Toxins

24 pages, 3732 KB

Open AccessReview

The Elias University Hospital Approach: A Visual Guide to Ultrasound-Guided Botulinum Toxin Injection in Spasticity, Part IV—Distal Lower Limb Muscles

by Marius Nicolae Popescu, Claudiu Căpeț, Cristina Popescu and Mihai Berteanu

Toxins 2025, 17(10), 508; https://doi.org/10.3390/toxins17100508 (registering DOI) - 16 Oct 2025

Abstract

Spasticity of the distal lower limb substantially impairs stance, gait, and quality of life in patients with upper motor neuron lesions. Although ultrasound-guided botulinum toxin A (BoNT-A) injections are increasingly employed, structured, muscle-specific visual guidance for the distal lower limb remains limited. This [...] Read more.

Spasticity of the distal lower limb substantially impairs stance, gait, and quality of life in patients with upper motor neuron lesions. Although ultrasound-guided botulinum toxin A (BoNT-A) injections are increasingly employed, structured, muscle-specific visual guidance for the distal lower limb remains limited. This study provides a comprehensive guide for ultrasound-guided BoNT-A injections across ten key distal lower limb muscles: gastrocnemius, soleus, tibialis posterior, flexor hallucis longus, flexor digitorum longus, tibialis anterior, extensor hallucis longus, flexor digitorum brevis, flexor hallucis brevis, and extensor digitorum longus. For each muscle, we present (1) Anatomical positioning relative to osseous landmarks; (2) Sonographic identification cues and dynamic features; (3) Zones of intramuscular neural arborization optimal for injection; (4) Practical injection protocols derived from literature and clinical experience. High-resolution ultrasound images and dynamic videos illustrate real-life muscle behavior and guide injection site selection. This guide facilitates precise targeting by correlating sonographic signs with optimal injection zones, addresses common spastic patterns—including equinus, varus, claw toe, and hallux deformities—and integrates fascial anatomy with motor-point mapping. This article completes the Elias University Hospital visual series, providing clinicians with a unified framework for effective spasticity management to improve gait, posture, and patient autonomy. Full article

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22 pages, 6094 KB

Open AccessArticle

Susceptibility to Secondary Bacterial Infections in Growing Rabbits Exposed to Ochratoxin A and Protected or Not by Herbal Supplements

by Kalina Zhivkova, Stoycho Stoev, Vladimir Petrov and Vesselin Ivanov

Toxins 2025, 17(10), 507; https://doi.org/10.3390/toxins17100507 - 15 Oct 2025

Abstract

The protective effects of the herbal feed supplements Silybum marianum, Silymarin, Withania somnifera, and Centella asiatica against ochratoxin A (OTA) toxicity were studied in 48 New Zealand White rabbits (37-day-old) during an 80-day experiment. OTA was given at 2 ppm, whereas Silybum [...] Read more.

The protective effects of the herbal feed supplements Silybum marianum, Silymarin, Withania somnifera, and Centella asiatica against ochratoxin A (OTA) toxicity were studied in 48 New Zealand White rabbits (37-day-old) during an 80-day experiment. OTA was given at 2 ppm, whereas Silybum marianum, Silymarin, Withania somnifera, and Centella asiatica were given at feed levels of 5000 ppm, 25,000 ppm, 4000 ppm, and 4600 ppm, respectively. All rabbits were immunized against Rabbit Hemorrhagic Disease Virus (RHDV). OTA was found to induce an immunosuppressive effect on the humoral immune response. Reliable protection against OTA-provoked immunosuppression by Silimarin and Withania somnifera was found. The OTA-induced immunosuppression was responsible for secondary bacterial infection (pasteurellosis) and the death of two rabbits from the OTA-exposed group and one rabbit each from the groups protected with Silybum marianum and Centella asiatica. A decreased body weight was found in rabbits exposed to OTA, but the decrease was slighter in the rabbits protected with herbal supplements. The target organs damaged by OTA exposure were the liver, kidneys, and spleen, while weaker lesions were found in other internal organs, except in the cases of secondary pasteurellosis, in which the strongest damage was found in the lung. All investigated herbal supplements appeared to have stronger protective effects against OTA-induced damage to the kidneys and liver, with slightly protective effects observed in the lungs, myocardium, spleen, brain, intestine, testicles, and ovaries. Full article

(This article belongs to the Section Mycotoxins)

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21 pages, 8380 KB

Open AccessArticle

Comprehensive Study of Some Cyanobacteria in Moscow Waterbodies (Russia), Including Characteristics of the Toxigenic Microcystis aeruginosa Strains

by Elena Kezlya, Elina Mironova, Ekaterina Chernova, Maria Gololobova, Andrei Mironov, Ekaterina Voyakina, Yevhen Maltsev, Dina Snarskaya and Maxim Kulikovskiy

Toxins 2025, 17(10), 506; https://doi.org/10.3390/toxins17100506 - 14 Oct 2025

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Abstract

The current study focuses on the diversity, distribution and toxic potential of cyanobacteria in the waterbodies of Moscow, Russia. The research involves the sampling of natural and artificial water environments situated within the Moscow city agglomeration, including the waterbodies of recreational importance. A [...] Read more.

The current study focuses on the diversity, distribution and toxic potential of cyanobacteria in the waterbodies of Moscow, Russia. The research involves the sampling of natural and artificial water environments situated within the Moscow city agglomeration, including the waterbodies of recreational importance. A total of 20 strains of cyanobacteria, namely representatives of Anabaena, Aphanizomenon, Argonema, Dolichospermum, Microcystis and Woronichinia, are isolated from the collected samples. The morphology of the newly obtained strains is analyzed through light microscopy. The results of morphological identification are compared to the molecular data. The molecular phylogeny of the cyanobacterial strains is assessed on the basis of 16S rRNA sequencing. The detection of cyanotoxin-producing genes through PCR reveals two strains of Microcystis aeruginosa capable of microcystin synthesis. Further analysis using HPLC-HRMS demonstrates that microcystin production includes a high proportion (20–28%) of exceptionally toxic microcystin–leucine arginine compounds. Hereby, we discuss the morphology and phylogeny of the analyzed strains and provide comments on the toxic potential of cyanobacteria within the waterbodies of Moscow. Full article

(This article belongs to the Special Issue Prospective Studies on Harmful Cyanobacteria and Cyanotoxins)

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2 pages, 628 KB

Open AccessCorrection

Correction: Thenuwara et al. Recent Advancements in Lateral Flow Assays for Food Mycotoxin Detection: A Review of Nanoparticle-Based Methods and Innovations. Toxins 2025, 17, 348

by Gayathree Thenuwara, Perveen Akhtar, Bilal Javed, Baljit Singh, Hugh J. Byrne and Furong Tian

Toxins 2025, 17(10), 505; https://doi.org/10.3390/toxins17100505 - 14 Oct 2025

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Abstract

Figure/Legend [...] Full article

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

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15 pages, 1416 KB

Open AccessArticle

Profiling the Paralytic Effects and Lethality of Cone Snail Venom Toxins Using Nanofractionation Analytics with In Vivo Zebrafish Larvae Assays

by Jeroen Kool, Arif Arrahman, Haifeng Xu, Jiaxing Liu, Richard J. Lewis, Christian Tudorache and Fernanda C. Cardoso

Toxins 2025, 17(10), 504; https://doi.org/10.3390/toxins17100504 - 13 Oct 2025

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Abstract

This study presents nanofractionation analytics coupled with in vivo profiling of zebrafish embryo paralysis and lethality in response to toxins in cone snail venoms. The focus of this study is on the development of this approach using venoms of Conus marmoreus, Conus [...] Read more.

