Toxins

18 pages, 363 KB

Open AccessReview

Overview of Current Regulatory and Methodological Approaches for the Risk Assessment of Mycotoxins

by Bozidar Udovicki, Dragan Milicevic and Andreja Rajkovic

Toxins 2026, 18(7), 294; https://doi.org/10.3390/toxins18070294 - 5 Jul 2026

Risk assessment is a dynamic and continuously evolving process aimed at characterizing the potential adverse effects on life and health arising from exposure to hazards. Among these hazards, mycotoxins represent one of the most significant and widely investigated contaminants in food and feed. [...] Read more.

Risk assessment is a dynamic and continuously evolving process aimed at characterizing the potential adverse effects on life and health arising from exposure to hazards. Among these hazards, mycotoxins represent one of the most significant and widely investigated contaminants in food and feed. This review aims to summarize current knowledge on mycotoxin risk assessment practice, both for single substances and for cumulative risk assessment, and to provide practical guidance for future researchers. As individual substances, mycotoxins are well characterized from a toxicological perspective, and numerous risk assessments have been conducted globally across a wide range of food products. Although well-established methodological frameworks exist to support the cumulative risk assessment of mycotoxins, further efforts are needed to define common assessment groups, especially considering the pleiotropic nature of these compounds. Full article

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

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27 pages, 7238 KB

Open AccessReview

SELEX-Based Aptamer Technologies for Toxin Analysis: Screening, Optimization, and Computational Assisted Design

by Xinrui Shang, Chengming Yang, Huiyun Deng, Lianghua Wang and Mingjuan Sun

Toxins 2026, 18(7), 293; https://doi.org/10.3390/toxins18070293 - 3 Jul 2026

Abstract

The accurate and sensitive detection of toxin contamination remains a pressing challenge for food safety, environmental integrity, and public health, because conventional analytical methods suffer from high costs, poor field stability, and inadequate sensitivity for trace-level emerging contaminants. In this review, we provide [...] Read more.

The accurate and sensitive detection of toxin contamination remains a pressing challenge for food safety, environmental integrity, and public health, because conventional analytical methods suffer from high costs, poor field stability, and inadequate sensitivity for trace-level emerging contaminants. In this review, we provide a comprehensive overview of biosensor technologies for toxin detection, with a dedicated focus on nucleic acid aptamers and SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology. We systematically categorize nine SELEX variants developed for toxin detection, covering target-immobilized, library-immobilized, non-immobilized, cell-based, and high-throughput platforms, with an emphasis on their selection principles, applicability, and limitations. This review discusses computationally assisted aptamer discovery (e.g., AI-based sequence generation and molecular docking) as well as experimental post-SELEX optimization strategies such as cyclization, multivalent assembly, and structure-switching design. We then discuss key challenges and future perspectives, highlighting the shift from method-oriented to demand-oriented aptamer development through integrated SELEX strategies and AI-assisted design. Overall, this review covers mainstream SELEX technologies, aptamer selection, computational design, experimental optimization, and sensor integration to serve as a reference for next-generation toxin detection applications. Full article

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3 pages, 189 KB

Open AccessReply

Reply to Ståhl et al. Comment on “Honndorf et al. Comparative Analytics and Pharmacodynamics of the Complex Protein-Free Botulinum Toxin Type A Formulations DaxibotulinumtoxinA, IncobotulinumtoxinA and RelabotulinumtoxinA. Toxins 2026, 18, 142”

by Stefanie Honndorf, Katja Kühbach, Karl-Heinz Eisele, Alina Shokurova, Philipp Buch, Claudia Jatzke, Harold Victor Taylor and Klaus Fink

Toxins 2026, 18(7), 292; https://doi.org/10.3390/toxins18070292 - 3 Jul 2026

Abstract

We appreciate the comment [...] Full article

(This article belongs to the Section Bacterial Toxins)

11 pages, 4499 KB

Open AccessArticle

Benefits of Incobotulinumtoxin A in Pain, Spasticity and Functionality—A 5 Years Review

by André Cruz

Toxins 2026, 18(7), 291; https://doi.org/10.3390/toxins18070291 - 3 Jul 2026

Abstract

Introduction: Pain is a major contributor to functional impairment in neurological patients. Botulinum toxin type A (BT-A) is well-established for focal spasticity and has shown some benefits in pain reduction. Long-term data from large cohorts remain limited. Material and Methods: This retrospective study [...] Read more.

