056 control patients (1:4) by age, sex, and socioeconomic status, excluding those with prior cerebrovascular disease. Stroke outcomes were defined using ICD-10 diagnostic codes and healthcare utilization criteria. After a 1-year lag period was applied to minimize reverse causation, multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios for total, ischemic, and hemorrhagic strokes. During 10 years of follow-up, snake envenomation was associated with a significantly increased risk of total stroke (aHR 1.42 (95% CI 1.01–1.99)), particularly hemorrhagic stroke (aHR 2.55 (95% CI 1.12–5.80)), whereas no significant association was observed with ischemic stroke. Interaction analyses showed a stronger association among men with diabetes mellitus, particularly for hemorrhagic stroke. In addition, severe envenomation with disseminated intravascular coagulation or requiring transfusion was associated with a higher long-term risk of hemorrhagic stroke. These findings highlight the need for further investigations of long-term cerebrovascular complications of snake envenomation, particularly hemorrhagic stroke in vulnerable populations. Full article

(This article belongs to the Section Animal Venoms)

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19 pages, 4853 KB

Open AccessCommunication

Ustiloxins and Ustilaginoidins in the Sclerotia Generated from Rice False Smut Balls and Their Contents

by Dan Xu, Xuwen Hou, Liyao Liu, Xingyi Luo, Pengfei Wang, Jiankun Miao, Hai Dong, Daowan Lai and Ligang Zhou

Toxins 2026, 18(6), 264; https://doi.org/10.3390/toxins18060264 - 11 Jun 2026

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Abstract

Rice false smut (RFS) caused by the ascomycete Ustilaginoidea virens (teleomorph: Villosiclava virens) is a destructive fungal disease all over the world. The RFS balls are ball-like colonies transformed from individual grains through the infection of U. virens. The sclerotia, which [...] Read more.

Rice false smut (RFS) caused by the ascomycete Ustilaginoidea virens (teleomorph: Villosiclava virens) is a destructive fungal disease all over the world. The RFS balls are ball-like colonies transformed from individual grains through the infection of U. virens. The sclerotia, which are dormant structures, typically generate from the late-stage RFS balls, and produce ascospores that play a dominant role in the life cycle of the pathogen. U. virens can produce mycotoxins, mainly including ustiloxins and ustilaginoidins, that are toxic to rice plants and animals and pose a serious threat to their health. Though ustiloxins and ustilaginoidins have been isolated from the RFS balls, their distribution and contents in the sclerotia remain unclear. In this study, a systematic content analysis of main mycotoxins was conducted on the sclerotia and other parts of the late-stage RFS balls. Ustiloxins were predominantly found in the sclerotia and middle layer, whereas ustilagnoidins mainly accumulated in the outer and middle layers and rarely accumulated in the sclerotia and inner layer of RFS balls. The findings were further supported by transcriptome and RT–qPCR analysis data. The different accumulation and distribution of these two kinds of mycotoxins in the sclerotia and other parts of the RFS balls may be related to their specific physiological functions and deserve further investigation. Full article

(This article belongs to the Special Issue Mycotoxin Contamination in Food and Feed)

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17 pages, 4427 KB

Open AccessArticle

Study of In Silico Binding Interactions and In Vitro Biosorption of Type A Trichothecenes Using Devil Fish Chitosan

by Martha Elena Aguilera Morales, Olga Nelly Rodríguez-Peña, Luis Barbo Hernández-Portilla and Cesar Mateo Flores-Ortíz

Toxins 2026, 18(6), 263; https://doi.org/10.3390/toxins18060263 - 10 Jun 2026

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Abstract

Trichothecenes are the most common Fusarium mycotoxin contaminants of grains and their related products. Searching for effective adsorbents remains a major challenge in mycotoxicology, due to the low polarity and bulky chemical structure of type A trichothecenes. This study aimed to investigate in [...] Read more.

Trichothecenes are the most common Fusarium mycotoxin contaminants of grains and their related products. Searching for effective adsorbents remains a major challenge in mycotoxicology, due to the low polarity and bulky chemical structure of type A trichothecenes. This study aimed to investigate in silico chitosan binding to type A trichothecenes such as diacetoxyscirpenol (DAS), neosolaniol (NEO), T-2 toxin (T2), and HT-2 toxin (HT2) and to study in vitro the devil fish chitosan biosorption capacity under two pH conditions (pHs 3 and 8). Molecular dynamic experiments showed that the chitosan monomers D-glucosamine and N-acetyl-D-glucosamine mostly bound to trichothecenes through the O in hydroxyls and glycosidic bonds and through their functional groups containing nitrogen. DAS exhibited a 9.44-, 6.39-, and 4.54-fold increase in the number of intermolecular contacts with chitosan compared to NEO, HT2 and T2, respectively. Moreover, in vitro experiments showed that at pH 3, chitosan exhibited a significant DAS sorption efficiency of 31.60% (p < 0.005), corresponding to a mass-normalized sorption capacity of 126.4 ng/mg. In contrast, no significant differences in sorption were observed at pH 8 (p > 0.05). Regarding NEO, T2, and HT2, no significant adsorption was detected under either pH condition (p > 0.05). This study is the first attempt to elucidate chitosan’s capacity to bind DAS and propose a mechanism for that interaction. Full article

(This article belongs to the Special Issue Advanced Detoxification Technologies for Mycotoxins)

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10 pages, 367 KB

Open AccessCommunication

Survey on Ochratoxin A Occurrence in Cured Meat Products in The Netherlands

by Marta Magdalena Sopel, Hester van den Top, Josipa Grzetic Martens and Monique de Nijs

Toxins 2026, 18(6), 262; https://doi.org/10.3390/toxins18060262 - 9 Jun 2026

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Abstract

Ochratoxin A (OTA) is a toxic metabolite produced by fungi, that can be present on various food products, cereals and plant-derived (raw) feed (materials). It was demonstrated that OTA has toxic effects after consumption by both animals and humans. Therefore, the European Food [...] Read more.

