Toxins

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 2350

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)

► Show Figures

Figure 1

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

Viewed by 7161

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

► Show Figures

Figure 1

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

Viewed by 1107

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)

► Show Figures

Figure 1

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

Viewed by 1429

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)

► Show Figures

Figure 1

18 pages, 2032 KB

Open AccessEditor’s ChoiceArticle

Inter- and Intraspecific Venom Variation in the Reclusive Rear-Fanged Black-Striped Snakes (Coniophanes)

by John Henry Fowler, Ramses Alejandro Rosales-García, Rhett M. Rautsaw, Michael P. Hogan, Erich P. Hofmann, Andrew J. Mason, Ramon Nagesan, Miguel Borja, Luis Herrera, Gamaliel Castañeda-Gaytan, Alison R. Davis Rabosky, Darin R. Rokyta and Christopher L. Parkinson

Toxins 2026, 18(2), 108; https://doi.org/10.3390/toxins18020108 - 20 Feb 2026

Viewed by 1998

Abstract

Our current understanding of snake venom is highly biased towards species known to be medically significant in human envenomations. This vastly under-represents the true evolutionary and ecological breadth of snake venom, with gaps spanning entire clades and unique lifestyles. As a result, many [...] Read more.

Our current understanding of snake venom is highly biased towards species known to be medically significant in human envenomations. This vastly under-represents the true evolutionary and ecological breadth of snake venom, with gaps spanning entire clades and unique lifestyles. As a result, many genera of rear-fanged snakes lack well-understood venom profiles despite these taxa composing around 65% of known extant snake species. Methodological challenges associated with venom extraction have long been a key reason responsible for the lack of venom research on this group. Modern advancements in venomics technologies have allowed researchers to overcome many of these challenges and investigate the venom components of understudied genera. The genus Coniophanes (black-striped snakes) presents an ideal system for investigating venom and the venom delivery system in a rear-fanged venomous species with well-documented accounts of human envenomations. We sequenced and annotated de novo transcriptomes of the Duvernoy’s gland (DVG) for seven individuals across four species of Coniophanes (Dipsadidae) and confirmed toxin expression in representative venom proteomes. We assessed interspecific venom variation within this genus and further examined intraspecific venom variation within C. imperialis. We found that toxins account for 38.8% to 66% of the total DVG transcriptomes and that 18 toxin families are represented in this genus, with prominent expression of cystine-rich secretory proteins (CRiSPs) in three species and snake venom metalloproteinases (SVMPs) in all four species. In addition, we used diffusible iodine-based contrast-enhanced computed tomography (diceCT) to better understand the venom delivery system for C. fissidens, a widespread species within this genus, showcasing enlarged, grooved, rear fangs in close proximity to a prominent DVG. We provide the first ever characterization of the venom profiles of Coniophanes, highlight venom variation between and within species, and outline the venom delivery system of this understudied genus. Full article

(This article belongs to the Special Issue Snake Venom Genes Expression, Evolution and Variation)

► Show Figures

Figure 1

11 pages, 1135 KB

Open AccessEditor’s ChoiceArticle

Skin Irritation-Associated Dinoflagellate Vulcanodinium rugosum Isolated from Cienfuegos Bay, Cuba: Toxin Profile and Cell Growth Characterization Under Laboratory Conditions

by Angel R. Moreira-Gonzalez, Catarina Churro, Vera Marques, Lisbet Díaz-Asencio, Donaida Chamero Lago and Pedro Reis Costa

Toxins 2026, 18(2), 96; https://doi.org/10.3390/toxins18020096 - 14 Feb 2026

Viewed by 1629

Abstract

Blooms of the marine dinoflagellate Vulcanodinium rugosum have been associated with skin lesion outbreaks in Cuba and elsewhere. In this study, cell growth and toxin production were investigated under laboratory-controlled conditions in two strains isolated from Cienfuegos Bay, Cuba. Strains were cultured with [...] Read more.

Blooms of the marine dinoflagellate Vulcanodinium rugosum have been associated with skin lesion outbreaks in Cuba and elsewhere. In this study, cell growth and toxin production were investigated under laboratory-controlled conditions in two strains isolated from Cienfuegos Bay, Cuba. Strains were cultured with and without a mechanical agitation and toxins were analyzed at two stages of the culture growth (exponential and stationary). Although blooms in Cienfuegos Bay occur in a semi-enclosed system characterized by calm waters with no agitation, the results of this study suggest that V. rugosum cells may also exhibit growth capacity under agitated conditions, or in open waters, comparable to that observed in systems with low hydrodynamic energy. Higher toxin levels, as determined by liquid chromatography with mass spectrometry (LC-MS/MS), were detected after exponential growth. Portimine-A and pinnatoxin-F (PnTX-F) were the dominant toxins (up to 1.75 and 1.0 pg·cell⁻¹, respectively). PnTX-E, -D and Portimine-B were also detected at minor concentrations. This study contributes the first data necessary for a proper interpretation of monitoring programs aiming to assess the impact of V. rugosum blooms, particularly when used alongside forecasting models. Full article

(This article belongs to the Special Issue Unveiling the Toxic Effects of Harmful Algal Blooms: 2nd Edition)

► Show Figures

Figure 1

28 pages, 1112 KB

Open AccessEditor’s ChoiceArticle

Microcystin-LR Drives Early NAFLD Pathogenesis via Hepatic Cholesterol Accumulation: Dysregulation of Ldlr and Abcg1 Expression Uncoupled from Srebp2

by Hideaki Kawahara, Yoshihito Koto, Yuuka Hitsuda, Koichi Kurata, Keisuke Yoshikiyo, Ayumi Hashiguchi, Hideaki Maseda, Kunihiro Okano, Norio Sugiura, Kazuya Shimizu and Hidehisa Shimizu

Toxins 2026, 18(2), 92; https://doi.org/10.3390/toxins18020092 - 11 Feb 2026

Cited by 1 | Viewed by 937

Abstract

Chronic exposure to the cyanotoxin microcystin-LR is an emerging environmental driver of non-alcoholic fatty liver disease (NAFLD); however, the initiating molecular events at sub-lethal, environmentally relevant concentrations remain elusive. Current safety guidelines focus primarily on acute injury, potentially overlooking silent metabolic disruption. The [...] Read more.

Chronic exposure to the cyanotoxin microcystin-LR is an emerging environmental driver of non-alcoholic fatty liver disease (NAFLD); however, the initiating molecular events at sub-lethal, environmentally relevant concentrations remain elusive. Current safety guidelines focus primarily on acute injury, potentially overlooking silent metabolic disruption. The present study investigates the early metabolic toxicity of chronic low-dose microcystin-LR (10 µg/L) in a 7-week rat model, specifically focusing on pre-symptomatic perturbations in lipid homeostasis. By integrating biochemical profiling with multivariate systems toxicology (LASSO and PLS-DA), we identified a specific phenotype of “Silent Hepatic Total Cholesterol Accumulation” (T-CHOL +16%, p = 0.01) occurring in the absence of systemic dyslipidemia or overt liver injury. Mechanistic analysis revealed a specific dual failure of cholesterol homeostasis, characterized by the paradoxical upregulation of the influx transporter Ldlr (LASSO coef +0.661) and the suppression of the efflux transporter Abcg1 (PLS1 loading −0.358). Crucially, Ldlr upregulation occurred despite the concomitant transcriptional downregulation of Srebp2 (Spearman ρ = −0.585), indicating a regulatory uncoupling mechanism. We propose that microcystin-LR-induced protein phosphatase 2A (PP2A) inhibition likely drives this uncoupling via a post-transcriptional override—possibly involving ERK/RSK-mediated Ldlr mRNA stabilization. Concurrently, this inhibition appears to block LXR-mediated Abcg1 expression through sustained AMPK hyperactivation resulting from the loss of dephosphorylation. These findings indicate liver-specific cholesterol accumulation as the critical first step of environmental NAFLD pathogenesis, suggesting that current WHO guidelines (1 µg/L) may require re-evaluation regarding metabolic safety. We propose the hepatic Ldlr/Abcg1 ratio as a potential early biomarker for revised risk assessment. Full article

(This article belongs to the Special Issue Advances in Detecting, Monitoring, Predicting, Managing and Controlling Harmful Algal Blooms)

► Show Figures

Figure 1

35 pages, 1336 KB

Open AccessEditor’s ChoiceReview

Aflatoxins and Human Health: Global Exposure, Disease Burden, and One Health Strategies

by Jill Koshiol, Amit Yadav, John D. Groopman and Usha Dutta

Toxins 2026, 18(2), 90; https://doi.org/10.3390/toxins18020090 - 10 Feb 2026

Cited by 2 | Viewed by 3179

Abstract

Mycotoxin contamination represents a major public health and economic burden worldwide. Aflatoxins, particularly aflatoxin B₁, are the most detrimental for human health. In this review, we discuss the sources of exposure and geographic distribution. The prevalence of aflatoxin–albumin/lysine adduct detection in [...] Read more.

Mycotoxin contamination represents a major public health and economic burden worldwide. Aflatoxins, particularly aflatoxin B₁, are the most detrimental for human health. In this review, we discuss the sources of exposure and geographic distribution. The prevalence of aflatoxin–albumin/lysine adduct detection in humans varies dramatically across the world, from 0% reported in two European studies to up to 100% reported in studies from parts of Africa and Asia. We also summarize the disease outcomes that aflatoxins are associated with in humans. We focus particularly on cancer outcomes, which aflatoxins can cause through mutagenic DNA adducts, oxidative stress, mitochondrial dysfunction, immune effects, and epigenetic changes. Synergy with hepatitis B virus and potentially with other mycotoxins can also increase risk. Minimization of aflatoxin exposure requires an integrative approach, beginning at the farm level and continuing through pre-harvest, post-harvest, storage, and the consumer level. New developments in technology, such as electrochemical biosensors and artificial intelligence algorithms, are being piloted and could help improve detection and decontamination efforts. Further, new tests for aflatoxin exposure in humans (e.g., blood spot assays) could assist biomonitoring efforts. Despite regulatory standards in most countries for the maximum allowable level of aflatoxins in food products and animal feed, exposure remains high in many parts of the world and might be increasing even in countries with historically low exposure. Integration of these tools in a One Health framework is essential to reduce the current and future burden of aflatoxin-related disease. Full article

(This article belongs to the Special Issue Biomonitoring and Human Exposure on Mycotoxins: One Health)

► Show Figures

Figure 1

22 pages, 1604 KB

Open AccessEditor’s ChoiceReview

Strategies for Removal of Protein-Bound Uremic Toxins in Hemodialysis

by Joost C. de Vries, João G. Brás, Geert M. de Vries, Jeroen C. Vollenbroek, Fokko P. Wieringa, Joachim Jankowski, Marianne C. Verhaar, Dimitrios Stamatialis, Rosalinde Masereeuw and Karin G. F. Gerritsen

Toxins 2026, 18(1), 57; https://doi.org/10.3390/toxins18010057 - 22 Jan 2026

Cited by 2 | Viewed by 2265

Abstract

The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In [...] Read more.