Introduction: Pain is a major contributor to functional impairment in neurological patients. Botulinum toxin type A (BT-A) is well-established for focal spasticity and has shown some benefits in pain reduction. Long-term data from large cohorts remain limited. Material and Methods: This retrospective study (2017–2022) analyzed 20 variables from spastic patients treated with Incobotulinumtoxin A (INCO) for pain and spasticity. Functional analysis was classified into 5 major domains: Pain, Spasticity spectrum, Mobility, Activities of daily living, and Gait. Results: A total of 1575 records from 67 patients were collected. The mean age was 57.7 years, mostly female (n = 35), and stroke was the leading etiology (n = 40). The most typical patterns were wrist flexion (80%) and ankle flexion (94.9%). It was injected with 50 to 400 units of INCO, targeting an average of 3.47 upper-limb and 2.34 lower-limb muscles per session. Functional improvement was observed across all domains (GAS change 27.4), with the greatest effects in pain (GAS change 26.9; 5.16 VAS reduction). Discussion: The findings, derived from one of the largest datasets, support that INCO, and probably BT-A, should be indicated for the pain of spastic patients, regardless of etiology. Conclusions: Promising functionality outcomes, especially in this group, warrant further, more comprehensive studies. Full article

(This article belongs to the Special Issue Botulinum Toxin: Advancing Treatments for Spasticity)

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3 pages, 159 KB

Open AccessComment

Comment on Honndorf et al. Comparative Analytics and Pharmacodynamics of the Complex Protein-Free Botulinum Toxin Type A Formulations DaxibotulinumtoxinA, IncobotulinumtoxinA and RelabotulinumtoxinA. Toxins 2026, 18, 142

by Ulf Ståhl, Emil Hamnevik, Åsa Liljegren Sundberg, Cecilia Persson and Inna Prygova

Toxins 2026, 18(7), 290; https://doi.org/10.3390/toxins18070290 - 3 Jul 2026

Abstract

In their recent paper comparing three complexing protein-free botulinum toxin A products available on the market [...] Full article

(This article belongs to the Section Bacterial Toxins)

20 pages, 1781 KB

Open AccessArticle

Mycotoxin Contamination in Smallholder Maize Production: Farmers’ Perceptions, Control Practices, and Influencing Factors in South Africa

by Steven Sifiso Shange, Temitope Oluwaseun Olorunfemi and Oluwasogo David Olorunfemi

Toxins 2026, 18(7), 289; https://doi.org/10.3390/toxins18070289 - 30 Jun 2026

Abstract

Globally, mycotoxin contamination of maize is a fundamental concern due to significant economic losses and toxic health effects on humans and animals. This study analyses the perceived effects of mycotoxin contamination and the use of control measures among smallholder maize farmers in South [...] Read more.

Globally, mycotoxin contamination of maize is a fundamental concern due to significant economic losses and toxic health effects on humans and animals. This study analyses the perceived effects of mycotoxin contamination and the use of control measures among smallholder maize farmers in South Africa using Mbombela as a case study. A two-stage sampling procedure was used to select 152 registered smallholder maize farmers in Mbombela, South Africa. Data was collected with a structured questionnaire administered by trained enumerators. Descriptive and multiple linear regression analyses were carried out using SPSS (Version 28). The findings revealed that many farmers had a high perception of the effects of mycotoxin contamination, and the most prominent prevention and control practices were good field management, storage of maize in clean, well-ventilated stores, and proper sorting of harvested grains. Multiple linear regression results revealed that farming experience, media exposure, extension visit, mycotoxin-related training, mycotoxin awareness, and perception index significantly influenced farmers’ utilization of mycotoxin prevention and control practices. The study recommended that agricultural professionals develop robust mycotoxin-related training and advisory services to enhance and strengthen farmers’ awareness and perceptions, and to promote the sustained use of effective agricultural practices to combat mycotoxin contamination. Full article

(This article belongs to the Section Mycotoxins)

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17 pages, 917 KB

Open AccessCase Report

Post-Mortem Effects as a Variation Factor in Lachesis muta Venom

by Mariana Silva Tavares, Melissa Inácio Moitas, Caroline Serino-Silva, Savio Stefanini Sant’Anna, Kathleen Fernandes Grego and Anita Mitico Tanaka-Azevedo

Toxins 2026, 18(7), 288; https://doi.org/10.3390/toxins18070288 - 30 Jun 2026

Abstract

Snakebite incidents could occur even with deceased animals due to improper animal manipulation, since the venom may retain biochemical activity. However, it is unclear what alterations death may cause in snake venom, because even in well-preserved genera, such as Lachesis, venom is susceptible [...] Read more.