Ochratoxin A (OTA) is a toxic metabolite produced by fungi, that can be present on various food products, cereals and plant-derived (raw) feed (materials). It was demonstrated that OTA has toxic effects after consumption by both animals and humans. Therefore, the European Food Safety Authority (EFSA) concluded that contribution to human exposure of OTA from (processed) meats should not be ignored. The objective of this study was to assess the occurrence of OTA; thus, data on OTA in cured meats were collected. An in-house validated analytical method using methanol extraction, clean-up with an immunoaffinity columns and LC-MS/MS detection was applied. Quantification was done through the external calibration of standards in solvent using ¹³C₂₀ OTA internal standard, with a reporting limit of 0.2 µg/kg and LOQ of 0.04 µg/kg. A total of 50 cured meat products were obtained from Dutch supermarkets. OTA was detected at or above the reporting limit in four samples of cured ham (range 0.30 µg/kg to 79.8 µg/kg) and two samples of sausages (0.2 µg/kg and 0.41 µg/kg). Overall, OTA was detected in twenty samples, and it was concluded that OTA occurred above the LOQ in 40% of cured meats analyzed. Full article

(This article belongs to the Special Issue Advances in Contamination, Detection and Risk Assessment of Mycotoxins)

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17 pages, 10285 KB

Open AccessArticle

Regional Brain Localization of Botulinum Toxin Type A-Truncated Synaptosomal-Associated Protein 25 After Injection into the Rat Hind Paw

by Dalia Nemanić, Mihael Grdunac, Petra Šoštarić Mužić, Patrik Meglić, Ivica Matak and Lidija Bach-Rojecky

Toxins 2026, 18(6), 261; https://doi.org/10.3390/toxins18060261 - 9 Jun 2026

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Abstract

We previously demonstrated that botulinum neurotoxin A (BoNT-A) exerts bilateral antinociceptive effects, involving trans-synaptic transport at the level of the lumbar spinal cord. However, the potential distribution of the toxin to supraspinal sites has not yet been investigated. In the present study, we [...] Read more.

We previously demonstrated that botulinum neurotoxin A (BoNT-A) exerts bilateral antinociceptive effects, involving trans-synaptic transport at the level of the lumbar spinal cord. However, the potential distribution of the toxin to supraspinal sites has not yet been investigated. In the present study, we examined the distribution of cleaved SNAP-25 (cl-SNAP-25), a marker of BoNT-A activity, in the rat brain following peripheral unilateral BoNT-A administration. Brain tissues from rats treated with BoNT-A (7 U/kg, into the hind paw) were analyzed using immunofluorescent tyramide signal amplification to detect cl-SNAP-25. To assess the contribution of trans-synaptic transport, a BoNT-A-neutralizing antitoxin (2 IU) was administered intrathecally 24 h after BoNT-A injection. Signal intensity was evaluated using a semi-quantitative immunohistochemical scoring method based on cl-SNAP-25-positive nerve fibers. Bilateral cl-SNAP-25 immunoreactivity was observed in multiple supraspinal regions, most prominently within the trigeminal complex and the facial and gracile nuclei. Signal intensity was significantly reduced by intrathecal antitoxin, indicating that trans-synaptic transport contributes to central BoNT-A distribution. Peripherally administered BoNT-A reaches distant supraspinal regions, possibly via neuronal retrograde and trans-synaptic transport. Further studies are warranted to clarify exact pathways and alternative distribution routes, determine the functional relevance of central BoNT-A presence, and assess its clinical implications. Full article

(This article belongs to the Section Bacterial Toxins)

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19 pages, 7081 KB

Open AccessArticle

Effects of Chlorogenic Acid on Deoxynivalenol (DON)-Induced Ferroptosis in Porcine Alveolar Macrophages

by Jinglan Zhang, Xinuo Lai, Zhiwei Na, Junliang Deng, Zhihua Ren and Tong Fu

Toxins 2026, 18(6), 260; https://doi.org/10.3390/toxins18060260 - 9 Jun 2026

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Abstract

Deoxynivalenol (DON) is a mycotoxin commonly found in food crops and animal feed worldwide. Its pronounced toxicity in pigs poses a serious risk to the swine industry and to human health. This study focused on two central features of ferroptosis—iron metabolism and lipid [...] Read more.

Deoxynivalenol (DON) is a mycotoxin commonly found in food crops and animal feed worldwide. Its pronounced toxicity in pigs poses a serious risk to the swine industry and to human health. This study focused on two central features of ferroptosis—iron metabolism and lipid peroxidation—and examined how chlorogenic acid (CGA) affects DON-induced ferroptosis in porcine alveolar macrophages (PAMs) via cell-based assays and oxidative lipid metabolomics. These findings show that DON disrupts intracellular iron homeostasis by altering iron-handling proteins (upregulating TFR1 and DMT1 and downregulating FPN1), which may lead to iron overload. Concurrently, DON impairs the GPX4 antioxidant axis (downregulating GPX4, SLC3A2, SLC7A11, and GCLC) and increases ROS, and exposure led to a significant increase in numerous oxidized lipid metabolites, consistent with elevated lipid peroxidation, culminating in ferroptosis in PAMs. CGA mitigates these effects by restoring iron homeostasis and reestablishing GPX4 axis function, thereby reducing oxidative stress. Moreover, CGA suppresses lipid peroxidation pathways, notably linoleic acid oxidation metabolism. In conclusion, CGA protects PAMs and mitigates the proferroptotic effects of DON. 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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21 pages, 4930 KB

Open AccessReview

Fusarium Mycotoxins and Their Modified Forms—Occurrence, Toxicity and Analytical Aspects

by Sanja Furmeg, Vesna Jaki Tkalec, Manuela Zadravec and Ana Vulić

Toxins 2026, 18(6), 259; https://doi.org/10.3390/toxins18060259 - 5 Jun 2026

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Abstract

Fusarium mycotoxins pose a major challenge for agriculture and the food industry due to their frequent occurrence in cereals. In addition to conventional mycotoxins, modified mycotoxins, including the subgroup of masked mycotoxins, are receiving increasing attention. These compounds are formed through plant defence [...] Read more.

