Toxins

18 pages, 51163 KB

Open AccessArticle

Gut Epithelium of the Highly Toxic Ribbon Worm Cephalothrix cf. simula (Palaeonemertea, Nemertea) Contains Tetrodotoxin-Positive Bacterial Endosymbionts

by Timur Yu. Magarlamov and Grigorii V. Malykin

Toxins 2026, 18(3), 152; https://doi.org/10.3390/toxins18030152 - 23 Mar 2026

Viewed by 741

Abstract

Tetrodotoxin (TTX), widely known as pufferfish venom, is a low-molecular-weight guanidinium neurotoxin. It can accumulate to extremely high concentrations in certain animals, including pufferfish, blue-ringed octopuses, flatworms, and nemerteans. However, the origin of TTX and the mechanisms that enable such extreme accumulation in [...] Read more.

Tetrodotoxin (TTX), widely known as pufferfish venom, is a low-molecular-weight guanidinium neurotoxin. It can accumulate to extremely high concentrations in certain animals, including pufferfish, blue-ringed octopuses, flatworms, and nemerteans. However, the origin of TTX and the mechanisms that enable such extreme accumulation in these animals remain poorly understood. In this study, using confocal laser scanning microscopy combined with electron immunocytochemistry and ultrastructural analysis, we demonstrate the presence of TTX-positive bacteria associated with specialized cellular structures—type II phagosomes of gut enterocytes—in the highly toxic nemertean Cephalothrix cf. simula. We hypothesize that TTX production in C. cf. simula results from interactions between the nemertean host and its endosymbionts. These findings clarify the origin and accumulation of the toxin in nemerteans and have broader implications for other TTX-bearing species. Full article

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

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13 pages, 1033 KB

Open AccessArticle

Therapeutic Effects of Single and Combined Anti-Disseminated Intravascular Coagulation (DIC) Drugs in a Rat Venom-Induced Consumption Coagulopathy (VICC) Model Using Yamakagashi (Rhabdophis tigrinus) Venom

by Akihiko Yamamoto, Takashi Ito and Toru Hifumi

Toxins 2026, 18(3), 151; https://doi.org/10.3390/toxins18030151 - 23 Mar 2026

Viewed by 818

Abstract

Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved [...] Read more.

Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved treatment, and its storage capacity is limited, preventing its prompt administration. Therefore, we investigated the application of commercially available drugs, namely tranexamic acid and antithrombin III, in the treatment of VICC caused by yamakagashi venom in a rat model. Furthermore, we investigated the combination of each drug with recombinant thrombomodulin α. Administration of tranexamic acid or antithrombin III alone failed to extend rat survival or correct changes in blood coagulation markers, such as prothrombin time, fibrinogen concentrations, and D-dimer levels, in yamakagashi venom-treated rats. However, combined administration of recombinant thrombomodulin α and tranexamic acid extended rat survival and partially restored blood coagulation markers. Therefore, the combination of recombinant thrombomodulin α and tranexamic acid might represent a useful therapeutic regimen for yamakagashi venom exposure. Full article

(This article belongs to the Section Animal Venoms)

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16 pages, 11015 KB

Open AccessArticle

Occurrence, Distribution Characteristics, Risk Assessment, and Climatic Drivers of Type B Trichothecenes and Their Transformation Products in Major Wheat-Producing Areas of China

by Jie Wang, Yu Wu, Di Cai, Li Li, Songshan Wang, Yu Zhang, Xiaomin Han, Songxue Wang, Leiqing Pan and Jin Ye

Toxins 2026, 18(3), 150; https://doi.org/10.3390/toxins18030150 - 21 Mar 2026

Viewed by 574

Abstract

Type B trichothecenes (B-TCTs), predominant mycotoxins in wheat, threaten human health. However, their contamination profile in China, a major wheat producer, remains unclear. This study analyzed 1337 wheat samples (2022–2024) from main production areas using liquid chromatography-mass spectrometry and deterministic assessment to investigate [...] Read more.

Type B trichothecenes (B-TCTs), predominant mycotoxins in wheat, threaten human health. However, their contamination profile in China, a major wheat producer, remains unclear. This study analyzed 1337 wheat samples (2022–2024) from main production areas using liquid chromatography-mass spectrometry and deterministic assessment to investigate B-TCTs’ watershed-scale distribution, spatiotemporal variations, associated health risks, and key climatic drivers. Results indicate that deoxynivalenol (DON) and its transformation product DON-3-glucoside (DON-3G) were the predominant contaminants, while nivalenol (NIV) was detected in specific river basins. Although overall exposure was low, elevated risks were identified in certain basins during particular years, especially for young children. DON-3G contributed 23.5% to total DON exposure. Relative humidity (rs = 0.34, p < 0.01), precipitation (rs = 0.37, p < 0.01), and its duration (rs = 0.38, p < 0.01) during the flowering-to-harvest period were identified as critical climatic drivers. The findings highlight the need to include DON-3G in food safety regulations and to develop climate-adapted control strategies. Full article

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

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27 pages, 1089 KB

Open AccessReview

Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap

by Mingzhu Li, Shuhong Huang, Jinze Jia, Yixing Feng and Jing Zhang

Toxins 2026, 18(3), 149; https://doi.org/10.3390/toxins18030149 - 19 Mar 2026

Viewed by 1135

Abstract

Human organoids and organ-on-chip/microphysiological systems (OoC/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across [...] Read more.

Human organoids and organ-on-chip/microphysiological systems (OoC/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across major toxin classes, including bacterial enterotoxins (e.g., cholera toxin, heat-stable enterotoxins, Shiga toxins), mycotoxins (e.g., aflatoxin B1, ochratoxin A, deoxynivalenol), and algal/cyanobacterial toxins (e.g., saxitoxin, domoic acid, microcystins, biliatresone). We emphasize studies that clearly define toxin identity and exposure context and that demonstrate mechanism-critical model competencies under assay conditions. We highlight decision-informative functional endpoints that align with the dominant pathophysiology. These include cystic fibrosis transmembrane conductance regulator (CFTR)-dependent secretion in human enteroids/colonoids, transporter-linked proximal tubular injury in kidney MPS, gut–kidney axis injury from Shiga toxin-producing E. coli in microfluidic systems, and multi-electrode array (MEA) network readouts in human 3D neural tissues. We then summarize best practices that improve cross-study comparability. These include reporting delivered versus nominal exposure, assessing recovery/mass balance and device/material interactions, applying proportional biological qualification (polarity, transporter/enzymatic competence, functional stability), defining a minimal comparable endpoint core, and preserving QIVIVE readiness in reporting. Finally, we outline near-term priorities for the field, including chronic low-dose and mixture designs, harmonized reference panels and acceptance criteria, and fit-for-purpose escalation to coupled OoC/MPS only when perfusion or organ–organ coupling is expected to change the interpretation. Full article

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27 pages, 5153 KB

Open AccessEditor’s ChoiceReview

Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis

by Qing Tang, Ho Yung Chan, Yanxi Huang and Yung H. Wong

Toxins 2026, 18(3), 148; https://doi.org/10.3390/toxins18030148 - 18 Mar 2026

Cited by 1 | Viewed by 2430

Abstract

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gα_i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). [...] Read more.

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gα_i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium’s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx’s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit’s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx’s dual functionality, distinguishing its G_i protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive G_i signaling and the interplay between PTx and ACT shape host–pathogen interaction in pertussis pathogenesis. Full article

(This article belongs to the Section Bacterial Toxins)

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10 pages, 251 KB

Open AccessArticle

Early Use of Botulinum Toxin in Post-Stroke Spasticity Has the Potential to Prevent Post-Stroke Upper Limb Pain—A Secondary Analysis of the EUBoSS Randomised Controlled Trial

by Cameron Lindsay, Fraser Philp and Anand D. Pandyan

Toxins 2026, 18(3), 147; https://doi.org/10.3390/toxins18030147 - 18 Mar 2026

Viewed by 799

Abstract

Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain [...] Read more.

Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain prevalence in people post-stroke with severe upper limb impairment and spasticity in a hyper/acute setting, identify if botulinum toxin Type-A (BoNTA) could prevent pain developing and reduce pain if already present and evaluate differences in analgesic use between BoNTA and placebo groups. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ninety-three participants (48F:45M) were randomised at a median of 11 days post-stroke (IQR 8–19) and included in the intention-to-treat analysis. Pain prevalence increased from 29.0% (95% CI [20.1–37.9%]) to 63.4% (95% CI [54.0–72.9%]) at six months. BoNTA treatment may prevent the development of pain at six months (OR = 0.42, 95% CI [0.18 to 1.01]) but not at three months (OR = 0.57, 95% CI [0.25 to 1.32]). The odds ratio for being on at least one analgesic at six months in the BoNTA group was 0.35 ([95% 0.14 to 0.87]). This secondary analysis suggests that early treatment of spasticity with BoNTA may potentially help prevent post-stroke upper limb pain and reduce analgesic use but appears less effective once pain is established. Further prospective studies are required to verify the hypotheses generated from this secondary analysis. Full article

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

17 pages, 1354 KB

Open AccessArticle

Marginal Orbicularis Oris Hyperactivity (MOOH): An Exploratory Case Series of Inversion-Dominant Upper Lip Dynamics Following Intraoral Botulinum Toxin Type A

by Andrea Felice Armenti

Toxins 2026, 18(3), 146; https://doi.org/10.3390/toxins18030146 - 17 Mar 2026

Viewed by 712

Abstract

Excessive gingival display (EGD) is most commonly attributed to vertical upper lip elevation, short lip length, or dentoalveolar disproportion. However, some patients exhibit gingival or mucosal visibility during smiling despite minimal vertical upper lip displacement, suggesting the presence of alternative dynamic patterns. This [...] Read more.

Excessive gingival display (EGD) is most commonly attributed to vertical upper lip elevation, short lip length, or dentoalveolar disproportion. However, some patients exhibit gingival or mucosal visibility during smiling despite minimal vertical upper lip displacement, suggesting the presence of alternative dynamic patterns. This exploratory case series examined an inversion-dominant smile presentation and its documented modulation in association with conservative intraoral chemodenervation directed toward the marginal region of the orbicularis oris. Ninety-four patients with dynamic inversion during smiling were assessed using a qualitative rating aid (Armenti Inversion Scale, AIS) and a quantitative composite proportional measure of vermilion loss (ΔLv%). All patients received low-dose intraoral Onabotulinum toxin A (4–6 U) as part of routine aesthetic care. At Day 15 follow-up, a shift toward lower inversion grades was observed across the cohort, with a large proportion of patients showing minimal residual inversion. Quantitative ΔLv% values showed proportional changes that were directionally consistent with shifts in AIS grade. The functional alterations were mild, transient, and self-resolving. Preliminary inter-rater agreement for AIS and measurement repeatability for ΔLv% suggested acceptable internal consistency for exploratory reporting tools. These findings suggest that inward vermilion inversion may represent a potentially distinct dynamic contributor to gingival or mucosal exposure in selected individuals, and that conservative marginal chemodenervation was associated with transient modulation of this pattern with generally preserved oral competence. AIS and ΔLv% are preliminary documentation tools. Further studies incorporating objective neuromuscular assessment, three-dimensional imaging, and comparative designs are required to refine phenotypic characterization. Full article

(This article belongs to the Section Bacterial Toxins)

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17 pages, 4712 KB

Open AccessArticle

Botulinum Toxin Treatment Can Enlarge Eye Appearance in Asian Patients and Improves Social and Emotional Attributes

by Maurício de Maio, Kiyoko Kato, Momoko Sato, Yuki Horiuchi, Takuya Toyama, Akiko Imaizumi and Hidenori Ishii

Toxins 2026, 18(3), 145; https://doi.org/10.3390/toxins18030145 - 15 Mar 2026

Viewed by 1408

Abstract

Aesthetic patients in East Asia are commonly concerned about small apparent eye size. Simultaneous treatment of the glabellar and lateral canthal areas with botulinum neurotoxin has potential to provide improvements. This case series evaluated changes in eye size following treatment of these two [...] Read more.

Aesthetic patients in East Asia are commonly concerned about small apparent eye size. Simultaneous treatment of the glabellar and lateral canthal areas with botulinum neurotoxin has potential to provide improvements. This case series evaluated changes in eye size following treatment of these two areas using standard on-label doses of onabotulinumtoxinA in patients from Japan or China. Outcomes were assessed based on standardised frontal photographs taken before and after treatment (at rest, maximum smile, and maximum frowning). Changes in eye size were examined using a 4-point Likert scale, as evaluated by three independent groups: six injectors; six non-injecting observers; and treated patients. Furthermore, improvements in overall facial impression were analysed using two established tools: ‘emotional attributes’ and ‘social attributes’. Twenty East Asian subjects were included (n = 17 women; mean age: 37.5 ± 6.4 years). The majority of evaluators in all three groups rated patients’ eye size as ‘significantly’ or ‘mildly’ improved post-treatment, whether assessed at rest, when smiling, or during frowning. Furthermore, almost all evaluators noted improvements in one or more emotional and social attributes. This approach has significant potential as a culturally adapted aesthetic technique for improving eye size in East Asian patients. Larger multicentre studies are warranted. Full article

(This article belongs to the Special Issue Application of Botulinum Toxin in Facial Diseases)

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21 pages, 1306 KB

Open AccessEditor’s ChoiceArticle

Are Baby Rattlesnakes More Dangerous than Adults? Origin, Transmission, and Prevalence of a Media-Driven Myth, with Evidence of Effective Messaging to Dispel It

by William K. Hayes and M. Cale Morris

Toxins 2026, 18(3), 144; https://doi.org/10.3390/toxins18030144 - 14 Mar 2026

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Abstract

The easily defanged myth that baby rattlesnakes (genera Crotalus and Sistrurus) are more dangerous than adults has persisted in North America despite all evidence to the contrary. The most often cited reason for the babies-more-dangerous (BMD) myth is the venom-dump (VD) hypothesis: [...] Read more.

The easily defanged myth that baby rattlesnakes (genera Crotalus and Sistrurus) are more dangerous than adults has persisted in North America despite all evidence to the contrary. The most often cited reason for the babies-more-dangerous (BMD) myth is the venom-dump (VD) hypothesis: babies, in contrast to adults, cannot control how much venom they expend, and therefore inject all of it when biting. We undertook three approaches to explore the origin, transmission, and prevalence of this myth and its most frequent explanation. First, we examined historical newspaper accounts. From 130 newspaper stories mentioning the relative danger of baby rattlesnakes, we identified a timeline in which (1) most stories prior to 1969 were factually correct; (2) the BMD myth and VD hypothesis likely originated in the mid-to-late 1960s and became entrenched in California, especially, from 1970 to 1999; (3) factually incorrect statements subsequently prevailed throughout North America from 2000 to 2014; and (4) factually correct stories regained prominence with apparent effective messaging success from 2015 onward. We further learned that general information stories about rattlesnakes, more often citing subject experts like university professors, were much more likely to provide accurate information than local snakebite stories, which more often cited health professionals (e.g., physicians, veterinarians, pharmacists) and emergency responders (e.g., police and fire officers) who frequently supplied misinformation. Second, we surveyed familiarity with the BMD myth and VD hypothesis among 53 university classrooms (including one high school) representing 3751 students across 29 states within the United States. Consistent with the California media’s outsized influence on misinformation transmission, familiarity with the myth was greatest in the southwestern states (52.6%) and declined moving north and east, with the least familiarity in the northeastern states (16.4%). Third, a small survey of 75 emergency responders and health professionals from Southern California revealed that a whopping 73.3% actually believed the BMD myth. Numerous organizations generally regarded as authoritative further amplified the misinformation, especially on the internet, where some content persists to this day. Unfortunately, belief in the BMD myth and VD hypothesis can lead to negative consequences, including misinformed risk-taking by those encountering snakes, unwarranted fear among snakebite victims, and inappropriate care delivered by misinformed or patient/family-pressured medical professionals. Our findings target health professionals and emergency responders as priority audiences for education. Full article

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11 pages, 644 KB

Open AccessArticle

OnabotulinumToxinA Reduces Pharmacological Burden in Chronic Migraine Patients: A Two-Center Prospective Cohort Study

by Danilo Antonio Montisano, Alessandra Parisi, Alberto Raggi, Claudia Altamura, Luigi D’Onofrio, Marilena Marcosano, Luisa Fofi, Alessia Marcassoli, Fabrizio Vernieri and Licia Grazzi

Toxins 2026, 18(3), 143; https://doi.org/10.3390/toxins18030143 - 14 Mar 2026

Viewed by 844

Abstract

Background: Chronic migraine (CM) is a highly disabling and difficult-to-manage condition with a high pharmacological and economic burden. OnabotulinumtoxinA (BTx) was the first treatment specifically approved for CM. The main aim of this study was to assess whether the initiation of BTx is [...] Read more.