This study presents nanofractionation analytics coupled with in vivo profiling of zebrafish embryo paralysis and lethality in response to toxins in cone snail venoms. The focus of this study is on the development of this approach using venoms of Conus marmoreus, Conus ebraeus, and Conus bandanus. In brief, cone snail venoms were separated using reversed-phase chromatography following high-resolution nanofractionation on microplates with parallel mass spectrometry, enabled via a post-column flow split. All collected fractions were dried overnight, followed by assays on zebrafish embryos. For the paralysis assessment, we monitored swimming behavior and swimming distance and found that exposure to cone snail toxins led to paralysis and decreased movement and swim distance. To correlate the masses of eluted toxins with their paralyzing effects and potency, we compared the fractionation retention time versus normalized swimming distance. This allowed identification of the masses of toxins with paralyzing bioactivity, which were predominantly conopeptides. To assess lethality, zebrafish embryos were exposed to fractionated toxins for 24 h, after which they were inspected. The lethal doses and correlated toxins were identified by comparing retention times of fractionation versus the lethal dose values calculated for each fraction. We found that the most lethal venom was from C. bandanus, displaying the largest number of lethal peptides, followed by C. marmoreus and C. ebraeus. On the other hand, the most paralytic venom was from C. ebraeus, presenting a higher number of peptides with non-lethal paralytic effects, followed by C. bandanus and C. marmoreus. This study provides a pipeline to rapidly identify paralytic and lethal cone snail venom toxins using the zebrafish embryo model. Full article

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

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Graphical abstract

11 pages, 266 KB

Open AccessReview

Botulinum Toxin Treatment in Hereditary Spastic Paraplegia—A Comprehensive Review and Update

by Bahman Jabbari, Samira Comtesse and Fattaneh Tavassoli

Toxins 2025, 17(10), 503; https://doi.org/10.3390/toxins17100503 - 13 Oct 2025

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Abstract

Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the [...] Read more.

Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the ten studies was double-blind and placebo-controlled. The search strategy included only articles published in English and articles providing basic information such as the type of the study, type and dose of the toxin and results of the treatment. Articles not in English, case reports and review articles were excluded. A total of 258 patients were included across all studies. The injected toxin in the open-label studies was botulinumtoxin-A (Botox or Dysport or Xeomin), whereas in the blinded study, the investigators used Prosigne. All open-label studies, which used FDA approved botulinumtoxin-A neurotoxins, demonstrated a degree of motor and non-motor improvement, whereas treatment with Prosigne did not improve patients’ function. The possible reasons for this discrepancy between the blinded study and the open-label studies are discussed. We found no studies on the effect of BoNTs on bladder dysfunction in HSP. There is a need for double-blind, placebo-controlled studies assessing the efficacy of FDA-approved botulinum neurotoxins in children and adults affected by hereditary spastic paraparesis. Such studies should also investigate the effect(s) of early botulinum neurotoxin therapy in this disorder. The novelty of this review is that it represents a comprehensive and critical literature review on this subject, with no other studies of this kind published previously. It also includes data not present in previous reviews of this subject. Full article

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

23 pages, 10020 KB

Open AccessArticle

Microbiological and Mycotoxicological Quality of Stored Wheat, Wholemeal Flour and Bread: The Impact of Extreme Weather Events in Romania in the 2024 Summer

by Valeria Gagiu, Elena Mirela Cucu (Chirtu), Elena Iulia Lazar (Banuta), Cristian Mihai Pomohaci, Alina Alexandra Dobre, Gina Pusa Pirvu, Oana Alexandra Oprea, Cristian Lazar, Elena Mateescu and Nastasia Belc

Toxins 2025, 17(10), 502; https://doi.org/10.3390/toxins17100502 - 11 Oct 2025

Viewed by 563

Abstract

This study examines the effects of the extreme drought and heatwaves that occurred in Romania during the summer of 2024 on the microbiological and mycotoxicological quality of wheat (Triticum aestivum) stored until April 2025, as well as on the quality of [...] Read more.

This study examines the effects of the extreme drought and heatwaves that occurred in Romania during the summer of 2024 on the microbiological and mycotoxicological quality of wheat (Triticum aestivum) stored until April 2025, as well as on the quality of wholemeal flour and bread derived from it. Comparative analyses were conducted against the contamination in wheat harvested in 2024. The hot and dry conditions significantly influenced the microbial and mycotoxicological contamination of both freshly harvested and stored wheat, as well as the derived flour and bread, due to their notably reduced moisture content and water activity. Although levels of total fungi, Fusarium-damaged kernels, and mycotoxins deoxynivalenol, aflatoxin B1, and ochratoxin A remained well below regulatory thresholds, higher contamination was observed in Transylvania and Moldavia—particularly in the Curvature Carpathians, likely due to their cooler and wetter microclimates. The observed quality changes were strongly associated with alterations in physico-chemical, rheological, and colorimetric parameters, posing potential economic challenges for the milling and baking industries. The study recommends implementing integrated regional strategies to enhance wheat resilience, optimize production systems, and improve contamination control in response to increasing climate stress across Southeastern Europe. Full article

(This article belongs to the Collection Impact of Climate Change on Fungal Population and Mycotoxins)

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16 pages, 2289 KB

Open AccessFeature PaperArticle

RelabotulinumtoxinA, a Ready-to-Use Formulation Neuromodulator Manufactured with PEARL™ Technology to Maintain High Biological and Specific Activity

by Ulf Ståhl, Emilia Lekholm, Emil Hamnevik, Robert Fredriksson, Sachin M. Shridharani, Keywan Taghetchian, Joel L. Cohen, Mark S. Nestor and Åsa Liljegren Sundberg

Toxins 2025, 17(10), 501; https://doi.org/10.3390/toxins17100501 - 9 Oct 2025

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Abstract

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of [...] Read more.

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

(This article belongs to the Section Bacterial Toxins)

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20 pages, 3594 KB

Open AccessArticle

Ganglioside Binding Assay: A Complementary Approach for Enhanced Tetanus Toxoid Quality Control

by Yuki Tanoue, Chie Shitada, Mariko Nakamichi, Naomi Nakamichi, Chiyomi Sakamoto, Hyun Kim, Kohsuke Kumeda, Masaki Ochiai, Susumu Yamaori, Mitsutoshi Senoh and Motohide Takahashi

Toxins 2025, 17(10), 500; https://doi.org/10.3390/toxins17100500 - 9 Oct 2025

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Abstract

Vaccine quality control has long relied on animal testing, which involves time, cost, and ethical constraints. This study introduces a ganglioside binding (GB) assay as a complementary in vitro screening tool for tetanus toxoid quality control, which was validated in a single-laboratory environment [...] Read more.