Fusarium mycotoxins pose a major challenge for agriculture and the food industry due to their frequent occurrence in cereals. In addition to conventional mycotoxins, modified mycotoxins, including the subgroup of masked mycotoxins, are receiving increasing attention. These compounds are formed through plant defence mechanisms, food processing or biological transformations and are often undetectable using conventional analytical methods. Due to their potential reactivation in the digestive system of humans and animals, masked mycotoxins represent a hidden threat to food safety. This article examines the mechanisms of formation of modified mycotoxins, their occurrence in the food chain and their potential health risks. Particular emphasis is placed on the analytical methods required for their detection, including advanced chromatographic and spectrometric techniques. Understanding modified mycotoxins is crucial for the development of more effective control and prevention strategies. Improved agronomic practices, proper storage and advances in detection methods are essential to reduce exposure to these compounds and ensure food safety. This study provides a comprehensive overview of the current state of research on modified mycotoxins and underlines the need for further scientific research and regulatory guidance to protect consumer health and maintain confidence in the food industry. Full article

(This article belongs to the Special Issue Advances in Contamination, Detection and Risk Assessment of Mycotoxins)

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33 pages, 5559 KB

Open AccessArticle

Algicidal Monoterpenes Against Toxin-Producing Microcystis aeruginosa with Reduced Toxicity Toward Chlorella sorokiniana: In Vitro, Molecular Docking, and ADMET Study

by El Mehdi Darrag, Yasser Essadki, Saad Zekri, Halima Chernane, Abderrahmane Romane, Ismail Hdoufane, Driss Cherqaoui, Brahim Oudra, Abdelilah Meddich, Vitor Vasconcelos and Abdelaziz Baçaoui

Toxins 2026, 18(6), 258; https://doi.org/10.3390/toxins18060258 - 5 Jun 2026

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Abstract

Harmful algal blooms pose a persistent threat to the integrity of freshwater ecosystems and public health. However, there are no selective chemical control agents available to suppress cyanobacterial growth without damaging beneficial phytoplankton. In this study, ten structurally diverse monoterpenes were assessed in [...] Read more.

Harmful algal blooms pose a persistent threat to the integrity of freshwater ecosystems and public health. However, there are no selective chemical control agents available to suppress cyanobacterial growth without damaging beneficial phytoplankton. In this study, ten structurally diverse monoterpenes were assessed in vitro for their differential activity against the potent toxin-producing cyanobacterium Microcystis aeruginosa and the ecologically valuable microalga Chlorella sorokiniana using disc diffusion (DDM) and minimum inhibitory concentration (MIC) assays. Inhibition zones against M. aeruginosa ranged from 6.9 to 43.6 mm, with thymol recording the largest zone (43.6 mm). MIC values ranged from 0.25 to >1 mg/mL for both organisms, and selectivity indices identified camphor and carvone as the most cyanobacterium-preferential compounds, while carene and α-pinene showed the inverse selectivity pattern. Molecular docking against six AlphaFold2-predicted target proteins, photosynthetic complexes, Adenosine Triphosphate (ATP) synthase subunits, and superoxide dismutase (SOD) from both organisms, revealed binding affinities between −3.9 and −6.2 kcal/mol. Phenolic monoterpenes consistently engaged active-site glutamate and aspartate residues via hydrogen bonds and Pi–Anion interactions, most strikingly in the M. aeruginosa ATP synthase, whereas the M. aeruginosa SOD represented the least amenable target for all compounds. Computational ADMET profiling confirmed favorable pharmacokinetic properties and low predicted toxicity for the full panel. Full article

(This article belongs to the Section Marine and Freshwater Toxins)

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17 pages, 4711 KB

Open AccessArticle

Recombinant Human Fab Antibodies Differentially Neutralize Shiga Toxin in Renal Epithelial and Endothelial Cells

by Fernando D. Gómez, Daniela Luz, Isabel Chinen, Daniel Girón, Raissa L. Ferreira, Camila Henrique, Ariela O. P. Bom, Izabella M. Henrique, Wanderson Marques da Silva, Flavia Sacerdoti, Elizabeth S. Miliwebsky, Gang Chen, Claudia C. Carbonari, Sachdev S. Sidhu, Roxane M. F. Piazza and María Marta Amaral

Toxins 2026, 18(6), 257; https://doi.org/10.3390/toxins18060257 - 5 Jun 2026

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Abstract

Hemolytic Uremic Syndrome (HUS) is a severe clinical manifestation primarily triggered by Shiga toxin-producing Escherichia coli (STEC). While Shiga toxins (Stx) are central to the development of systemic endothelial damage, current recombinant antibody developments have overwhelmingly focused on neutralizing the Stx2 subtype. However, [...] Read more.

Hemolytic Uremic Syndrome (HUS) is a severe clinical manifestation primarily triggered by Shiga toxin-producing Escherichia coli (STEC). While Shiga toxins (Stx) are central to the development of systemic endothelial damage, current recombinant antibody developments have overwhelmingly focused on neutralizing the Stx2 subtype. However, numerous STEC isolates produce Stx1 either independently or alongside Stx2, revealing a critical need to diversify the antibody repertoire for comprehensive antitoxin therapies. To address this, we characterized two novel, fully human recombinant Fabs targeting Stx1 (FabB6:Stx1 and FabC8:Stx1) selected from a synthetic library via phage display. We evaluated their binding specificity and neutralizing activity in Vero and human proximal tubular epithelial (HK-2) cells, as well as in primary human glomerular endothelial cells (HGEC exposed to HUS-derived STEC supernatants. Both Fabs exhibited high specificity and nanomolar affinity for Stx1. Notably, they displayed cell-type-dependent neutralization profiles, with FabC8:Stx1 demonstrating superior and more consistent neutralization in HK-2 cells. Crucially, when evaluated alongside previously characterized anti-Stx2 antibodies (FabC11:Stx1/Stx2 and FabF8:Stx2), the Stx1-specific Fabs conferred complementary protection against clinical STEC isolates. These findings support the inclusion of Stx1-targeting recombinant antibodies into broader multi-toxin neutralization strategies, thereby expanding the therapeutic potential against STEC-associated diseases. Full article