Background: Chronic migraine (CM) is a highly disabling and difficult-to-manage condition with a high pharmacological and economic burden. OnabotulinumtoxinA (BTx) was the first treatment specifically approved for CM. The main aim of this study was to assess whether the initiation of BTx is associated with discontinuation of previously prescribed preventive therapies. Methods: This study was a prospective cohort investigation conducted in two headache centers: Carlo Besta (Milan) and Policlinico Campus Bio-Medico (Rome). We included patients with CM and previous oral preventive treatments initiating BTx. We analyzed persistence with preventive therapies over 12 months of follow-up and evaluated the conversion rate from chronic to episodic migraine (EM), along with change in migraine days, symptomatic intake, and HIT-6. Results: A total of 95 patients were included in the main analysis, showing a discontinuation of treatment in 28.4% of patients at 12 months. In the exploratory analysis, a CM to EM conversion rate of 58.9% was achieved at 12 months; meanwhile, HIT-6, migraine days, and symptomatic intake showed a sizeable improvement. Conclusion: Treatment with BTx was associated with a reduction in drug burden at 12 months and a CM to EM conversion rate of almost 60% at 12 months, also contributing to a reduction in the economic burden of the disease. Full article

(This article belongs to the Section Bacterial Toxins)

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19 pages, 3428 KB

Open AccessArticle

Comparative Analytics and Pharmacodynamics of the Complex Protein-Free Botulinum Toxin Type A Formulations DaxibotulinumtoxinA, IncobotulinumtoxinA and RelabotulinumtoxinA

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

Toxins 2026, 18(3), 142; https://doi.org/10.3390/toxins18030142 - 14 Mar 2026

Viewed by 1226

Abstract

Botulinum neurotoxin type A (BoNT/A) is intramuscularly injected for the treatment of, e.g., spasticity, cervical dystonia or facial lines. Several BoNT/A products with or without complexing proteins, with non-interchangeable dose units and various duration of effect claims, are approved but hard to compare. [...] Read more.

Botulinum neurotoxin type A (BoNT/A) is intramuscularly injected for the treatment of, e.g., spasticity, cervical dystonia or facial lines. Several BoNT/A products with or without complexing proteins, with non-interchangeable dose units and various duration of effect claims, are approved but hard to compare. The goal of this study was to compare the complexing protein-free approved BoNT/A products IncobotulinumtoxinA (INCO), DaxibotulinumtoxinA (DAXI) and RelabotulinumtoxinA (RELA) in vitro and in vivo. BoNT/A protein content per 100 U was lowest in INCO and highest in DAXI (INCO 0.44, RELA 0.46, DAXI 0.58 ng/100 U). Relative bioactivity of INCO, DAXI and RELA was comparable (116, 104 and 117 U/100 labeled units). INCO and DAXI caused a maximum mouse digit abduction score (DAS) 2–3 days after IM injection of 20 or 40 U/kg. The DAS after 20 U/kg INCO was higher and showed a 10 days longer paralysis than DAXI at equivalent dosing. The in vivo spread of DAXI in the mouse gastrocnemius muscle was indistinguishable from that after INCO, and the spread of RELA ex vivo in porcine muscle was larger than INCO but equal to 0.9% NaCl. These results show the differences between 150 kDa botulinum type A toxin products beyond the published claims. Full article

(This article belongs to the Section Bacterial Toxins)

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16 pages, 1164 KB

Open AccessArticle

Effect of Pre-Exposure to Deoxynivalenol on the Response of Porcine Intestinal Epithelial Cells to F18 E. coli Infection

by Madison Brackett, Paul Oladele, Hang Lu, Nathan Horn and Kolapo M. Ajuwon

Toxins 2026, 18(3), 141; https://doi.org/10.3390/toxins18030141 - 14 Mar 2026

Viewed by 704

Abstract

The mycotoxin deoxynivalenol (DON) is a common contaminant found in swine diets, causing decreased growth performance and poor health. Additionally, F18 enterotoxigenic E. coli is a leading cause of post-weaning diarrhea. Nursery pigs are often exposed to each of them after weaning; however, [...] Read more.

The mycotoxin deoxynivalenol (DON) is a common contaminant found in swine diets, causing decreased growth performance and poor health. Additionally, F18 enterotoxigenic E. coli is a leading cause of post-weaning diarrhea. Nursery pigs are often exposed to each of them after weaning; however, it is unknown what impact the combination of these stressors has on gastrointestinal health. Therefore, the objective of this study was to investigate the effect of pre-exposure to DON on the response of intestinal porcine epithelial cells (IPEC-J2) to challenge with enterotoxigenic F18 E. coli. Four groups were compared: Control (untreated cells), DON (cells treated with 0.5 μM DON for 24 h), F18 E. coli (multiplicity of infection 5:1, varied duration) and DON + E. coli (DON treatment with subsequent E. coli infection). Gene expression of IL-8, IL-6 and TNFα was significantly increased in cells infected with E. coli for 3 h vs. uninfected cells (p < 0.0001, p < 0.0001 and p < 0.0001, respectively). There was an interactive effect between DON and E. coli on IL-8 gene expression; cells pretreated with DON before E. coli infection had a higher expression of IL-8 than those not pretreated (p < 0.05). The concentration of IL-8 protein was significantly increased by E. coli (p < 0.0001). Claudin 1 and Occludin protein abundance were reduced by E. coli as measured by Western blot. Cytotoxicity was increased by E. coli vs. Control (p < 0.05). Pretreatment with DON increased the amount of E. coli that adhered to IPEC-J2 cells (p < 0.01) 30 min post-infection. FITC-dextran passage was increased in the DON + E. coli treatment vs. E. coli alone (p < 0.0001). Transepithelial electrical resistance (TEER) was decreased by DON when compared to untreated cells at 0 h (p < 0.0001). Similarly, DON + E. coli exhibited lower TEER vs. E. coli alone at 2 h post-infection (p < 0.0001). Taken together, these results indicate that DON pre-exposure increased the severity of E. coli infection on endpoints such as barrier permeability and E. coli adhesion. Full article

(This article belongs to the Special Issue Mycotoxin Contamination in Animal Nutrition and Its Mitigation Strategies)

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23 pages, 1022 KB

Open AccessArticle

Effects of Preharvest Application of Oxalic Acid, γ-Aminobutyric Acid, and Melatonin on the Microbiological and Physicochemical Quality of Dried Figs at Commercial Harvest and During Storage

by Cristina Hidalgo, Santiago Ruiz-Moyano, Alicia Rodríguez, María G. Cordoba, Margarita López-Corrales and Manuel J. Serradilla

Toxins 2026, 18(3), 140; https://doi.org/10.3390/toxins18030140 - 13 Mar 2026

Viewed by 672

Abstract

The objective of this study was to evaluate the preharvest application of γ-aminobutyric acid (GABA), melatonin (MT), and oxalic acid (OA), at different concentrations and application frequencies, on the physicochemical and microbiological quality of dried figs (cv. Calabacita) at commercial harvest and after [...] Read more.