The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In this review, PBUT removal with current state-of-the-art dialysis technologies and future perspectives are discussed. Strategies to enhance PBUT clearance include methods that interfere with PBUT–albumin binding, such as chemical displacers, high ionic strength, pH changes, or electromagnetic fields, thereby increasing the free fraction available for dialysis. While these methods have shown promise in vitro, and some also in vivo, long-term safety data are lacking. PBUT removal can also be increased by adsorption, either directly via hemoperfusion, or indirectly, e.g., via sorbents incorporated in a mixed-matrix membrane or dissolved in the dialysate. In the kidney, PBUTs are secreted in the proximal tubules; hence, a cell-based bioartificial kidney (BAK) that secretes PBUTs is proposed as an add-on to current dialysis. Yet both PBUT adsorption strategies and, in particular, BAKs face considerable challenges in upscaling and mass production at acceptable costs. In conclusion, many novel technologies are under development, all requiring further (pre)clinical testing and upscaling before these strategies can be applied in the clinic. Full article

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

► Show Figures

Graphical abstract

21 pages, 692 KB

Open AccessEditor’s ChoiceSystematic Review

Botulinum Toxin Type A for the Prevention of Migraines: An Umbrella Review of Systematic Reviews

by Goli Chamani, Hajer Jasim, Ava Minston, Marlon Ferreira Dias, Rodrigo Lorenzi Poluha, Daniela A. Godoi Gonçalves, Maria Christidis, Essam Ahmed Al-Moraissi, Nikolaos Christidis, Giancarlo De la Torre Canales and Malin Ernberg

Toxins 2026, 18(1), 33; https://doi.org/10.3390/toxins18010033 - 9 Jan 2026

Cited by 2 | Viewed by 1989

Abstract

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An [...] Read more.

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An umbrella review was conducted following PRISMA guidelines and registered in PROSPERO. High-quality systematic reviews with meta-analysis evaluating BoNT-A efficacy were identified through five databases up to August 2024. Primary outcomes included monthly headache frequency and severity. Methodological quality and risk of bias were assessed using the umbrella review checklist. Fourteen articles were included. Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Though the adverse events were frequent, BoNT-A was generally well-tolerated. Comparative data suggested superior tolerability versus topiramate and a safety profile like CGRPmAbs. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments. Full article

(This article belongs to the Special Issue Botulinum Toxins: Beyond the SNAP-25 Cleavage and New Insights on Pain Relief Mechanisms)

► Show Figures

Figure 1

24 pages, 2476 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence (AI) in Saxitoxin Research: The Next Frontier for Understanding Marine Dinoflagellate Toxin Biosynthesis and Evolution

by Buhari Lawan Muhammad, Han-Sol Kim, Ibrahim Aliyu, Harisu Abdullahi Shehu and Jang-Seu Ki

Toxins 2026, 18(1), 26; https://doi.org/10.3390/toxins18010026 - 5 Jan 2026

Cited by 1 | Viewed by 1475

Abstract

Saxitoxin (STX) is one of the most potent marine neurotoxins, produced by several species of freshwater cyanobacteria and marine dinoflagellates. Although omics-based approaches have advanced our understanding of STX biosynthesis in recent decades, the origin, regulation, and ecological drivers of STX in dinoflagellates [...] Read more.

Saxitoxin (STX) is one of the most potent marine neurotoxins, produced by several species of freshwater cyanobacteria and marine dinoflagellates. Although omics-based approaches have advanced our understanding of STX biosynthesis in recent decades, the origin, regulation, and ecological drivers of STX in dinoflagellates remain poorly resolved. Specifically, dinoflagellate STX biosynthetic genes (sxt) are extremely fragmented, inconsistently expressed, and unevenly distributed between toxic and non-toxic taxa. Environmental studies further report inconsistent relationships between abiotic factors and STX production, suggesting regulation across multiple genomic, transcriptional, post-transcriptional, and epigenetic levels. These gaps prevent a comprehensive understanding of STX biosynthesis in dinoflagellates and limit the development of accurate predictive models for harmful algal blooms (HABs) and paralytic shellfish poisoning (PSP). Artificial intelligence (AI), including machine learning and deep learning, offers new opportunities in ecological pattern recognition, molecular annotation, and data-driven prediction. This review explores the current state of knowledge and persistent knowledge gaps in dinoflagellate STX research and proposes an AI-integrated multi-omics framework highlighting recommended models for sxt gene identification (e.g., DeepFRI, ProtTrans, ESM-2), evolutionary reconstruction (e.g., PhyloGAN, GNN, PhyloVAE, NeuralNJ), molecular regulation (e.g., MOFA+, LSTM, GRU, DeepMF), and toxin prediction (e.g., XGBoost, LightGBM, LSTM, ConvLSTM). By integrating AI with diverse biological datasets, this novel framework outlines how AI can advance fundamental understanding of STX biosynthesis and inform future applications in HAB monitoring, seafood safety, and PSP risk management in aquaculture and fisheries. Full article

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

► Show Figures

Graphical abstract

34 pages, 3177 KB

Open AccessEditor’s ChoiceReview

Scorpion Venom Neurotoxins: Molecular Diversity, Mechanisms, and Drug Scaffolds

by Yun Huang, Peter Muiruri Kamau, Jiamin Wang, Mingyue Gao and Bowen Li

Toxins 2026, 18(1), 25; https://doi.org/10.3390/toxins18010025 - 1 Jan 2026

Cited by 1 | Viewed by 2734

Abstract

Venom is a key evolutionary innovation of venomous organisms in the long-term process of survival adaptation. As one of the oldest arthropods, scorpions produce venom rich in bioactive peptides that also constitute a valuable pharmacological resource. Omics-driven discovery and structural biology have expanded [...] Read more.

Venom is a key evolutionary innovation of venomous organisms in the long-term process of survival adaptation. As one of the oldest arthropods, scorpions produce venom rich in bioactive peptides that also constitute a valuable pharmacological resource. Omics-driven discovery and structural biology have expanded the peptide catalog and clarified structure–function principles across disulfide-bridged (DBPs) and non-disulfide-bridged peptides (NDBPs). Within this arsenal, ion-channel targeting neurotoxins predominantly modulate Nav, Kv, Calcium, Chloride, and TRP channels to achieve predation, defense, and competition. Owing to their unique mechanisms of action and significant therapeutic potential, scorpion venom peptides have attracted sustained interest as leads and scaffolds for drug development. This review synthesizes current knowledge of scorpion venom composition, with an emphasis on the pivotal role of neurotoxins, covering their molecular diversity, structural features, and modes of ion-channel modulation, as well as emerging applications in disease treatment. Full article

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

► Show Figures

Figure 1

21 pages, 2443 KB

Open AccessEditor’s ChoiceArticle

Mycotoxins and Beyond: Unveiling Multiple Organic Contaminants in Pet Feeds Through HRMS Suspect Screening

by Dafni Dematati, Dimitrios Gkountouras, Vasiliki Boti and Triantafyllos Albanis

Toxins 2026, 18(1), 22; https://doi.org/10.3390/toxins18010022 - 30 Dec 2025

Viewed by 6370

Abstract

This study evaluated 65 commercially available pet feed samples, including 33 cat feeds and 32 dog feeds (dry and wet formulations), for the presence of organic contaminants. These included mycotoxins, pesticides, pharmaceutical residues/veterinary drugs, and plant-based bioactive compounds. A suspect screening strategy was [...] Read more.

This study evaluated 65 commercially available pet feed samples, including 33 cat feeds and 32 dog feeds (dry and wet formulations), for the presence of organic contaminants. These included mycotoxins, pesticides, pharmaceutical residues/veterinary drugs, and plant-based bioactive compounds. A suspect screening strategy was employed using QuEChERS extraction followed by LC-LTQ/Orbitrap HRMS analysis. A total of 29 compounds were tentatively identified within 186 detections. In total, 76.9% of the samples were contaminated with mycotoxins. Aflatoxins (B1, B2, G1, and G2), T2 toxins, and HT2 toxins were dominant, with Aflatoxin B1 occurring in 33.8% of the samples and exhibiting a higher prevalence in dry feeds than in wet feeds. Pesticides were present in 72.0% of the dry formulations, including aclonifen and pirimiphos-methyl, but were present in only 11% of the wet formulations. Plant-based bioactive compounds, including phytoestrogens, were identified in 51% of the samples, highlighting toxicologically relevant candidates that merit prioritization for targeted confirmation, particularly in cat feeds. Pharmaceuticals were found in 23.8% of dry feeds (sparfloxacin and fumagillin). Overall, the HRMS-based, standard-free suspect screening workflow provides an early-warning overview of multi-class co-occurrence patterns in complex pet feed matrices and supports the prioritization of candidates for subsequent confirmatory analysis. Full article

(This article belongs to the Special Issue Analytical Novelties and Challenges for the Detection of Natural Toxins)

► Show Figures

Figure 1

27 pages, 3378 KB

Open AccessEditor’s ChoiceArticle

Probiotic Supplementation in Chronic Kidney Disease: Outcomes on Uremic Toxins, Inflammation, and Vascular Calcification from Experimental and Clinical Models

by Teresa Obrero, María Victoria Pendón-Ruiz de Mier, Jose E. Gordillo-Arnaud, María José Jiménez Moral, Victoria Vidal, Fátima Guerrero, Andrés Carmona, María Encarnación Rodríguez-Ortiz, Ana Isabel Torralbo, Raquel Ojeda, Cayetana Moyano, Mercedes Sanchez-Ramade, Juan Mesa, Daniel J. López-Ruiz, Karen Valdés-Díaz, Raquel María García-Sáez, Daniel Jurado-Montoya, Cristian Rodelo-Haad, María Álvarez-Benito, Griet Glorieux, Mariano Rodríguez, Sagrario Soriano-Cabrera and Juan Rafael Muñoz-Castañeda Show full author list Hide full author list

Toxins 2026, 18(1), 6; https://doi.org/10.3390/toxins18010006 - 20 Dec 2025

Cited by 2 | Viewed by 2448

Abstract

Chronic kidney disease (CKD) is associated with gut microbiota alterations that contribute to increased inflammation and the generation of uremic toxins and may worsen the disease progression. While probiotics may improve the pro-inflammatory cytokine profile, their effects on mineral metabolism, vascular calcification (VC), [...] Read more.

Chronic kidney disease (CKD) is associated with gut microbiota alterations that contribute to increased inflammation and the generation of uremic toxins and may worsen the disease progression. While probiotics may improve the pro-inflammatory cytokine profile, their effects on mineral metabolism, vascular calcification (VC), and CKD progression remain unclear. We aimed to evaluate the impact of a commercial probiotic (Probimel) supplementation on kidney function, mineral metabolism, inflammation and VC in both an experimental rat model and patients with advanced CKD and VC. The experimental model of VC was performed through 5/6 nephrectomy (Nx), a high-phosphate diet, and calcitriol. Animals were divided into three groups: Sham, Nephrectomy, and Nephrectomy + Probiotic. In the exploratory clinical study, 23 patients with advanced stage 5 CKD and VC were randomized and either received or did not receive daily probiotics for 6 months. Kidney function, mineral metabolism, uremic toxins, inflammation, VC, and fecal microbiota were evaluated. Probiotic supplementation decreased interleukin-6 (IL-6) and interpheron-γ (IFN-γ) and levels of the uremic toxin, indoxyl sulfate (IS), in the experimental model. However, no clear evidence of improvement in kidney function or vascular calcification was observed in either rats or patients with this probiotic. Under our experimental and clinical conditions, the selected probiotic did not modify key parameters related to CKD progression or VC. Full article

(This article belongs to the Special Issue The Role of Uremic Toxins in Comorbidities of Chronic Kidney Disease)

► Show Figures

Graphical abstract

20 pages, 618 KB

Open AccessEditor’s ChoiceReview

Occurrence of Staphylococcus aureus TSST-1 in Foods: A Review

by Maria Govari and Andreana Pexara

Toxins 2025, 17(12), 606; https://doi.org/10.3390/toxins17120606 - 18 Dec 2025

Cited by 2 | Viewed by 1864

Abstract

Toxic Shock Syndrome Toxin-1 (TSST-1) is produced by Staphylococcus aureus strains encoded by the tst gene. Toxic shock syndrome (TSS) is a severe disease caused by TSST-1 toxin and associated with staphylococcal food poisoning (SFP). The aim of the present review was to [...] Read more.