Snakebite incidents could occur even with deceased animals due to improper animal manipulation, since the venom may retain biochemical activity. However, it is unclear what alterations death may cause in snake venom, because even in well-preserved genera, such as Lachesis, venom is susceptible to variation due to several factors. Therefore, the purpose of this research is to compare Lachesis muta venom characteristics before and after its death. The investigation encompasses protein profile analyses, immune recognition by antivenom, and enzymatic and biological activities. Venom samples were collected from the same individual at three distinct time points: two samples while the specimen was alive and a sample post-mortem. In RP-HPLC, a shift in peak intensity was observed in the peptide and protease elution regions. The post-mortem sample presented more PLA₂ and LAAO enzymatic activities and a decrease in the coagulation capacity. All samples were well immuno-recognized by anti-Bothrops/Lachesis serum. Data suggest that L. muta venom maintains its functional and immunological integrity throughout senescence and following the animal’s death. The preservation of its biochemical properties supports the clinical relevance of accidents involving dead snakes and justifies the inclusion of such venoms in antivenom manufacturing protocols, providing a strategic alternative during supply shortages. Full article

(This article belongs to the Section Animal Venoms)

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23 pages, 382 KB

Open AccessArticle

Botulinum Toxin Type A in Spasticity and Cervical Dystonia: Practical Clinical Recommendations from a Mexican Multidisciplinary Panel of Specialist Injectors

by Jorge Hernández Franco, Salvador J. Santamaría Molina, José J. Zorrilla Sánchez, Jorge Carranza del Río, Israel Sánchez Villavicencio, Sofía D. Hernández, Emmanuel Duvignau Dondé, Héctor A. González Usigli, Yadira S. González López, Roberto Leal Ortega, Azael A. Flores Salinas, Laura A. Mejía Alonso, Juan F. J. Gómez Hernández, Moisés Fernández Bravo and Pedro I. Arias Vázquez

Toxins 2026, 18(7), 287; https://doi.org/10.3390/toxins18070287 - 30 Jun 2026

Abstract

Cervical dystonia and spasticity are debilitating neuromuscular disorders that substantially impair quality of life. Botulinum toxin type A (BoNT-A) is a cornerstone therapy; however, heterogeneity in dosing, muscle selection, and guidance techniques can limit outcomes, and Mexico-specific practical guidance is limited. We convened [...] Read more.

Cervical dystonia and spasticity are debilitating neuromuscular disorders that substantially impair quality of life. Botulinum toxin type A (BoNT-A) is a cornerstone therapy; however, heterogeneity in dosing, muscle selection, and guidance techniques can limit outcomes, and Mexico-specific practical guidance is limited. We convened a multidisciplinary panel of Mexican rehabilitation and neurology specialists with extensive experience in BoNT-A injection; recommendations were developed through a three-phase process: a targeted literature search, a structured online survey of Mexican rehabilitation and neurology specialists, and an in-person meeting (21 February 2025) where clinicians reviewed aggregated survey results and refined practical recommendations through structured deliberation. The manuscript provides pragmatic guidance on evaluation and goal setting, muscle selection, working dilutions, dosing ranges, and reinjection intervals, emphasizing ultrasound (US) and/or electromyography (EMG) for deep or high-risk targets. It also summarizes key adverse events and proposes a stepwise approach to inadequate response, prioritizing reassessment of diagnosis, goals, targeting, and techniques before considering immunogenicity testing, product switching, or alternative interventions. These recommendations aim to improve standardization, safety, and goal attainment in routine Mexican practice. Full article

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

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47 pages, 20748 KB

Open AccessReview

Animal Venoms Targeting Cellular Mechanisms: Advances and Implications for Drug Discovery and Disease Therapy

by Lucienne Mathai, Bipin G. Nair and Aswathy Alangode

Toxins 2026, 18(7), 286; https://doi.org/10.3390/toxins18070286 - 30 Jun 2026

Abstract

Animal venoms are complex biochemical systems composed of proteins, peptides, and small molecules with bioactivity. Traditionally regarded as toxic agents, venom components are increasingly recognized as valuable molecular libraries that can modulate cellular processes in human disease pathophysiology. This review highlights the translational [...] Read more.