(This article belongs to the Special Issue Antibodies for Innovative Studies of Bacterial Toxins)

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17 pages, 6662 KB

Open AccessArticle

Qualitative and Quantitative Proteomic Analysis of Venoms from Mexican Rattlesnakes

by Lizbeth Hernández-Ancheyta, Víctor Hugo Reynoso, Juan Carlos López-Vidal, Javier Hernández-Sánchez, Karen Delgadillo-Gutiérrez, María Lilia Domínguez-López and Julieta Luna-Herrera

Toxins 2026, 18(6), 256; https://doi.org/10.3390/toxins18060256 - 5 Jun 2026

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Abstract

Despite the vast biodiversity of Mexican vipers, venom of endemic species has been barely studied. Here we analyzed the venom composition of three endemic species of rattlesnakes: Crotalus aquilus, C. triseriatus, and C. ravus. We used quantitative chromato-mass-spectrometry and compared [...] Read more.

Despite the vast biodiversity of Mexican vipers, venom of endemic species has been barely studied. Here we analyzed the venom composition of three endemic species of rattlesnakes: Crotalus aquilus, C. triseriatus, and C. ravus. We used quantitative chromato-mass-spectrometry and compared venoms with C. molossus, a species commonly found in North America, in a comparative and phylogenetic framework. In total, we identified 165 proteins grouped in 19 main protein families, consistent with previous reports for viperid venoms. In C. aquilus and C. triseriatus, the most predominant protein-family type was Serine Proteases, and in C. triseriatus and C. molossus it was Snake Venom Metalloproteases. The Label-free quantification revealed a high proportion of Snake Venom Metalloproteases in C. aquilus, C. triseriatus, and C. molossus, reaching 28–47% of the total venom. In contrast, in C. ravus 47% of the venom was composed of Phospholipases A₂. Among the four species analyzed, C. triseriatus and C. aquilus were most similar in compositional profiles and their profiles are highly correlated. Venom composition in terminal clades and taxa were better explained by protein losses than evolution of new proteins. The triseriatus group share seven proteins, while the clade C. aquilus + C. triseriatus share seven derived protein features, of which six are protein losses. Full article

(This article belongs to the Section Animal Venoms)

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20 pages, 865 KB

Open AccessArticle

Unveiling Hidden Aconitum Alkaloids in a Poisoning-Implicated Tincture by Untargeted Screening and Molecular Networking

by Qian He, Micong Jin, Jing Zhou, Hongshun Zhang and Chengye Sun

Toxins 2026, 18(6), 255; https://doi.org/10.3390/toxins18060255 - 5 Jun 2026

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Abstract

Aconitum poisoning is a major public health concern in East Asia, and remains difficult to diagnose when the causative toxins are not covered by routine targeted assays. In a poisoning incident that occurred in 2018, 15 individuals were affected, including five fatalities, after [...] Read more.

Aconitum poisoning is a major public health concern in East Asia, and remains difficult to diagnose when the causative toxins are not covered by routine targeted assays. In a poisoning incident that occurred in 2018, 15 individuals were affected, including five fatalities, after accidentally consuming a medicinal tincture during a shared meal. The comprehensive alkaloid profile of the tincture implicated in the poisoning was achieved through the integration of targeted analysis, molecular networking, and untargeted screening based on ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry, aiming to clarify the causative agents. Targeted quantitative analysis detected nine alkaloids derived from Aconitum plants, confirming the presence of Aconitum ingredients in the medicinal tincture. However, these alkaloids were either present at low concentrations or exhibited low toxicity, and thus were not the principal causative agents of this poisoning incident. Molecular networking revealed additional hidden diester-diterpenoid alkaloids (DDAs) and monoester-diterpenoid alkaloids (MDAs) that were undetected by targeted analysis. Untargeted screening identified 58 Aconitum alkaloids, including 15 DDAs, 17 MDAs, 17 amino-diterpenoid alkaloids (ADAs), 2 C20-diterpenoid alkaloids, and seven unclassified alkaloids. The three most abundant alkaloids were structurally identified as pseudoaconitine, 8-deacetylpseudoaconitine, and 3′-methoxyacoforestinine, and were identified as the main causative agents of this poisoning. To our knowledge, this is the first detection of these alkaloids in Aconitum poisoning in China. These findings demonstrate that integrated targeted and untargeted toxicological analysis can identify undocumented toxins in poisoning events of unknown origin and clarify the chemical etiology of unusual Aconitum poisoning. Full article

(This article belongs to the Special Issue Toxic and Protective Compounds from Poisonous and Medicinal Plants: Toxicological, Mechanistic, Analytical, and Therapeutic Aspects)

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15 pages, 1359 KB

Open AccessArticle

Effects of the Temperature and Limosilactobacillus fermentum Co-Inoculation on the Expression of AFB1-Synthesis Genes and the Level of Toxin Produced by Aspergillus flavus Zt41 in Corn Silage

by Szilamér Ferenczi, Ildikó Bata-Vidács, Judit Kosztik, István Nagy, Katalin Inotai, Olívia Csernus, Natália Szeőcs, Zsuzsanna Szőke, Mónika Varga, András Szekeres and József Kukolya

Toxins 2026, 18(6), 254; https://doi.org/10.3390/toxins18060254 - 4 Jun 2026

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Abstract

Aflatoxin B1 (AFB1), a highly potent Group 1 human carcinogen produced by Aspergillus flavus (A. flavus), poses a significant contamination risk to corn silage, a threat that is further intensified by rising global temperatures. This study aimed to characterize the combined [...] Read more.