Vaccine quality control has long relied on animal testing, which involves time, cost, and ethical constraints. This study introduces a ganglioside binding (GB) assay as a complementary in vitro screening tool for tetanus toxoid quality control, which was validated in a single-laboratory environment as a foundational proof-of-concept. The assay reproduces tetanus toxin binding to gangliosides on microplates using simplified procedures. Validation with samples at different inactivation stages showed excellent linearity (0.0002–0.0156 Lf/mL), reproducibility, and a strong correlation with Ramon’s flocculation (R² = 0.999). The assay clearly distinguished between toxins and toxoids, with the toxoid results remaining at control levels. The time-course inactivation samples were consistent with the animal tests: partially inactivated samples (days 1–3) showed significant GB activity (p < 0.001) and caused 100% mortality, whereas samples from day 4 onward showed no activity and zero mortality. These findings demonstrate that the GB assay reliably differentiates active toxins from toxoids, which aligns with in vivo outcomes. The practical advantages include a simplified protocol, reduced complexity, and improved efficiency for routine testing of samples. As a complementary screening approach, this single-laboratory validation supports the 3Rs principle by demonstrating the potential for reducing animal use while ensuring quality assurance. Broader applicability requires multicenter validation and cross-reactivity, and multicenter validation is ongoing. Full article

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16 pages, 1361 KB

Open AccessArticle

Renal Effects of Sulfated Polysaccharides from the Seaweed Gracilaria cornea

by Terentia Batista Sá Norões, Sophia Moinhos, Helena Serra Azul Monteiro, Alice Maria Costa Martins, Ricardo Parente Garcia Vieira and Claudio Gleidiston Silva

Toxins 2025, 17(10), 499; https://doi.org/10.3390/toxins17100499 - 9 Oct 2025

Viewed by 279

Abstract

Sulfated polysaccharides (SPs) are abundant in seaweed and have several industrial and biomedical applications, but their renal effects remain unclear. This study evaluated the effects of total sulfated polysaccharides (TSPs) from Gracilaria cornea using an isolated rat kidney perfusion model. TSP at 3 [...] Read more.

Sulfated polysaccharides (SPs) are abundant in seaweed and have several industrial and biomedical applications, but their renal effects remain unclear. This study evaluated the effects of total sulfated polysaccharides (TSPs) from Gracilaria cornea using an isolated rat kidney perfusion model. TSP at 3 µg/mL increased perfusion pressure and renal vascular resistance at 90–120 min, while 4.5 µg/mL induced earlier and more pronounced changes (from 60 min). Urinary flow decreased at 1 µg/mL (90 min) but increased at 4.5 µg/mL (90–120 min). Sodium transport was reduced at all concentrations, whereas potassium and chloride transport remained unchanged. Histological analysis revealed protein deposits in tubules and urinary space, indicating tubular injury. In vitro, TSP reduced MDCK cell viability in a concentration-dependent manner and induced apoptosis, with some cells progressing to secondary necrosis. In conclusion, TSP altered renal physiology and morphology and triggered apoptotic pathways in renal cells, highlighting the need for further mechanistic and translational studies. Full article

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18 pages, 966 KB

Open AccessArticle

Computational Modelling Suggests Bacteriostatic Saline Does Not Reverse Botulinum Toxin-Induced Brow Ptosis

by Eqram Rahman, Alain Michon, Parinitha Rao, A. Q. M. Omar Sharif, William Richard Webb and Jean D. A. Carruthers

Toxins 2025, 17(10), 498; https://doi.org/10.3390/toxins17100498 - 7 Oct 2025

Viewed by 645

Abstract

Anecdotal reports have recently circulated suggesting that intramuscular injection of bacteriostatic saline (BS)—which contains benzyl alcohol (BnOH)—can reverse botulinum toxin type A (BoNTA)-induced brow ptosis. Given the well-established intracellular persistence of BoNTA’s light chain and its irreversible cleavage of SNAP-25, such rapid functional [...] Read more.

Anecdotal reports have recently circulated suggesting that intramuscular injection of bacteriostatic saline (BS)—which contains benzyl alcohol (BnOH)—can reverse botulinum toxin type A (BoNTA)-induced brow ptosis. Given the well-established intracellular persistence of BoNTA’s light chain and its irreversible cleavage of SNAP-25, such rapid functional recovery challenges existing pharmacological understanding. This study employed high-resolution pharmacokinetic/pharmacodynamic (PK/PD) modelling using the AesthetiSim™ platform to systematically evaluate this hypothesis. A total of 30,000 virtual patients were randomized to receive BoNTA alone, BoNTA followed by BS injection, or BoNTA followed by normal saline (NS) at Day 7. The model incorporated BoNTA diffusion, internalization, SNAP-25 cleavage, neuromuscular output, and transient BS effects on membrane permeability and endosomal trafficking. Simulated recovery trajectories were tracked over 90 days. The primary outcome, time to 80% restoration of baseline frontalis muscle force (T₈₀), averaged 42.0 days in the BoNTA-only group and 35.5 days in the BS group (Δ = −6.5 days; p < 0.001). Only 13.9% of BS-treated patients reached the T₈₀ threshold by Day 30. Partial reactivation (T₃₀) occurred earlier with BS (21.8 ± 5.3 days vs. 27.3 ± 4.9 days), and the area under the effect curve (AUEC) was increased by 9.7%, reflecting higher overall muscle function over time. In molecular simulations, BnOH produced a minor rightward shift in the BoNTA–SNAP-25 dissociation curve, but receptor occupancy remained above 90% at therapeutic toxin concentrations, suggesting no meaningful impairment of binding affinity. A global Sobol sensitivity analysis demonstrated that the primary driver of recovery kinetics was intracellular LC degradation (49% of T₈₀ variance), while BS-modulated extracellular parameters collectively contributed less than 20%. These findings indicate that BS does not reverse the molecular action of BoNTA but may transiently influence recovery kinetics via non-receptor-mediated pathways such as increased membrane permeability or altered vesicular trafficking. The magnitude and variability of this effect do not support the notion of a true pharmacologic reversal. Instead, these results emphasize the need for mechanistic scrutiny when evaluating rapid-reversal claims, particularly those propagated through anecdotal or social media channels without supporting biological plausibility. Full article

(This article belongs to the Section Bacterial Toxins)

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57 pages, 4553 KB

Open AccessReview

Properties and Pharmacology of Scorpion Toxins and Their Biotechnological Potential in Agriculture and Medicine

by Cháriston André Dal Belo, Stephen Hyslop and Célia Regina Carlini

Toxins 2025, 17(10), 497; https://doi.org/10.3390/toxins17100497 - 7 Oct 2025

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Abstract

Scorpion venoms contain a wide range of toxins that interact with a variety of target molecules (ion channels, receptors and enzymes) associated with synaptic transmission, action potential propagation, cardiac function, hemostasis and other physiological systems. Scorpion toxins are also active towards bacteria, viruses, [...] Read more.