The objective of this study was to evaluate the preharvest application of γ-aminobutyric acid (GABA), melatonin (MT), and oxalic acid (OA), at different concentrations and application frequencies, on the physicochemical and microbiological quality of dried figs (cv. Calabacita) at commercial harvest and after 3 and 6 months of refrigerated storage. A further aim was to determine their impact on fungal populations and mycotoxin production. The results showed that untreated dried figs had a higher frequency of Aspergillus welwitschiae, A. tubingensis, and Aspergillus section Flavi, whereas elicitor-treated figs exhibited a lower incidence of toxigenic fungi. A. welwitschiae was the main ochratoxin A (OTA)-associated species detected, although the proportion of OTA-positive figs was lower in elicitor-treated samples than in the control. Aflatoxins (AFs) were detected only sporadically in 2 mM OA treatments, consistent with the limited activity of A. flavus at low storage temperatures. Conversely, Penicillium spp. were widespread but were associated with citrinin (CIT) production only under 2 mM OA treatments. Among the Alternaria toxins, alternariol (AOH) was detected solely in dried figs treated with 1 mM OA. Notably, all investigated mycotoxins were below the limit of detection (<LOD) in dried figs treated with 0.5 mM MT. Moderate elicitor concentrations (e.g., 0.5 mM MT and 50 mM GABA) and multiple preharvest applications generally provided the best balance between fungal suppression and fruit quality, significantly reducing Aspergillus spp. occurrence without promoting the growth of undesirable species. Overall, elicitor treatments decreased the incidence of toxigenic fungi, most likely through direct antifungal effects in senescent dried fruit rather than by inducing host defences. The combined use of preharvest elicitors with appropriate drying and storage conditions is a promising strategy to control fungal contamination and mycotoxin accumulation in dried figs while maintaining quality from preharvest storage. Further research is needed to optimise elicitor concentrations and application timing. Full article

(This article belongs to the Section Mycotoxins)

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17 pages, 952 KB

Open AccessArticle

Pharmacological Treatments and Adverse Reactions Following Snake Antivenom Therapy: A Collaborative Study by Healthcare Professionals in the Southernmost Region of Thailand

by Panuwat Promsorn, Wittawat Chantkran, Musleeha Chesor and Janeyuth Chaisakul

Toxins 2026, 18(3), 139; https://doi.org/10.3390/toxins18030139 - 12 Mar 2026

Viewed by 1559

Abstract

The administration of specific immunoglobulin G-based antivenoms is a key strategy for treating snakebite envenoming victims. However, serious adverse reactions, such as anaphylaxis or serum sickness, are frequently observed following such administration. In addition, inflammation associated with delayed wound healing considerably drives the [...] Read more.

The administration of specific immunoglobulin G-based antivenoms is a key strategy for treating snakebite envenoming victims. However, serious adverse reactions, such as anaphylaxis or serum sickness, are frequently observed following such administration. In addition, inflammation associated with delayed wound healing considerably drives the irrational use of antibiotics or anti-inflammatory agents, which may be linked to adverse reactions following antivenom treatment. In this study, we evaluated the factors contributing to adverse effects following the administration of snake antivenom, especially pharmacological treatment and premedication intended to prevent adverse reactions. Our retrospective study was conducted by healthcare professionals in Narathiwat, the southernmost province in Thailand, and it involved 980 patients confirmed to have been snakebitten from 2016 to 2021. Of these cases, 513 were treated with antivenom. Prevalence rates and 95% confidence intervals were calculated, and univariate and multivariate analyses were performed to determine the correlation between adverse reactions and medications. Following antivenom administration, the majority of the patients exhibited no adverse reactions (86.7%). Nevertheless, skin rash, itching, wheezing, angioedema, chest tightness, and fever were observed in 13.3% of those receiving snake antivenom. After the administration of antivenom for Malayan pit viper bite, adverse reactions occurred in 11.7% of the sample, especially among referral patients (p < 0.001). Epinephrine and antihistamines were prescribed as prevention and treatment for hypersensitivity due to antivenom administration. Antibiotics, Non-steroidal Anti-inflammatory drugs (NSAIDs), and acetaminophen were not associated with antivenom-induced adverse reactions. Interestingly, tramadol and antihistamines significantly reduced the occurrence of adverse reactions after antivenom administration (p < 0.05). Well-trained staff, close monitoring alongside resuscitation equipment and medications that can minimise the severity of anaphylactic reactions must be promptly available whenever antivenom is administered. Full article

(This article belongs to the Special Issue Snake Bite and Related Injury)

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32 pages, 5169 KB

Open AccessConference Report

Report from the 31st Meeting on Toxinology, “Toxins: Playing with and Fighting Them!”, Organized by the French Society for Toxinology on 1–2 December 2025

by Sylvie Diochot, Raphaële Le Garrec, Michel M. Dugon and Pascale Marchot

Toxins 2026, 18(3), 138; https://doi.org/10.3390/toxins18030138 - 11 Mar 2026

Viewed by 908

Abstract

The French Society for Toxinology (SFET) held its 31st annual meeting (RT31) on 1–2 December 2025 at Hôtel Le Saint Paul in Nice, France, on the famous French Riviera. The meeting, which gathered 75 participants from around the world, was organised there for [...] Read more.

The French Society for Toxinology (SFET) held its 31st annual meeting (RT31) on 1–2 December 2025 at Hôtel Le Saint Paul in Nice, France, on the famous French Riviera. The meeting, which gathered 75 participants from around the world, was organised there for the second consecutive year, while previous editions were all held in Paris. The RT31 main theme, “Toxins: Playing with and fighting them”, explored recent, cutting-edge research in the field of animal venoms and of toxins from algal, animal, bacterial, fungal, plant and microbial origins, in emphasizing the evolution of the toxins, their modes of action and roles, and ways of counteracting intoxinations. These key topics were largely covered through 26 oral and 18 poster communications, organized into three main thematic areas covering three specific aspects of toxinology, along with a traditional fourth, more general session enabling participants to present recent data outside of these themes but nevertheless providing valuable information to the field. This report presents the abstracts of nine of the invited lectures, 14 of the selected lectures, and 16 of the posters, in accordance with the authors’ agreement to publish them. Also, we announce the winners of the “Best Oral Communication” and “Best Poster Communication” awards, which recognize the outstanding contributions of young researchers and their inventive work in toxinology. Full article

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12 pages, 259 KB

Open AccessArticle

Innovative Management of Spastic Shoulder Contractures: A Retrospective Cohort Analysis of Combined Percutaneous Cryoneurolysis and Tenotomy

by Paul Winston, Mahdis Hashemi, Fraser MacRae, Samuel Herzog, Maxime Billot and Romain David

Toxins 2026, 18(3), 137; https://doi.org/10.3390/toxins18030137 - 11 Mar 2026

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Abstract

Shoulder spasticity is a common consequence of upper motor neuron lesions and may be associated with soft tissue contractures, limiting functional recovery. While both cryoneurolysis and tendon lengthening procedures are used individually in refractory cases, their combined effect has not been clearly established. [...] Read more.

Shoulder spasticity is a common consequence of upper motor neuron lesions and may be associated with soft tissue contractures, limiting functional recovery. While both cryoneurolysis and tendon lengthening procedures are used individually in refractory cases, their combined effect has not been clearly established. It is consequently necessary to assess the efficacy of combining cryoneurolysis and percutaneous pectoral tenotomy in reducing shoulder spasticity and improving passive range of motion in patients with refractory shoulder spasticity and contracture. This retrospective, single-centre cohort study included 15 adults (≥19 years) with chronic shoulder spasticity and clinically confirmed musculotendinous contracture, previously treated with botulinum toxin injections without sufficient functional response, and free of pharmacological effects (last injection >4 months prior). All patients underwent cryoneurolysis targeting motor branches to the pectoral muscles. Outcomes included Modified Ashworth Scale (MAS) and shoulder Passive Range Of Motion (PROM). The combined approach provided significant improvements in spasticity severity for shoulder flexion (p < 0.01) and abduction (p < 0.01), and significant improvements in maximum PROM for shoulder flexion (p < 0.0001) and abduction (p < 0.0001). Combining cryoneurolysis and pectoral tenotomy appears feasible, safe, and clinically beneficial in selected patients with both spasticity and tendon contracture. Cryoneurolysis addresses the neural component, while tenotomy may restore mechanical excursion. This sequential diagnostic and therapeutic approach may enhance personalized management of mixed spastic–contracture shoulder limitations and could be applicable to other joints. Full article

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

16 pages, 3119 KB

Open AccessArticle

Sequential UV-C Irradiation and Sphingopyxis sp. m6 Biodegradation for Enhanced Degradation and Detoxification of Microcystin-LR

by Qin Ding, Tongtong Liu, Zhuoxiao Li, Rongli Sun, Juan Zhang, Lihong Yin and Yuepu Pu

Toxins 2026, 18(3), 136; https://doi.org/10.3390/toxins18030136 - 10 Mar 2026

Viewed by 542

Abstract

Microcystins (MCs), a group of potent hepatotoxins from cyanobacterial blooms, threaten global water security due to the resistance to conventional treatment processes and multi-organ toxicity to human. This study innovatively proposed a novel sequential process combining UV irradiation with biodegradation by Sphingopyxis sp. [...] Read more.