Animal venoms are complex biochemical systems composed of proteins, peptides, and small molecules with bioactivity. Traditionally regarded as toxic agents, venom components are increasingly recognized as valuable molecular libraries that can modulate cellular processes in human disease pathophysiology. This review highlights the translational potential of venom-derived molecules, with emphasis on clinically approved venom-derived drugs such as captopril, while also discussing their therapeutic potential for diseases such as cancer, autoimmunity, cardiovascular diseases, chronic pain, neuropsychiatric disorders, and infectious diseases. Special emphasis is given to the mechanisms by which these toxins modulate ion channels, enzymes, and receptor systems. Recent advances in venomics, harnessing proteomics, transcriptomics, and high-throughput screening, are also discussed, which can accelerate the clinical translation of venom-derived therapeutics. Key challenges related to assessing the immunogenicity of the venom-derived compounds, bioavailability, and safety have also been addressed alongside emerging strategies to overcome them. Collectively, these advances can provide a logical framework for developing novel therapeutics, bridging the gap between toxinology and drug discovery. Full article

(This article belongs to the Special Issue Toxins from Venoms and Poisons)

37 pages, 4117 KB

Open AccessArticle

A Comprehensive Chemical–Biological Investigation of the Moderately Toxic Plant Prospero autumnale: Insights into Its Bioactive Potential Using In Vitro and In Vivo Models

by Maroua Korichi, Ouanissa Smara, Lilya Harchaoui, Gilda D’Urso, Latifa Khattabi, Agostino Casapullo, Gianluigi Lauro, Maria Giovanna Chini, Giuseppe Bifulco, Alessio Cimmino, Hocine Dendougui, Wafa Zahnit, Marco Masi and Mahdi Belguidoum

Toxins 2026, 18(7), 285; https://doi.org/10.3390/toxins18070285 - 30 Jun 2026

Abstract

Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of [...] Read more.

Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of extracts derived from its aerial (AgP) and underground (UgP) parts. The phytochemical constituents of various P. autumnale extracts were analyzed using LC-MS/MS, and their phenolic content was quantified. The biological activities were evaluated through in vitro assays—including antioxidant, anti-inflammatory, acetylcholinesterase-inhibitory, and photoprotection assessments—and in vivo experiments, including evaluations of acute oral toxicity, anti-inflammatory, and analgesic effects. UgP extracts demonstrated significant antioxidant activity, with the methanolic extract exhibiting the highest reducing and superoxide scavenging capacities. Dichloromethane and ethyl acetate extracts performed exceptionally well in ABTS and DPPH assays. The aqueous extract from AgP exhibited noteworthy anti-inflammatory and analgesic effects, surpassing diclofenac in vitro and demonstrating efficacy in vivo. It also showed considerable acetylcholinesterase inhibition, while the ethyl acetate extract displayed high photoprotective potential. The acute toxicity was moderate (LD₅₀: 300–400 mg/kg), indicating dose-dependent risks. LC-MS/MS analysis revealed diverse phenolics potentially contributing to both therapeutic and adverse effects. This research enhances the medicinal prospects of P. autumnale, provides new perspectives on plant utilization, and suggests its potential as a natural anti-inflammatory agent. However, due to moderate toxicity and dose-dependent effects, cautious application is advised. These findings underscore the importance of toxicological evaluation alongside bioactivity screening in ethnopharmacology to ensure safety. Full article

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

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12 pages, 5880 KB

Open AccessArticle

Aflrpn4 Represents a Promising Target for Mitigating Aspergillus flavus Growth and Aflatoxin Contamination

by Xingsai Liu, Yanli Xin, Kashif Iqbal Sahibzada, Xiujia Zhang, Cunjian Tu, Shan Wei, Yuansen Hu and Yangyong Lv

Toxins 2026, 18(7), 284; https://doi.org/10.3390/toxins18070284 - 29 Jun 2026

Abstract

Aspergillus flavus and its primary secondary metabolite, aflatoxin B1, pose a persistent threat to global food security and public health, highlighting the need to identify novel molecular targets for the development of highly specific fungicides. In this study, the transcription factor Aflrpn4 was [...] Read more.