Scorpion venoms contain a wide range of toxins that interact with a variety of target molecules (ion channels, receptors and enzymes) associated with synaptic transmission, action potential propagation, cardiac function, hemostasis and other physiological systems. Scorpion toxins are also active towards bacteria, viruses, fungi and parasites. Such interactions make scorpion toxins useful lead molecules for developing compounds with biotechnological and therapeutic applications, and as tools for cell biology. In addition, scorpion toxins act as insectotoxins, with promising applications as insecticides. This review describes the range of scorpion toxins and discusses their usefulness for the development of insecticides and therapeutic drugs. Full article

(This article belongs to the Special Issue New Insights into Structure and Function of Arthropod Toxins and Other Toxins: Tribute to Professor Hervé Rochat)

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20 pages, 6584 KB

Open AccessArticle

Compromised Regeneration, Damage to Blood Vessels and the Endomysium Underpin Permanent Muscle Damage Induced by Puff Adder (Bitis arietans) Venom

by Sodiq Opeyemi Adeyemi, Nicholas John Richards, Ali Alqallaf, Husain Bin Haidar, Mustafa Jawad Jalil Al-Asady, Jarred Williams, José R. Almeida and Ketan Patel

Toxins 2025, 17(10), 496; https://doi.org/10.3390/toxins17100496 - 6 Oct 2025

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Abstract

The puff adder (Bitis arietans) is a clinically relevant viper species found throughout Africa, and it is responsible for a greater incidence of health-related envenomations than all other snake species on the continent combined. Unresolved skeletal muscle damage is a common [...] Read more.

The puff adder (Bitis arietans) is a clinically relevant viper species found throughout Africa, and it is responsible for a greater incidence of health-related envenomations than all other snake species on the continent combined. Unresolved skeletal muscle damage is a common consequence of B. arietans envenomation that can result in long-term morbidity and even death. Antivenom treatment can mitigate the systemic effects of the venom but offers little protection against local tissue damage. Identifying the mechanisms through which B. arietans venom induces tissue damage and impedes skeletal muscle regeneration could identify possible treatment alternatives that could help alleviate the long-term consequences of envenomation. Skeletal muscle has an innate ability to regenerate, but constituents within the venom can impede multiple stages of this regeneration process. In this study, we employed a combination of biochemical analyses, cell-based assays, and in vivo experiments to assess the toxicological implications of B. arietans envenomation and its impacts on key processes of regeneration. Our findings demonstrate that the pathological characteristics of permanent muscle damage resulting from B. arietans envenomation may be attributed to the venom’s effects on muscle stem cell precursors, the extracellular matrix (ECM), and the influence of blood-borne proteins that promote fibrosis. Full article

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

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29 pages, 2554 KB

Open AccessReview

Toxic Alexandrium Treatment in Western Australia: Investigating the Efficacy of Modified Nano Clay

by Cherono Sheilah Kwambai, Houda Ennaceri, Alan J. Lymbery, Damian W. Laird, Jeff Cosgrove and Navid Reza Moheimani

Toxins 2025, 17(10), 495; https://doi.org/10.3390/toxins17100495 - 4 Oct 2025

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Abstract

Alexandrium spp. blooms produce a range of toxins, including spirolides, goniodomins, and paralytic shellfish toxins (PSTs). Of these, PSTs are the most impactful due to their high affinity for voltage-gated sodium ion channels in nerve cell membranes. This interaction can cause neurological effects [...] Read more.

Alexandrium spp. blooms produce a range of toxins, including spirolides, goniodomins, and paralytic shellfish toxins (PSTs). Of these, PSTs are the most impactful due to their high affinity for voltage-gated sodium ion channels in nerve cell membranes. This interaction can cause neurological effects such as paralysis and, in severe cases, may lead to death. Given the implications of Alexandrium blooms on public health, all mitigation, prevention, and treatment strategies aim to reduce their socioeconomic impacts. However, monitoring harmful algal blooms remains difficult due to confounding influences such as pollution, climate change, and the inherent variability of environmental conditions. These factors can complicate early detection and management efforts, especially as the intensity and frequency of blooms continue to rise, further exacerbating their socioeconomic consequences. This review offers insights into several management approaches to prevent and control Alexandrium blooms, focusing on modified nano-clays as a promising emergency mitigation measure for low-density toxic algal blooms, especially in areas predominantly used for recreational fishing. However, it is recommended that treatment be coupled with monitoring to alleviate reliance on treatment alone. Full article

(This article belongs to the Special Issue Harmful Algal Blooms in Waters: Characterization, Monitoring and Management)

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19 pages, 1292 KB

Open AccessReview

Ricin and Abrin in Biosecurity: Detection Technologies and Strategic Responses

by Wojciech Zajaczkowski, Ewelina Bojarska, Elwira Furtak, Michal Bijak, Rafal Szelenberger, Marcin Niemcewicz, Marcin Podogrocki, Maksymilian Stela and Natalia Cichon

Toxins 2025, 17(10), 494; https://doi.org/10.3390/toxins17100494 - 3 Oct 2025

Viewed by 595

Abstract

Plant-derived toxins such as ricin and abrin represent some of the most potent biological agents known, posing significant threats to public health and security due to their high toxicity, relative ease of extraction, and widespread availability. These ribosome-inactivating proteins (RIPs) have been implicated [...] Read more.

Plant-derived toxins such as ricin and abrin represent some of the most potent biological agents known, posing significant threats to public health and security due to their high toxicity, relative ease of extraction, and widespread availability. These ribosome-inactivating proteins (RIPs) have been implicated in politically and criminally motivated events, underscoring their critical importance in the context of biodefense. Public safety agencies, including law enforcement, customs, and emergency response units, require rapid, sensitive, and portable detection methods to effectively counteract these threats. However, many existing screening technologies lack the capability to detect biotoxins unless specifically designed for this purpose, revealing a critical gap in current biodefense preparedness. Consequently, there is an urgent need for robust, field-deployable detection platforms that operate reliably under real-world conditions. End-users in the security and public health sectors demand analytical tools that combine high specificity and sensitivity with operational ease and adaptability. This review provides a comprehensive overview of the biochemical characteristics of ricin and abrin, their documented misuse, and the challenges associated with their detection. Furthermore, it critically assesses key detection platforms—including immunoassays, mass spectrometry, biosensors, and lateral flow assays—focusing on their applicability in operational environments. Advancing detection capabilities within frontline services is imperative for effective prevention, timely intervention, and the strengthening of biosecurity measures. Full article

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15 pages, 1129 KB

Open AccessArticle

Building Sub-Saharan African PBPK Populations Reveals Critical Data Gaps: A Case Study on Aflatoxin B1

by Orphélie Lootens, Marthe De Boevre, Sarah De Saeger, Jan Van Bocxlaer and An Vermeulen

Toxins 2025, 17(10), 493; https://doi.org/10.3390/toxins17100493 - 3 Oct 2025

Viewed by 684

Abstract

Physiologically based pharmacokinetic (PBPK) models allow to simulate the behaviour of compounds in diverse physiological populations. However, the categorization of individuals into distinct populations raises questions regarding the classification criteria. In previous research, simulations of the pharmacokinetics of the mycotoxin aflatoxin B1 (AFB1), [...] Read more.