Toxic Shock Syndrome Toxin-1 (TSST-1) is produced by Staphylococcus aureus strains encoded by the tst gene. Toxic shock syndrome (TSS) is a severe disease caused by TSST-1 toxin and associated with staphylococcal food poisoning (SFP). The aim of the present review was to present data on the occurrence of S. aureus TSST-1 in foods published in various countries. PCR-based assays are most frequently used for the detection of S. aureus TSST-1 in foods. S. aureus TSST-1 is predominantly detected in foods of animal origin. The highest occurrence has been observed in mastitic ruminants’ milk, indicating that mastitis is a risk of milk contamination with the pathogen. High occurrence rates of S. aureus TSST-1 have also been identified in raw milk and artisanal cheeses. Various occurrence levels have also been reported in beef, pork, lamb, and chicken meat. Low occurrence levels have also been reported for fish or other seafood products. The tst gene was also found in combination with other toxigenic genes in S. aureus TSST-1 isolates (e.g., MRSA or Panton-Valentine Leukocidin, PVL). Monitoring S. aureus TSST-1 in food is important for public health because food can be a vehicle for transmitting the antibiotic-resistant pathogen to humans. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins：Presence and Detection in Human, Animals and Food)

► Show Figures

Figure 1

19 pages, 2956 KB

Open AccessEditor’s ChoiceArticle

Ultrasound Evaluation of Upper Facial Muscles to Guide Botulinum Toxin Application

by Dominika Jaguś, Anna Pawłowska and Robert Krzysztof Mlosek

Toxins 2025, 17(12), 595; https://doi.org/10.3390/toxins17120595 - 14 Dec 2025

Cited by 3 | Viewed by 1271

Abstract

Background: Botulinum toxin injection is one of the most common esthetic procedures, yet complications may occur due to anatomical variability or suboptimal injection technique. This study aimed to evaluate the upper facial muscles using ultrasound, focusing on inter- and intraindividual variability. Methods: The [...] Read more.

Background: Botulinum toxin injection is one of the most common esthetic procedures, yet complications may occur due to anatomical variability or suboptimal injection technique. This study aimed to evaluate the upper facial muscles using ultrasound, focusing on inter- and intraindividual variability. Methods: The study involved volunteers aged 21–40 years, excluding those with prior facial treatments, trauma, or muscle disorders. The muscles examined included the occipitofrontalis (frontal belly), procerus, corrugator supercilii, and orbicularis oculi. Muscle thickness and distance from the epidermis were measured using high-frequency ultrasound. Statistical analyses included descriptive statistics, correlation with age and BMI, sex comparisons, and symmetry assessment. Results: A total of 127 participants (103 women and 24 men) were enrolled, with a mean age of 28.8 ± 4.4 years. Age showed no significant correlation with muscle thickness or depth, supporting the internal consistency of the studied age group. BMI showed moderate correlations with the depth of the selected forehead muscles. Males showed greater thickness in the frontal and procerus muscles. Relative side-to-side asymmetry coefficients reached 40% for both thickness and depth, indicating notable individual laterality. Conclusions: The study provides normative ultrasound parameters for the upper facial muscle in healthy adults. The results demonstrate significant anatomical variability depending on sex, BMI, and facial laterality, supporting individualized ultrasound-guided approaches for botulinum toxin injection. Full article

► Show Figures

Figure 1

18 pages, 2187 KB

Open AccessEditor’s ChoiceArticle

Acute Amanita muscaria Toxicity: A Literature Review and Two Case Reports in Elderly Spouses Following Home Preparation

by Stanila Stoeva-Grigorova, Ivanesa Yarabanova, Maya Radeva-Ilieva, Diana Ivanova, Snezha Zlateva and Petko Marinov

Toxins 2025, 17(12), 570; https://doi.org/10.3390/toxins17120570 - 25 Nov 2025

Cited by 2 | Viewed by 9785

Abstract

Amanita muscaria (L.) Lam., commonly known as fly agaric, remains an uncommon yet clinically important cause of acute mushroom intoxication. Although typically associated with mild to moderate neuropsychiatric disturbances, the mushroom’s toxic profile is highly variable and continues to attract scientific, toxicological, [...] Read more.

Amanita muscaria (L.) Lam., commonly known as fly agaric, remains an uncommon yet clinically important cause of acute mushroom intoxication. Although typically associated with mild to moderate neuropsychiatric disturbances, the mushroom’s toxic profile is highly variable and continues to attract scientific, toxicological, and public health interest. This work provides an integrative review of the biochemical composition, toxicodynamics, and clinical manifestations associated with A. muscaria exposure, with particular emphasis on the pharmacological actions of its principal constituents, ibotenic acid and muscimol. The review is complemented by two contemporaneous cases of severe intoxication in elderly individuals, illustrating the real-world clinical expression of the toxidrome and the challenges in diagnosis and management. Both cases presented with rapid-onset gastrointestinal symptoms, profound central nervous system depression, and cholinergic features, requiring intensive supportive therapy, atropine infusion, and continuous monitoring. Full recovery was achieved in both patients. These clinical observations contextualize the broader toxicological framework discussed in the review and underscore the need for increased clinical vigilance, improved public education, and strengthened diagnostic and therapeutic preparedness regarding psychoactive wild mushroom exposures. Full article

► Show Figures

Figure 1

12 pages, 438 KB

Open AccessEditor’s ChoiceArticle

Early Botulinum Toxin Type A Injection May Improve Motor Recovery in Patients with Post-Stroke Spasticity: A Secondary Analysis from a Longitudinal Cohort Study

by Alessandro Picelli, Andrea Santamato, Michela Cosma, Alessio Baricich, Carmelo Chisari, Marzia Millevolte, Cristina Del Prete, Ilenia Mazzù, Rita Di Censo, Nicola Smania and Mirko Filippetti

Toxins 2025, 17(11), 558; https://doi.org/10.3390/toxins17110558 - 13 Nov 2025

Cited by 3 | Viewed by 2180

Abstract

Spasticity after stroke impairs motor control, delays recovery, and reduces quality of life. Botulinum toxin type A is the first-line treatment, but it is often administered in the chronic phase, potentially limiting its impact on rehabilitation. Emerging evidence suggests that earlier treatment may [...] Read more.

Spasticity after stroke impairs motor control, delays recovery, and reduces quality of life. Botulinum toxin type A is the first-line treatment, but it is often administered in the chronic phase, potentially limiting its impact on rehabilitation. Emerging evidence suggests that earlier treatment may enhance recovery, though functional benefits remain uncertain. We conducted a secondary analysis of a multicenter, open-label, longitudinal cohort study to investigate whether the timing of the first botulinum toxin type A injection influences outcomes in post-stroke patients naïve to this treatment. All participants received botulinum toxin injections combined with conventional rehabilitation. Assessments were performed at baseline and at 4, 12, and 24 weeks post-injection. The primary outcome was muscle tone; secondary outcomes included motor strength, sensorimotor recovery, and global disability. Statistical analyses used mixed-effects models and trend tests. Patients treated within 90 days of stroke onset showed greater reductions in spasticity at 4 and 12 weeks compared with later treatment. Despite having more severe baseline impairments, early treated patients demonstrated faster and more pronounced improvements in upper-limb strength, sensorimotor recovery, and global disability. Early toxin administration is associated with enhanced reduction in spasticity and improved motor recovery, particularly in patients with severe initial deficits. Full article

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

► Show Figures

Figure 1

22 pages, 2245 KB

Open AccessEditor’s ChoiceReview

Adsorption–Degradation Integrated Approaches to Mycotoxin Removal from Food Matrices: A Comprehensive Review

by Xiyu Yang, Mingjian Yao, Wenchao Liao and Xiaoyang Li

Toxins 2025, 17(11), 556; https://doi.org/10.3390/toxins17110556 - 12 Nov 2025

Cited by 4 | Viewed by 2347

Abstract

Mycotoxin contamination is a crucial issue in food safety. However, the removal of trace amounts of mycotoxins from complex food and feed matrices without significant loss of nutritional and flavor quality remains a significant challenge. The integrated adsorption–catalysis strategy involves immobilizing catalytic modules [...] Read more.

Mycotoxin contamination is a crucial issue in food safety. However, the removal of trace amounts of mycotoxins from complex food and feed matrices without significant loss of nutritional and flavor quality remains a significant challenge. The integrated adsorption–catalysis strategy involves immobilizing catalytic modules onto adsorption materials, enabling in situ degradation while enriching the mycotoxins. This approach can significantly reduce the dosage of detoxification agents and achieve efficient removal of trace mycotoxins in food. This review provides an overview of adsorbents with enrichment capabilities and their applications in the targeted removal of mycotoxins from food. The adsorption–degradation coupled systems are categorized into the following two main types: adsorption–photocatalysis coupled systems and adsorption–biocatalysis coupled systems. The review introduces recent advances in the design of bifunctional catalysts, focusing on their synergistic mechanisms and practical applications for detoxifying various mycotoxins in food matrices. Finally, the review discusses current industrial challenges and offers insights into future directions for this field. Full article

(This article belongs to the Special Issue Advances in Detection and Removal of Mycotoxins in Food)

► Show Figures

Figure 1

20 pages, 3842 KB

Open AccessEditor’s ChoiceReview

Deoxynivalenol and Its Metabolites: Contamination, Metabolism, and Toxicity

by Yukai Lin, Ruibiao Wang, Suxian Liu, Hanqing Zhao, Bo Wen, Songbiao Chen, Rongxian Guo, Lei Wang, Xiaojing Xia, Yanzhao Xu and Ke Ding

Toxins 2025, 17(11), 555; https://doi.org/10.3390/toxins17110555 - 11 Nov 2025

Cited by 7 | Viewed by 2796

Abstract

Deoxynivalenol (DON), a toxic secondary metabolite produced by Fusarium graminearum in infected cereal crops, has emerged as a major global contaminant in food and feed due to its stable physicochemical properties and resistance to degradation during conventional processing. This contamination poses a serious [...] Read more.