Aspergillus flavus and its primary secondary metabolite, aflatoxin B1, pose a persistent threat to global food security and public health, highlighting the need to identify novel molecular targets for the development of highly specific fungicides. In this study, the transcription factor Aflrpn4 was investigated by constructing gene deletion and complementation strains to elucidate its regulatory mechanisms in controlling the growth, development, and pathogenicity of A. flavus. Phenotypic analysis revealed that, compared with the wild-type and complemented strains, loss of Aflrpn4 severely restricted radial colony growth, reduced conidial yield, and caused structural defects in conidiophores. Furthermore, AFB1 content was reduced by 52% compared with the wild-type. In storage simulation assays using peanut and maize kernels, the ΔAflrpn4 strain exhibited significantly compromised colonization capacity, reduced biomass, and lower AFB1 accumulation. Under aflatoxin-inducing YES culture conditions, deletion of Aflrpn4 was associated with significant downregulation of key pathway-specific regulatory and structural genes, including aflR, aflS, and aflP. Furthermore, under osmotic stress induced by 1.2 M NaCl and KCl, the growth inhibition rates of the ΔAflrpn4 strain reached 70% and 59%, respectively, and cell membrane integrity was severely compromised. Loss of Aflrpn4 also disrupted intracellular redox homeostasis, characterized by a significant decrease in superoxide dismutase activity, compensatory increases in catalase and peroxidase activities, and substantial accumulation of reactive oxygen species. Collectively, these findings demonstrate that Aflrpn4 acts as a pivotal regulator coordinating vegetative growth, asexual development, stress adaptation, and aflatoxin biosynthesis in A. flavus. Consequently, Aflrpn4 represents a promising molecular target for developing targeted interventions to control A. flavus and aflatoxin contamination during grain storage. Full article

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

16 pages, 321 KB

Open AccessArticle

Viability of Commercially Available Rapid Test Strips for Mycotoxin Analysis Compared to Chromatographic Methods

by Klaudia Bucoń, Paweł Skrzydlewski, Robert Kosicki and Magdalena Twarużek

Toxins 2026, 18(7), 283; https://doi.org/10.3390/toxins18070283 - 29 Jun 2026

Abstract

Mycotoxins are toxic secondary metabolites produced primarily by molds of the genera Aspergillus, Fusarium, and Penicillium. These widespread food and feed contaminants can cause significant risks to human and animal health. The aim of this study was to compare the [...] Read more.

Mycotoxins are toxic secondary metabolites produced primarily by molds of the genera Aspergillus, Fusarium, and Penicillium. These widespread food and feed contaminants can cause significant risks to human and animal health. The aim of this study was to compare the performance of reference chromatographic methods (high-performance liquid chromatography coupled with either fluorescence detection (HPLC-FLD) or tandem mass spectrometry (HPLC-MS/MS)) with two commercially available rapid tests from two manufacturers. To that end, 90 randomly selected grain samples (barley n = 10, wheat n = 21, triticale n = 10, maize n = 49) collected in 2025 were analyzed for deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA), and the sum of T-2 and HT-2 toxins. None of the samples exceeded the maximum levels established by the European Union (EU); however, widespread contamination with one or more mycotoxins was observed. Results showed that although rapid test strips offer advantages such as low cost, short analysis time, and operational simplicity, their considerably higher limits of detection and quantification values make them unsuitable for advanced laboratory analysis. Therefore, HPLC-FLD and HPLC-MS/MS remain the gold-standard methods for reliable, sensitive, and precise mycotoxin determination. Full article

(This article belongs to the Section Mycotoxins)

14 pages, 748 KB

Open AccessArticle

Ergot Alkaloids Affect Foraging Activity of the Slime Mold Physarum polycephalum

by Jordan R. Sexstone, Abigail M. Jones and Daniel G. Panaccione

Toxins 2026, 18(7), 282; https://doi.org/10.3390/toxins18070282 - 27 Jun 2026

Abstract

We tested whether ergot alkaloids would affect the interaction of a protist with an ergot alkaloid-producing fungus by studying the response of the plasmodial slime mold Physarum polycephalum to cultures of Aspergillus leporis. Ergot alkaloid profiles were manipulated by culturing A. leporis [...] Read more.

We tested whether ergot alkaloids would affect the interaction of a protist with an ergot alkaloid-producing fungus by studying the response of the plasmodial slime mold Physarum polycephalum to cultures of Aspergillus leporis. Ergot alkaloid profiles were manipulated by culturing A. leporis and its easD knockout derivative on media for 6 or 13 days. Six-day-old, wild-type A. leporis samples contained abundant lysergic acid α-hydroxyethylamide (LAH) that was greatly depleted by 13 days. The intermediate chanoclavine-I was the predominant ergot alkaloid in all samples of the easD knockout. Inoculum of P. polycephalum was placed equidistant between the fungus-colonized agar medium explant, and the preference of the slime mold for either fungal explant was observed. When offered 6-day-old samples of wild-type A. leporis (containing mainly LAH) or the easD knockout (containing mainly chanoclavine-I), plasmodia of P. polycephalum preferred the easD knockout strain over wild type by a significant margin (p = 0.0002). When given the same options at 13 days, there was no longer a preference for the easD knockout over wild type, which by that time had lost more than 90% of its LAH. Our data demonstrate that ergot alkaloids, including LAH and chanoclavine-I, affect the interaction of P. polycephalum with A. leporis. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 641 KB