Physiologically based pharmacokinetic (PBPK) models allow to simulate the behaviour of compounds in diverse physiological populations. However, the categorization of individuals into distinct populations raises questions regarding the classification criteria. In previous research, simulations of the pharmacokinetics of the mycotoxin aflatoxin B1 (AFB1), were performed in the black South African population, using PBPK modeling. This study investigates the prevalence of clinical CYP450 phenotypes (CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5) across Sub-Saharan Africa (SSA), to determine the feasibility of defining SSA as a single population. SSA was subdivided into Central, East, South and West Africa. The phenotype data were assigned to the different regions and a fifth SSA group was composed of all regions’ weighted means. Available data from literature only covered 7.30% of Central, 56.9% of East, 38.9% of South and 62.9% of West Africa, clearly indicating critical data gaps. A pairwise proportion test was performed between the regions on enzyme phenotype data. When achieving statistical significance (p < 0.05), a Cohen’s d-test was performed to determine the degree of the difference. Next, per region populations were built using SimCYP starting from the available SSA based SouthAfrican_Population FW_Custom population, supplemented with the phenotype data from literature. Simulations were performed using CYP probe substrates in all populations, and derived PK parameters (C_max, T_max, AUC_ss and CL) were plotted in bar charts. Significant differences between the African regions regarding CYP450 phenotype frequencies were shown for CYP2B6, CYP2C19 and CYP2D6. Limited regional data challenge the representation of SSA populations in these models. The scarce availability of in vivo data for SSA regions restricted the ability to fully validate the developed PBPK populations. However, observed literature data from specific SSA regions provided partial validation, indicating that SSA populations should ideally be modelled at a regional level rather than as a single entity. The findings, emerging from the initial AFB1-focused PBPK work, underscore the need for more extensive and region-specific data to enhance model accuracy and predictive value across SSA. 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, 723 KB

Open AccessReview

Mycotoxin Research in Algeria: A Comprehensive Review of Trends, Challenges, and Future Directions

by Yamina Ben Miri, Imene Chentir, Aldjia Taoudiat, Amina Benabdallah and Marta Herrera

Toxins 2025, 17(10), 492; https://doi.org/10.3390/toxins17100492 - 3 Oct 2025

Viewed by 406

Abstract

This review offers a comprehensive overview of mycotoxin research and related publications in Algeria, outlining key trends, existing challenges, and prospects for future advancement. Despite limited exploration of mycotoxins in Algeria, researchers have made significant progress in understanding mycotoxin contamination and its effects [...] Read more.

This review offers a comprehensive overview of mycotoxin research and related publications in Algeria, outlining key trends, existing challenges, and prospects for future advancement. Despite limited exploration of mycotoxins in Algeria, researchers have made significant progress in understanding mycotoxin contamination and its effects on food safety and public health. The review delves into both research achievements and the challenges encountered in resource-limited settings, while also exploring strategies employed to surmount these obstacles. Through an analysis of existing literature, key themes emerge regarding mycotoxin identification, detection methods, mitigation strategies, and their implications. The importance of collaborative efforts among academia and government agencies is underscored as pivotal in addressing mycotoxin-related challenges. Moreover, this review identified gaps in current research and offered recommendations for future investigations, aiming to advance mycotoxin research in Algeria and beyond. Full article

(This article belongs to the Special Issue Mycotoxins in Food Chain: Occurrence, Analysis and Risk Management)

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17 pages, 2248 KB

Open AccessArticle

Expression of L-Amino Acid Oxidase (Ml-LAAO) from the Venom of the Micrurus lemniscatus Snake in a Mammalian Cell System

by Ari Junio de Oliveira Costa, Alessandra Matavel, Patricia Cota Campos, Jaqueline Leal dos Santos, Ana Caroline Zampiroli Ataide, Sophie Yvette Leclercq, Valéria Gonçalves de Alvarenga, Sergio Caldas, William Castro-Borges and Márcia Helena Borges

Toxins 2025, 17(10), 491; https://doi.org/10.3390/toxins17100491 - 2 Oct 2025

Viewed by 421

Abstract

Animal venoms are rich in bioactive molecules with promising biotechnological potential. They comprise both protein and non-protein toxins. Among the protein toxins are enzymes, such as phospholipases A₂, proteases and L-amino acid oxidases (LAAOs). LAAOs exhibit antimicrobial, antiparasitic, antiviral, and anticancer [...] Read more.

Animal venoms are rich in bioactive molecules with promising biotechnological potential. They comprise both protein and non-protein toxins. Among the protein toxins are enzymes, such as phospholipases A₂, proteases and L-amino acid oxidases (LAAOs). LAAOs exhibit antimicrobial, antiparasitic, antiviral, and anticancer effects, making them potential candidates for biotechnological applications. These activities are linked to their ability to catalyze oxidative reactions that convert L-amino acids into α-keto acids, releasing ammonia and hydrogen peroxide, which contribute to the immune response, pathogen elimination, and oxidative stress. However, in snakes of the Micrurus genus, LAAOs generally represent a small portion of the venom (up to ~7%), which limits their isolation and study. To overcome this, the present study aimed to produce Ml-LAAO, the enzyme from Micrurus lemniscatus, through heterologous expression in mammalian cells. The gene sequence was inferred from its primary structure and synthesized into the pSecTag2B vector for expression in HEK293T cells. After purification using a His Trap-HP column, the presence of recombinant Ml-LAAO (Ml-LAAOrec) was confirmed by Western blot and mass spectrometry, validating its identity. These results support successful recombinant expression of Ml-LAAO and highlight its potential for scalable production and future biotechnological applications. Full article

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

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16 pages, 2336 KB

Open AccessArticle

Bioremediation of Contaminated Water: The Potential of Aquatic Plants Ceratophyllum demersum and Pistia stratiotes Against Toxic Bloom

by Fatma Zohra Tamer, Hadjer Zaidi, Hichem Nasri, Larisa Lvova, Nada Nouri, Fateh Sedrati, Amina Amrani, Nassima Beldjoudi and Xi Li

Toxins 2025, 17(10), 490; https://doi.org/10.3390/toxins17100490 - 2 Oct 2025

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Abstract

Toxic cyanobacteria, including Microcystis, produce harmful toxins that affect aquatic ecosystems and human health. Biotreatment using macrophytes shows promise in mitigating these blooms. This study investigates the bioaccumulation dynamics and biochemical responses of two aquatic macrophytes, Pistia stratiotes and Ceratophyllum demersum, [...] Read more.