Microcystins (MCs), a group of potent hepatotoxins from cyanobacterial blooms, threaten global water security due to the resistance to conventional treatment processes and multi-organ toxicity to human. This study innovatively proposed a novel sequential process combining UV irradiation with biodegradation by Sphingopyxis sp. m6 for efficient microcystin-LR (MC-LR) removal. Results revealed that sequential UV-C pretreatment followed by Sphingopyxis sp. m6 biodegradation achieved complete degradation of 1 mg/L of MC-LR within 1 h of the biological phase, drastically reducing the treatment time compared to biodegradation alone (5 h). Mechanistic investigation revealed that low-dose UV-C (50 mJ/cm²) pretreatment induced MC-LR photoisomerization consistently with previously reported Adda geometric isomers. These photoisomers, along with residual parent MC-LR, were subsequently mineralized by Sphingopyxis sp. m6. Enzymatic pathway analysis confirmed a dual-pathway degradation, where Mlr enzymes processed both the native toxin and its isomeric forms, leading to a series of linearized peptides and Adda-derived products. Critically, the process achieved efficient detoxification, as confirmed by the restoration of HepG2 cell proliferation and protein phosphatase 2A activity. Moreover, response surface methodology optimized the key parameters (31.49 °C, pH of 7.36, 0.23 mg/L) for the highest degradation efficiency. This work provides an energy- and cost-efficient strategy for MC-LR remediation and elucidates the molecular mechanism of UV-induced photoisomerization facilitating subsequent biodegradation. Full article

(This article belongs to the Special Issue Marine Biotoxins: Bioactivities, Identification, and Potential Bioprocesses)

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15 pages, 2042 KB

Open AccessArticle

Matrix Effect Variability in Urine Samples from Different Cohorts and Implications on LC-ESI-MS Mycotoxin Biomarker Analysis

by Michael Kuhn, Åsa Svanström, Nicholas N. A. Kyei, Sanna Lignell, Hans-Ulrich Humpf and Benedikt Cramer

Toxins 2026, 18(3), 135; https://doi.org/10.3390/toxins18030135 - 10 Mar 2026

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Abstract

Matrix effects (ME) during LC-ESI-MS analysis are a commonly acknowledged issue for a variety of matrices and analytes. Although sample preparation techniques are steadily evolving to reduce ME, the complexity and variability of the urine matrix remain a challenge, especially for multi-analyte methods. [...] Read more.

Matrix effects (ME) during LC-ESI-MS analysis are a commonly acknowledged issue for a variety of matrices and analytes. Although sample preparation techniques are steadily evolving to reduce ME, the complexity and variability of the urine matrix remain a challenge, especially for multi-analyte methods. To investigate the extent of ME implications on method performance and quantification, we used stable isotope-labelled standards (SIL-IS) of 11 mycotoxins to evaluate the magnitude and variability of ME in urine samples from two cohorts: Bangladeshi adult women (n = 50) and Swedish children of both sexes (n = 340). Significant ME differences were observed between the two cohorts for eight of the 11 mycotoxins. Additionally, intra-cohort ME variability turned out to be very high with interquartile ranges (IQR) above 15% for 14 out of 22 analyte-cohort combinations. Maximum IQR values were observed for sterigmatocystin in the Bangladeshi cohort (318%), strongly impacting quantitative results obtained with matrix(-matched) calibration. Further experiments on a small German cohort of four subjects, each providing four to five urine samples, revealed high variability of ME within each individual. Factors influencing ME were investigated, showing little to no impact of sex and a moderate impact of age for some analytes in the Swedish cohort. Nonetheless, especially the more polar analytes, showing stronger signal suppression, demonstrated clear correlation of ME with density and creatinine concentration of the urine samples. As a result, urine samples with very high or low density or creatinine values require careful handling in regard to sensitivity or quantification errors when matrix(-matched) calibration without SIL-IS is applied. Full article

(This article belongs to the Special Issue Advanced Analytical Technologies in Mycotoxins Detection for the One-Health)

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19 pages, 2381 KB

Open AccessEditor’s ChoiceArticle

RTP004 Peptide Binds to Botulinum Neurotoxin, Increases Cell Surface Binding, and Enhances Cellular SNAP-25 Cleavage

by Andre F. Batista, Ratnesh Singh, Frank Lee, Shaoqiu Zhuo, Dmitri Leonoudakis and Conor J. Gallagher

Toxins 2026, 18(3), 134; https://doi.org/10.3390/toxins18030134 - 10 Mar 2026

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Abstract

DaxibotulinumtoxinA for injection (DAXI) is a botulinum neurotoxin (BoNT) drug product comprising the 150 kDa pure BoNT/A1 as the drug substance formulated with a proprietary stabilizing excipient, RTP004. We hypothesized that RTP004 facilitates localization of BoNT/A1 to the neuronal membrane, resulting in increased [...] Read more.

DaxibotulinumtoxinA for injection (DAXI) is a botulinum neurotoxin (BoNT) drug product comprising the 150 kDa pure BoNT/A1 as the drug substance formulated with a proprietary stabilizing excipient, RTP004. We hypothesized that RTP004 facilitates localization of BoNT/A1 to the neuronal membrane, resulting in increased BoNT internalization and cleavage of the synaptosomal-associated protein of 25 kDa (SNAP-25) within synaptic terminals. We characterized the interaction between RTP004 and BoNT/A1 using in silico and in vitro techniques. In vitro analyses revealed that negative charges on the BoNT/A1 surface were located on the light chain (LC, the catalytic domain) and the C-terminus of the heavy chain (H_C, the receptor-binding domain), potentially providing sites for interaction with the positively charged RTP004 peptide. RTP004 bound to BoNT/A1, but not to human serum albumin (HSA), in both static and dynamic conditions. RTP004, not HSA, enhanced binding of BoNT to artificial membranes and RTP004 dissociated from BoNT under conditions that mimicked physiological conditions of the synaptic vesicle. RTP004 also increased binding of BoNT to the synaptosomal cell membrane and enhanced cleavage of SNAP-25 in a dose-dependent manner. These findings demonstrate that RTP004, not the excipient HSA common in other BoNT/A1 drug products, enhances binding of BoNT to the cell surface, facilitates internalization of BoNT into the cell, and increases SNAP-25 cleavage. Full article

(This article belongs to the Section Bacterial Toxins)

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18 pages, 1241 KB

Open AccessArticle

An ELISA-Based Alternative to Mouse Bioassays for Quantitative Evaluation of Tetanus Toxin

by Chie Shitada, Chiyomi Sakamoto, Kohsuke Kumeda, Susumu Yamaori and Motohide Takahashi

Toxins 2026, 18(3), 133; https://doi.org/10.3390/toxins18030133 - 9 Mar 2026

Viewed by 784

Abstract

Tetanus toxin evaluation has traditionally relied on mouse LD₅₀ bioassays, which require extensive animal use and time, necessitating development of alternative methods in accordance with 3R principles (Replacement, Reduction, and Refinement). We developed and validated a sandwich enzyme-linked immunosorbent assay (ELISA) as [...] Read more.