Deoxynivalenol (DON), a toxic secondary metabolite produced by Fusarium graminearum in infected cereal crops, has emerged as a major global contaminant in food and feed due to its stable physicochemical properties and resistance to degradation during conventional processing. This contamination poses a serious threat to livestock production and animal health. This review provides a comprehensive overview of the current status of DON contamination, its transmission through the food chain, metabolic pathways in animals, and the comparative toxicity of its metabolites. Furthermore, we analyze DON-induced toxic effects, including acute toxicity, cytotoxicity, immunotoxicity, neurotoxicity, gastrointestinal toxicity, and hepatotoxicity. By integrating domestic and international regulatory thresholds with current mitigation strategies, we highlight future research directions focusing on biodegradation technologies and genetic regulation approaches to alleviate DON contamination in livestock feeds. Advancing efficient DON-degradation strategies could open new avenues for sustainable feed management and mycotoxin detoxification technologies. Full article

► Show Figures

Figure 1

16 pages, 356 KB

Open AccessEditor’s ChoiceReview

Mycotoxins and the Intestinal Epithelium: From Barrier Injury to Stem Cell Dysfunction

by Wenying Huo, Yingying Qiao, Xiangru He, Cailing Wang, Ruiqing Li, Long Che and Enkai Li

Toxins 2025, 17(11), 534; https://doi.org/10.3390/toxins17110534 - 30 Oct 2025

Cited by 7 | Viewed by 2291

Abstract

Mycotoxins are toxic secondary metabolites produced by filamentous fungi that contaminate agricultural commodities, posing risks to food safety, animal productivity, and human health. The gastrointestinal tract is the first and most critical site of exposure, where the intestinal epithelium functions as both a [...] Read more.

Mycotoxins are toxic secondary metabolites produced by filamentous fungi that contaminate agricultural commodities, posing risks to food safety, animal productivity, and human health. The gastrointestinal tract is the first and most critical site of exposure, where the intestinal epithelium functions as both a physical and immunological barrier against luminal toxins and pathogens. While extensive research has demonstrated that mycotoxins disrupt epithelial integrity through tight junction impairment, oxidative stress, apoptosis, and inflammation, their effects on the intestinal stem cell (ISC) compartment and epithelial regeneration remain insufficiently understood. This review integrates recent findings from in vivo, cell culture, and advanced 3D intestinal organoid and gut-on-chip models to elucidate how mycotoxins such as deoxynivalenol and zearalenone impair ISC proliferation, alter Wnt/Notch signaling, and compromise mucosal repair. We also discuss dose relevance, species differences, and the modulatory roles of the microbiome and short-chain fatty acids, as well as emerging evidence of additive or synergistic toxicity under co-exposure conditions. By bridging well-established mechanisms of barrier disruption with the emerging concept of ISC-driven regenerative failure, this review identifies a critical knowledge gap in mycotoxin toxicology and highlights the need for integrative models that link epithelial damage to impaired regeneration. Collectively, these insights advance understanding of mycotoxin-induced intestinal dysfunction and provide a foundation for developing nutritional, microbial, and pharmacological strategies to preserve gut integrity and repair. Full article

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

18 pages, 553 KB

Open AccessEditor’s ChoiceArticle

AI and Biotechnology to Combat Aflatoxins: Future Directions for Modern Technologies in Reducing Aflatoxin Risk

by Charitha J. Gamlath and Felicia Wu

Toxins 2025, 17(11), 524; https://doi.org/10.3390/toxins17110524 - 23 Oct 2025

Cited by 4 | Viewed by 1899

Abstract

Although a decades-old problem in food safety, aflatoxin has largely resisted human control methods. This situation could be mitigated using new technologies that could provide better control all along the food supply chain, for crops frequently infected with the causative fungi Aspergillus flavus [...] Read more.

Although a decades-old problem in food safety, aflatoxin has largely resisted human control methods. This situation could be mitigated using new technologies that could provide better control all along the food supply chain, for crops frequently infected with the causative fungi Aspergillus flavus and A. parasiticus, which produce aflatoxin. Generative artificial intelligence (AI) and modern biotechnology could offer, and have offered, a suite of potential solutions to reducing both fungal infection and aflatoxin contamination of foods. In this paper, we describe these technologies, as well as means by which they may be utilized to reduce aflatoxin risk along the food supply chain. We discuss how regulatory frameworks worldwide may be restrictive for biotechnologies in certain parts of the world, but are relatively less stringent for AI at present. To the extent that these technologies can be harnessed and deployed safely to combat the problem of aflatoxins, we encourage research and development in these areas to improve the precision, accuracy, and speed by which to deal with this food safety risk. Full article

(This article belongs to the Special Issue 65 Years On from Aflatoxin Discovery—a Themed Issue in Honor of Professor John D. Groopman)

► Show Figures

Figure 1

24 pages, 2023 KB

Open AccessEditor’s ChoiceReview

New Insights into Mycotoxin Contamination, Detection, and Mitigation in Food and Feed Systems

by Marija Kovač Tomas and Iva Jurčević Šangut

Toxins 2025, 17(10), 515; https://doi.org/10.3390/toxins17100515 - 20 Oct 2025

Cited by 10 | Viewed by 5461

Abstract

Mycotoxins are ubiquitous and unavoidable contaminants in food and feed, posing significant health risks through toxicity syndromes collectively referred to as mycotoxicoses. With climate change enhancing the conditions favorable for fungal growth and mycotoxin production, concerns over food and feed safety are increasingly [...] Read more.

Mycotoxins are ubiquitous and unavoidable contaminants in food and feed, posing significant health risks through toxicity syndromes collectively referred to as mycotoxicoses. With climate change enhancing the conditions favorable for fungal growth and mycotoxin production, concerns over food and feed safety are increasingly pressing. Although regulatory frameworks have been established to monitor and limit the exposure, effective mitigation remains a challenge. This paper provides a comprehensive overview of recent advances in the prevention, detection, and control of mycotoxins, with particular emphasis on innovative strategies such as plant-derived bioactives, nanotechnology-based systems, genetic engineering approaches, antibody-mediated technology, and emerging non-thermal processing methods. Full article

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

► Show Figures

Graphical abstract

57 pages, 4553 KB

Open AccessEditor’s ChoiceReview

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

Cited by 3 | Viewed by 6931

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)

► Show Figures

Figure 1

19 pages, 1292 KB

Open AccessEditor’s ChoiceReview

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

Cited by 5 | Viewed by 3033

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

► Show Figures

Figure 1

14 pages, 1031 KB

Open AccessEditor’s ChoiceReview

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

Cited by 6 | Viewed by 3078

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)

► Show Figures

Figure 1

25 pages, 726 KB

Open AccessEditor’s ChoiceReview

Anticancer Activity of Snake Venom Against Breast Cancer: A Scoping Review

by Eun-Jin Kim, Jang-Kyung Park, Soo-Hyun Sung and Hyun-Kyung Sung

Toxins 2025, 17(10), 477; https://doi.org/10.3390/toxins17100477 - 25 Sep 2025

Cited by 3 | Viewed by 3582

Abstract

Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. This scoping review summarizes experimental evidence on the anticancer activity of snake venom and its bioactive components against breast cancer, drawing from a variety of in vitro and in [...] Read more.

Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. This scoping review summarizes experimental evidence on the anticancer activity of snake venom and its bioactive components against breast cancer, drawing from a variety of in vitro and in vivo studies. Aimed at critically evaluating the therapeutic potential and underlying mechanisms, this review consolidates findings on venoms from multiple snake species, including both crude preparations and purified proteins or peptides, revealing a diversity of mechanisms of action. Reported effects include induction of apoptosis, generation of reactive oxygen species, disruption of cell membrane integrity, inhibition of cell proliferation and metastasis, and modulation of oncogenic signaling pathways. In vivo findings further indicate tumor growth inhibition and, in some cases, enhanced efficacy when venom-based agents are combined with nanoparticle delivery systems or conventional anticancer drugs. However, a significant proportion of evidence is limited to in vitro studies, with substantial heterogeneity in venom sources, extraction methods, dosages, and cancer models, which constrains generalizability. There is also a lack of systematic data on long-term toxicity, immunogenicity, off-target effects, pharmacokinetics, and formulation challenges. Taken together, these findings highlight snake venom-derived compounds as promising multi-targeted anticancer agents but underscore the urgent need for standardized formulations, rigorous preclinical safety assessments, and translational research to bridge the gap to clinical application. Future investigations should aim to isolate novel venom-derived compounds, refine delivery strategies, and undertake rigorous preclinical safety and pharmacokinetic studies—ultimately moving toward early-phase clinical evaluation to bridge the translational gap and assess the therapeutic potential of these agents. Full article

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

► Show Figures

Figure 1

21 pages, 805 KB

Open AccessEditor’s ChoiceArticle

Unilateral EMG-Guided Botulinum Toxin for Retrograde Cricopharyngeus Dysfunction: A Prospective Clinical and Neurophysiological Study

by Giuseppe Cosentino, Chiara Zaffina, Clara Zoccola, Mauro Fresia, Sara Merli, Simone Mauramati, Giulia Bertino, Massimiliano Todisco, Shayan Dodge, Sami Barmada, Enrico Alfonsi and Cristina Tassorelli

Toxins 2025, 17(9), 458; https://doi.org/10.3390/toxins17090458 - 12 Sep 2025

Cited by 5 | Viewed by 2434

Abstract

Retrograde cricopharyngeus dysfunction (R-CPD) is a recently recognized condition characterized by the inability to burp, typically accompanied by gurgling noises, bloating, and flatulence. Percutaneous botulinum neurotoxin (BoNT) injection into the cricopharyngeus muscle is a minimally invasive treatment with promising effects, although current evidence [...] Read more.

Retrograde cricopharyngeus dysfunction (R-CPD) is a recently recognized condition characterized by the inability to burp, typically accompanied by gurgling noises, bloating, and flatulence. Percutaneous botulinum neurotoxin (BoNT) injection into the cricopharyngeus muscle is a minimally invasive treatment with promising effects, although current evidence remains limited. In this prospective, open-label study, we evaluated the clinical effects of increasing doses (10 to 30 U) of EMG-guided unilateral BoNT injection in 67 patients with R-CPD. Symptom severity and quality of life were assessed at baseline and at 1 and 4 months post-treatment. The electromyographic (EMG) parameters of the cricopharyngeus were recorded to explore their association with symptom burden and treatment response. At a 1-month follow-up, 55.2% of patients were classified as responders (satisfaction score ≥ 6/10), with a higher rate (64.4%) observed at higher doses, particularly in female patients. Both symptom severity and quality of life improved significantly at 1 month and were sustained at 4 months. Higher cricopharyngeus EMG activity was associated with more severe symptoms and lesser treatment responses. Unilateral EMG-guided BoNT injection is a safe and effective treatment for R-CPD. Further studies should explore the potential role of electromyography in clarifying the pathophysiological aspects of R-CPD and guiding treatment. Full article

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

► Show Figures

Figure 1

20 pages, 1235 KB

Open AccessEditor’s ChoiceReview

Research Progress on the Detection Methods of Botulinum Neurotoxin

by Shuo Wang, Huajie Zhang, Yanhua Xue, Yingchao Yang and Liyong Yuan

Toxins 2025, 17(9), 453; https://doi.org/10.3390/toxins17090453 - 8 Sep 2025

Cited by 6 | Viewed by 5802

Abstract

Botulinum neurotoxins (BoNTs), produced by the anaerobic spore-forming bacterium Clostridium botulinum, are among the most potent known biological toxins. BoNTs cause lethal botulism via contaminated food, wound infections, or infant intestinal colonization, posing significant threats to public health. Although the mouse bioassay is [...] Read more.