Toxic cyanobacteria, including Microcystis, produce harmful toxins that affect aquatic ecosystems and human health. Biotreatment using macrophytes shows promise in mitigating these blooms. This study investigates the bioaccumulation dynamics and biochemical responses of two aquatic macrophytes, Pistia stratiotes and Ceratophyllum demersum, in removing microcystin from contaminated water. P. stratiotes showed high initial bioaccumulation rates with rapid microcystin uptake, which is effective for short-term bioremediation. C. demersum has shown stable bioaccumulation. Biochemical analyses have revealed the activation of plant antioxidant defenses, with both macrophytes showing an increase in carotenoids, glutathione (GSH), and antioxidant enzymes such as superoxide dismutase (SOD) and glutathione-S-transferase (GST) concentrations. In particular, C. demersum has maintained higher antioxidant levels, contributing to its sustained capacity and resilience. Fluctuations in malondialdehyde (MDA) indicated oxidative stress, with P. stratiotes managing such stress through its defenses. Principal Component Analysis (PCA) supports these findings: Pistia’s first two components explained 25.09% and 20.71% of the variance, with Carotenoid and Chl contributing strongly to PC1, and MDA and GST influencing both components. For C. demersum, PC1 and PC2 explained 21.79% and 19.78% of the variance, with Carotenoid and Chl a being major contributors, while SOD and GSH played significant roles in sample differentiation. Integrating both plants into bioremediation strategies could optimize microcystin removal: P. stratiotes offers rapid initial detoxification, while C. demersum ensures continuous, long-term remediation. This combined approach enhances the efficiency and sustainability of phytoremediation. Future research should optimize environmental conditions and explore synergistic effects among multiple plant species for more effective and sustainable bioremediation solutions. Full article

(This article belongs to the Section Bacterial Toxins)

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14 pages, 1349 KB

Open AccessArticle

ProToxin, a Predictor of Protein Toxicity

by Yang Yang, Haohan Zhang and Mauno Vihinen

Toxins 2025, 17(10), 489; https://doi.org/10.3390/toxins17100489 - 1 Oct 2025

Viewed by 468

Abstract

Toxins are naturally poisonous small compounds, peptides and proteins that are produced in all three kingdoms of life. Venoms are animal toxins and can contain even hundreds of different compounds. Numerous approaches have been used to detect toxins, including prediction methods. We developed [...] Read more.

Toxins are naturally poisonous small compounds, peptides and proteins that are produced in all three kingdoms of life. Venoms are animal toxins and can contain even hundreds of different compounds. Numerous approaches have been used to detect toxins, including prediction methods. We developed a novel machine learning-based predictor for detecting protein toxins from their sequences. The gradient boosting method was trained on carefully selected training data. Initially, we tested 2614 features, which were reduced to 88 after a comprehensive feature selection procedure. Out of the four tested algorithms, XGBoost was chosen to train the final predictor. Comparison to available predictors indicated that ProToxin showed significant improvement compared to state-of-the-art predictors. On a blind test dataset, the accuracy was 0.906, the Matthews correlation coefficient was 0.796, and the overall performance measure was 0.796. ProToxin is a fast and efficient method and is freely available. It can be used for small and large numbers of sequences. Full article

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21 pages, 4001 KB

Open AccessArticle

Exploring the Venom Diversity of Australian Taipans: Comparative Characterization of Oxyuranus microlepidotus and Oxyuranus scutellatus

by Guilherme Gonelli Paz, Patrick Jack Spencer, Daniel Carvalho Pimenta and Emidio Beraldo-Neto

Toxins 2025, 17(10), 488; https://doi.org/10.3390/toxins17100488 - 1 Oct 2025

Viewed by 571

Abstract

The genus Oxyuranus, which includes some of the most venomous snakes in the world, presents a complex venom composition with potent neurotoxic and procoagulant effects. This study provides a comparative proteomic analysis of the venom of Oxyuranus microlepidotus (Inland Taipan) and Oxyuranus [...] Read more.

The genus Oxyuranus, which includes some of the most venomous snakes in the world, presents a complex venom composition with potent neurotoxic and procoagulant effects. This study provides a comparative proteomic analysis of the venom of Oxyuranus microlepidotus (Inland Taipan) and Oxyuranus scutellatus (Coastal Taipan), aiming to elucidate the molecular basis underlying their distinct toxicological profiles. Using high-resolution chromatographic fractionation and LC-MS/MS, we identified a core set of nine protein families shared between both species, including phospholipases A₂ (PLA₂), three-finger toxins (3FTx), natriuretic peptides (NTP), nerve growth factors (NGF), and prothrombin activators (PTA). O. microlepidotus venom exhibited greater diversity of 3FTxs and unique protein families, such as Waprin and 5′-nucleotidases, suggesting lineage-specific functional adaptations. Quantitative analysis revealed a greater relative abundance of PLA₂s in O. scutellatus (66%) compared to O. microlepidotus (47%), whereas 3FTXs were more prominent in O. microlepidotus (33% vs. 9%). These interspecific differences likely underlie the distinct clinical manifestations of envenomation and reflect evolutionary divergence in the venom composition. Our findings provide molecular insights into taipan venom complexity and highlight novel toxin candidates with potential biomedical applications in neurobiology, hemostasis, and anti-infective therapy. Full article

(This article belongs to the Special Issue Animal Venoms: Unraveling the Molecular Complexity (2nd Edition))

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18 pages, 1671 KB

Open AccessArticle

Toxigenic Aspergillus Diversity and Mycotoxins in Organic Spanish Grape Berries

by Clara Melguizo, Andrea Tarazona, Jéssica Gil-Serna, Fernando Mateo, Belén Patiño and Eva María Mateo

Toxins 2025, 17(10), 487; https://doi.org/10.3390/toxins17100487 - 30 Sep 2025

Viewed by 488

Abstract

Grapes are frequently contaminated by Aspergillus section Nigri fungi and ochratoxin A (OTA), with A. niger also capable of producing substantial fumonisin B₂ (FB₂) levels. Emerging evidence suggests that aflatoxigenic fungi may eventually replace ochratoxigenic fungi in certain regions due [...] Read more.

Grapes are frequently contaminated by Aspergillus section Nigri fungi and ochratoxin A (OTA), with A. niger also capable of producing substantial fumonisin B₂ (FB₂) levels. Emerging evidence suggests that aflatoxigenic fungi may eventually replace ochratoxigenic fungi in certain regions due to better adaptation to changes in climatic conditions. However, research on the toxigenic fungal community and mycotoxins in grapes from organic vineyards remains limited. Research on Spanish conventional grapes is also deficient, with most of the available literature being outdated. The present study investigates the diversity of toxigenic fungi and the presence of mycotoxins in organically cultivated grape berries in Spain, which are renowned for their significant oenological tradition. This study employed species-specific PCR protocols for fungal characterization and optimized methods for the analysis of OTA, FB₂, and aflatoxin B₁ (AFB₁) by UPLC–ESI–MS/MS. The most prevalent species present were Aspergillus flavus, A. niger, A. parasiticus, A. steynii, A. carbonarius, and A. westerdijkiae (67.1%, 43.5%, 20.0%, 14.1%, 14.1%, and 11.8% of the samples, respectively). OTA was detected only in 16 samples (19%), averaging 0.48 ng/g and peaking at 0.7 ng/g, which were lower than previously reported for conventional grapes. There was no FB₂ or AFB₁ detected. This study is pioneering in its exploration of the occurrence of toxigenic mycobiota, beyond Nigri fungi, and subsequent potential for other serious mycotoxins to contaminate Spain’s organic grapes. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Determination: From Risk Assessment to Global Management Strategies)

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22 pages, 1921 KB

Open AccessArticle

Proteome Analysis of the Six-Eyed Sand-Spider Sicarius thomisoides Venom

by Tomás Arán-Sekul, Juan San Francisco, José Rojas, Kyung-Mee Moon, Leonard Foster and Alejandro Catalán

Toxins 2025, 17(10), 486; https://doi.org/10.3390/toxins17100486 - 28 Sep 2025

Viewed by 537

Abstract

Spiders of the Sicarius genera (Araneae: Sicariidae) are commonly known as six-eyed sand spiders. Of the species described in Latin America, the species S. thomisoides has previously been shown to possess venom with a toxic potential comparable to that observed in the venom [...] Read more.