Aflatoxin B1 (AFB1), a highly potent Group 1 human carcinogen produced by Aspergillus flavus (A. flavus), poses a significant contamination risk to corn silage, a threat that is further intensified by rising global temperatures. This study aimed to characterize the combined effects of temperature and co-inoculation with the lactic acid bacterium Limosilactobacillus fermentum (L. fermentum) on AFB1 production and the expression of key biosynthetic genes in A. flavus colonizing corn silage. Corn silage was incubated at 20 °C, 30 °C, and 37 °C with and without L. fermentum. Using qRT-PCR and HPLC, we found that elevated temperatures, particularly 37 °C, strongly induced the expression of the aflatoxin biosynthetic cluster, including the regulatory gene aflR and structural genes such as omtA and ordA. Co-inoculation with L. fermentum consistently reduced in the final AFB1 concentration by approximately 50–60% at all three temperatures. Molecular analysis revealed that this reduction was associated with transcriptional repression at 30 °C and 37 °C. L. fermentum consistently and markedly down-regulated the expression of aflR and all structural genes. A particularly pronounced suppression was observed for the late-pathway gene ordA at 30 °C. These findings provide molecular evidence supporting the incorporation of selected L. fermentum strains into silage inoculant formulations to mitigate the AFB1 risk under high-temperature conditions. Full article

(This article belongs to the Special Issue Prevention and Remediation of Mycotoxins)

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22 pages, 15863 KB

Open AccessReview

Facial Paralysis Treatment and Facial Symmetrization with Botulinum Neurotoxin: A Narrative Review with Illustrative Clinical Cases

by Monica Renga, Roberta D’Emilio, Giovanni Salti, Selene Mogavero, Marco Papagni, Federico Biglioli and Alessandro Lozza

Toxins 2026, 18(6), 253; https://doi.org/10.3390/toxins18060253 - 4 Jun 2026

Viewed by 618

Abstract

Facial paralysis leads to static and dynamic asymmetry, hyperkinesis of the non-paralyzed side, and synkinesis, with major functional and psychosocial consequences for patients. Botulinum neurotoxin serotype A (BoNT-A) injections are an effective therapeutic option since they denervate overactive muscles, thereby reducing hyperkinesis or [...] Read more.

Facial paralysis leads to static and dynamic asymmetry, hyperkinesis of the non-paralyzed side, and synkinesis, with major functional and psychosocial consequences for patients. Botulinum neurotoxin serotype A (BoNT-A) injections are an effective therapeutic option since they denervate overactive muscles, thereby reducing hyperkinesis or synkinesis and eventually improving asymmetry. This narrative review summarizes relevant literature on the use of BoNT-A for facial paralysis. It provides a summary of dosing strategies and treatment plans, discusses the use of functional scales for assessing facial paralysis and improvement after treatment, and outlines the use of electromyography (EMG) or ultrasound-guided injections to improve treatment outcomes. Finally, it discusses its potential role in the preparation for functional microsurgery. We also present the authors’ anecdotal experience, with three case reports: a woman with facial paralysis caused by Ramsay Hunt Syndrome, treated with a full-face and neck BoNT-A protocol and followed-up for 18 months with photographic documentation, to further assess the aesthetic improvement; a young woman with familiarity of facial paralysis, contralateral hyperkinesis, and synkinesis, managed with EMG-guided and landmark-guided injections; and her mother, with recurrent facial paralysis and chronic synkinesis, treated with stepwise BoNT-A sessions. All three cases demonstrated clinically meaningful improvements, as evidenced by the photographic material and functional grading scores presented. Full article

(This article belongs to the Special Issue Study on Botulinum Toxin in Facial Diseases and Aesthetics)

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21 pages, 2278 KB

Open AccessArticle

Cyclopiazonic Acid Induces Mitochondrial Oxidative Stress in SH-SY5Y Cells: Protective Effects of Extra Virgin Olive Oil Phenolics

by Carmen Martínez-Alonso, Yelko Rodríguez-Carrasco and María-José Ruiz

Toxins 2026, 18(6), 252; https://doi.org/10.3390/toxins18060252 - 2 Jun 2026

Viewed by 468

Abstract

Cyclopiazonic acid (CPA), a neurotoxin produced by Penicillium and Aspergillus genera, induces oxidative stress and neuronal damage, mechanisms implicated in neurodegenerative diseases. This study investigates the oxidative stress induced by CPA in SH-SY5Y human neuroblastoma cells, focusing on mitochondrial membrane potential, mitochondrial superoxide [...] Read more.

Cyclopiazonic acid (CPA), a neurotoxin produced by Penicillium and Aspergillus genera, induces oxidative stress and neuronal damage, mechanisms implicated in neurodegenerative diseases. This study investigates the oxidative stress induced by CPA in SH-SY5Y human neuroblastoma cells, focusing on mitochondrial membrane potential, mitochondrial superoxide levels, ROS production, lipid peroxidation and gene expression. Additionally, the cytoprotective effects of extra virgin olive oil (EVOO) extract, along with its major polyphenols oleuropein (OLE) and tyrosol (TYR), were evaluated. CPA exposure increased mitochondrial superoxide levels and lipid peroxidation, reducing mitochondrial membrane potential, although no intracellular ROS generation was observed. Gene expression analysis revealed downregulation of antioxidant defense genes (nrf2, nos2, ho1, cat, keap1, nqo1, gpx1 and gsr), with the strongest repression observed for nos2 (93%), nqo1 (83%) and ho1 (79%) at the highest CPA concentration, consistent with oxidative stress markers. EVOO extract demonstrated protective effects, enhancing cell viability across all CPA assayed concentrations (400–600 nM). Conversely, TYR and OLE exhibited variable and concentration-dependent effects, also showing protection to a lesser extent, while EVOO extract proved to be more effective due to synergistic interactions among its phenolic components. Overall, CPA induces mitochondrial oxidative damage as a key mechanism of neurotoxicity, while EVOO phenolics mitigate this toxicity. Full article