Botulinum neurotoxins (BoNTs), produced by the anaerobic spore-forming bacterium Clostridium botulinum, are among the most potent known biological toxins. BoNTs cause lethal botulism via contaminated food, wound infections, or infant intestinal colonization, posing significant threats to public health. Although the mouse bioassay is still being considered as the gold standard for detecting BoNTs, its drawbacks, including the lengthy experimental duration, high costs, and ethical issues, highlight the urgent need to develop alternative methods to fulfill the detection requirements. In recent years, frequent botulism poisoning incidents haves put forward higher requirements for detection technology. On-site detection is expected to be rapid and immediate, while laboratory detection requires high sensitivity and serotype discrimination capabilities. This review comprehensively introduces current detection approaches, including mouse bioassay, cell-based assays, immunological methods, endopeptidase–mass spectrometry, biosensors, chromatography, and mass spectrometry techniques. Notably, cell-based assays have been used for the potency testing of commercialized botulinum toxin type A and are considered the most promising alternative to the mouse bioassay. Biosensors based on nanomaterials demonstrate advantages in real-time detection due to their rapid response and portability, while endopeptidase–mass spectrometry achieves high sensitivity and effective serotype identification by specifically recognizing toxin-cleaved substrates. Future works shall aim to completely replace MBA, developing a detection system suitable for multiple scenarios such as clinical diagnosis, food safety monitoring, and environmental monitoring. The detection methods should also have matrix compatibility and serotype discrimination capabilities. Full article

(This article belongs to the Section Bacterial Toxins)

► Show Figures

Figure 1

18 pages, 4803 KB

Open AccessEditor’s ChoiceArticle

Exploring the Potential of Genista ulicina Phytochemicals as Natural Biocontrol Agents: A Comparative In Vitro and In Silico Analysis

by Roukia Zatout, Ouided Benslama, Fatima Zohra Makhlouf, Alessio Cimmino, Maria Michela Salvatore, Anna Andolfi, Radhia Manel Kolla and Marco Masi

Toxins 2025, 17(9), 452; https://doi.org/10.3390/toxins17090452 - 6 Sep 2025

Cited by 8 | Viewed by 1322

Abstract

Development of new sustainable pesticides represents a real challenge for researchers due to environmental issues and public health aspects. In fact, the overuse of chemical pesticides has led to environmental damage, loss of biodiversity, and pesticide-resistant pests. In a framework characterized by the [...] Read more.

Development of new sustainable pesticides represents a real challenge for researchers due to environmental issues and public health aspects. In fact, the overuse of chemical pesticides has led to environmental damage, loss of biodiversity, and pesticide-resistant pests. In a framework characterized by the necessity of new sustainable agricultural practices, this study investigates the plant Genista ulicina as a producer of bioactive compounds for potential application as eco-friendly biopesticides. First, both roots and aerial parts of G. ulicina were extracted and the main compounds in the crude extracts were identified via GC-MS. Subsequently, the crude extracts were submitted to antifungal and phytotoxic assays. In particular, the antifungal effects were evaluated on three common phytopathogenic fungi, Fusarium oxysporum, Alternaria alternata, and Botrytis cinerea, while phytotoxic activity was evaluated on two weed species: Euphorbia peplus L. and Oxalis corniculata L. Further insights were obtained on the herbicidal potential of phytochemical compounds produced by G. ulicina through in silico investigations. In particular, molecular docking analyses were performed against three key enzymes involved in essential plant metabolic pathways: acetohydroxyacid synthase (AHAS), 4-hydroxyphenylpyruvate dioxygenase (HPPD), and protoporphyrinogen oxidase (PPO). Among the compounds identified, linolelaidic acid methyl ester, 1-monolinolein, stearic acid, and palmitic acid derivatives showed promising binding affinities and favorable interaction patterns compared to reference ligands. Selected phytochemicals from G. ulicina show potential as inhibitors of key herbicide targets, suggesting their value as promising leads in the development of sustainable bio-based weed control agents. Full article

(This article belongs to the Section Plant Toxins)

► Show Figures

Figure 1

23 pages, 2745 KB

Open AccessEditor’s ChoiceArticle

Pioneering Comparative Proteomic and Enzymatic Profiling of Amazonian Scorpion Venoms Enables the Isolation of Their First α-Ktx, Metalloprotease, and Phospholipase A₂

by Karla C. F. Bordon, Gabrielle C. Santos, Jonas G. Martins, Gisele A. Wiezel, Fernanda G. Amorim, Thomas Crasset, Damien Redureau, Loïc Quinton, Rudi E. L. Procópio and Eliane C. Arantes

Toxins 2025, 17(8), 411; https://doi.org/10.3390/toxins17080411 - 15 Aug 2025

Cited by 7 | Viewed by 2883

Abstract

Scorpionism is a growing public health concern in Brazil, with the Amazon region presenting the highest mortality rates but remaining understudied, especially regarding local scorpion venoms composition. This study presents the first comprehensive biochemical characterization of venoms from three Amazonian species—Tityus metuendus [...] Read more.

Scorpionism is a growing public health concern in Brazil, with the Amazon region presenting the highest mortality rates but remaining understudied, especially regarding local scorpion venoms composition. This study presents the first comprehensive biochemical characterization of venoms from three Amazonian species—Tityus metuendus (TmetuV), Tityus silvestris (TsilvV), and Brotheas amazonicus (BamazV)—using an integrated approach combining Multi-Enzymatic Limited Digestion (MELD)-based bottom-up proteomics, high-resolution LC-MS/MS, chromatography, zymography, and enzymatic assays. Tityus serrulatus venom was included as a reference. Significant biochemical differences were observed: TsilvV was rich in 20–30 kDa proteins and showed strong metalloprotease activity; BamazV exhibited high molecular weight proteins and potent phospholipase A₂ (PLA₂) activity but lacked proteolytic and fibrinogenolytic activities; TmetuV showed the highest hyaluronidase activity and abundance of α-KTx neurotoxins. Zymography revealed a conserved ~45 kDa hyaluronidase in all species. Three novel components were partially characterized: BamazPLA₂ (Group III PLA₂), Tmetu1 (37-residue α-KTx), and TsilvMP_A (a metalloprotease homologous to antarease). This is the first application of MELD-based proteomics to Amazonian scorpion venoms, revealing molecular diversity and functional divergence within Tityus and Brotheas, emphasizing the need for region-specific antivenoms. These findings provide a foundation for future pharmacological studies and the discovery of bioactive peptides with therapeutic potential. Full article

(This article belongs to the Special Issue Unlocking the Deep Secrets of Toxins)

► Show Figures

Graphical abstract

16 pages, 574 KB

Open AccessEditor’s ChoiceArticle

In Vitro Evaluation of Aflatoxin B1 Detoxification by Lactobacillus, Pediococcus, and Bacillus Strains

by Sarra Rafai, Ana Moreno, Alessandra Cimbalo, Pilar Vila-Donat, Lara Manyes and Giuseppe Meca

Toxins 2025, 17(8), 403; https://doi.org/10.3390/toxins17080403 - 11 Aug 2025

Cited by 4 | Viewed by 2580

Abstract

Biologically based detoxification strategies are increasingly being explored as alternatives to conventional methods for the removal of toxic contaminants in food products. Among these, aflatoxin B1 (AFB1) is one of the most potent mycotoxins due to its high toxicity, genotoxicity, and persistence in [...] Read more.

Biologically based detoxification strategies are increasingly being explored as alternatives to conventional methods for the removal of toxic contaminants in food products. Among these, aflatoxin B1 (AFB1) is one of the most potent mycotoxins due to its high toxicity, genotoxicity, and persistence in the human body once ingested. In this study, the detoxification potential of bacterial strains belonging to the genera Lactobacillus/Pediococcus (n = 10) and Bacillus (n = 10) was evaluated using extracts from naturally contaminated corn flour. Detoxification was assessed after incubation for 12, 24, and 48 h in specific culture media. AFB1 quantification and metabolite profiling were performed at each time point using Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS). The highest detoxification rates were observed with Lactobacillus curvatus 14 (L. curvatus 14) (41.1 ± 19.3%) and Pediococcus pentosaceus 4 (P. pentosaceus 4) (25.4 ± 11.3%) after 48 h, and Bacillus firmus 6 (B. firmus 6) (25.1 ± 12.9%) after 24 h. An in vitro digestion model was also applied to assess detoxification under gastrointestinal conditions. Results showed substantial AFB1 reduction at the colonic stage, reaching 72.26 ± 7.54% for P. pentosaceus 4 and 69.67 ± 9.70% for L. curvatus 14. These findings underscore the potential application of Lactobacillus, Pediococcus, and Bacillus strains in biological detoxification strategies to reduce dietary exposure to AFB1. Full article

(This article belongs to the Special Issue Aflatoxins: Contamination, Analysis and Control)

► Show Figures

Figure 1

15 pages, 2398 KB

Open AccessEditor’s ChoiceArticle

Heating up the Blunts: Prothrombin Activation, with Factor Va as an Obligate Cofactor, Is the Dominant Procoagulant Mechanism of Blunt-Nosed Viper Venoms (Macrovipera Species)

by Patrick S. Champagne, Lorenzo Seneci and Bryan G. Fry

Toxins 2025, 17(8), 398; https://doi.org/10.3390/toxins17080398 - 8 Aug 2025

Cited by 6 | Viewed by 3569

Abstract

Venoms of the Palearctic vipers in the Macrovipera genus cause severe procoagulant clinical effects, yet the precise molecular targets remain incompletely defined. To fill this toxicological knowledge gap, we tested five Macrovipera venoms—M. lebetina cernovi, M. l. obtusa, M. l. [...] Read more.

Venoms of the Palearctic vipers in the Macrovipera genus cause severe procoagulant clinical effects, yet the precise molecular targets remain incompletely defined. To fill this toxicological knowledge gap, we tested five Macrovipera venoms—M. lebetina cernovi, M. l. obtusa, M. l. turanica (Turkmenistan and Uzbekistan localities), and M. schweizeri—using plasma clotting assays, Factors VII, X, XI, and XII and prothrombin zymogen activation assays, and SDS-PAGE to visualise Factor V (FV) cleavage. All venoms induced extremely rapid clot formation (10.5–12.5 s) compared with the negative control (spontaneous clotting) of 334.6 ± 3.6 s) and the positive control (kaolin trigger) of 55.8 ± 1.9 s. Activation of FVII or FXI was negligible, whereas consistent FX activation and species-variable FXII activation, both moderate, were observed. Prothrombin remained inert in the absence of cofactors, but the presence of FV or FVa elicited potent thrombin generation. SDS-PAGE confirmed proteolytic conversion of the 330 kDa FV zymogen into the ~105 kDa heavy and ~80 kDa light chains of FVa by the venoms of all species. This data demonstrates that Macrovipera venoms rely on a dual enzyme strategy: (i) activation of FV to FVa by serine proteases and (ii) FVa-dependent prothrombin activation by metalloproteases. These results reveal that prothrombin activation is the dominant procoagulant pathway and overshadows the historically emphasised FX activation. This mechanism mirrors, yet is evolutionarily independent from, the FXa:FVa prothrombinase formation seen in Australian elapid venoms, highlighting convergent evolution of cofactor-hijacking strategies among snakes. The discovery of potent FVa-mediated prothrombin activation in Macrovipera challenges existing paradigms of viperid venom action, prompts re-evaluation of related genera (e.g., Daboia), and underpins the design of targeted antivenom and therapeutic interventions. Full article

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

► Show Figures

Graphical abstract

14 pages, 510 KB

Open AccessEditor’s ChoiceArticle

Is There a “Non-Motor Effect” of Botulinum Toxin Treatment in Cervical Dystonia in Addition to Its Effects on Motor Symptoms?

by Małgorzata Dudzic, Anna Pieczyńska, Artur Drużdż, Anna Rajewska and Katarzyna Hojan

Toxins 2025, 17(8), 396; https://doi.org/10.3390/toxins17080396 - 6 Aug 2025

Cited by 5 | Viewed by 1717

Abstract

The efficacy of botulinum toxin A (BoNT) in alleviating motor symptoms of cervical dystonia (CD) has been well established, and it is the treatment of choice in this disease. Lately, the effect of BoNT on non-motor symptoms (NMS) such as cognitive function, depression, [...] Read more.