Spiders of the Sicarius genera (Araneae: Sicariidae) are commonly known as six-eyed sand spiders. Of the species described in Latin America, the species S. thomisoides has previously been shown to possess venom with a toxic potential comparable to that observed in the venom of the spider L. laeta. Although identifying the phospholipase D activity in the venom of S. thomisoides, it is still unknown what other components are part of the venom. In this study, we described the identification of the main protein components of S. thomisoides venom, revealing that the phospholipase D family were the majority toxins, followed by Astacin-like metalloproteinases and serine proteases. Additionally, the presence of CRISP-type allergens and peptides from the U-PHTX-Pmx family was identified for the first time in venoms from Sicarius genera. Identifying the components of the Sicarius spider venom is an essential step to understanding its toxicological potential. Full article

(This article belongs to the Section Animal Venoms)

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4 pages, 197 KB

Open AccessEditorial

Introduction to Toxins Special Issue on Botulinum Toxins: New Uses in the Treatment of Diseases (2nd Edition)

by Siro Luvisetto

Toxins 2025, 17(10), 485; https://doi.org/10.3390/toxins17100485 - 28 Sep 2025

Viewed by 433

Abstract

Clostridium botulinum strains produce seven antigenically distinct botulinum neurotoxins (BoNTs), referred to as serotypes A–G, and a hybrid toxin called F/A [...] Full article

(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases (2nd Edition))

16 pages, 4821 KB

Open AccessArticle

Evaluating the Potential Inhibition of PP2A by Nodularin-R Disinfection By-Products: Effect and Mechanism

by Mengchen Li, Chunyu Fu, Qiannan Shi, Shaocong Yang and Wansong Zong

Toxins 2025, 17(10), 484; https://doi.org/10.3390/toxins17100484 - 26 Sep 2025

Viewed by 371

Abstract

The secondary contamination of nodularin disinfection by-products (NOD-DBPs) is a problem worthy of attention. In this study, prototypical NOD-R-DBPs were prepared, and their toxicity was assessed using conventional protein phosphatase (PPs) inhibition assay, confirming that structural changes in “Adda³” during chlorination [...] Read more.

The secondary contamination of nodularin disinfection by-products (NOD-DBPs) is a problem worthy of attention. In this study, prototypical NOD-R-DBPs were prepared, and their toxicity was assessed using conventional protein phosphatase (PPs) inhibition assay, confirming that structural changes in “Adda³” during chlorination are key factors leading to a significant reduction in NOD-R toxicity. However, some NOD-R-DBPs still exhibit certain levels of toxicity (2.8–81% of NOD-R). To elucidate the mechanism underlying the potential inhibitory effect of NOD-R-DBPs on protein phosphatase 2A (PP2A), molecular simulations were employed to establish interaction models between prototypical NOD-R-DBPs and PP2A using homology modeling strategies, and molecular docking was used to obtain candidate interaction parameters between prototypical NOD-R-DBPs and PP2A. Structural changes in “Adda³” weakened the hydrogen bonds “Adda³”Asn₁₁₇ and “Adda³”His₁₁₈. Subsequently, the disruption of “Adda³” altered key interactions between NOD-R-DBPs and PP2A (hydrogen bond Mdhb⁵ ← Arg₈₉, ionic bond Glu⁴-Arg₈₉, metal bond His₂₄₁-Mn₁²⁺, etc.). The changes in these interactions further altered the interactions between conserved amino acids and the catalytic center Mn²⁺ (ionic bond Asp₅₇-Mn₂²⁺), thereby increasing Mn²⁺ exposure. Meanwhile, the retained interactions promoted the binding of -PO₄ with the conserved amino acids His₁₁₈ and Arg₈₉. Prototypical NOD-R-DBPs retained the aforementioned key interactions and thus exhibit potential inhibitory effects on PP2A. The varying degrees of damage to the Adda³ structure led to significant differences in the inhibitory effects of different NOD-R-DBPs on PP2A. Full article

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

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16 pages, 520 KB

Open AccessArticle

Co-Occurrence of Major Mycotoxins and Emerging Alternaria Toxins in Couscous Marketed in Algeria

by Sarah Mohammedi-Ameur, Terenzio Bertuzzi, Roberta Battaglia, Federico Siboni, Paola Giorni and Dahmane Mohammedi

Toxins 2025, 17(10), 483; https://doi.org/10.3390/toxins17100483 - 26 Sep 2025

Viewed by 465

Abstract

Cereal contamination by mycotoxins represents a major food safety concern. This study aimed to assess the co-occurrence of 15 mycotoxins in 50 couscous samples marketed in Algeria using HPLC/FLD and LC-MS/MS techniques. The samples included various couscous types, differing in ingredients, production method [...] Read more.

Cereal contamination by mycotoxins represents a major food safety concern. This study aimed to assess the co-occurrence of 15 mycotoxins in 50 couscous samples marketed in Algeria using HPLC/FLD and LC-MS/MS techniques. The samples included various couscous types, differing in ingredients, production method (organic or conventional), processing operations, and granularity. The most frequently detected mycotoxins were tentoxin (76%), deoxynivalenol (74%), tenuazonic acid (72%), and ochratoxin A (54%). For the regulated mycotoxins, none of the concentrations exceeded the maximum levels set by the European Union. In contrast, tenuazonic acid and tentoxin, which are not yet regulated, were the most common compounds detected. Contamination with multiple mycotoxins was commonly observed: 90% of the samples contained at least two mycotoxins, with some containing up to seven. The most frequent combination involved tenuazonic acid-tentoxin-ochratoxin A. These findings highlight the need for frequent and systematic monitoring of couscous and other processed cereal-based products. Full article

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

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14 pages, 1031 KB

Open AccessReview

Comprehensive Review of Dietary Probiotics in Reducing Aflatoxin B₁ Toxicity

by Dasol Choi, Xingrui Fan and Jae-Hyuk Yu

Toxins 2025, 17(10), 482; https://doi.org/10.3390/toxins17100482 - 26 Sep 2025

Viewed by 639

Abstract

Aflatoxin B₁ (AFB₁), the most potent and widespread mycotoxin produced by Aspergillus flavus and Aspergillus parasiticus, poses a significant global threat to food safety and human health, with chronic exposure strongly linked to hepatocellular carcinoma (HCC). While physical and [...] Read more.