(This article belongs to the Special Issue Strategies for Mitigating Mycotoxin Contamination in Food and Feed)

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18 pages, 4079 KB

Open AccessArticle

Biopesticidal Properties of the Probiotic Brevibacillus laterosporus Strain B.O.D.

by M. Florencia Gil, Alessia Vinci, Manuela Casada and Luca Ruiu

Toxins 2026, 18(6), 251; https://doi.org/10.3390/toxins18060251 - 31 May 2026

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Abstract

Brevibacillus laterosporus strain B.O.D. is a well-established commercial probiotic and antimicrobial microorganism that finds use in human health and in agriculture as a biofertilizer. On the other hand, while B. laterosporus is a well-known entomopathogenic species, the possible insecticidal potential of strain B.O.D. [...] Read more.

Brevibacillus laterosporus strain B.O.D. is a well-established commercial probiotic and antimicrobial microorganism that finds use in human health and in agriculture as a biofertilizer. On the other hand, while B. laterosporus is a well-known entomopathogenic species, the possible insecticidal potential of strain B.O.D. remains unexplored. To address this knowledge gap, this study combined genome sequencing and comparative analysis with other B. laterospours strains and insect bioassays. The genome of B. laterosporus B.O.D. was found to harbor a wide range of genes related to entomopathogenicity encoding putative proteases, chitinases, collagenase-like proteases, mosquitocidal proteins, bacillolysin, and spore-surface proteins. Antimicrobial compounds such as gramicidin and surfactin were also found. Sequence alignment with other well-characterized B. laterosporus strains and analysis revealed significant differences, which support the corresponding differences in insecticidal activity observed when comparing strain B.O.D. with others against a variety of lepidopteran and dipteran pest species. This study reports for the first time the genome of strain B.O.D., providing a comparative analysis and highlighting its insecticidal properties, which appear more moderate compared to previously characterized entomopathogenic strains of the same species. Everything considered, B. laterosporus strain B.O.D. appears to be remarkably versatile, underscoring wide biotechnological potential. Full article

(This article belongs to the Section Bacterial Toxins)

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18 pages, 1709 KB

Open AccessArticle

Burden of Mortality and Morbidity Caused by Snakebites Contributes to Economic Loss in a Rural Population in India

by Swapnil Kiran, Siripuram Srinivas and Karthikeyan Vasudevan

Toxins 2026, 18(6), 250; https://doi.org/10.3390/toxins18060250 - 29 May 2026

Viewed by 828

Abstract

Snakebite envenoming is a major public health concern in India that causes economic hardship for the rural populations. We estimated the per capita economic burden of snakebites in a rural population by quantifying mortality and morbidity rates. We interviewed for outcomes of snake [...] Read more.

Snakebite envenoming is a major public health concern in India that causes economic hardship for the rural populations. We estimated the per capita economic burden of snakebites in a rural population by quantifying mortality and morbidity rates. We interviewed for outcomes of snake envenomation of 541 participants from 205 villages in Jagtial, Telangana, from 2010 to 2020 using a community-based snowball sampling approach. Snakebites caused 24.21% morbidity and 12.75% mortality. The age-adjusted mortality rate and age-adjusted morbidity rate were 11.72 and 22.8 per 100,000 people, respectively. The overall annual burden of snakebites was 31.96 Disability-Adjusted Life Years (DALYs) per 100,000 people. The mean annual earning opportunity cost and the mean annual mortality cost were USD 321.27 and USD 24,016.54 per person, respectively. We highlight the need for targeted public health interventions such as monetary compensation and community support schemes to reduce the morbidity and mortality rates in rural areas. Full article

(This article belongs to the Section Animal Venoms)

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21 pages, 4489 KB

Open AccessArticle

Analgesic and Neurorestorative Effects of αO-Conotoxin GeXIVA[1,2] in Diabetic Neuropathic Pain and Postherpetic Neuralgia

by Rongyan He, Shuting Xiao, Xiaoying Liang, Qiuyu Cao, Shaoxian Wu and Sulan Luo

Toxins 2026, 18(6), 249; https://doi.org/10.3390/toxins18060249 - 29 May 2026

Viewed by 485

Abstract

Chronic neuropathic pain, particularly diabetic neuropathic pain and postherpetic neuralgia, severely impairs patients’ quality of life due to their complex mechanisms and recurrent, long-term nature, making treatment challenging. This study aimed to evaluate the analgesic efficacy of α-conotoxin GeXIVA[1,2], a selective antagonist of [...] Read more.

Chronic neuropathic pain, particularly diabetic neuropathic pain and postherpetic neuralgia, severely impairs patients’ quality of life due to their complex mechanisms and recurrent, long-term nature, making treatment challenging. This study aimed to evaluate the analgesic efficacy of α-conotoxin GeXIVA[1,2], a selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR), in rat models of diabetic neuropathic pain and postherpetic neuralgia and investigate its associated physiological and pathological effects. GeXIVA[1,2] was administered continuously for three weeks, with mechanical hypersensitivity assessed through pain sensitivity tests, and behavioral assessments conducted to examine motor coordination and gait. Additionally, neural tissue structure and inflammation were analyzed. The results demonstrated that GeXIVA[1,2] significantly alleviated mechanical hypersensitivity in both diabetic neuropathic pain and postherpetic neuralgia models, with greater efficacy than gabapentin and no signs of tolerance. Behavioral tests indicated no significant effects on motor coordination or gait. Further analysis revealed that GeXIVA[1,2] reduced pro-inflammatory cytokine levels, decreased immune cell infiltration, and promoted repair of damaged nerve fibers. Overall, these findings suggest that GeXIVA[1,2] exerts analgesic effects through anti-inflammatory and neuroprotective mechanisms, providing a potential new therapeutic strategy for diabetic neuropathic pain and postherpetic neuralgia. Full article