Open AccessReview

Microcystins and Reproductive Dysfunction: Mechanisms and Consequences

by Zhixin Chen, Zhihan Shi, Ziyu Chai, Jiayue Su and Xueqiong Yao

Toxins 2026, 18(7), 281; https://doi.org/10.3390/toxins18070281 - 25 Jun 2026

Abstract

Accelerating eutrophication of aquatic ecosystems worldwide has increased concern regarding cyanotoxin exposure as an emerging environmental and public health issue, with Microcystin-LR (MC-LR) among the most extensively studied congeners due to its widespread occurrence and high toxicity. Evidence from experimental animal and cellular [...] Read more.

Accelerating eutrophication of aquatic ecosystems worldwide has increased concern regarding cyanotoxin exposure as an emerging environmental and public health issue, with Microcystin-LR (MC-LR) among the most extensively studied congeners due to its widespread occurrence and high toxicity. Evidence from experimental animal and cellular studies indicates that MC-LR elicits pronounced toxic impacts on both the male and female reproductive systems. In males, MC-LR induces overt testicular injury, compromises the structural and functional integrity of the blood–testis barrier, and triggers severe disorders in reproductive hormone synthesis and secretion. In females, it precipitates ovarian dysfunction, impedes normal follicular maturation and development, and induces distinct embryotoxic effects. The underlying pathogenic mechanisms involve the synergistic interplay of multiple signaling pathways, primarily including oxidative stress induction, aberrant apoptosis activation, endocrine disruption, and epigenetic modifications. Of particular significance, emerging evidence suggests that parental exposure to MC-LR may induce intergenerational or potentially transgenerational reproductive effects through epigenetic modifications in germ cells, impairing fertility and developmental outcomes in subsequent offspring and thus posing a sustained, long-term threat to population-level health. This review systematically delineates the reproductive toxicity profiles and underlying molecular mechanisms of MC-LR, evaluates its transgenerational health hazards, and aims to furnish robust scientific evidence for the formulation of targeted environmental health policies and risk management strategies. Full article

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

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16 pages, 303 KB

Open AccessReview

Botulinum Toxin in Parkinson’s Disease Tremor: A Critical Evaluation of the Evidence and Clinical Practice

by Shivam Om Mittal and Wolfgang H. Jost

Toxins 2026, 18(7), 280; https://doi.org/10.3390/toxins18070280 - 25 Jun 2026

Abstract

Approximately 30% of patients with tremor-dominant Parkinson’s disease (PD) have rest tremor that persists despite optimal dopaminergic therapy. When deep brain stimulation and focused ultrasound are unavailable or declined, the therapeutic options narrow. Botulinum toxin (BoNT) offers a targeted, titratable, reversible approach, but [...] Read more.

Approximately 30% of patients with tremor-dominant Parkinson’s disease (PD) have rest tremor that persists despite optimal dopaminergic therapy. When deep brain stimulation and focused ultrasound are unavailable or declined, the therapeutic options narrow. Botulinum toxin (BoNT) offers a targeted, titratable, reversible approach, but whether a peripheral neuromuscular blocking agent makes sense for a centrally generated tremor is a legitimate question that deserves a direct answer. This narrative critical review appraises what is currently known across PD and non-PD tremor conditions, defines the technical requirements for safe and effective injection, and provides a practical framework for patient selection and clinical management. The PD-specific literature rests on a single positive double-blind randomized controlled trial of 30 patients; all remaining data are open-label or extrapolated from other tremor conditions, and this narrative synthesis combines heterogeneous conditions, outcome scales, and toxin protocols. A recurring technical observation is that, in the available trials, individualized, EMG-guided injection has been associated with substantially lower rates of hand weakness than fixed-dose injection (reported reductions from roughly 30–70% to below 15%) while maintaining tremor reduction, although the degree of benefit and weakness risk vary with the tremor syndrome, injected muscles, baseline impairment, dose, and guidance method. The careful patient selection this approach requires helps the individual clinician and patient achieve tremor relief, but it departs from the unselected real-world PD population and introduces selection bias that makes a large, statistically representative cohort difficult to assemble. In well-selected patients at centers with the appropriate expertise, BoNT may be a clinically useful option, but routine adoption is not yet supported. Full article

(This article belongs to the Special Issue Botulinum Toxins: Past Successes and New Goals)

18 pages, 8085 KB

Open AccessArticle

A Mechanistic Model of Cry2Ab12 Toxicity Against Myzus persicae via HSP60-Mediated OLA1 Inhibition

by Xiaodi Zhao, Xuemei Hong, Liang Jin and Yi Lin

Toxins 2026, 18(7), 279; https://doi.org/10.3390/toxins18070279 (registering DOI) - 24 Jun 2026

Abstract

Bacillus thuringiensis Cry toxins are well known for their high insecticidal activity against Lepidoptera, Diptera, and Coleoptera and have been widely used in Bt transgenic crops. However, their activity against Hemipteran aphids remains relatively low. Identifying novel Cry proteins and elucidating their action [...] Read more.