The efficacy of botulinum toxin A (BoNT) in alleviating motor symptoms of cervical dystonia (CD) has been well established, and it is the treatment of choice in this disease. Lately, the effect of BoNT on non-motor symptoms (NMS) such as cognitive function, depression, anxiety, pain, and sleep disturbance has been observed in patients with CD. A comprehensive clinical and functional assessment of motor (dystonia severity, gait) and non-motor symptoms (cognitive functions, depression, anxiety, sleep, and pain) has been performed in a total of 34 adult patients with cervical dystonia before and after BoNT treatment. Results have also been compared to a control group. Significant improvements in the scales assessing dystonia severity have been observed, which is in line with previous studies on the effect of BoNT on motor symptoms in dystonia. Interestingly, the results also clearly indicate that BoNT has a positive effect on NMS. Among the studied non-motor domains, depression and cognitive functions improved the most after the treatment procedure. The study highlights the potential of BoNT to positively influence non-motor symptoms in patients with cervical dystonia, although its effect on various NMS is not equal. Full article

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

► Show Figures

Figure 1

24 pages, 3858 KB

Open AccessEditor’s ChoiceReview

Emerging Strategies for Aflatoxin Resistance in Peanuts via Precision Breeding

by Archana Khadgi, Saikrisha Lekkala, Pankaj K. Verma, Naveen Puppala and Madhusudhana R. Janga

Toxins 2025, 17(8), 394; https://doi.org/10.3390/toxins17080394 - 6 Aug 2025

Cited by 5 | Viewed by 3868

Abstract

Aflatoxin contamination, primarily caused by Aspergillus flavus, poses a significant threat to peanut (Arachis hypogaea L.) production, food safety, and global trade. Despite extensive efforts, breeding for durable resistance remains difficult due to the polygenic and environmentally sensitive nature of resistance. [...] Read more.

Aflatoxin contamination, primarily caused by Aspergillus flavus, poses a significant threat to peanut (Arachis hypogaea L.) production, food safety, and global trade. Despite extensive efforts, breeding for durable resistance remains difficult due to the polygenic and environmentally sensitive nature of resistance. Although germplasm such as J11 have shown partial resistance, none of the identified lines demonstrated stable or comprehensive protection across diverse environments. Resistance involves physical barriers, biochemical defenses, and suppression of toxin biosynthesis. However, these traits typically exhibit modest effects and are strongly influenced by genotype–environment interactions. A paradigm shift is underway with increasing focus on host susceptibility (S) genes, native peanut genes exploited by A. flavus to facilitate colonization or toxin production. Recent studies have identified promising S gene candidates such as AhS5H1/2, which suppress salicylic acid-mediated defense, and ABR1, a negative regulator of ABA signaling. Disrupting such genes through gene editing holds potential for broad-spectrum resistance. To advance resistance breeding, an integrated pipeline is essential. This includes phenotyping diverse germplasm under stress conditions, mapping resistance loci using QTL and GWAS, and applying multi-omics platforms to identify candidate genes. Functional validation using CRISPR/Cas9, Cas12a, base editors, and prime editing allows precise gene targeting. Validated genes can be introgressed into elite lines through breeding by marker-assisted and genomic selection, accelerating the breeding of aflatoxin-resistant peanut varieties. This review highlights recent advances in peanut aflatoxin resistance research, emphasizing susceptibility gene targeting and genome editing. Integrating conventional breeding with multi-omics and precision biotechnology offers a promising path toward developing aflatoxin-free peanut cultivars. Full article

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

► Show Figures

Figure 1

23 pages, 9844 KB

Open AccessEditor’s ChoiceArticle

Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation

by Tiantaixi Tu, Tongtong Zheng, Hangqi Lin, Peifeng Cheng, Ye Yang, Bolin Liu, Xinwang Ying and Qingfeng Xie

Toxins 2025, 17(8), 390; https://doi.org/10.3390/toxins17080390 - 5 Aug 2025

Cited by 4 | Viewed by 2838

Abstract

This study explores how aristolochic acid I (AAI) drives hepatocellular carcinoma (HCC). We first employ network toxicology and machine learning to map the key molecular target genes. Next, our research utilizes molecular docking to evaluate how AAI binds to these targets, and finally [...] Read more.

This study explores how aristolochic acid I (AAI) drives hepatocellular carcinoma (HCC). We first employ network toxicology and machine learning to map the key molecular target genes. Next, our research utilizes molecular docking to evaluate how AAI binds to these targets, and finally confirms the stability and dynamics of the resulting complexes through molecular dynamics simulations. We identified 193 overlapping target genes between AAI and HCC through databases such as PubChem, OMIM, and ChEMBL. Machine learning algorithms (SVM-RFE, random forest, and LASSO regression) were employed to screen 11 core genes. LASSO serves as a rapid dimension-reduction tool, SVM-RFE recursively eliminates the features with the smallest weights, and Random Forest achieves ensemble learning through decision trees. Protein–protein interaction networks were constructed using Cytoscape 3.9.1, and key genes were validated through GO and KEGG enrichment analyses, an immune infiltration analysis, a drug sensitivity analysis, and a survival analysis. Molecular-docking experiments showed that AAI binds to each of the core targets with a binding affinity stronger than −5 kcal mol⁻¹, and subsequent molecular dynamics simulations verified that these complexes remain stable over time. This study determined the potential molecular mechanisms underlying AAI-induced HCC and identified key genes (CYP1A2, ESR1, and AURKA) as potential therapeutic targets, providing valuable insights for developing targeted strategies to mitigate the health risks associated with AAI exposure. Full article

(This article belongs to the Section Plant Toxins)

► Show Figures

Graphical abstract

14 pages, 556 KB

Open AccessEditor’s ChoiceReview

Animal Venom in Modern Medicine: A Review of Therapeutic Applications

by Euikyung Kim, Du Hyeon Hwang, Ramachandran Loganathan Mohan Prakash, Ravi Deva Asirvatham, Hyunkyoung Lee, Yunwi Heo, Al Munawir, Ramin Seyedian and Changkeun Kang

Toxins 2025, 17(8), 371; https://doi.org/10.3390/toxins17080371 - 28 Jul 2025

Cited by 17 | Viewed by 7663

Abstract

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of [...] Read more.

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of medical conditions. This review provides a comprehensive analysis of the pharmacological potential of venom-derived compounds, highlighting their mechanisms of action, such as ion channel modulation, receptor targeting, and enzyme inhibition. Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. We discuss therapeutic applications in cardiovascular diseases, chronic pain, cancer, thrombosis, and infectious diseases, as well as emerging peptide candidates in clinical development. Technological advancements in omics, structural biology, and synthetic peptide engineering have significantly enhanced the discovery and optimization of venom-based therapeutics. Despite challenges related to stability, immunogenicity, and ecological sustainability, the integration of AI-driven drug discovery and personalized medicine is expected to accelerate progress in this field. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders. Full article

(This article belongs to the Section Animal Venoms)

► Show Figures

Figure 1

22 pages, 3176 KB

Open AccessEditor’s ChoiceArticle

Maresin 2, a Specialized Pro-Resolution Lipid Mediator, Reduces Pain and Inflammation Induced by Bothrops jararaca Venom in Mice

by Kassyo L. S. Dantas, Beatriz H. S. Bianchini, Matheus D. V. da Silva, Maiara Piva, Joice M. da Cunha, Janaina M. Zanoveli, Fernanda C. Cardoso, Fabiana T. M. C. Vicentini, Camila R. Ferraz, Patricia B. Clissa, Rubia Casagrande and Waldiceu A. Verri

Toxins 2025, 17(8), 367; https://doi.org/10.3390/toxins17080367 - 25 Jul 2025

Cited by 3 | Viewed by 1771

Abstract

The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model [...] Read more.

The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model of BjV-evoked pain and inflammation. Mice received a single intraperitoneal (i.p.) injection of MaR2 30 min before the intraplantar BjV injection. MaR2 treatment significantly attenuated mechanical (electronic aesthesiometer) and thermal (hot plate) hyperalgesia in a dose-dependent manner. Additionally, MaR2 restored the balance for the hind-paw static weight distribution. When BjV (0.01, 0.1, and 1 μg) stimulus was administered intraperitoneally, pre-treatment with MaR2 (0.3, 1, or 3 ng) ameliorated mechanical and thermal hyperalgesia in a dose-dependent manner. Moreover, MaR2 (3 ng) effectively reduced the levels of myeloperoxidase activity and cytokines (TNF-α, IL-1β, and IL-6) and superoxide anion (O₂^•−) production induced by intraplantar injection of BjV while enhancing total antioxidant levels (ABTS scavenging). For the peritonitis model induced by BjV, MaR2 pretreatment decreased leukocyte recruitment, hemorrhage, nitric oxide (NO), and O₂^•− generation and gp91phox and inducible nitric oxide synthase (iNOS) mRNA expression. In conclusion, this study presents the first evidence that MaR2 effectively mitigated BjV-induced pain, hemorrhage, and inflammation. Full article

(This article belongs to the Section Animal Venoms)

► Show Figures

Figure 1

28 pages, 531 KB

Open AccessEditor’s ChoiceReview

Multiple Mycotoxin Contamination in Livestock Feed: Implications for Animal Health, Productivity, and Food Safety

by Oluwakamisi F. Akinmoladun, Fabia N. Fon, Queenta Nji, Oluwaseun O. Adeniji, Emmanuel K. Tangni and Patrick B. Njobeh

Toxins 2025, 17(8), 365; https://doi.org/10.3390/toxins17080365 - 25 Jul 2025

Cited by 22 | Viewed by 6936

Abstract

Mycotoxins are toxic secondary metabolites produced by various fungi that contaminate livestock feed, posing serious threats to animal health, productivity, and food safety. Although historical research has often examined individual mycotoxins in isolation, real-world conditions typically involve the simultaneous presence of multiple mycotoxins, [...] Read more.

Mycotoxins are toxic secondary metabolites produced by various fungi that contaminate livestock feed, posing serious threats to animal health, productivity, and food safety. Although historical research has often examined individual mycotoxins in isolation, real-world conditions typically involve the simultaneous presence of multiple mycotoxins, resulting in additive or synergistic toxic effects that are often more severe than those observed with single toxin exposures. This review comprehensively synthesizes recent findings on multi-mycotoxin contamination in livestock feed, highlighting their physiological effects, mechanisms of action, and implications for regulatory frameworks. Multi-mycotoxin interactions exacerbate oxidative stress, immune suppression, impaired reproduction, and organ damage across species, leading to reduced growth performance, decreased milk and egg production, compromised carcass and wool quality, and increased mortality rates. A major concern is that current international regulatory standards mainly address individual mycotoxins, overlooking the compounded risks of co-occurrence. Global surveillance studies consistently reveal high prevalence rates of mycotoxin mixtures in feedstuffs, especially combinations involving DON, ZEN, AFB₁, FB₁, and OTA. Understanding these interactions and their underlying cellular mechanisms is critical for improving risk assessment models, formulating integrated mitigation strategies, and safeguarding both livestock productivity and human food security. Full article

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

► Show Figures

Figure 1

51 pages, 17514 KB

Open AccessEditor’s ChoiceReview

Variations in “Functional Site” Residues and Classification of Three-Finger Neurotoxins in Snake Venoms

by R. Manjunatha Kini and Cho Yeow Koh

Toxins 2025, 17(8), 364; https://doi.org/10.3390/toxins17080364 - 24 Jul 2025

Cited by 4 | Viewed by 2280

Abstract

Three-finger toxins (3FTxs) are the largest group of nonenzymatic toxins found in snake venoms. Among them, neurotoxins that target nicotinic acetylcholine receptors are the most well-studied ligands. In addition to the classical neurotoxins, several other new classes have been characterized for their structure, [...] Read more.