(This article belongs to the Section Marine and Freshwater Toxins)

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17 pages, 2552 KB

Open AccessReview

Botulinumtoxin Type-A (BoNTA) in the Management of Refractory Trigeminal Neuralgia: An Expert-Opinion, Practice-Oriented Narrative Review on Behalf of the GRASP Study Group

by Andreas A. Argyriou, Emmanouil V. Dermitzakis, Dimitrios Rikos, Georgia Xiromerisiou, Panagiotis Soldatos, Maria Chondrogianni, Eleni Mavraki and Michail Vikelis

Toxins 2026, 18(6), 248; https://doi.org/10.3390/toxins18060248 - 29 May 2026

Viewed by 571

Abstract

Trigeminal neuralgia (TN) ranks among the most excruciating neuropathic pain syndromes, characterized clinically by multiple daily episodes of unilateral, paroxysmal, electric shock-like facial pain. The daily activities and quality of life of affected patients are profoundly diminished. First-line pharmacological agents, such as carbamazepine [...] Read more.

Trigeminal neuralgia (TN) ranks among the most excruciating neuropathic pain syndromes, characterized clinically by multiple daily episodes of unilateral, paroxysmal, electric shock-like facial pain. The daily activities and quality of life of affected patients are profoundly diminished. First-line pharmacological agents, such as carbamazepine and oxcarbazepine, provide initial relief for many patients. However, a significant proportion eventually develops refractory symptoms or experience intolerable adverse effects, leading to the discontinuation of traditional oral medications. For these patients with complex clinical phenotypes who fail to respond or are intolerant to these therapies, alternative pharmacological strategies are required before considering invasive surgical procedures. Over the past two decades, botulinumtoxin type-A (BoNTA) has become an effective and safe, minimally invasive therapeutic option for refractory TN. This review provides a practical framework for BoNTA use in the clinical setting of refractory TN. To connect the pathophysiological background with clinical patient care, we summarize the current understanding of TN pathophysiology, the proposed mechanisms by which BoNTA exerts its antinociceptive effects and the evolving clinical evidence supporting its efficacy and safety. We also critically examine dosing protocols, injection techniques, long-term outcomes and the integration of BoNTA into the management algorithm of refractory TN. Full article

(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)

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14 pages, 13099 KB

Open AccessArticle

Identification and Analysis of the Mpp5Ab1-Interacting Protein in the Midgut of the Colaphellus bowringi Baly

by Yaning Huang, Qiao Li, Jiaqi Wang, Yulei Wang, Daolong Liao, Xiaodong Sun and Haitao Li

Toxins 2026, 18(6), 247; https://doi.org/10.3390/toxins18060247 - 29 May 2026

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Abstract

To elucidate the mode of action of Mpp5Ab1 against Colaphellus bowringi Baly larvae, this study aimed to identify midgut proteins interacting with the toxin. A validated bait plasmid, pBT3-SUC-mpp5Ab1, was used to screen a larval midgut cDNA library via the split-ubiquitin yeast two-hybrid [...] Read more.

To elucidate the mode of action of Mpp5Ab1 against Colaphellus bowringi Baly larvae, this study aimed to identify midgut proteins interacting with the toxin. A validated bait plasmid, pBT3-SUC-mpp5Ab1, was used to screen a larval midgut cDNA library via the split-ubiquitin yeast two-hybrid system. A total of 33 positive clones representing five distinct proteins were obtained, among which bioinformatic analyses prioritized three candidates: Cb-RP-L23e, Cb-CTSL, and Cb-TsetseEP. Subsequent bimolecular fluorescence complementation (BiFC) assays in Sf9 cells specifically confirmed interactions between Mpp5Ab1 and both Cb-CTSL and Cb-TsetseEP, whereas no fluorescence signal was observed for Cb-RP-L23e. Molecular docking further supported stable interactions between Mpp5Ab1 and the validated candidate proteins through hydrogen bonds, salt bridges, and hydrophobic interactions. These findings suggest that Cb-CTSL and Cb-TsetseEP may function as candidate interacting proteins associated with the activity of Mpp5Ab1 in the larval midgut of C. bowringi. Overall, this study provides new insight into the molecular interactions of Mpp5Ab1 and establishes a foundation for future functional studies on its insecticidal mechanism and receptor validation. Full article

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11 pages, 266 KB

Open AccessArticle

Serum Acrolein and Peripheral Arterial Stiffness in Non-Dialysis Chronic Kidney Disease: A Cross-Sectional Study

by Ho-Hsiang Chang, Yu-Li Lin, Chi-Chong Tang, Chiu-Huang Kuo, Chih-Hsien Wang and Bang-Gee Hsu

Toxins 2026, 18(6), 246; https://doi.org/10.3390/toxins18060246 - 29 May 2026

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Abstract

Background: Arterial stiffness is a major predictor of cardiovascular-related mortality in chronic kidney disease (CKD). While acrolein—an endogenous reactive aldehyde that accumulates with declining renal function—may be linked to vascular injury, its association with high peripheral arterial stiffness (HPAS) remains unclear. Methods: This [...] Read more.