Bacillus thuringiensis Cry toxins are well known for their high insecticidal activity against Lepidoptera, Diptera, and Coleoptera and have been widely used in Bt transgenic crops. However, their activity against Hemipteran aphids remains relatively low. Identifying novel Cry proteins and elucidating their action mechanisms can facilitate the development of effective aphid control strategies. In this study, we found that ingestion of Cry2Ab12 did not kill Myzus persicae adults but significantly reduced their offspring number and exerted a lethal effect on M. persicae nymphs. After identifying Cry2Ab12 toxin-binding proteins in M. persicae, we further characterized the interaction with Obg-like ATPase 1 (OLA1), a conserved protein involved in growth regulation. Bio-layer interferometry (BLI), ELISA, and enzyme activity assays revealed that Cry2Ab12 and OLA1 do not interact directly. Interestingly, heat shock protein 60 (HSP60) was shown to mediate the interaction among Cry2Ab12, HSP60, and OLA1, leading to inhibition of OLA1 enzymatic activity. Based on these findings and bioinformatics simulations, we proposed a mechanistic model for Cry2Ab12 toxicity against M. persicae: upon ingestion of a sufficient amount of Cry2Ab12, the formation of the Cry2Ab12–HSP60–OLA1 complex impairs the cellular stress response, disrupts normal OLA1 expression, and ultimately restricts larval growth and development, resulting in lethality. This study provides new insights into the action of Cry toxins in aphids and offers a basis for developing enhanced aphid biocontrol strategies. Full article

(This article belongs to the Section Bacterial Toxins)

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25 pages, 5882 KB

Open AccessArticle

Enhanced Protection Against Toxicity of Nemopilema nomurai Venom Using a PEG-EGCG/Tetracycline Hydrochloride Micellar Nanocomplex

by Jie Li, Yanan Hu, Yunfeng Qian, Sai Luo, Juxingsi Song, Shaoqian Zhu, Minglei Wang, Huiliang Gan, Qianqian Wang and Liming Zhang

Toxins 2026, 18(7), 278; https://doi.org/10.3390/toxins18070278 - 24 Jun 2026

Abstract

Jellyfish stings are the most common type of marine life injuries. However, at present, the treatment measures against jellyfish stings are mostly empirical and supportive, with uncertain therapeutic outcomes, and there is a lack of specific antidotes based on the toxic mechanism of [...] Read more.

Jellyfish stings are the most common type of marine life injuries. However, at present, the treatment measures against jellyfish stings are mostly empirical and supportive, with uncertain therapeutic outcomes, and there is a lack of specific antidotes based on the toxic mechanism of jellyfish venom in clinical practice. In our previous study, polyphenol epigallocatechin-3-gallate (EGCG) was found to neutralize the toxicity of jellyfish Nemopilema nomurai venom (NnV) in vivo and in vitro. Herein we further demonstrated that EGCG exerted its antagonistic effect against NnV through inhibiting the oxidative stress, pro-apoptotic proteins, and systemic inflammatory responses. Subsequently, we constructed a polyethylene glycol (PEG)-EGCG/tetracycline hydrochloride (HTC) co-loaded micellar nanocomplex in order to enhance the stability and bioavailability of EGCG in vivo, which successfully integrated the membrane-repair function of PEG, the enzyme inhibitory effect of HTC and the antioxidant properties of EGCG. Notably, this micellar nanocomplex demonstrated significant protective effects against both functional damage and pathological alterations in a non-lethal NnV-envenomed mouse model. When administered 1 h after NnV envenomation, EGCG (40 mg/kg), HTC and PEG-EGCG (containing 40 mg/kg EGCG) only partially improved abnormal blood biochemical indicators and moderately alleviated histopathologic damage, and PEG-EGCG/HTC containing merely 8 mg/kg EGCG completely mitigated the toxic reactions in envenomed mice. In the preventive regimen, the administration of EGCG, HTC or PEG-EGCG 30 min before exposure showed no significant improvement in abnormal blood biochemical indicators and histopathologic damage, while PEG-EGCG/HTC could still significantly improve the functional impairments and histopathologic damage of the heart and liver in NnV-envenomed mice. These findings suggest the clinical translational potential of PEG-EGCG/HTC against jellyfish envenomation. Full article