Aflatoxin B₁ (AFB₁), the most potent and widespread mycotoxin produced by Aspergillus flavus and Aspergillus parasiticus, poses a significant global threat to food safety and human health, with chronic exposure strongly linked to hepatocellular carcinoma (HCC). While physical and chemical detoxification approaches exist, their limitations have led to an increased interest in biological strategies, particularly probiotic interventions. In this review, we synthesize current in vivo and clinical evidence on the ability of probiotic lactic acid bacteria—including Lactobacillus casei Shirota, Lactobacillus rhamnosus GG, Lactobacillus rhamnosus LC705, Lactococcus lactis, and selected Bifidobacterium species—to reduce AFB₁ absorption and toxicity. We summarize mechanistic insights into cell wall adsorption, gut microbiota modulation, intestinal barrier protection, and antioxidant enhancement. Clinical trials have shown reductions in AFB₁ biomarkers following probiotic supplementation, supporting their translational potential for human health. However, clinical evidence remains limited by small sample sizes, short intervention periods, and variability in endpoints. Collectively, this review consolidates mechanistic, preclinical, and clinical findings to position probiotic lactic acid bacteria as promising biological countermeasures against AFB1-induced hepatocellular carcinoma. Full article

(This article belongs to the Section Mycotoxins)

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19 pages, 2845 KB

Open AccessArticle

Neurotoxic Sleight of Fang: Differential Antivenom Efficacy Against Mamba (Dendroaspis spp.) Venom Spastic-Paralysis Presynaptic/Synaptic vs. Flaccid-Paralysis Postsynaptic Effects

by Lee Jones, Mimi Lay, Lorenzo Seneci, Wayne C. Hodgson, Ivan Koludarov, Tobias Senoner, Raul Soria and Bryan G. Fry

Toxins 2025, 17(10), 481; https://doi.org/10.3390/toxins17100481 - 26 Sep 2025

Viewed by 4956

Abstract

Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in the rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green [...] Read more.

Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in the rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green coloured, forest dwelling type, with the tan/grey coloured, savannah dwelling D. polylepis (Black Mamba) representing a derived state both ecologically and morphologically. However, it has not been tested whether these changes are paralleled by changes in venom biochemistry or if there are differential molecular evolutionary patterns. To fill these knowledge gaps, this study evaluated the neurotoxic effects of all Dendroaspis species venoms using the chick biventer cervicis nerve-muscle preparation, assessed the neutralizing efficacy of three antivenoms commercially available in Africa, and reconstructed the molecular evolutionary history of the toxin types to ascertain whether some were unique to particular species. All Dendroaspis venoms demonstrated potent flaccid-paralysis due to postsynaptic neurotoxicity. The only exception was D. angusticeps venom, which conversely exhibited spastic-paralysis due to presynaptic/synaptic neurotoxicity characterised by potentiation of acetylcholine presynaptic release and sustained synaptic activity of this neurotransmitter. Antivenom efficacy varied significantly. All three antivenoms neutralized to some degree the flaccid-paralysis postsynaptic effects for all species, with D. viridis venom being the best neutralized, and this pattern extended to all the antivenoms. However, neutralisation of flaccid-paralysis postsynaptic effects unmasked spastic-paralysis presynaptic/synaptic neurotoxicity within non-angusticeps venoms. Spastic-paralysis presynaptic effects were poorly neutralized for all species by all antivenoms, consistent with prior clinical reports of poor neutralisation of spastic-paralytic effects. Geographic variation in D. polylepis venom was evident for the relative neutralisation of both spastic-paralysis presynaptic/synaptic and flaccid-paralysis postsynaptic/synaptic neurotoxic pathophysiological effects, with differential neutralization capabilities noted between the Kenyan and South African populations studied. Molecular phylogenetic analyses confirmed spastic-paralysis and flaccid- paralysis toxins to be a trait that emerged in the Dendroaspis last common ancestor, with all species sharing all toxin types. Therefore, differences in venoms’ pathophysiological actions between species are due to differential expression of toxin isoforms rather than the evolution of species-specific novel toxins. Our findings highlight the synergistic nature of flaccid-paralysis postsynaptic and spastic-paralysis presynaptic/synaptic toxins, while contributing significant clinical and evolutionary knowledge of Dendroaspis venoms. These data are crucial for the continued development of more effective therapeutic interventions to improve clinical outcomes and for evidence-based design of clinical management strategies for the envenomed patient. Full article

(This article belongs to the Special Issue Venom Genes and Genomes of Venomous Animals: Evolution and Variation)

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4 pages, 171 KB

Open AccessEditorial

Botulinum Toxin: Previous Developments, Current Status, and Perspectives

by Wolfgang H. Jost and Alexandre Kreisler

Toxins 2025, 17(10), 480; https://doi.org/10.3390/toxins17100480 - 26 Sep 2025

Viewed by 538

Abstract

For many years, botulinum toxin has been successfully applied in various fields [...] Full article

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

21 pages, 3542 KB

Open AccessSystematic Review

Comparison of Different Treatment Outcomes for Refractory Overactive Bladder: A Systematic Review and Meta-Analysis

by Maria Patricia Roman, Răzvan Ciortea, Stergios K. Doumouchtsis, Andrei Mihai Măluțan, Carmen Elena Bucuri, Cristina Mihaela Ormindean, Viorela Elena Suciu, Ionel Daniel Nati, Andreea Căilean and Dan Mihu

Toxins 2025, 17(10), 479; https://doi.org/10.3390/toxins17100479 - 26 Sep 2025

Viewed by 721

Abstract

Background: Refractory overactive bladder (OAB) poses a significant clinical burden, often severely impacting quality of life (QoL). While intradetrusor onabotulinumtoxinA (BoNT-A) and sacral neuromodulation (SNM) are established therapeutic options, a direct comparison of their efficacy and safety profiles is essential to guide clinical [...] Read more.

Background: Refractory overactive bladder (OAB) poses a significant clinical burden, often severely impacting quality of life (QoL). While intradetrusor onabotulinumtoxinA (BoNT-A) and sacral neuromodulation (SNM) are established therapeutic options, a direct comparison of their efficacy and safety profiles is essential to guide clinical decision-making. This study compares BoNT-A against placebo and SNM for the management of refractory OAB in women. Methods: Following PRISMA guidelines, PubMed, Scopus, CENTRAL, and Google Scholar were searched until February 2025 for randomized controlled trials (RCTs) and cohort studies on treatment alternatives for refractory OAB. Treatment outcomes at 3- (BoNT-A vs. placebo) and 6-month (BoNT-A vs. SNM) follow-up were analyzed. Odds ratios (ORs) and mean differences (MDs) were calculated for dichotomous and continuous variables, respectively, with heterogeneity assessed via I² test. Study quality was evaluated using CASP tools. Results: Pooled data from 12 studies (2645 patients) indicated that BoNT-A significantly reduced urgency urinary incontinence (UUI) episodes compared to placebo (p = 0.02) and SNM (p = 0.0008). Additionally, a ≥75% reduction in UUI episodes was more likely with BoNT-A compared to both placebo (p < 0.00001) and SNM (p < 0.00001). Complete resolution of UUI was more likely with BoNT-A compared to placebo (p < 0.00001); however, when compared to SNM, the latter demonstrated a higher rate of complete UUI resolution (p < 0.00001). Patient-reported QoL did not show significant differences between BoNT-A and SNM (p = 0.2). Urinary tract infection (UTI) risk was higher with BoNT-A than both comparators. Conclusions: While BoNT-A offers robust symptom control, its safety profile necessitates careful patient selection. SNM remains a viable alternative for those prioritizing fewer adverse events. The study highlights the need for standardized outcome reporting, long-term cost-effectiveness analyses, and personalized treatment approaches. Full article

(This article belongs to the Section Bacterial Toxins)

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