Tetanus toxin evaluation has traditionally relied on mouse LD₅₀ bioassays, which require extensive animal use and time, necessitating development of alternative methods in accordance with 3R principles (Replacement, Reduction, and Refinement). We developed and validated a sandwich enzyme-linked immunosorbent assay (ELISA) as an alternative to animal testing for evaluating tetanus toxin biological activity using 18 environmental and clinical isolates of Clostridium tetani, complemented by an immunochromatographic (IC) assay for rapid screening. The ELISA demonstrated excellent analytical performance with a lower limit of quantification of 2.4 ng/mL (equivalent to 85.4 LD₅₀/mL), favorable linearity (R² = 0.999), precision (CV < 1.7–8.2%), and specificity (<1% cross-reactivity with C. septicum, C. novyi, and C. perfringens). Correlation analysis between ELISA relative potency and observed minimum lethal dose values revealed a robust positive correlation (r = 0.974). Both parallel line assay and single-point quantification methods showed strong correlations with mouse bioactivity measurements (r = 0.998). The IC assay successfully detected all isolates within 15 min. The measurement range of 2.4–45.6 ng/mL effectively covered diverse toxin-production capabilities spanning a 600-fold concentration range. This validated ELISA and IC assay combination provides a reliable, rapid alternative to animal experimentation for tetanus toxin evaluation. Full article

(This article belongs to the Section Bacterial Toxins)

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18 pages, 1375 KB

Open AccessArticle

Simultaneous Determination of Multiclass Cyanotoxins in Aquatic Products, Vegetables and Algal Dietary Supplements Using Dispersive Solid-Phase Extraction (dSPE)-UHPLC-MS/MS

by Baiyu Lai, Guanxiang Yuan, Qing Luo, Xiaoyun Qin, Zhaoying Lv, Haojia Ma, Huiling Chen, Honghe Liu, Guihua Liu and Jie Jiang

Toxins 2026, 18(3), 132; https://doi.org/10.3390/toxins18030132 - 6 Mar 2026

Viewed by 627

Abstract

Cyanotoxins, prevalent in eutrophic aquatic ecosystems, pose significant health risks via contaminated food, yet analytical methods for detecting multiple toxin classes in foodstuffs remain limited. In the current study, a method based on dispersive solid-phase extraction (dSPE) coupled with ultra-high-performance liquid chromatography–tandem mass [...] Read more.

Cyanotoxins, prevalent in eutrophic aquatic ecosystems, pose significant health risks via contaminated food, yet analytical methods for detecting multiple toxin classes in foodstuffs remain limited. In the current study, a method based on dispersive solid-phase extraction (dSPE) coupled with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was developed to simultaneously determine four common classes of cyanotoxins (i.e., microcystins, cylindrospermopsins, nodularins, and anatoxins) in aquatic products, vegetables and algal dietary supplements. Following initial extraction with 80% aqueous methanol, sample purification was performed using anhydrous sodium sulfate (400 mg) and C₁₈ sorbent (50 mg). For plant-based foods, additional graphitized carbon black (GCB, 15 mg) was also included. The method was successfully validated in eight different food matrices, demonstrating recoveries of 65–122% and relative standard deviations below 19%. The limits of detection and quantification across all matrices ranged from 0.1 to 3.4 μg/kg dry weight (dw) and 0.4 to 11.4 μg/kg dw, respectively. When applied to 96 food samples, this method detected multiple cyanotoxins in Tilapia and Spirulina-based dietary supplements. The proposed method provides a rapid, cost-effective, high-throughput, and sensitive analytical tool suitable for monitoring multiple cyanotoxins in various foodstuffs. Full article

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

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20 pages, 2358 KB

Open AccessArticle

Impact of Aspergillus flavus Infection on the Rhizosphere Bacterial Microbiota of Peanut (Arachis hypogaea L.)

by Qiujun Lin, Xianxin Wu, Lina Li, Tianshu Peng, Xun Zou, Guang Li, Jianzhong Wang, Xiaoqian Tang, Xiaofeng Yue, Chunjing Guo and Peiwu Li

Toxins 2026, 18(3), 131; https://doi.org/10.3390/toxins18030131 - 5 Mar 2026

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Abstract

This study investigated the effects of inoculating peanuts with two Aspergillus flavus strains (Aspergillus flavus CGMCC 3.4408 and A. flavus LNZW 23) on plant growth and the rhizosphere bacterial community. Infection significantly inhibited peanut growth. By 60 days post-inoculation (dpi), plant height [...] Read more.

This study investigated the effects of inoculating peanuts with two Aspergillus flavus strains (Aspergillus flavus CGMCC 3.4408 and A. flavus LNZW 23) on plant growth and the rhizosphere bacterial community. Infection significantly inhibited peanut growth. By 60 days post-inoculation (dpi), plant height in inoculated groups (CGMCC 3.4408, 26.4 cm; LNZW 23, 25.5 cm) was significantly lower than in the non-inoculated control (CK, 32.3 cm), with concomitant significant reductions in shoot and root biomass. Analysis of rhizosphere microbiota revealed that early infection (7 dpi) reduced bacterial species richness and phylogenetic diversity. Beta diversity analysis (PCoA) confirmed a significant divergence in microbial community structure between inoculated and control groups over time, with a statistically significant difference also observed between the two inoculated strains (p = 0.016). In terms of community composition, Proteobacteria, Acidobacteriota, and Actinobacteria were the three dominant phyla. At the genus level, infection altered the relative abundance of key taxa; genera such as KD4-96, Vicinamibacteraceae, and RB41 decreased at 7 dpi, while Sphingomonas remained relatively stable. By 60 dpi, community dominance increased, marked by rising abundances of Actinobacteria and Proteobacteria. In conclusion, A. flavus infection not only suppresses peanut growth but also persistently alters its rhizosphere microbial community, with effects demonstrating both time-dependency and strain-specificity. 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)

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10 pages, 826 KB

Open AccessReview

Botulinum Toxin Treatment of Stiff Person Syndrome—A Critical Review and Update

by Ava Grace Tohidian, Samira Marie Comtesse, Shahroo Etemadmoghadam and Bahman Jabbari

Toxins 2026, 18(3), 130; https://doi.org/10.3390/toxins18030130 - 5 Mar 2026

Viewed by 1098

Abstract

Stiff person syndrome (SPS) is an autoimmune disorder with muscle stiffness and spasms, for which current therapies provide incomplete relief. Botulinum neurotoxin (BoNT) has been explored as an adjunctive symptomatic treatment. The aim of this review was to critically evaluate the clinical evidence [...] Read more.

Stiff person syndrome (SPS) is an autoimmune disorder with muscle stiffness and spasms, for which current therapies provide incomplete relief. Botulinum neurotoxin (BoNT) has been explored as an adjunctive symptomatic treatment. The aim of this review was to critically evaluate the clinical evidence for BoNT therapy in SPS. Using Medline, Scopus and Google Scholar, we identified nine reports that were published up to 1 January 2026. English articles and articles with information on study type, type/dose of BoNT and treatment results were included. One study was double-blind and placebo-controlled, one was retrospective and seven were single-case reports, comprising 46 patients. Open-label trials used botulinumtoxin-A (Botox, Dysport or Xeomin), while the blind study applied abobotulinumA (Dysport). All but one study (a case report) demonstrated motor improvement and a reduction in painful spasms associated with patient satisfaction. Reported doses ranged from 300 to 800 units for onabotulinumtoxinA and incobotulinumtoxinA and from 700 to 1000 units for abobotulinumtoxinA. The literature highlights the need for randomized clinical trials in larger cohorts, with careful selection of dose, injection sites, and adjunct physiotherapy, as well as an evaluation of early BoNT therapy in SPS. The novelty of this review lies in its critical synthesis of reported data and inclusion of most recent reports. Full article

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

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14 pages, 2042 KB

Open AccessArticle

Boosting Sensitivity, Stability, and Speed: A Polydopamine-Engineered Silver Nanoparticle Lateral Flow Immunoassay for Aflatoxin B₁ in Maize

by Xinge Mo, Shuhong Zhang, Zixuan He, Xiaoyang Li, Xiangmin Li, Yonghua Xiong and Hu Jiang

Toxins 2026, 18(3), 129; https://doi.org/10.3390/toxins18030129 - 3 Mar 2026

Viewed by 637

Abstract

Conventional colorimetric lateral flow immunoassays (LFIAs) often suffer from insufficient sensitivity for detecting trace low-molecular-weight contaminants like mycotoxins. The development of colorimetric probes with a high molar extinction coefficient is therefore critical for enhancing detection performance. Although silver nanoparticles (AgNPs) exhibit an extremely [...] Read more.