Three-finger toxins (3FTxs) are the largest group of nonenzymatic toxins found in snake venoms. Among them, neurotoxins that target nicotinic acetylcholine receptors are the most well-studied ligands. In addition to the classical neurotoxins, several other new classes have been characterized for their structure, receptor subtype, and species selectivity. Here, we systematically analyzed over 700 amino acid sequences of three-finger neurotoxins that interact with nicotinic acetylcholine receptors. Based on the amino acid residue substitutions in the functional sites and structural features of various classes of neurotoxins, we have classified them into over 150 distinct subgroups. Currently, only a small number of typical examples representing these subgroups have been studied for their structure, function, and subtype selectivity. The functional site residues responsible for their interaction with specific receptor subtypes of several toxins are yet to be identified. The molecular details of each subgroup representative toxin with its target receptor will contribute towards the understanding of subtype- and/or interface-selectivity. Thus, this review will provide new impetus in the toxin research and pave the way for the design of potent, selective ligands for nicotinic acetylcholine receptors. Full article

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

► Show Figures

Figure 1

46 pages, 3249 KB

Open AccessEditor’s ChoiceReview

Recent Advancements in Lateral Flow Assays for Food Mycotoxin Detection: A Review of Nanoparticle-Based Methods and Innovations

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

Toxins 2025, 17(7), 348; https://doi.org/10.3390/toxins17070348 - 11 Jul 2025

Cited by 10 | Viewed by 5944

Abstract

Mycotoxins are responsible for a multitude of diseases in both humans and animals, resulting in significant medical and economic burdens worldwide. Conventional detection methods, such as enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS), are highly effective, [...] Read more.

Mycotoxins are responsible for a multitude of diseases in both humans and animals, resulting in significant medical and economic burdens worldwide. Conventional detection methods, such as enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS), are highly effective, but they are generally confined to laboratory settings. Consequently, there is a growing demand for point-of-care testing (POCT) solutions that are rapid, sensitive, portable, and cost-effective. Lateral flow assays (LFAs) are a pivotal technology in POCT due to their simplicity, rapidity, and ease of use. This review synthesizes data from 78 peer-reviewed studies published between 2015 and 2024, evaluating advances in nanoparticle-based LFAs for detection of singular or multiplex mycotoxin types. Gold nanoparticles (AuNPs) remain the most widely used, due to their favorable optical and surface chemistry; however, significant progress has also been made with silver nanoparticles (AgNPs), magnetic nanoparticles, quantum dots (QDs), nanozymes, and hybrid nanostructures. The integration of multifunctional nanomaterials has enhanced assay sensitivity, specificity, and operational usability, with innovations including smartphone-based readers, signal amplification strategies, and supplementary technologies such as surface-enhanced Raman spectroscopy (SERS). While most singular LFAs achieved moderate sensitivity (0.001–1 ng/mL), only 6% reached ultra-sensitive detection (<0.001 ng/mL), and no significant improvement was evident over time (ρ = −0.162, p = 0.261). In contrast, multiplex assays demonstrated clear performance gains post-2022 (ρ = −0.357, p = 0.0008), largely driven by system-level optimization and advanced nanomaterials. Importantly, the type of sample matrix (e.g., cereals, dairy, feed) did not significantly influence the analytical sensitivity of singular or multiplex lateral LFAs (Kruskal–Wallis p > 0.05), confirming the matrix-independence of these optimized platforms. While analytical challenges remain for complex targets like fumonisins and deoxynivalenol (DON), ongoing innovations in signal amplification, biorecognition chemistry, and assay standardization are driving LFAs toward becoming reliable, ultra-sensitive, and field-deployable platforms for high-throughput mycotoxin screening in global food safety surveillance. Full article

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

► Show Figures

Graphical abstract

20 pages, 1188 KB

Open AccessEditor’s ChoiceReview

Increased Cardiovascular Mortality in Hemodialysis: The Role of Chronic Inflammation, Complement Activation, and Non-Biocompatibility

by Ákos Géza Pethő, Tibor Fülöp, Petronella Orosz, Gábor Szénási, Mihály Tapolyai and László Dézsi

Toxins 2025, 17(7), 345; https://doi.org/10.3390/toxins17070345 - 10 Jul 2025

Cited by 5 | Viewed by 3248

Abstract

Background: Chronic kidney disease (CKD) is an established global health problem, with the increased prevalence of vascular inflammation, accelerated atherogenesis, and thrombotic risk all contributing to overall cardiovascular risk. The major CKD-specific risk factor is presumed to be the accumulation of uremic toxins [...] Read more.

Background: Chronic kidney disease (CKD) is an established global health problem, with the increased prevalence of vascular inflammation, accelerated atherogenesis, and thrombotic risk all contributing to overall cardiovascular risk. The major CKD-specific risk factor is presumed to be the accumulation of uremic toxins in circulation and tissues, further accelerating the progression of CKD and its co-morbidities, including those of bone mineral disorders and cardiovascular diseases. Materials and Methods: In our narrative review, we focused on non-traditional cardiovascular risk factors, as they evolve with declined kidney function and are potentially further modulated by the choice of kidney replacement therapy. Results: Based on the data from the literature to date, the pre-eminent role of non-traditional risk factors emerges to mediate inflammation and increased cardiovascular mortality. In particular, patients receiving hemodialysis (HD) display dramatically increased CVD-mediated mortality. This intensified state of inflammation may be linked to the direct exposure of the bloodstream to a bio-incompatible environment in HD; for both complement-mediated and non-complement-mediated reactions, the possible contribution of neutrophil extracellular traps and complement activation-related pseudoallergy are reviewed in detail. Conclusions: Our narrative review emphasizes key elements of a bio-incompatible HD environment that may contribute to increased cardiovascular mortality in patients receiving HD. Summarizing these results may provide conceptual opportunities to develop new therapeutic targets. Full article

(This article belongs to the Section Uremic Toxins)

► Show Figures

Figure 1

27 pages, 768 KB

Open AccessEditor’s ChoiceReview

Pre-Harvest Aflatoxin Contamination in Crops and Climate Change Factors: A European Overview

by Ainhoa Bereziartua, Anke Huss, Jannigje G. Kers, Lidwien A. M. Smit, Roel Vermeulen and Daniel Martins Figueiredo

Toxins 2025, 17(7), 344; https://doi.org/10.3390/toxins17070344 - 8 Jul 2025

Cited by 7 | Viewed by 3155

Abstract

Aflatoxin (AF) contamination of crops during the pre-harvest period is a significant global concern for food and feed safety (FFS). In Europe, climate change presents a growing threat to agricultural products by increasing the risk of AF contamination. This umbrella review evaluates the [...] Read more.

Aflatoxin (AF) contamination of crops during the pre-harvest period is a significant global concern for food and feed safety (FFS). In Europe, climate change presents a growing threat to agricultural products by increasing the risk of AF contamination. This umbrella review evaluates the scope and quality of pre-harvest data on climate-related AF contamination in Europe, addressing key questions: What insights do researchers provide on the relationship between climate change and pre-harvest AF contamination, and what data are lacking? Which crops are the focus of current research, and where in Europe are these studies concentrated? How is the data presented, and is it standardized? We conducted an umbrella literature review, extracting relevant studies from PubMed and Scopus up to 14 October 2024. Our findings indicate that rising temperatures, droughts, and shifting rainfall patterns increasingly favor the growth of aflatoxigenic fungi and pre-harvest AF contamination in European crops, posing risks to FFS and agricultural stability. However, inconsistencies in data collection and reporting limit cross-regional comparisons and hinder the development of effective mitigation strategies. Standardizing methodologies and improving data accessibility will enhance predictive modeling, strengthen risk assessments, and support targeted adaptation efforts, providing actionable insights for policymakers and agricultural stakeholders. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Graphical abstract

19 pages, 1475 KB

Open AccessEditor’s ChoiceArticle

Chemical and Morphological Constitutive Defensive Traits of Cyanobacteria Have Different Effects on the Grazing of a Small Tropical Cladoceran

by Luciana Machado Rangel, Marcella Coelho Berjante Mesquita, Shara Rosa de Barros, Vinicius Neres-Lima, Michael Ribas Celano, Mauro Cesar Palmeira Vilar, Sandra Maria Feliciano de Oliveira e Azevedo and Marcelo Manzi Marinho

Toxins 2025, 17(7), 343; https://doi.org/10.3390/toxins17070343 - 5 Jul 2025

Cited by 4 | Viewed by 1714

Abstract

Antipredator defenses of bloom-forming cyanobacteria species maximize their fitness but can reduce carbon and energy transfer efficiency to higher trophic levels, making them a key regulator of plankton communities in eutrophic waters. We investigated the grazing responses of the tropical cladoceran Moina micrura [...] Read more.

Antipredator defenses of bloom-forming cyanobacteria species maximize their fitness but can reduce carbon and energy transfer efficiency to higher trophic levels, making them a key regulator of plankton communities in eutrophic waters. We investigated the grazing responses of the tropical cladoceran Moina micrura to different strains of the cyanobacteria Microcystis aeruginosa and Planktothrix isothrix, using a good food source (green algae Mono-raphidium capricornutum) as a control. Both Microcystis strains grow as unicellular and are microcystins producers; however, this cyanotoxin was not detected on the filamentous Planktothrix strains. M. micrura ingested all cyanobacteria at reduced rates compared to single diets with Monoraphidium. In mixed diets, food type had a significant effect on grazing responses, which differed interspecifically. Planktothrix was more grazed than Microcystis strains. Feeding selectivity on Monoraphidium was negatively affected by the increase of cyanobacteria in the diet. We observed varied responses across treatments, ranging from feeding inhibition to different degrees of tolerance toward cyanobacteria, particularly in non-microcystin-producing species. We also highlight the selectivity of small tropical cladocerans, a pattern that is not yet well documented. These findings emphasize that studies incorporating phyto- and zooplankton with a history of coexistence can provide more meaningful insights into natural ecosystem dynamics. Full article

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

► Show Figures

Figure 1

27 pages, 2201 KB

Open AccessEditor’s ChoiceReview

Toxicity, Mitigation, and Chemical Analysis of Aflatoxins and Other Toxic Metabolites Produced by Aspergillus: A Comprehensive Review

by Habtamu Fekadu Gemede

Toxins 2025, 17(7), 331; https://doi.org/10.3390/toxins17070331 - 30 Jun 2025

Cited by 29 | Viewed by 13416

Abstract

Aflatoxins, toxic secondary metabolites produced primarily by Aspergillus flavus and Aspergillus parasiticus, pose significant risks to food safety, public health, and global trade. These mycotoxins contaminate staple crops such as maize and peanuts, particularly in warm and humid regions, leading to economic [...] Read more.

