Toxins

17 pages, 415 KB

Open AccessArticle

Simultaneous Quantification of Fumonisins and Their Hydrolyzed Metabolites in Donkey Matrices: A Tool for Exposure Assessment and Toxicokinetic Studies

by Dongying Tian, Yunduo Zheng, Yandong Li, Qianwen Xing, Gang Lin, Ronghua Zhu, Quigang Ma, Peilong Wang and Ruiguo Wang

Toxins 2026, 18(2), 80; https://doi.org/10.3390/toxins18020080 - 4 Feb 2026

Abstract

A novel, sensitive, and robust LC-MS/MS method was developed and fully validated for the simultaneous determination of fumonisins (FB₁, FB₂, FB₃) and their hydrolyzed metabolites (HFB₁, HFB₂, HFB₃) in donkey plasma, [...] Read more.

A novel, sensitive, and robust LC-MS/MS method was developed and fully validated for the simultaneous determination of fumonisins (FB₁, FB₂, FB₃) and their hydrolyzed metabolites (HFB₁, HFB₂, HFB₃) in donkey plasma, urine, and feces—three critical matrices for toxicokinetic studies. Sample preparation was optimized for each matrix: salting-out assisted liquid–liquid extraction (SALLE) with perchloric acidification for urine and feces, and a dilute–evaporate–shoot (DES) approach for plasma. Chromatographic separation was achieved on a BEH C₁₈ column with water-ACN containing 0.5% formic acid. The method demonstrated excellent linearity (R² ≥ 0.99), acceptable accuracy (mean recoveries: 73.3–111.5%), and good precision (intra- and inter-day RSDs < 20%). The limits of quantification (LOQ) for FBs and HFBs were 0.1–0.15 μg/L in plasma, 1.0 μg/L in urine, and 60 μg/kg in feces. To our knowledge, this is the first reported method capable of quantifying this comprehensive panel of analytes across multiple biological matrices in donkeys, providing an essential tool for future exposure assessments and pharmacokinetic research in this species. Full article

(This article belongs to the Special Issue Risk Assessment and Advanced, Sustainable, and Intelligent Solutions for Mycotoxin Management Along the Food/Feed Chain)

12 pages, 354 KB

Open AccessArticle

Good Clinical Practices for the Management of Cervical Dystonia with BoNT-A: A Delphi-Based Approach from the Italian Expert Group

by Roberto Eleopra, Marcello Esposito, Anna Rita Bentivoglio, Maria Concetta Altavista, Roberto Erro, Patrizia Maria Caglioni and Anna Castagna

Toxins 2026, 18(2), 79; https://doi.org/10.3390/toxins18020079 - 2 Feb 2026

Abstract

Cervical dystonia (CD) is the most common adult-onset focal dystonia, with heterogeneous clinical presentation and significant functional impairment. Currently, no structured Italian good clinical practice documents specifically addressing CD have been published. Optimizing CD management requires expert-based recommendations to guide diagnosis, treatment, and [...] Read more.

Cervical dystonia (CD) is the most common adult-onset focal dystonia, with heterogeneous clinical presentation and significant functional impairment. Currently, no structured Italian good clinical practice documents specifically addressing CD have been published. Optimizing CD management requires expert-based recommendations to guide diagnosis, treatment, and follow-up. A two-round Delphi process was conducted, involving a scientific board of six neurologists with expertise in CD management and an external panel of 56 Italian experts (neurologists and physiatrists managing CD patients). Fifty-two statements were developed, discussed, and voted using a 5-point Likert scale, with consensus defined as ≥75% agreement (‘strongly agree’ or ‘somewhat agree’). In Round 1, 48 of 52 statements (92.4%) reached consensus; the four remaining statements were revised, and two were re-voted in Round 2, both achieving consensus. Final recommendations emphasize comprehensive patient assessment in multiple postural conditions; individualized botulinum neurotoxin type A (BoNT-A) dosing taking into account tonic and phasic components, pain, and dysphagia; the use of instrumental guidance; standardized outcome measures; and integration of physiotherapy and psychological support. This article provides structured good clinical practice recommendations for CD management and offers clinicians, especially those with limited experience, a practical framework to standardize care, optimize treatment, and improve patient outcomes. Full article

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30 pages, 1564 KB

Open AccessArticle

A Community Engagement Approach to Snakebite Prevention in Rural Uganda: Exploring Knowledge, Attitudes, and Practices

by Kevin Arbuckle, Yowasi Byaruhanga, Hazel J. Nichols, Cris M. Kaseke, Francis Mwanguhya and Jessica Mitchell

Toxins 2026, 18(2), 78; https://doi.org/10.3390/toxins18020078 - 2 Feb 2026

Abstract

Snakebite envenoming is classified as a Neglected Tropical Disease and causes mortality, morbidity, and economic impacts for hundreds of thousands of people per year, particularly in tropical, low- and middle-income countries. Most research on snakebite interventions focuses on improving clinical management rather than [...] Read more.