Conventional colorimetric lateral flow immunoassays (LFIAs) often suffer from insufficient sensitivity for detecting trace low-molecular-weight contaminants like mycotoxins. The development of colorimetric probes with a high molar extinction coefficient is therefore critical for enhancing detection performance. Although silver nanoparticles (AgNPs) exhibit an extremely high molar extinction coefficient, their practical application in LFIA is hindered by inherent chemical instability and suboptimal visual contrast. To address these limitations, we have engineered robust and high-performance polydopamine-functionalized AgNPs (Ag@PDA NPs) as advanced LFIA signal probes, which were successfully used for detecting aflatoxin B₁ (AFB₁) in maize. The multifunctional PDA nanoshell effectively shields the Ag core from oxidation and other destabilizing factors, ensuring superior long-term stability and significantly enhancing colorimetric contrast. Moreover, it improves the colloidal hydrophilicity, enabling faster and more uniform migration kinetics along the test strip. Leveraging these engineered properties, the developed assay achieved a limit of detection (LOD) of 0.23 ng mL⁻¹ for AFB₁ in buffer, representing a remarkable 2.17-fold sensitivity enhancement over conventional colloidal gold-based LFIAs. Validation in spiked maize samples confirmed high reliability, with recoveries ranging from 95.70% to 119.28% and precision (inter-/intra-assay CVs) below 13.03%. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 1385 KB

Open AccessArticle

Paediatric Snakebite Toxicity up to Compartment Syndrome: A Ten-Year Retrospective Study in Iasi, Romania

by Bogdan Caba, Sidonia Petronela Susanu, Ioana Cezara Caba, Tamara Roșu-Solange, Bogdan Huzum, Vasile Eduard Roșu, Ileana Katerina Ioniuc, Maria Adriana Mocanu and Iuliana Magdalena Starcea

Toxins 2026, 18(3), 128; https://doi.org/10.3390/toxins18030128 - 2 Mar 2026

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Abstract

Viper bites are medical emergencies that can develop into serious clinical complications and can endanger the life of the paediatric patient. This observational retrospective study analyses 24 cases of viper bites involving paediatric patients (<18 years) encountered over 10 years (2016–2025) in the [...] Read more.

Viper bites are medical emergencies that can develop into serious clinical complications and can endanger the life of the paediatric patient. This observational retrospective study analyses 24 cases of viper bites involving paediatric patients (<18 years) encountered over 10 years (2016–2025) in the emergency department of Saint Mary Emergency Hospital of Iasi, Romania, with a focus on those requiring specialised surgical monitoring. Sociodemographic factors, toxicity, and surgical management of snakebites were analysed. In 83.33% cases, viper bites were found on the lower limb. The retrospective study was completed through an in-depth analysis of two representative cases, with a particular focus on the evolution up to compartment syndrome. Of the 24 cases presented in the Emergency Department, one was a rare and severe case, which evolved into compartment syndrome and required fasciotomy to save the limb in the Plastic Surgical Department. Another one, with the bite localised at the upper limb, had perilesional oedema, without skin colour changes or secretions, preservation of joint contours, and normal nail colouration. Both were analysed and described in detail with all available data (images, investigations, etc.) to highlight pathophysiological and therapeutic aspects. Appropriate, multidisciplinary treatment considerably improves the functional prognosis of patients with viper bites; administration of antivenom and selective fasciotomy contribute to successful outcomes. The study emphasises that viper bites in children remain a public health problem in Romania and require prompt and multidisciplinary treatment. Full article

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

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19 pages, 1891 KB

Open AccessArticle

Sea Bindweed Prevents Mycotoxin Intoxication Through Antioxidant, Anti-Inflammatory and Cytoprotective Activities

by Nolwenn Hymery, Halima Boussaden, Stéphane Cérantola, Xavier Dauvergne and Christian Magné

Toxins 2026, 18(3), 127; https://doi.org/10.3390/toxins18030127 - 2 Mar 2026

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Abstract

Mycotoxins are the most frequently occurring natural contaminant in food and feed products. Through the deployment of diverse agricultural strategies or biological, chemical, or physical treatments of crop products, mycotoxin contamination remains a persistent issue for the agricultural sector and food/feed industry. We [...] Read more.

Mycotoxins are the most frequently occurring natural contaminant in food and feed products. Through the deployment of diverse agricultural strategies or biological, chemical, or physical treatments of crop products, mycotoxin contamination remains a persistent issue for the agricultural sector and food/feed industry. We previously suggested that halophytes, thanks to their high antioxidant activity, could protect animal cell lines from mycotoxin contamination. Here, a hydroalcoholic extract of Calystegia soldanella L. leaves was evaluated for in vitro total antioxidant capacity (TAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-quenching bioassays, as well as anti-inflammatory (ELISA measurement of IL-8 secretion), ROS-inhibiting production (CellROX Green assay), and calcium influx restoration (fluorescent probe Fura2-QBT assay) activities in two animal cells upon mycotoxin intoxication. C. soldanella extract displayed high antioxidant activities (DPPH IC₅₀ < 80 μg·mL⁻¹ and TAC of 90 mg AAE·g⁻¹ DW. Moreover, it exhibited a significant protective action on renal (MDBK) and intestinal (IPEC-J2) cells against zearalenone (ZEA) or T2-toxin contamination, restoring about 75% of cell viability (MTS bioassay) at 1 μg·mL⁻¹. This effect was accompanied by strong anti-inflammatory, ROS-inhibition, and membrane integrity restoration activities. A bio-guided study revealed that the fraction of C. soldanella extract eluted from C18-bound silica with 60% methanol was the most active one. Upon HPLC and 1D- and 2D-NMR analyses, major compounds identified in this fraction were flavonol-type flavonoids, including quercetin-3-O-glucose (X1), quercetin-3-O-rutinoside (X2), and quercetin-3-O-glucose-6″-acetate (X3). Enriched sub-fractions containing these compounds largely contributed to the cytoprotective effects of C. soldanella, supporting its potential use as a food/feed ingredient. Full article

(This article belongs to the Special Issue Mycotoxin Contamination in Animal Nutrition and Its Mitigation Strategies)

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27 pages, 1328 KB

Open AccessReview

Uremic Toxins and the Lung Alveolar Capillary Barrier: A Narrative Review

by Saleh Kaysi, Maxime Taghavi, Alissa El Mourabi, Marie-Hélène Antoine, Eric De Prez and Joëlle Nortier

Toxins 2026, 18(3), 126; https://doi.org/10.3390/toxins18030126 - 2 Mar 2026

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Abstract

Introduction: Uremic toxins have been shown to cause adverse pulmonary effects by inducing endothelial and epithelial dysfunction, disrupting the alveolar-capillary barrier, and increasing inflammation and oxidative stress. This article reviews these effects with a specific focus on chronic kidney disease and the mechanisms [...] Read more.

Introduction: Uremic toxins have been shown to cause adverse pulmonary effects by inducing endothelial and epithelial dysfunction, disrupting the alveolar-capillary barrier, and increasing inflammation and oxidative stress. This article reviews these effects with a specific focus on chronic kidney disease and the mechanisms by which uremic toxins affect lung tissue. Methods: A narrative review was conducted using keywords related to uremic toxins and lung injury to search the PubMed database. An advanced literature review was conducted in PubMed to identify studies explaining the mechanisms underlying lung pathophysiology in chronic kidney disease (CKD), with particular focus on CKD-induced pulmonary epithelial and endothelial dysfunction. Additionally, to highlight the pathological processes of lung congestion in CKD, studies on CKD-induced dysfunction of the alveolar-capillary barrier were retrieved. Studies published up to November 2025 were evaluated. Results: A total of 148 articles were reviewed in full text. Uremic toxins negatively impact lung tissue structure and function through multiple mechanisms, including oxidative stress, inflammation, and direct effects. Uremic toxins appear to share signaling pathways in endothelial cells, including those linked to Mitogen-activated protein kinases (MAPK), the Aryl Hydrocarbon Receptor (AhR), the receptor for advanced glycation end products (RAGE), and pro-inflammatory transcription factors such as nuclear factor κB (NF-κB). Additionally, oxidative stress acts as a pro-inflammatory signal shared by several uremic toxins. The mechanisms behind the harmful interactions between CKD and lung disease are mostly unknown, although more evidence exists for acute kidney injury (AKI). Conclusions: Chronic kidney disease, which leads to the buildup of uremic toxins, negatively affects the lungs. Overall, the accumulation of uremic toxins in CKD impairs endothelial and epithelial cells and the alveolar capillary barrier. Further research is needed to understand the specific mechanisms underlying these effects and to identify therapeutic options to protect the lungs in these patients. Full article