Background: Arterial stiffness is a major predictor of cardiovascular-related mortality in chronic kidney disease (CKD). While acrolein—an endogenous reactive aldehyde that accumulates with declining renal function—may be linked to vascular injury, its association with high peripheral arterial stiffness (HPAS) remains unclear. Methods: This cross-sectional study used the cardio-ankle vascular index (CAVI) to examine the association between serum acrolein levels and HPAS (CAVI ≥ 9.0) in 204 adults with non-dialysis CKD stages 3–5. Results: HPAS was identified in 90 patients (44.1%) and was associated with a higher prevalence of diabetes (p = 0.047), older age (p = 0.023), higher spot urine protein–creatinine ratio (UPCR, p = 0.046), higher serum fasting glucose (p = 0.041), higher interleukin-6 (p = 0.025), and higher acrolein (p = 0.008). In multivariable logistic regression analysis, serum acrolein (odds ratio, 1.015; 95% confidence interval, 1.002–1.028; p = 0.025), age (p = 0.010), and UPCR (p = 0.046) remained independently associated with HPAS. Log-transformed acrolein was positively correlated with bilateral CAVI (all p < 0.001) and log-transformed UPCR (p < 0.001) but negatively correlated with the estimated glomerular filtration rate (p = 0.001). Conclusions: Elevated serum acrolein is independently associated with HPAS in non-dialysis CKD stages 3–5. Full article

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

17 pages, 2110 KB

Open AccessArticle

Intradermal and Subcutaneous Botulinum Toxin Type A Injections Do Not Differ in the Induction of Neutralizing Antibody Formation

by Stefanie Honndorf, Jessica Moser and Klaus Fink

Toxins 2026, 18(6), 245; https://doi.org/10.3390/toxins18060245 - 27 May 2026

Viewed by 811

Abstract

The neurotoxin botulinum toxin type A (BoNT/A), produced by the bacteria Clostridium botulinum, is commonly injected intramuscularly (IM) for the management of chronic muscle hyperactivity, such as post-stroke spasticity. New indications such as peripheral neuropathic pain require alternative routes of BoNT/A administration, [...] Read more.

The neurotoxin botulinum toxin type A (BoNT/A), produced by the bacteria Clostridium botulinum, is commonly injected intramuscularly (IM) for the management of chronic muscle hyperactivity, such as post-stroke spasticity. New indications such as peripheral neuropathic pain require alternative routes of BoNT/A administration, such as subcutaneous (SC) or intradermal (ID). While IM BoNT/A injections may elicit anti-drug-antibodies (ADAs), their occurrence following SC or ID administration is unknown. Therefore, we investigated whether repeated SC or ID injections of 150 kDa BoNT/A can elicit ADAs in a dose-dependent manner, and whether these differ depending upon the route of administration. Mice were injected 5 times ID or SC with 150 kDa BoNT/A or, for higher doses, inactive mutant BoNT/A (DRBoNT/A) or inactivated toxoid (IA-BoNT/A). Total ADAs were analyzed by an immunoassay and the subgroup of neutralizing ADAs by an in vivo digit abduction score (DAS) assay following a challenge of 0.6 U BoNT/A IM. DRBoNT/A and IA-BoNT/A injections elicit ADAs (22.7 U/mL vs. 460.5 U/mL for ID; 4.7 U/mL vs. 339.4 U/mL for SC), while therapeutic doses of 150 kDa BoNT/A do not. Whereas mice with repeated 150 kDa BoNT/A injections at therapeutic dose show an unrestricted DAS of 3.7 (ID) or 3.4 (SC), mice injected repeatedly with 1.8 µg/kg DRBoNT/A or 500 µg/kg IA-BoNT/A show only a minimal DAS of ≤0.7, indicating a high titer of neutralizing ADAs. No differences were observed between administration routes. Accordingly, repeated ID or SC injections of pure 150 kDa BoNT/A at therapeutic doses fail to induce ADA formation in mice. On the other hand, DRBoNT/A ID injections induce higher ADA concentrations than SC, but generate similar amounts of neutralizing ADAs. IA-BoNT/A injections induce ADAs and neutralizing ADAs similarly after ID and SC injections. ADA development at intermediate BoNT/A doses can be higher after ID injection, but does not lead to differences in neutralizing ADAs. Our data demonstrate that the antibody response to botulinum toxin depends predominantly on the protein load, and less on the administration route. Full article

(This article belongs to the Special Issue The Neutralization Mechanism and Immunological Studies of Botulinum Neurotoxin)

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28 pages, 4961 KB

Open AccessReview

Mechanisms of Aflatoxin Detoxification: Adsorption and Inhibition Strategies

by Yilin Tang, Lu Ding, Shujuan Sun, Mengmeng Mi, Minqi Shao, Yan Zhao, Mingxia Zhu, Yun Wang, Muhammad Zahoor Khan, Changfa Wang and Mengmeng Li

Toxins 2026, 18(6), 244; https://doi.org/10.3390/toxins18060244 - 25 May 2026

Viewed by 454

Abstract

Aflatoxins (AFs), toxic secondary metabolites produced by Aspergillus species, represent a major threat to food safety and public health due to their pronounced hepatotoxic, carcinogenic, and mutagenic effects. With increasing global contamination risks driven by climate change and agricultural practices, the development of [...] Read more.

Aflatoxins (AFs), toxic secondary metabolites produced by Aspergillus species, represent a major threat to food safety and public health due to their pronounced hepatotoxic, carcinogenic, and mutagenic effects. With increasing global contamination risks driven by climate change and agricultural practices, the development of effective detoxification strategies has become a critical priority. This review provides a comprehensive and mechanistic overview of current aflatoxin (AF) decontamination approaches, focusing on two principal pathways: adsorption and inhibition strategies. Adsorption mechanisms involve the physicochemical sequestration of aflatoxins by inorganic materials, biological adsorbents, and engineered nanocomposites, thereby reducing toxin bioavailability. In contrast, inhibition strategies target fungal growth, toxin biosynthesis pathways, or promote enzymatic and microbial degradation of aflatoxins, offering more specific and potentially sustainable control. We critically analyze the underlying mechanisms, advantages, and limitations of each approach, including issues related to specificity, environmental stability, safety, and interactions with food matrices. Particular emphasis is placed on the toxicological implications of detoxification processes, including the reduction in aflatoxin-induced health risks and the safety of degradation products. Finally, this review highlights the importance of integrating adsorption and inhibition strategies to achieve synergistic decontamination and detoxification effects. Future perspectives on multifunctional materials, biological control systems, and intelligent monitoring technologies are discussed to advance the development of efficient, safe, and sustainable aflatoxin mitigation strategies. Full article

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

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Toxins, Volume 18, Issue 6 (June 2026) – 36 articles

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