Snakebite envenoming is classified as a Neglected Tropical Disease and causes mortality, morbidity, and economic impacts for hundreds of thousands of people per year, particularly in tropical, low- and middle-income countries. Most research on snakebite interventions focuses on improving clinical management rather than bite prevention. However, prevention may provide a better mechanism to minimise snakebite impacts, particularly in rural areas where access to effective medical treatment is limited. This study reports on the preliminary testing phase of a participatory workshop intervention run in rural Uganda in 2022–23, which used a community engagement approach designed to reduce snakebites through discussing snake behaviour and biology. A mixed methods survey and semi-structured interviews were conducted, both with workshop attendees and non-attendees, after the delivery of the workshops. We found that a fearful attitude toward snakes often led to human–snake conflict, with snake killings occurring commonly, and some bites occurring during attempted killings. Workshops appeared to challenge negative attitudes, as understanding snake behaviour seemed to build compassion toward snakes and therefore has the potential to reduce human–snake conflict. Those who attended workshops were more likely to suggest ‘giving snakes space,’ rather than attempting to kill them, and were more likely to suggest hospital treatment if bitten. We also found that many effective methods for snakebite prevention are already known to the community, but those who attended the workshop were aware of a wider range of prevention methods and were more likely to implement less ecologically damaging and more effective strategies. This emphasises that appropriate knowledge resides within the community to prevent snakebites, and so community engagement approaches can improve prevention practices while recognising that the ownership and knowledge for such changes is generated by the local people themselves. Full article

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

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13 pages, 786 KB

Open AccessArticle

Development and Validation of an LC-MS/MS Method for the Determination of Alternaria Mycotoxins in Hepatic Tissue

by María García-Nicolás, Alicia Navarro-Botia, Natalia Arroyo-Manzanares and Pilar Viñas

Toxins 2026, 18(2), 77; https://doi.org/10.3390/toxins18020077 - 2 Feb 2026

Abstract

The presence of Alternaria mycotoxins in hepatic tissue of both human and animal origin remains unexplored. This work describes the development of an analytical method based on salt-assisted liquid–liquid extraction (SALLE) and ultrahigh-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry [...] Read more.

The presence of Alternaria mycotoxins in hepatic tissue of both human and animal origin remains unexplored. This work describes the development of an analytical method based on salt-assisted liquid–liquid extraction (SALLE) and ultrahigh-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) for the determination of six main Alternaria mycotoxins and related metabolites. Sample treatment was fully optimized, including sample mass, extraction solvent, and volume and sodium chloride mass. The method was validated, achieving calibration curve R² values above 0.99 and limits of detection between 0.01 and 1.46 µg kg⁻¹. Moreover, satisfactory trueness (apparent recoveries between 84% to 111%) and precision (RSD values below 10%) were achieved, complying with EU requirements. Matrix effects in terms of signal suppression/enhancement varied between 53% for TeA and 78% for AME. Applied to real liver samples (20 human and 20 animal), alternariol monomethyl ether (AME) was found in pig liver, while alternariol (AOH) and tentoxin (TEN) were found in human forensic liver tissues. No other Alternaria mycotoxin metabolites were detected. This methodology is the first validated approach for determining Alternaria mycotoxins in liver tissue. Full article

(This article belongs to the Special Issue Mycotoxins in Food and Feeds: Human Health and Animal Nutrition)

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18 pages, 2539 KB

Open AccessArticle

Squeeze-Excitation Attention-Guided 3D Inception ResNet for Aflatoxin B1 Classification in Almonds Using Hyperspectral Imaging

by Md. Ahasan Kabir, Ivan Lee and Sang-Heon Lee

Toxins 2026, 18(2), 76; https://doi.org/10.3390/toxins18020076 - 2 Feb 2026

Abstract

Almonds are a highly valued nut due to their rich protein and nutritional content. However, they are vulnerable to aflatoxin B1 (AFB1) contamination in warm and humid environments. Consumption of AFB1-contaminated almonds can pose serious health risks, including kidney damage, and may lead [...] Read more.

Almonds are a highly valued nut due to their rich protein and nutritional content. However, they are vulnerable to aflatoxin B1 (AFB1) contamination in warm and humid environments. Consumption of AFB1-contaminated almonds can pose serious health risks, including kidney damage, and may lead to significant economic losses. Consequently, a rapid and non-destructive detection method is essential to ensure food safety by identifying and removing contaminated almonds from the supply chain. Hyperspectral imaging (HSI) and 3D deep learning provide a non-destructive, efficient alternative to current AFB1 detection methods. This study presents an attention-guided Inception ResNet 3D Network (AGIR-3DNet) for fast and precise detection of AFB1 contamination in almonds utilizing HSI. The proposed model integrates multi-scale feature extraction, residual learning, and attention mechanisms to enhance spatial-spectral feature representation, enabling more precise classification. The proposed 3D model was rigorously tested, and its performance was compared against 3D Inception and various conventional machine learning models. Compared to conventional machine learning models and deep learning architectures, AGIR-3DNet outperformed and achieved superior validation accuracy of 93.30%, an F1-score (harmonic mean of precision and recall) of 0.94, and an area under the receiver operating characteristic curve (AUC) value of 0.98. Furthermore, the model enhances processing efficiency, making it faster and more suitable for real-time industrial applications. Full article

(This article belongs to the Special Issue Mycotoxins in Food and Feeds: Human Health and Animal Nutrition)

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24 pages, 15660 KB

Open AccessArticle

Low-Dose Deoxynivalenol Induces Subclinical Multi-Organ Toxicity in Weaned Piglets

by Ying Liu, Sunlin Luo, Xinchun Zou, Wenjun He, Ruiqi Tan, Yongpeng Jin, Gaoyi Liu, Qiaomin Duan, Wenjun Yang and Yiqiang Chen

Toxins 2026, 18(2), 75; https://doi.org/10.3390/toxins18020075 - 2 Feb 2026

Abstract

Deoxynivalenol (DON) is a common mycotoxin in cereal crops such as corn, wheat, and their processed products. It can cause feed refusal and growth retardation in piglets. This study systematically evaluated the effects of dietary exposure to purified DON at low doses of [...] Read more.

Deoxynivalenol (DON) is a common mycotoxin in cereal crops such as corn, wheat, and their processed products. It can cause feed refusal and growth retardation in piglets. This study systematically evaluated the effects of dietary exposure to purified DON at low doses of 0.25, 0.5, 1.0, and 2.0 mg/kg on growth performance, blood biochemistry, antioxidant capacity, immune function, intestinal health, and reproductive development in female weaned piglets over a 42-day period. Although dietary exposure to 0.25–2.0 mg/kg of DON did not significantly affect growth performance, it induced subclinical multi-organ toxicity. Notably, decreased platelet count (PLT) at 0.25–2.0 mg/kg and increased serum alanine aminotransferase (ALT) activity at 2.0 mg/kg were observed. DON exposure also impaired antioxidant function with reduced serum total antioxidant capacity (T-AOC) at 0.25–2.0 mg/kg, and elevated malondialdehyde (MDA) content in the jejunum and ileum at 0.5–2.0 mg/kg. Furthermore, at all doses tested (0.25–2.0 mg/kg), DON suppressed anti-inflammatory cytokine interleukin-10 (IL-10) levels in both serum and intestine, reduced duodenal villus height (VH), and decreased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Additionally, histopathological injuries of liver, kidney, duodenum, jejunum, ileum, uterus and ovaries were also observed at doses of 1.0–2.0 mg/kg. In summary, this study confirms the multi-organ toxicity of low-dose DON in piglets. Our findings suggest that DON concentrations in pig feed should be more strictly controlled and highlight the importance of considering subclinical health endpoints, such as oxidative stress markers and immune parameters, in future risk assessments of mycotoxin exposure. Full article

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

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17 pages, 2761 KB

Open AccessArticle

SIRT3, NF-κB/TNF-α and PI3K/Akt Pathways Mediate the Hepatoprotective Activity of Gossypin Against Concanavalin A-Induced Hepatic Fibrosis

by Hani M. Alrawili, Mahmoud Elshal, Marwa S. Serrya and Dina S. El-Agamy

Toxins 2026, 18(2), 74; https://doi.org/10.3390/toxins18020074 - 2 Feb 2026

Abstract

Chronic liver damage usually results in a pathological state of excessive deposition of extracellular matrix that is known as liver fibrosis. This study was designed to examine the potential preventive effect of the pentahydroxyglucosyl flavone, gossypin (GPN), against concanavalin A (Con A)-induced liver [...] Read more.

Chronic liver damage usually results in a pathological state of excessive deposition of extracellular matrix that is known as liver fibrosis. This study was designed to examine the potential preventive effect of the pentahydroxyglucosyl flavone, gossypin (GPN), against concanavalin A (Con A)-induced liver fibrosis in BALB/c albino mice. Methods: Liver fibrosis was induced by intravenous (IV) injection of Con A (10 mg/kg) once weekly for 4 weeks. GPN (10 and 20 mg/kg) was administered orally three times weekly for 4 weeks. At the end of the experiment, serum and liver tissue were obtained and used for different biochemical, histological, histochemical and molecular assessments. GPN (10 and 20 mg/kg) considerably ameliorated liver fibrosis induced by Con A. A marked decrease in serum levels of ALT, AST and LDH was observed upon GPN treatment, confirmed by histopathological analysis by H&E. GPN markedly reduced collagen deposition as confirmed by MT staining, reduced hepatic levels of Col-1 and TGF-β as well as inhibited α-SMA immunostaining. The hepatic oxidative stress biomarker, MDA, was markedly reduced, whereas hepatic antioxidant defense, TAC, was significantly enhanced. Furthermore, GPN effectively enhanced gene and protein expression of SIRT3. GPN downregulated hepatic proinflammatory biomarkers, NF-κB and TNF-α. Additionally, GPN caused a noticeable increase in the hepatic levels and expression of PI3K and Akt. GPN effectively attenuated Con A-induced liver fibrosis via reducing liver damage and collagen deposition majorly by lessening inflammation, oxidative stress and fibrosis. GPN modulated SIRT3, NF-κB/TNF-α and PI3K/Akt pathways. Full article

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12 pages, 267 KB

Open AccessArticle

Botulinum Toxin Injections for Drooling Improve Dysphagia in Patients with Parkinson’s Disease

by Domenico Antonio Restivo, Mario Stampanoni Bassi, Angelo Alito, Simona Portaro, Adriana Tisano, Salvatore Greco, Rosario Marchese-Ragona and Angelo Quartarone

Toxins 2026, 18(2), 73; https://doi.org/10.3390/toxins18020073 - 2 Feb 2026

Abstract

Drooling and dysphagia are frequent and disabling complications in Parkinson’s disease (PD) and often coexist, with drooling mainly resulting from impaired saliva clearance due to reduced oral motor control and potentially worsening swallowing function. This study aimed to evaluate whether botulinum toxin type [...] Read more.

Drooling and dysphagia are frequent and disabling complications in Parkinson’s disease (PD) and often coexist, with drooling mainly resulting from impaired saliva clearance due to reduced oral motor control and potentially worsening swallowing function. This study aimed to evaluate whether botulinum toxin type A (BoNT/A) injections into the major salivary glands, beyond controlling drooling, could also improve swallowing performance using clinical and neurophysiological measures. Twenty PD patients with severe drooling and dysphagia underwent bilateral ultrasound-guided BoNT/A injections into the parotid and submandibular glands. Assessments were performed at baseline and at 1, 8, and 12 weeks post-injection. Dysphagia severity was evaluated using the Penetration–Aspiration Scale and the Dysphagia Severity Rating Scale. Neurophysiological assessment included electromyographic recordings from suprahyoid/submental and cricopharyngeal muscles, together with mechanomyography analysis of laryngeal movement during swallowing. Following BoNT/A treatment, a consistent reduction in drooling was observed, accompanied by significant improvements in clinical dysphagia scores and neurophysiological swallowing parameters across all follow-up time points. These findings suggest that incobotulinumtoxinA injections into salivary glands not only reduce drooling but also enhance swallowing function in PD patients, possibly by facilitating oral floor and oropharyngeal motor coordination secondary to improved saliva management. Full article

(This article belongs to the Special Issue Advances in the Treatment of Movement Disorders with Botulinum Toxins)

21 pages, 1130 KB

Open AccessReview

Indoxyl Sulfate in the Gut–Kidney Axis: Pathophysiology and Clinical Significance in CKD-Associated Colorectal Cancer

by Hidehisa Shimizu and Toshimitsu Niwa

Toxins 2026, 18(2), 72; https://doi.org/10.3390/toxins18020072 - 30 Jan 2026

Abstract

Chronic Kidney Disease (CKD) and Colorectal Cancer (CRC) share a profound epidemiological link, supported by Mendelian randomization studies suggesting causality. This review articulates a refined Gut–Kidney Axis, focusing on the pathophysiology of indole-derived uremic toxins. CKD-induced dysbiosis drives hepatic synthesis and systemic accumulation [...] Read more.

Chronic Kidney Disease (CKD) and Colorectal Cancer (CRC) share a profound epidemiological link, supported by Mendelian randomization studies suggesting causality. This review articulates a refined Gut–Kidney Axis, focusing on the pathophysiology of indole-derived uremic toxins. CKD-induced dysbiosis drives hepatic synthesis and systemic accumulation of indoxyl sulfate, which is proposed to promote carcinogenesis via Aryl Hydrocarbon Receptor (AhR) and Akt signaling, ultimately upregulating c-Myc and EGFR. We propose a two-compartment model: while systemic indoxyl sulfate reflects the total gut indole pool (mainly from planktonic bacteria), adherent bacteria like Fusobacterium nucleatum may create high-concentration indole hotspots within the tumor microenvironment. Clinically, we advocate for protein-independent DNA methylation biomarkers (SEPT9, SDC2) to avoid renal confounding. Furthermore, we propose a novel diagnostic panel integrating serum indoxyl sulfate (systemic load) and urinary indoxyl sulfate (gut production) to guide therapy. Therapeutically, targeting upstream drivers (AhR/Akt) may bypass resistance to anti-EGFR therapies in KRAS-mutated tumors. We also discuss the repurposing of the oral adsorbent AST-120 and emerging bacteriophage therapies as strategies to disrupt this oncogenic axis. This review offers a comprehensive framework for stratified management of CKD-associated CRC. Full article

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

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11 pages, 610 KB

Open AccessArticle

Elevated Indoxyl Sulfate Levels Correlate with Increased Aortic Stiffness in Patients Undergoing Kidney Transplantation

by Hsiao-Hui Yang, Chin-Hung Liu, Yen-Cheng Chen and Bang-Gee Hsu

Toxins 2026, 18(2), 71; https://doi.org/10.3390/toxins18020071 - 30 Jan 2026

Abstract

Although kidney transplantation (KT) restores renal function, residual uremic toxins, such as indoxyl sulfate (IS), may persist and contribute to vascular remodeling and aging. Aortic stiffness, reflected by carotid–femoral pulse wave velocity (cfPWV), is a strong predictor of cardiovascular events. This study enrolled [...] Read more.

Although kidney transplantation (KT) restores renal function, residual uremic toxins, such as indoxyl sulfate (IS), may persist and contribute to vascular remodeling and aging. Aortic stiffness, reflected by carotid–femoral pulse wave velocity (cfPWV), is a strong predictor of cardiovascular events. This study enrolled KT recipients to examine the association of circulating IS with aortic stiffness. Using the SphygmoCor system, we assessed aortic stiffness, which was defined as cfPWV > 10 m/s. Serum IS concentrations were measured by liquid chromatography–tandem mass spectrometry. Of 94 KT recipients, 26 (27.7%) met the criteria for aortic stiffness. Compared with patients without aortic stiffness, those with aortic stiffness were older (p = 0.017) and had significantly higher systolic blood pressure (p = 0.011) and fasting glucose levels (p = 0.002), a higher prevalence of diabetes (p = 0.043), and higher IS levels (p = 0.002). According to multivariable logistic regression, serum IS remained independently associated with aortic stiffness (p = 0.017). According to stepwise linear regression, log-transformed IS further showed a positive correlation with cfPWV (p = 0.016). Serum IS remained an independent determinant of aortic stiffness in KT recipients, highlighting the burden of residual uremic toxins as a contributor to post-transplant vascular aging. Full article

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

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27 pages, 6706 KB

Open AccessArticle

From Surface Colonies to Internal Contamination: A Comprehensive Investigation of Alternaria alternata Growth, Toxinogenesis, and Mycotoxin Migration Dynamics in Cherry Tomato Fruit Matrix

by Huynh Minh Tan Trinh, Léna Dole, Coline Nazet, Christophe Jourdan, Véronique Martinez, Charlie Poss, Noël Durand, Caroline Strub, Angélique Fontana-Tachon and Sabine Schorr-Galindo

Toxins 2026, 18(2), 70; https://doi.org/10.3390/toxins18020070 - 27 Jan 2026

Abstract

Alternaria alternata is a common postharvest mold affecting tomato products, including cherry tomatoes, and causing their contamination with mycotoxins. When consumers encounter moldy fruits, some may remove the visibly contaminated part and consume the rest, to reduce waste. However, the extent to which [...] Read more.

Alternaria alternata is a common postharvest mold affecting tomato products, including cherry tomatoes, and causing their contamination with mycotoxins. When consumers encounter moldy fruits, some may remove the visibly contaminated part and consume the rest, to reduce waste. However, the extent to which A. alternata toxins migrate beyond visible fungal growth remains unclear, potentially posing health risks. This study investigated (i) the within-fruit migration of A. alternata in cherry tomatoes together with the associated mycotoxin production, and (ii) the diffusion of purified Alternaria toxins in tomatoes in the absence of any fungal activity. Toxins were quantified using LC-MS/MS, while fungal colonization was assessed through visual inspection and DNA quantification across fruit sections. In the absence of fungal growth, toxins remained largely confined to the spiking site and were degraded over time. In contrast, in inoculated samples, Alternaria DNA was detected at notable levels even in sections lacking visible fungal growth, while Alternaria toxins were found both in these regions and in lower fruit sections where fungal DNA was below the qPCR detection limit. These findings highlight the limitations of relying solely on visual inspection to assess food safety. A consumer recommendation is proposed to help minimize health risks while reducing food waste. Full article

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

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35 pages, 1531 KB

Open AccessReview

Exploring the Pain-Relieving Potential: Unveiling Antinociceptive Properties in Animal Venoms and Toxins

by Davi Gomes Angstmam, Bruna Cristina Jeronimo, Joeliton dos Santos Cavalcante, Ana Flávia Marques Pereira, Cristiane Flora Villarreal, Daniel Carvalho Pimenta and Rui Seabra Ferreira Junior

Toxins 2026, 18(2), 69; https://doi.org/10.3390/toxins18020069 - 27 Jan 2026

Abstract

Currently, commercially available pain medications can cause adverse effects. Within this framework, researchers have been exploring new drug candidates derived from animal venoms and toxins. The objective of this study was to investigate the number of molecules with potential for pain relief derived [...] Read more.

Currently, commercially available pain medications can cause adverse effects. Within this framework, researchers have been exploring new drug candidates derived from animal venoms and toxins. The objective of this study was to investigate the number of molecules with potential for pain relief derived from animal venoms and toxins, which could potentially contribute to the development of new biopharmaceuticals. We conducted a literature search in January 2025, covering the period from 1960 to 2025, in two Latin American and nine international scientific databases. The results consisted of 212 articles selected for review. From these articles, 152 toxins and venoms with analgesic potential were identified and classified into 14 different types of pharmacological targets. The peptides investigated, with masses between 500 Da and 5000 Da, are strong candidates for alternative biopharmaceuticals. Most of the toxins found interact with ion channels, representing an alternative to commercially available drugs. Full article

(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)

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13 pages, 904 KB

Open AccessArticle

Impact of Early Versus Late Treatment with Botulinum Toxin A on Goal Attainment in Post-Stroke Spasticity: A Retrospective Cohort Study

by Atul Patel, Jinming Zhang, Simon Page, Sarah Harding, Mathieu Beneteau, Colin Navickas and Alberto Esquenazi

Toxins 2026, 18(2), 68; https://doi.org/10.3390/toxins18020068 - 27 Jan 2026

Abstract

This study evaluated the effect of time of botulinum toxin A (BoNT-A) treatment on clinical outcomes in adults with post-stroke spasticity (PSS). Individual data were pooled from five studies. Eligible patients received ≥1 BoNT-A injection(s) for PSS and had goal attainment scaling (GAS) [...] Read more.

This study evaluated the effect of time of botulinum toxin A (BoNT-A) treatment on clinical outcomes in adults with post-stroke spasticity (PSS). Individual data were pooled from five studies. Eligible patients received ≥1 BoNT-A injection(s) for PSS and had goal attainment scaling (GAS) scores measured at baseline and 12 weeks. Patients were grouped according to time of treatment post-stroke: early (<1 year) or late (≥1 year). The primary endpoint was the total GAS (GAS-T) score change from baseline to 12 weeks. Secondary outcomes included the proportion of patients with a GAS-T score ≥ 50. Overall, 968 patients were included (166 early and 802 late). Median time post-stroke to BoNT-A treatment was 0.5 (early) versus 5.4 (late) years. Mean (standard deviation [SD]) baseline GAS scores were similar between cohorts (early: 36.9 [3.5]; late: 36.9 [3.6]). The mean (SD) change in the GAS-T score from baseline to 12 weeks was greater in the early versus late cohort (15.7 [8.9] vs. 13.1 [8.9]; p < 0.001). More patients in the early versus late cohort had a GAS-T score ≥ 50 (63.9% vs. 47.4%; p < 0.001) at 12 weeks. No new safety concerns were reported. Early treatment of PSS with BoNT-A has a positive impact on patients’ ability to achieve treatment goals. Plain Language Summary: After a stroke, people can experience muscle stiffness in their limbs, called post-stroke spasticity (PSS), which can lead to pain and make movement difficult. Treatment can include botulinum toxin A (BoNT-A) injections given directly into affected muscles. The aim of our study was to assess whether giving BoNT-A within a year after experiencing a stroke was more effective in treating PSS than delaying treatment. We combined data from 968 patients across five different studies. Most people (802 patients) received BoNT-A treatment 1 year or more after their stroke (late treatment group), while 166 people received treatment within a year of their stroke (early treatment group). In the studies, patients set treatment goals with their physician, for example being able to hold an object or walk a certain distance. After treatment, the extent to which each goal was achieved was assessed and scored based on whether the result was less than expected, as expected, or better than expected by the patient and physician. The scores from the two treatment groups were compared. People in the early treatment group did better in achieving their treatment goals compared with those in the late treatment group. We also looked at any side effects patients experienced. No unexpected side effects were reported. BoNT-A treatment of PSS can help patients achieve their treatment goals, and patients treated early (within 1 year after stroke) may do better than those treated later. This information may help in rehabilitation planning for stroke patients. Full article

(This article belongs to the Section Bacterial Toxins)

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3 pages, 186 KB

Open AccessEditorial

Toxin–Host Interaction of Clostridium Toxins

by Jonatan Dorca-Arévalo

Toxins 2026, 18(2), 67; https://doi.org/10.3390/toxins18020067 - 27 Jan 2026

Abstract

Clostridial toxins, involved in a wide range of serious diseases, affect humans and animals [...] Full article

(This article belongs to the Special Issue Toxin-Host Interaction of Clostridium Toxins)

13 pages, 746 KB

Open AccessReview

Exploratory Use of Proximal Cryoneurolysis and Distal Botulinum Toxin Type A for Upper-Limb Spasticity: A Case Report with Scoping Review

by Di Lorenzo Luigi, De Meo Bruno, Forte Alfonso Maria, Forte Francesco, Palmieri Vincenzo, Pirraglia Nicola and D’Avanzo Carmine

Toxins 2026, 18(2), 66; https://doi.org/10.3390/toxins18020066 - 27 Jan 2026

Abstract

Background: Upper-limb spasticity involving the shoulder girdle and elbow flexors often impairs functional hand use, and although Botulinum toxin type A (BoNT-A) is a first-line therapy, severe proximal synergies may persist while higher doses risk distal weakness. Methods: We report a case of [...] Read more.

Background: Upper-limb spasticity involving the shoulder girdle and elbow flexors often impairs functional hand use, and although Botulinum toxin type A (BoNT-A) is a first-line therapy, severe proximal synergies may persist while higher doses risk distal weakness. Methods: We report a case of a 47-year-old woman with neurodegenerative tetraparesis and marked shoulder and elbow flexor spasticity treated with bilateral percutaneous cryoneurolysis of the lateral pectoral, thoracodorsal, and musculocutaneous nerves, followed by distal BoNT-A injections, and we conducted a scoping review following Arksey and O’Malley, Levac, and PRISMA-ScR methods to contextualize the current evidence. Results: At one-month follow-up, the patient showed a reduction in MAS from 4 to 1–2, complete resolution of pain, improved passive shoulder abduction and elevation, preserved distal dexterity, and high satisfaction with no adverse events. The scoping review identified consistent MAS and range-of-motion improvements across multiple case reports and small series involving similar proximal nerve targets. Conclusions: The combined proximal cryoneurolysis–distal BoNT-A approach appears to be a feasible dual-modulation strategy for complex upper-limb spasticity when the preservation of hand function is essential, and the emerging literature supports its further investigation. Full article

(This article belongs to the Section Bacterial Toxins)

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29 pages, 7950 KB

Open AccessArticle

A Multi-Year Monitoring of Swiss Grain Maize: Which Cropping Factors Influence Fusarium Species Incidence and Associated Mycotoxins?

by Tomke Musa, Karen E. Sullam, Heike Rollwage, Michael Sulyok, Petr Karlovsky and Susanne Vogelgsang

Toxins 2026, 18(2), 65; https://doi.org/10.3390/toxins18020065 - 26 Jan 2026

Abstract

A complex of Fusarium species frequently infects maize, causing root, ear, and stem rot, yield losses, reduced seed quality, and mycotoxin accumulation. To quantify Fusarium species composition and mycotoxin contamination, we conducted a first nationwide monitoring in Swiss commercial grain maize over three [...] Read more.

A complex of Fusarium species frequently infects maize, causing root, ear, and stem rot, yield losses, reduced seed quality, and mycotoxin accumulation. To quantify Fusarium species composition and mycotoxin contamination, we conducted a first nationwide monitoring in Swiss commercial grain maize over three years (2008–2010), followed by grain maize hybrid experiments across five sites (2011–2013). Samples were analysed for species incidence, fungal DNA, and the mycotoxins deoxynivalenol, zearalenone, and fumonisins. For each field, crop management data were collected. Fusarium graminearum, F. verticillioides, F. subglutinans, and F. proliferatum were predominant, and deoxynivalenol was the most frequent toxin, with 55% of the samples exceeding the European pig feed guidance value (0.9 mg kg⁻¹). Overall, fumonisin contamination was low: only 11% of samples were above the limit of detection. The year, the length of the growing period, and the timing of the harvest were the principal determinants of F. graminearum infection and deoxynivalenol/zearalenone accumulation, whereas other agronomic factors, including crop rotation, soil management, and maturity class, showed only limited or inconsistent effects. Results from this study provide evidence that farmers should avoid long growing periods and late harvests to reduce the risk of high deoxynivalenol/zearalenone content. The maize hybrid experiments confirmed the overriding influence of weather conditions on Fusarium species incidence and mycotoxin content, leading to high inter-annual variability. These results highlight the need for standardised, long-term field experiments to disentangle agronomic effects and environmental drivers. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 3293 KB

Open AccessArticle

Gender Differences in Post-Stroke Spasticity Patients Treated with OnabotulinumtoxinA: Insights from the BOTOX Economic Spasticity Trial (BEST)

by Monica Verduzco-Gutierrez, Reema Kaloti, Akinpelumi A. Beckley, Adil Syed Hussain, Sima A. Desai, Kimberly Becker Ifantides and Natasha L. Romanoski

Toxins 2026, 18(2), 64; https://doi.org/10.3390/toxins18020064 - 26 Jan 2026

Abstract

Limited data are available on gender differences in patients with post-stroke spasticity (PSS) treated with onabotulinumtoxinA (onabotA). This subgroup analysis of data from the BOTOX^® Economic Spasticity Trial (BEST) focused on onabotA-treated patients stratified by gender. BEST was a double-blind, placebo-controlled, randomized [...] Read more.