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

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12 pages, 655 KB

Open AccessArticle

Two Toxins, One Disorder: Neurophysiological and Clinical Effects in Caput-Type of Cervical Dystonia at Waning and Peak Response Phases of BoNT-A Therapy

by Artur Drużdż, Małgorzata Dudzic, Igor Bednarski, Anna Sowińska, Natalie Górna and Agnieszka Przystańska

Toxins 2026, 18(7), 277; https://doi.org/10.3390/toxins18070277 - 24 Jun 2026

Abstract

Botulinum toxin type A (BoNT-A) is an established treatment for cervical dystonia (CD), but objective neurophysiological markers across the injection cycle and between preparations are not well defined. We assessed afferent conduction (captured by CSP parameters), efferent conduction (captured by F-wave parameters) and [...] Read more.

Botulinum toxin type A (BoNT-A) is an established treatment for cervical dystonia (CD), but objective neurophysiological markers across the injection cycle and between preparations are not well defined. We assessed afferent conduction (captured by CSP parameters), efferent conduction (captured by F-wave parameters) and clinical severity (TWSTRS) in 28 patients with caput-type cervical dystonia during waning (>14 weeks post-injection) and peak (4–6 weeks) phases, comparing onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO). F-wave measures changed only modestly: F–M latency increased with ONA, while F-wave persistence decreased with ABO. In contrast, CSP measures consistently increased at peak in both groups (CSP end latency and CSP duration; both p ≤ 0.001). Overall, BoNT-A treatment phase is better reflected by CSP-derived inhibitory measures than by F-wave indices. TWSTRS improved at peak for both toxins, with no difference between ONA and ABO in clinical change (ΔTWSTRS p = 0.5514). Full article

(This article belongs to the Special Issue Botulinum Toxins: Past Successes and New Goals)

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Open AccessArticle

Effects of Botulinum Toxin Type A in Essential Blepharospasm: Evidence from a Clinical and Neurophysiological Pilot Study

by Yan Tereshko, David De Monte, Bruno Hector Ercole, Chiara Dalla Torre, Enrico Belgrado, Mariarosaria Valente and Christian Lettieri

Toxins 2026, 18(7), 276; https://doi.org/10.3390/toxins18070276 - 24 Jun 2026

Abstract

Essential blepharospasm (BEB) is a focal dystonia characterized by abnormal brainstem excitability and impaired inhibitory control within trigeminal–facial circuits. Botulinum toxin type A (BoNT-A) is the established first-line treatment, primarily acting at the neuromuscular junction. However, whether BoNT-A also modulates central brainstem circuits [...] Read more.

Essential blepharospasm (BEB) is a focal dystonia characterized by abnormal brainstem excitability and impaired inhibitory control within trigeminal–facial circuits. Botulinum toxin type A (BoNT-A) is the established first-line treatment, primarily acting at the neuromuscular junction. However, whether BoNT-A also modulates central brainstem circuits in BEB patients remains unclear, and dedicated neurophysiological studies have yielded conflicting results. To investigate whether BoNT-A modulates brainstem interneuronal excitability in BEB using the blink reflex recovery cycle and to correlate clinical outcomes with neurophysiological results. Thirteen patients with BEB underwent neurophysiological and clinical evaluation before (T0) and one month after (T1) BoNT-A treatment. The blink reflex recovery cycle was assessed at interstimulus intervals (ISIs) of 200, 300, 500, and 1000 ms. Clinical severity was assessed using the BSPSS, JRS, and BDS scales. The R2 amplitude ratio showed a statistically significant decrease after treatment across all ISIs (all p ≤ 0.001), indicating reduced brainstem interneuronal excitability. All clinical scales demonstrated statistically significant improvement after treatment (BSPSS, JRS, BDS; all p < 0.001). This pilot study provides preliminary evidence that BoNT-A treatment may reduce brainstem interneuronal excitability in BEB patients, as evidenced by a substantial and consistent decrease in R2 amplitude ratios of the blink reflex recovery cycle. These findings are consistent with a central modulatory effect of BoNT-A beyond its established peripheral action. Larger controlled studies are warranted to confirm these results. Full article

(This article belongs to the Section Bacterial Toxins)

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