(This article belongs to the Special Issue Uremic Toxins and Hemodialysis: Mechanisms, Challenges, and Therapeutic Advances)

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35 pages, 2573 KB

Open AccessArticle

Stability and Efficacy of Fungicides Registered for Organic and Commercial Wheat Production in Hungary Against Fusarium Head Blight—A Comprehensive Methodology to Enhance Food Safety

by Tamás Meszlényi, Katalin Ács, Attila Berényi, Daniel Nagy and Ákos Mesterhazy

Toxins 2026, 18(3), 123; https://doi.org/10.3390/toxins18030123 - 2 Mar 2026

Viewed by 870

Abstract

Fusarium head blight (FHB) is one of the most significant diseases in wheat globally, affecting about 200 million tons of grain per year through mycotoxin contamination. Besides yield losses, mycotoxin contamination is a major concern. FHB resistance in wheat is partial and polygenic, [...] Read more.

Fusarium head blight (FHB) is one of the most significant diseases in wheat globally, affecting about 200 million tons of grain per year through mycotoxin contamination. Besides yield losses, mycotoxin contamination is a major concern. FHB resistance in wheat is partial and polygenic, and since the efficacy of plant protection measures is generally weak-to-moderate, an integrated approach is needed for successful control. We evaluated a more comprehensive methodology for improved protection; in this two-year study, five registered organic products and six conventional products were compared under artificial and natural infection conditions. The disease index (DI), Fusarium-damaged kernels (FDKs) and deoxynivalenol (DON) contamination were evaluated. The stability of the fungicides was also evaluated based on 10 epidemic conditions. The organic fungicides showed much lower efficacy than the conventional ones, although significant reductions in symptoms and DON contamination were observed. In each group, significant variability was detected. The best fungicides for DON contamination showed the lowest variance (highest stability) between 10 and 20 (Verben, Prosaro, Ascra Xpro). The organic fungicides were much less stable; the least stable showed a variance of 141 (Fusarium control: 264). The best organic fungicide was the Bordeaux mixture supported by sulfur addition (variance: 54). The DI and FDK values presented very similar trends. For the more resistant cultivar GK Pilis, the combined DON reduction exceeded 90% for all fungicides. For the most susceptible cultivar, GK Békés, the values were between 30 and 83%, respectively. High resistance to FHB and toxin contamination is the key to controlling FHB in both organic and conventional production. For efficient fungicide control, stable resistance to disease and toxin accumulation are equally required. Principal component analysis (PCA) verified the importance of considering all traits to identify the fungicidal “fingerprint” and demonstrated the differences between fungicides regardless of their organic or conventional nature. PC response differs for traits and fungicides, supporting the complex evaluation of plant and fungicide behavior. Knowledge of resistance levels, in addition to improving mycotoxin control, aids in disease forecasting and epidemic management. The results are applicable to both organic and conventional production systems. Due to the variability in resistance and fungicidal effects, there is an opportunity to improve food safety in both organic and conventional wheat production. Full article

(This article belongs to the Special Issue Diversity, Function, Biological Activity, Detoxification, Contamination, Biosynthesis and Metabolic Regulation of Mycotoxins)

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20 pages, 4381 KB

Open AccessEditor’s ChoiceArticle

Influence of Plant Age and Endophyte Status on the Nematotoxicity of Festulolium loliaceum to Trichodorus primitivus and Quantification of Active Phytochemicals

by Nyambura G. Mwangi, Timothy J. Gillanders, Mark Stevens, Alistair J. D. Wright, Simon G. Edwards, Martin C. Hare and Matthew A. Back

Toxins 2026, 18(3), 125; https://doi.org/10.3390/toxins18030125 - 1 Mar 2026

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Abstract

Festulolium hybrids are cool-season forage grasses that form symbiotic relationships with the fungus Epichloë uncinata, which produces loline alkaloids that protect the host from herbivores. This study evaluated the nematotoxicity of shoot and root extracts of Festulolium loliaceum against the stubby root [...] Read more.

Festulolium hybrids are cool-season forage grasses that form symbiotic relationships with the fungus Epichloë uncinata, which produces loline alkaloids that protect the host from herbivores. This study evaluated the nematotoxicity of shoot and root extracts of Festulolium loliaceum against the stubby root nematode Trichodorus primitivus. Methanolic root and shoot extracts from plants aged 8, 12, 16, and 20 weeks were tested in vitro at five concentrations (312.5–5000 µg mL⁻¹) over 24, 48, and 72 h. Nematode immobility, mortality, and phytochemical profiles, including flavonoids, loline alkaloids, and phenols, were quantified. Extracts from shoots caused significant concentration and time-dependent immobility of T. primitivus (p = 0.001), reaching ≥90% at 5000 µg mL⁻¹ after 72 h in 8–12-week-old plants. Endophyte presence enhanced nematotoxicity, where LD₅₀ values for E+ roots were two-fold lower at 12 weeks and fifty-fold lower at 20 weeks compared with E− root extracts. Shoot extracts of E+ grass had the highest nematicidal activity at 8 weeks, with a significantly lower LD₅₀ value than E− (p < 0.05). Loline alkaloid concentrations increased with plant age, while flavonoids and phenols declined. Nematotoxicity of F. loliaceum extracts was strongly influenced by plant age and endophyte presence. Younger E+ shoots produced the most potent shoot extracts, whereas older plants produced the most potent root extracts. Flavonoid content was negatively correlated with shoot biomass (R = −0.94, p < 0.001). Similarly, phenol content was negatively correlated to both root biomass (R = −0.79, p < 0.001) and shoot biomass (R = −0.67, p < 0.005). Full article

(This article belongs to the Section Plant Toxins)

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Open AccessArticle

Molecular Basis of the Inhibition of Voltage-Gated Potassium Channel Kv1.1 by Chinese Tarantula Peptide Huwentoxin-XI

by Xuan Luo, Yuan Yin, Fenghua Wang, Xinyu Li, Shujun Wang, Yumei Yang, Chunbing Zheng, Jing Liu and Meichun Deng

Toxins 2026, 18(3), 124; https://doi.org/10.3390/toxins18030124 - 1 Mar 2026

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Abstract

Huwentoxin-XI (HWTX-XI) is a 55-amino acid peptide belonging to the family of spider Kuntiz-type toxins (KTTs), isolated from the venom of the Chinese tarantula Cyriopagopus schmidti. Under whole-cell voltage-clamp conditions, HWTX-XI was found to block Kv1.1 potassium channels but had no effect [...] Read more.

Huwentoxin-XI (HWTX-XI) is a 55-amino acid peptide belonging to the family of spider Kuntiz-type toxins (KTTs), isolated from the venom of the Chinese tarantula Cyriopagopus schmidti. Under whole-cell voltage-clamp conditions, HWTX-XI was found to block Kv1.1 potassium channels but had no effect on other potassium channel subunits (Kv1.4, Kv2.1, Kv3.1 and Kv4.2), sodium channels or calcium channels. In the present study, it was found that the substitution of Tyr379 by the valine in the filter region significantly decreased the affinity of toxin HWTX-XI by about 90-fold, indicating that the Kv1.1 filter region is a critical determinant of HWTX-XI potassium channel activity. After intrathecal or intraplantar injections, HWTX-XI decreased the mechanical nociceptive threshold (hyperalgesia) for a long-lasting period. HWTX-XI also significantly increased the firing frequency in mouse DRG neurons. The novel function of HWTX-XI makes it a new tool for studying the relationship between spider toxins and Kv1.1 channels and suggests that Kv1.1 channels might be a novel potential target for preventing and/or treating neuropathic pain. Full article

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

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Toxins, Volume 18, Issue 3 (March 2026) – 37 articles

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