Limited data are available on gender differences in patients with post-stroke spasticity (PSS) treated with onabotulinumtoxinA (onabotA). This subgroup analysis of data from the BOTOX^® Economic Spasticity Trial (BEST) focused on onabotA-treated patients stratified by gender. BEST was a double-blind, placebo-controlled, randomized study with an open-label extension that allowed for up to five treatments. It evaluated the effectiveness of onabotA + Standard of Care (SC) vs. placebo + SC for the treatment of PSS. At baseline, out of 139 patients treated with onabotA, females (n = 54) had a slightly higher body mass index (BMI) compared to males (n = 85) (28.3 vs. 26.9 kg/m²), and a greater percentage of females (40.7%) took analgesic medications compared to males (31.8%). Scores from baseline assessments for pain, spasticity severity, and stroke recovery were comparable between groups. Despite these similarities at baseline, females received an average lower dose (range, 337–365 U) of onabotA compared to males (range, 343–421 U) across treatment sessions. Females also had lower changes from baseline compared to males on pain, spasticity severity, stroke recovery, and functional goal achievement assessments across most onabotA treatment sessions. There is a need for further investigation into treatment approaches to optimize outcomes for both males and females with PSS. Full article

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24 pages, 3687 KB

Open AccessReview

The Cardioprotective Potential of Marine Venom and Toxins

by Virginia Heaven Mariboto Siagian and Rina Fajri Nuwarda

Toxins 2026, 18(2), 63; https://doi.org/10.3390/toxins18020063 - 26 Jan 2026

Abstract

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological [...] Read more.

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological properties. Marine-derived toxins and venoms, including tetrodotoxin, ω-conotoxins, anthopleurins, palytoxin, brevetoxin, aplysiatoxin, and asterosaponins, exert cardioprotective effects through diverse mechanisms such as modulation of ion channels, inhibition of sympathetic overactivity, antioxidative actions, and enhancement of myocardial contractility. These properties make them potential candidates for addressing various CVD manifestations, including arrhythmia, hypertension, ischemia–reperfusion injury, and heart failure. However, despite their therapeutic promise, the clinical application of these marine compounds remains limited due to poor tissue selectivity, narrow therapeutic indices, proinflammatory activity, and limited metabolic stability. Structural modifications, advanced drug delivery platforms, and in vivo validation studies are crucial for overcoming these challenges. This review highlights the pharmacological actions, molecular targets, and cardiovascular relevance of selected marine toxins and venoms while also addressing key translational barriers. Advances in biotechnology and peptide engineering are enabling the safer and more targeted use of these compounds. Collectively, marine-derived toxins and venoms represent a largely untapped but highly promising frontier in cardiovascular drug discovery. Strategic research focused on elucidating mechanisms, optimizing delivery, and translating clinical applications will be critical to unlocking their full therapeutic potential. Full article

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12 pages, 434 KB

Open AccessArticle

Beyond Improvement of Motor Symptoms: Central Effects of Botulinum Toxin on Anxiety and Depression in Focal Dystonia, Hemifacial Spasm, and Blepharospasm

by Tihana Gilman Kuric, Zvonimir Popovic, Sara Matosa, Eleonora Strujic, Ivana Gacic, Tea Mirosevic Zubonja, Stjepan Juric, Melita Pecek Prpic, Vera Jelusic, Dubravka Biuk and Svetlana Tomic

Toxins 2026, 18(2), 62; https://doi.org/10.3390/toxins18020062 - 25 Jan 2026

Abstract

Cervical dystonia (CD), blepharospasm (BSP), and idiopathic hemifacial spasm (HFS) are focal hyperkinetic movement disorders with distinct underlying mechanisms. While CD and BSP involve central network dysfunctions within the basal ganglia-thalamo-cortical and cerebellar circuits, HFS primarily results from peripheral facial nerve hyperexcitability. Still, [...] Read more.

Cervical dystonia (CD), blepharospasm (BSP), and idiopathic hemifacial spasm (HFS) are focal hyperkinetic movement disorders with distinct underlying mechanisms. While CD and BSP involve central network dysfunctions within the basal ganglia-thalamo-cortical and cerebellar circuits, HFS primarily results from peripheral facial nerve hyperexcitability. Still, people living with all three conditions often struggle with mood issues like depression and anxiety, which can originate from both the burden of illness and changes in brain biology. We studied 61 patients (CD, n = 30; BSP, n = 9; HFS, n = 22) and assessed depression and anxiety before and three weeks after botulinum neurotoxin type A (BoNT-A) therapy, considering injection site and dose. BoNT-A significantly reduced depressive and anxiety symptoms across all groups, regardless of disease type, dose, or glabellar injection. These psychiatric improvements were not associated with the degree of motor symptom reduction, suggesting a partially independent mechanism of mood modulation. Our findings indicate that BoNT-A’s mood benefits may extend beyond local motor effects, possibly involving broader sensorimotor-limbic interactions. These results highlight the therapeutic potential of BoNT-A for addressing non-motor symptoms in both dystonic and non-dystonic hyperkinetic disorders. Future studies employing imaging and neurophysiological methods are necessary to explain the neural pathways underlying these effects. Full article

(This article belongs to the Section Bacterial Toxins)

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