Aflatoxins, toxic secondary metabolites produced primarily by Aspergillus flavus and Aspergillus parasiticus, pose significant risks to food safety, public health, and global trade. These mycotoxins contaminate staple crops such as maize and peanuts, particularly in warm and humid regions, leading to economic losses and severe health effects, including hepatocellular carcinoma, immune suppression, and growth impairment. In addition to aflatoxins, Aspergillus species produce other toxic metabolites such as ochratoxin A, sterigmatocystin, and cyclopiazonic acid, which are associated with nephrotoxic, carcinogenic, and neurotoxic effects, respectively. This review provides a comprehensive analysis of aflatoxin toxicity, mitigation strategies, and chemical detection methods. The toxicity of aflatoxins is discussed in relation to their biochemical mechanisms, carcinogenicity, and synergistic effects with other mycotoxins. Various mitigation approaches, including pre-harvest biocontrol, post-harvest storage management, and novel detoxification methods such as enzymatic degradation and nanotechnology-based interventions, are evaluated. Furthermore, advances in aflatoxin detection, including chromatographic, immunoassay, and biosensor-based methods, are explored to improve regulatory compliance and food safety monitoring. This review underscores the need for integrated management strategies and global collaboration to reduce aflatoxin contamination and its associated health and economic burdens. Future research directions should focus on genetic engineering for resistant crop varieties, climate adaptation strategies, and improved risk assessment models. Full article

(This article belongs to the Special Issue Toxicity, Mitigation and Chemical Analysis of Aflatoxins and Other Toxic Metabolites Produced by Aspergillus)

► Show Figures

Figure 1

20 pages, 1159 KB

Open AccessEditor’s ChoiceArticle

Assessing Alternaria Species and Related Mycotoxin Contamination in Wheat in Algeria: A Food Safety Risk

by Meriem Barkahoum Daichi, Mario Masiello, Miriam Haidukowski, Annalisa De Girolamo, Antonio Moretti, Amor Bencheikh, Noureddine Rouag and Stefania Somma

Toxins 2025, 17(6), 309; https://doi.org/10.3390/toxins17060309 - 18 Jun 2025

Cited by 11 | Viewed by 3455

Abstract

Alternaria species are important fungal pathogens occurring worldwide in wheat, causing both productive and qualitative losses, and posing a toxicological risk to human health due to the production of their mycotoxins in kernels. This study aimed to investigate the occurrence of Alternaria species [...] Read more.

Alternaria species are important fungal pathogens occurring worldwide in wheat, causing both productive and qualitative losses, and posing a toxicological risk to human health due to the production of their mycotoxins in kernels. This study aimed to investigate the occurrence of Alternaria species and their mycotoxins in 48 wheat grain samples collected from the northeast to the southeast of Algeria. Seventy-two representative Alternaria strains were molecularly analyzed using a multi-locus sequence approach and evaluated for their capability to produce mycotoxins under in vitro conditions. Alternaria alternata, representing 42% of the strains, was the dominant species, followed to a lesser extent by species included in the Infectoriae section (26%). In addition, three species not previously reported in Algerian wheat, A. eureka, A. consortialis and A. tellustris, were identified, accounting for 5% of the total strains. Mycotoxin analyses showed high contamination of grains with alternariol monomethyl ether, alternariol and tenuazonic acid, occurring in 75, 69 and 35% of the samples, respectively. Moreover, 41 out of 48 samples showed the co-occurrence of multiple Alternaria mycotoxins. This study provides, for the first, time a clear picture of the occurrence and the distribution of Alternaria species on wheat in Algeria. Finally, the extensive monitoring activities carried out revealed the great biodiversity of Alternaria species able to colonize wheat grains. Moreover, findings on mycotoxin contamination raise concerns about the significant mycotoxigenic risk in Algerian wheat, emphasizing the need for strict monitoring and regulatory measures on Alternaria mycotoxins in food and feed. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Graphical abstract

18 pages, 4121 KB

Open AccessEditor’s ChoiceArticle

Defence Against Desiccation and Predation in Lophyohylini Casque-Headed Tree Frogs

by César Alexandre, Pedro L. Mailho-Fontana, Bianca C. L. F. Távora, Marta M. Antoniazzi and Carlos Jared

Toxins 2025, 17(6), 303; https://doi.org/10.3390/toxins17060303 - 16 Jun 2025

Cited by 1 | Viewed by 4934

Abstract

Casque-headed tree frogs (Lophyohylini) can have a very large and distinctive head characterised by hyperossification of their cranial skin. This type of skull was primarily associated with phragmosis, a behaviour in which the frog enters holes backwards and seals them with its head [...] Read more.

Casque-headed tree frogs (Lophyohylini) can have a very large and distinctive head characterised by hyperossification of their cranial skin. This type of skull was primarily associated with phragmosis, a behaviour in which the frog enters holes backwards and seals them with its head to prevent water loss in challenging environments. Further investigations revealed that hyperossification also gives rise to bony spines interspersed with skin poison glands. These peculiar anatomical features of the head make it challenging for predators to prey on the frogs in phragmosis. When bitten on the head, the bite pressure causes the spines to cross the poison glands, allowing the injection of toxins into the predator’s mouth. We studied the head morphology of different Lophyohylini species along with some characteristics of their cutaneous poison, both in the field and in the laboratory. These frogs exemplify distinct chemical defence strategies, highlighting the differences between venom and poison. Notably, some species can cause self-poisoning in predators by injecting poison (in this case, venom) through their head spines, similar to the use of fangs by snakes. Full article

(This article belongs to the Collection Evolution of Venom Systems)

► Show Figures

Figure 1

21 pages, 7088 KB

Open AccessEditor’s ChoiceReview

The Biological Role of Conoporins, Actinoporin-like Pore-Forming Toxins from Cone Snails

by Matija Ruparčič, Gašper Šolinc, Simon Caserman, Juan Carlos Garcia Galindo, Manuel Jimenez Tenorio and Gregor Anderluh

Toxins 2025, 17(6), 291; https://doi.org/10.3390/toxins17060291 - 7 Jun 2025

Cited by 2 | Viewed by 3208

Abstract

Cone snails are a large group of marine gastropods that produce a complex mixture of toxic compounds to hunt prey and defend against predators. The majority of the venom comprises small toxic peptides named conotoxins, which target membrane receptors. In contrast, a smaller [...] Read more.

Cone snails are a large group of marine gastropods that produce a complex mixture of toxic compounds to hunt prey and defend against predators. The majority of the venom comprises small toxic peptides named conotoxins, which target membrane receptors. In contrast, a smaller part of the venom contains larger proteins and conoproteins, which are thought to be involved in conotoxin maturation and the envenomation process, respectively. Interestingly, many species of cone snails contain conoporins, which are similar to actinoporins—pore-forming toxins found in sea anemones. These actinoporin-like proteins (ALPs) have recently been detected in many molluscan species, and only a few have been experimentally characterized. Due to being highly expressed in the venom gland of many cone snail species, conoporins are thought to play an important part in the envenomation process. Despite this, the exact function of conoporins is currently unknown. We propose several hypotheses aiming to elucidate their biological role. Full article

(This article belongs to the Special Issue Structure, Function and Evolution of Conotoxins)

► Show Figures

Figure 1

14 pages, 263 KB

Open AccessEditor’s ChoiceArticle

Evaluating Bias in Self-Reported Symptoms During a Cyanobacterial Algal Bloom

by John S. Reif, Rebecca Koszalinski, Malcolm M. McFarland, Michael L. Parsons, Rachael Schinbeckler, Judyta Kociolek, Alex Rockenstyre and Adam M. Schaefer

Toxins 2025, 17(6), 287; https://doi.org/10.3390/toxins17060287 - 6 Jun 2025

Cited by 1 | Viewed by 1668

Abstract

Algal blooms produced by cyanobacteria liberate microcystins and other toxins that create a public health hazard. During the 2018 bloom of Microcystis aeruginosa in Florida, USA, residential and recreational exposures were associated with an increased risk of self-reporting respiratory, gastrointestinal, or ocular symptoms [...] Read more.

Algal blooms produced by cyanobacteria liberate microcystins and other toxins that create a public health hazard. During the 2018 bloom of Microcystis aeruginosa in Florida, USA, residential and recreational exposures were associated with an increased risk of self-reporting respiratory, gastrointestinal, or ocular symptoms for 125 participants. Subsequently, 207 persons were interviewed between 2019 and 2024 in the absence of large-scale algal blooms and were considered non-exposed. Analyses of cyanotoxins and brevetoxins in water and air showed only intermittent, background levels of toxins during the non-bloom period. The purpose of this report was to compare symptom reporting between active bloom and non-bloom periods. The assessment of information bias from self-reported symptoms is an important issue in epidemiologic studies of harmful algal blooms. During the non-bloom period, no statistically significant associations with residential, recreational, or occupational exposures were found for any symptom group. Estimated risks for respiratory, gastrointestinal, and ocular symptoms, headache, and skin rash were significantly higher for persons sampled during the bloom than the non-bloom period with odds ratios (ORs) of 2.3 to 8.3. ORs for specific respiratory symptoms were also significantly elevated. After adjustment for confounders and multiple exposures in multivariable analyses, the differences in symptom reporting between bloom and non-bloom periods remained statistically significant. In summary, the use of self-reported symptoms in this epidemiologic study of exposure to a cyanobacterial algal bloom did not appear to introduce substantial information bias. Full article

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

15 pages, 2495 KB

Open AccessEditor’s ChoiceArticle

Palytoxin Signal in LC-MS and UV: Preliminary Investigation on the Effect of Solvent and Temperature

by Chiara Melchiorre, Michela Varra, Valeria Tegola, Valentina Miele and Carmela Dell’Aversano

Toxins 2025, 17(6), 286; https://doi.org/10.3390/toxins17060286 - 6 Jun 2025

Cited by 3 | Viewed by 1855

Abstract

Palytoxins (PLTXs) and ovatoxins (OVTXs) are a group of highly potent marine toxins that pose significant health risks through seafood contamination and environmental exposure. OVTX-producing algae have been linked to dermatitis and respiratory distress in Mediterranean beachgoers, while serious public health concerns are [...] Read more.

Palytoxins (PLTXs) and ovatoxins (OVTXs) are a group of highly potent marine toxins that pose significant health risks through seafood contamination and environmental exposure. OVTX-producing algae have been linked to dermatitis and respiratory distress in Mediterranean beachgoers, while serious public health concerns are related to PLTX accumulation in seafood. In 2009, the European Food Safety Authority highlighted the need for analytical detection methods of the PLTX group of toxins and for the preparation of reference materials. This study investigates the stability of the palytoxin signal using liquid chromatography tandem mass spectrometry (LC-MRM-MS) and UV-Vis spectrophotometry under different experimental conditions: three concentrations (10, 1, and 0.5 µg/mL), three methanol–water mixtures (10%, 50%, and 90%), and two temperatures (6 °C and 25 °C). The results showed that the PLTX signal response is significantly influenced by the experimental conditions used. LC-MRM-MS analysis revealed the optimal response of PLTX in 50% and 90% MeOH at 25 °C, with minimal signal loss occurring over 16 h (9% and 6%). UV-Vis data indicated reduced absorbance in 10% MeOH, but a stable spectral intensity over 21 h in all the tested solvent mixtures. These results underscore the necessity of carefully controlled experimental conditions to ensure accurate and reproducible PLTX detection in environmental and food safety monitoring. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI