Toxins

16 pages, 1847 KB

Open AccessArticle

Study on the Dynamic Changes in Fungal Communities During the Storage of Polygalae Radix and the Antifungal Effects of Peppermint Essential Oil

by Hui Zhang, Yuying Su, Xinnan Wang, Ying Ren, Jinfeng Li and Jianping Han

Toxins 2025, 17(12), 585; https://doi.org/10.3390/toxins17120585 (registering DOI) - 6 Dec 2025

Abstract

Polygalae Radix, a traditional Chinese medicine for insomnia and memory disorders, is highly susceptible to fungal contamination and mycotoxin production (especially by Aspergillus flavus) during storage, compromising its safety and efficacy. Therefore, in this study, high-throughput sequencing was employed to evaluate the [...] Read more.

Polygalae Radix, a traditional Chinese medicine for insomnia and memory disorders, is highly susceptible to fungal contamination and mycotoxin production (especially by Aspergillus flavus) during storage, compromising its safety and efficacy. Therefore, in this study, high-throughput sequencing was employed to evaluate the dynamic changes in fungal communities during the storage of Polygalae Radix and to analyze common mycotoxin-producing genera. Furthermore, the inhibitory effects of peppermint essential oil (PEO) on A. flavus were assessed through fumigation treatments, combined with colony counting and quantification of aflatoxins. Results showed the following: (1) Storage for 1–3 months significantly altered the fungal structure, promoting saprophytic and pathogenic fungi (e.g., Wallemia, Paraphoma, Didymella, Cladosporium…) and increasing the relative abundance of mycotoxin producers like Penicillium, Aspergillus, and Fusarium (notably, Penicillium increased from 0.28–2.33% to 5.39–80.43%). Additionally, A. flavus, capable of producing aflatoxins, was detected in samples stored for two months (RM2). (2) Antifungal tests demonstrated that PEO significantly inhibited the common fungi in Polygalae Radix. At 10 μL/g, it suppressed fungal growth and significantly reduced aflatoxin B₁ (AFB₁) and total aflatoxins (AFT, including AFB₁, AFB₂, AFG₁, and AFG₂) levels (p < 0.05). At 10 μL/g, AFB₁ and AFT were reduced to undetectable levels. PEO can serve as a green and effective protective strategy to inhibit A. flavus during the storage of Polygalae Radix and control aflatoxin contamination. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 2188 KB

Open AccessArticle

Beta Toxins Isolated from the Scorpion Centruroides hirsutipalpus (Scorpiones; Buthidae) Affect the Function of Sodium Channels of Mammals

by Laura L. Valdez-Velazquez, Timoteo Olamendi-Portugal, Rita Restano-Cassulini, Lidia Riaño-Umbarila, Juana María Jiménez-Vargas, Fernando Zamudio, Hermenegildo Salazar-Monge, Baltazar Becerril and Lourival D. Possani

Toxins 2025, 17(12), 584; https://doi.org/10.3390/toxins17120584 (registering DOI) - 6 Dec 2025

Abstract

Scorpion venom toxins are important peptides being studied for their clinical significance. These peptides act by binding to ion channels in the membrane of nerve cells, causing the symptoms associated with scorpion stings (scorpionism). They principally affect the function of voltage-gated sodium channels [...] Read more.

Scorpion venom toxins are important peptides being studied for their clinical significance. These peptides act by binding to ion channels in the membrane of nerve cells, causing the symptoms associated with scorpion stings (scorpionism). They principally affect the function of voltage-gated sodium channels (Nav) and are valuable for studying ion channels. Scorpions from the Buthidae family contain toxins that affect sodium channels and have a high affinity for mammalian channels. In this study, two sodium toxins isolated from the venom of the scorpion Centruroides hirsutipalpus, a member of the Buthidae family, were identified as belonging to the beta-type subfamily. These toxins were purified from whole venom using molecular exclusion, cationic-exchange, and reverse-phase chromatography techniques. Their molecular masses were determined using mass spectrometry, while their amino acid sequences were obtained by Edman degradation. A comparative analysis revealed that the sequences are identical to ChiNaBet60 and ChiNaBet50 toxins (now named Chirp7 and Chirp9, respectively) previously identified in the venom gland transcriptomics from C. hirsutipalpus. Furthermore, toxicity studies showed that these toxins were lethal to mammals. Electrophysiological analysis revealed that these peptides act as sodium channel–modulating toxins. In addition, interaction assays with antibodies were performed to analyze the structural determinants governing the binding mechanism. Full article

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17 pages, 1831 KB

Open AccessReview

Snake Venom PLA₂ as Anticoagulant Agents: Role of Crotoxin, from Crotalus durissus Rattlesnake, in Hemostasis

by Lisele Maria Brasileiro-Martins, Greene Dias Marques, Jéssica Burlamaque Maciel, Márcia Neiva, Thaís Pinto Nascimento, David Jose Estrada Reyes, Alessandro Júnio Campelo Feitosa, Sofia Angiole-Cavalcante, Priscila Ferreira de Aquino, Jacqueline de Almeida Gonçalves Sachett, Wuelton Marcelo Monteiro and Marco Aurélio Sartim

Toxins 2025, 17(12), 583; https://doi.org/10.3390/toxins17120583 - 5 Dec 2025

Abstract

Snake venoms are rich sources of bioactive molecules that modulate hemostasis and, among these, anticoagulant snake venom phospholipases A₂ (sPLA₂) are found in a range of snake venoms. Crotoxin (CTX), from the Crotalus durissus rattlesnake, is a heterodimeric PLA₂ [...] Read more.

Snake venoms are rich sources of bioactive molecules that modulate hemostasis and, among these, anticoagulant snake venom phospholipases A₂ (sPLA₂) are found in a range of snake venoms. Crotoxin (CTX), from the Crotalus durissus rattlesnake, is a heterodimeric PLA₂ complex, and literature has reported its mechanisms in anticoagulant activity. The present review revisits the biological roles of anticoagulant sPLA₂ and critically examines evidence on CTX in hemostatic regulation, aiming to clarify its mechanisms and therapeutic promise. CTX exerts anticoagulant activity via enzymatic hydrolysis of procoagulant phospholipids and direct interaction with coagulation factors, disrupting key complex assembly. It also counteracts inflammation-induced coagulation by modulating leukocyte- and endothelial-derived mediators, restoring balance among anticoagulant, procoagulant, and fibrinolytic pathways. Effects on platelet function appear comparatively modest, ranging from less potent pro-aggregatory activity to negligible aggregation. The dual anticoagulant and anti-inflammatory properties of CTX highlight its potential as a model for novel antithrombotic agents in hypercoagulable and inflammation-driven disorders, despite toxicological concerns that necessitate cautious pharmacological exploration. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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2 pages, 166 KB

Open AccessCorrection

Correction: Muñoz-Zavala et al. Aflatoxins in Mexican Maize Systems: From Genetic Resources to Agroecological Resilience and Co-Occurrence with Fumonisins. Toxins 2025, 17, 531

by Carlos Muñoz-Zavala, Obed Solís-Martínez, Jessica Berenice Valencia-Luna, Kai Sonder, Ana María Hernández-Anguiano and Natalia Palacios-Rojas

Toxins 2025, 17(12), 582; https://doi.org/10.3390/toxins17120582 - 4 Dec 2025

Abstract

In the original publication [...] Full article

26 pages, 1235 KB

Open AccessReview

Molecular Mechanisms of Venom Diversity

by Marcela Akemi Ishihara, Adriana Rios Lopes and Milton Yutaka Nishiyama-Jr

Toxins 2025, 17(12), 581; https://doi.org/10.3390/toxins17120581 - 3 Dec 2025

Abstract

Animal venoms are valuable resources for drug discovery. They offer a wide variety of bioactive molecules with significant biotechnological potential. Venom composition shows extensive diversity not only between and within species, but also across the lifetime of an individual. This natural variation further [...] Read more.

Animal venoms are valuable resources for drug discovery. They offer a wide variety of bioactive molecules with significant biotechnological potential. Venom composition shows extensive diversity not only between and within species, but also across the lifetime of an individual. This natural variation further enhances the biotechnological potential of venoms, supporting the development and optimization of venom-derived drugs. Despite numerous studies highlighting the variability of venom, many lack a coherent framework to explain the underlying causes of this diversity. In this review, we explore the molecular and evolutionary mechanisms driving variations in venom composition and the evolution of venom systems, including gene regulation, point mutations, gene duplication events, modulation by miRNAs, alternative splicing and post-translational modifications as driving forces of venom component diversity. We also discuss the critical role of omics technologies and comparative studies in advancing our understanding of the diversity of venom and their contribution to the identification, development, and refinement of venom-based product candidates. The aspects reviewed here are relevant for future omics study designs to advance venom research and biodiscovery. Full article

(This article belongs to the Section Animal Venoms)

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17 pages, 2239 KB

Open AccessArticle

Overcoming Analytical Challenges for the Detection of 27 Cyanopeptides Using a UHPLC-QqQ-MS Method in Fish Tissues

by Audrey Roy-Lachapelle, François-Xavier Teysseire and Christian Gagnon

Toxins 2025, 17(12), 580; https://doi.org/10.3390/toxins17120580 - 2 Dec 2025

Abstract

The increasing occurrence of harmful cyanobacterial blooms in freshwater ecosystems poses important risks to aquatic organisms and human health due to the production of bioactive secondary metabolites such as cyanopeptides. While analytical methods for microcystins are well developed, there is a notable lack [...] Read more.

The increasing occurrence of harmful cyanobacterial blooms in freshwater ecosystems poses important risks to aquatic organisms and human health due to the production of bioactive secondary metabolites such as cyanopeptides. While analytical methods for microcystins are well developed, there is a notable lack of validated protocols for the broader spectrum of cyanopeptides in biota. This study presents the development and validation of a robust UHPLC-QqQ-MS method for the simultaneous extraction, cleanup, and quantification of 27 cyanopeptides, including microcystins, anabaenopeptins, microginins, aeruginosins, aeruginoguanidine, and nodularin, in fish muscle, liver, and whole fish tissues. Comprehensive optimization was conducted to minimize matrix effects and analyte losses during every step of sample preparation. The method demonstrated generally high recoveries (28–98%), good precision (RSD < 20%), and sensitivity, with MQLs below 0.5 ng g⁻¹ for most analytes. Microginins posed analytical challenges due to their amphiphilic structure, which contributed to significant losses during filtration and extraction; the reasoning is discussed. Application to wild fish collected after a mass mortality event revealed no detectable cyanopeptide contamination but confirmed the method’s suitability for comprehensive detection. This represents an important advancement in cyanopeptide analysis, offering a valuable tool for environmental risk assessment and food safety evaluation related to harmful cyanobacteria. Full article

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

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33 pages, 1939 KB

Open AccessReview

Ion Channel-Targeting Toxins: Structural Mechanisms of Activation, Inhibition, and Therapeutic Potential

by Narumi Aoki-Shioi, Shuhei Nomura, Yasuyoshi Tanaka and Shinichi Hirose

Toxins 2025, 17(12), 579; https://doi.org/10.3390/toxins17120579 - 2 Dec 2025

Abstract

Toxins as channel probes, small guanidinium alkaloids, such as tetrodotoxin and saxitoxin, canonical pore occlusion in voltage-gated Na⁺ channels. Cystine-rich peptides from spiders, scorpions, cone snails, and sea anemones, which act as pore blockers or gating modifiers targeting voltage-sensing domains. Recent structural [...] Read more.

Toxins as channel probes, small guanidinium alkaloids, such as tetrodotoxin and saxitoxin, canonical pore occlusion in voltage-gated Na⁺ channels. Cystine-rich peptides from spiders, scorpions, cone snails, and sea anemones, which act as pore blockers or gating modifiers targeting voltage-sensing domains. Recent structural and electrophysiological studies have identified specific binding sites on ion channels, including the S5–S6 pore loops, outer vestibule and turret regions, and S3–S4 “paddle” motifs in NaV, Kv, and CaV channels. These discrete binding epitopes are recognized by different peptide toxins, enabling isoform- and state-specific modulation; for example, μ-conotoxins bind the NaV pore, whereas charybdotoxin and agitoxin target the Kv outer vestibule. Beyond mechanistic insights, peptide toxins inspire translational strategies, including emerging therapies for retinal degenerative diseases. Photopharmacology using chemical photoswitches allows reversible, light-controlled modulation of ion channels in retinal ganglion cells without genetic manipulation or cell transplantation. Although BENAQ was discovered by small-molecule screening rather than toxin-guided design, its ion channel control demonstrates the potential of toxin-based molecular determinants for engineering synthetic compounds. This review thus integrates structural, functional, and translational perspectives, emphasizing the versatility of animal-derived peptide toxins as molecular probes and as blueprints for precision ion channel modulation in health and disease. Full article

(This article belongs to the Special Issue Venomics Insights into the Evolutionary Biology of Peptide Toxins in Marine and Terrestrial Organisms)

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20 pages, 1952 KB

Open AccessReview

Toxins and the Kidneys: A Two-Way Street

by Louis L. Huang, Anthony Longano and Lawrence P. McMahon

Toxins 2025, 17(12), 578; https://doi.org/10.3390/toxins17120578 - 1 Dec 2025

Abstract

Nephrotoxin-mediated kidney injury is an important clinical problem, as it can lead to acute kidney injury and chronic kidney disease. Both entities are associated with significant morbidity, increased hospitalisation, healthcare utilisation, and cardiovascular mortality. With the loss of kidney function, there is an [...] Read more.

Nephrotoxin-mediated kidney injury is an important clinical problem, as it can lead to acute kidney injury and chronic kidney disease. Both entities are associated with significant morbidity, increased hospitalisation, healthcare utilisation, and cardiovascular mortality. With the loss of kidney function, there is an accumulation of uraemic toxins, of which the protein-bound toxins—indoxyl sulphate and p-cresyl sulphate—can further inflict damage to the kidneys and the cardiovascular system, culminating in a vicious cycle. Therefore, it is imperative that clinicians have a firm understanding of the common causes and mechanisms of toxin-mediated kidney injury, as well as their clinical presentations and histopathologic features, in order to reduce the prevalence of this pernicious condition. Full article

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23 pages, 590 KB

Open AccessArticle

Assessing Kidney Injury Biomarkers and OTA Exposure in Urine of Lebanese Adolescents Amid Economic Crisis and Evolving Dietary Patterns

by Rouaa Daou, Maha Hoteit, Jad Chémali, Nikolaos Tzenios, Nassim Fares and André El Khoury

Toxins 2025, 17(12), 577; https://doi.org/10.3390/toxins17120577 - 30 Nov 2025

Abstract

Although ochratoxin A (OTA) contamination has been previously reported in Lebanon, this study is the first worldwide to assess its potential impact on renal health among adolescents aged 10 to 18 years. In this cross-sectional study, the aim was to evaluate the levels [...] Read more.

Although ochratoxin A (OTA) contamination has been previously reported in Lebanon, this study is the first worldwide to assess its potential impact on renal health among adolescents aged 10 to 18 years. In this cross-sectional study, the aim was to evaluate the levels of OTA, OTα, and kidney injury biomarkers, as well as creatinuria and total proteinuria, while correlating these findings with dietary patterns. Urinary concentrations of OTA, its main metabolite ochratoxin α (OTa), the three renal injury biomarkers (N-acetyl-β-D-glucosaminidase [NAG], Kidney Injury Molecule-1 [KIM-1], and human lipocalin-2 [NGAL]), and two renal function indicators (creatinine and total protein) were quantified. Associations between biomarker levels and dietary intake patterns were also evaluated. OTA and OTα were detected in 14.2% and 59.5% of urine samples, respectively. NGAL and NAG were found in all participants at low concentrations, with the NAG-to-creatinine ratio exceeding the clinical threshold in 1.5% of samples, while KIM-1 was detected in 86% of participants. A weak positive correlation between urinary OTα and NAG suggests subtle renal alterations possibly linked to OTA exposure. Correlations between biomarker levels and food consumption were generally weak and positive. Estimated dietary intake (EDI) of OTA generated from consumption patterns was shown to be less than the probable dietary intake (PDI) calculated from urinary OTA. However, this presented a limitation, as EDI was calculated from previous contamination data in Lebanon. Overall, these findings indicate that while renal injury biomarkers were present at low levels, they may reflect early kidney stress not yet manifesting as overt pathology and highlight the need for strengthened regulatory measures to limit OTA contamination in foods available on the Lebanese market and for longitudinal studies to confirm these preliminary findings. Full article

(This article belongs to the Special Issue Mycotoxins—Biomonitoring and Exposure)

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15 pages, 3247 KB

Open AccessArticle

Comprehensive Clinical Profile of Amanita exitialis Poisoning: Integrating Toxin Detection and Autopsy Pathology

by Chong-Gui Chen, Ping Xu, Ji-Pin Li, Xiao-Li Bi, Qun-Mei Yao, Cheng-Min Yu, Yan Tang, Cheng-Ye Sun, Zhi-Jun Wu, Jia-Ju Zhong and Hai-Ying Wu

Toxins 2025, 17(12), 576; https://doi.org/10.3390/toxins17120576 - 29 Nov 2025

Abstract

Amanita exitialis is a lethal mushroom species found in southern China. Its amatoxins can cause acute liver injury with a high case-fatality rate. However, reports combining toxin detection in clinical specimens with autopsy pathology remain limited. We conducted a retrospective analysis of A. [...] Read more.

Amanita exitialis is a lethal mushroom species found in southern China. Its amatoxins can cause acute liver injury with a high case-fatality rate. However, reports combining toxin detection in clinical specimens with autopsy pathology remain limited. We conducted a retrospective analysis of A. exitialis poisoning events treated at Chuxiong Yi Autonomous Prefecture People’s Hospital from 2019 to 2024. Toxins were measured in collected mushrooms, patient blood, and urine. Clinical data included demographics, complications, laboratory parameters, and autopsy findings. Associations between a time-weighted urinary amatoxin exposure metric and laboratory indices were assessed. Ten poisoning incidents involving 27 individuals were identified, including five deaths. We collected 10 mushroom samples, 120 urine samples, and 108 blood samples. α-amanitin, β-amanitin, phallacidin, and phallisacin were detected in mushrooms and urine. The detection rates of α-AMA, β-AMA, PCD, and PSC in urine samples were 31.67%, 5.00%, 38.33%, and 49.17%, respectively. Only three blood samples tested positive for α-AMA. The time-weighted urinary amatoxin exposure metric was positively correlated with total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR). Early symptoms included nausea, vomiting, diarrhea, abdominal pain, and distention; later findings involved injury to the liver, kidneys, intestines, heart, and lungs. On the fourth day following ingestion, there was a marked increase in bilirubin levels and a concurrent decrease in liver enzymes, indicating severe damage to the hepatocytes. Platelet count, white blood cell count, hemoglobin, and red blood cell count decreased over time. Autopsies demonstrated hepatic, renal, and myocardial injury, gastrointestinal mucosal exfoliation, and multiorgan hemorrhage. In summary, A. exitialis poisoning is primarily characterized by liver damage, accompanied by injuries to the kidneys, myocardium, and intestines, as well as multiorgan hemorrhaging, which may lead to blood toxicity. The detection rate of toxins in urine samples is relatively high, and early urine toxin testing can help clarify the diagnosis and guide treatment. Full article

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14 pages, 4099 KB

Open AccessArticle

Structure of Ribosome-Inactivating Protein from Mirabilis jalapa and Its L12-Stalk-Dependent Inhibition of Escherichia coli Ribosome

by Nanami Nishida, Yuki Ninomiya, Toru Yoshida, Takehito Tanzawa, Yasushi Maki, Hideji Yoshida, Hideaki Tsuge and Noriyuki Habuka

Toxins 2025, 17(12), 575; https://doi.org/10.3390/toxins17120575 - 28 Nov 2025

Abstract

Mirabilis antiviral protein (MAP) is the type I ribosome-inactivating protein (RIP), which consists of an RNA N-glycosylase domain with no carbohydrate-binding domain. Unlike many RIPs, such as ricin or trichosanthin, which inactivate eukaryotic ribosomes, MAP also inactivates the E. coli ribosome by [...] Read more.

Mirabilis antiviral protein (MAP) is the type I ribosome-inactivating protein (RIP), which consists of an RNA N-glycosylase domain with no carbohydrate-binding domain. Unlike many RIPs, such as ricin or trichosanthin, which inactivate eukaryotic ribosomes, MAP also inactivates the E. coli ribosome by cleaving the N-glycosidic bond at A2660 of 23S ribosomal RNA. The structure of the wild-type MAP has not been revealed yet. Here, we expressed, purified, and crystallized the plural recombinant MAPs, including both E168Q and R171Q mutations (MAP-EQRQ) in E. coli, and determined the crystal structure of MAP-EQRQ at 2.1 Å resolution. According to the predicted structure with RNA (sarcin-ricin loop) and the mutant protein’s activities using quantitative RT-PCR, we showed that residue R171 at the active site of MAP is a key residue to form the stable complex with target adenine. Furthermore, we showed that MAP bound the C-terminal domains of eukaryotic P2-stalk as well as E. coli L12-stalk. Full article

(This article belongs to the Section Plant Toxins)

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19 pages, 1624 KB

Open AccessArticle

Mycotoxin-Induced Oxidative Stress and Its Impact on Human Folliculogenesis: Examining the Link to Reproductive Health

by Zsuzsanna Szőke, Eszter Ruff, Patrik Plank, Zsófia Molnár, Lili Hruby, Apolka Szentirmay, Márkó Unicsovics, Bernadett Csókay, Katalin Varga, Tímea Buzder, Miklós Sipos, Katalin Sára-Popovics, Dóra Holéci, Katalin Posta and Levente Sára

Toxins 2025, 17(12), 574; https://doi.org/10.3390/toxins17120574 - 28 Nov 2025

Abstract

Climate change has contributed to increased mycotoxin contamination in food systems, posing a growing threat to human health, including reproductive health. Our study aimed to investigate how mycotoxins entering the follicular fluid affect oxidative stress processes. We analyzed 88 follicular fluid samples from [...] Read more.

Climate change has contributed to increased mycotoxin contamination in food systems, posing a growing threat to human health, including reproductive health. Our study aimed to investigate how mycotoxins entering the follicular fluid affect oxidative stress processes. We analyzed 88 follicular fluid samples from infertile patients for common mycotoxins, including deoxynivalenol (DON), zearalenone (ZEN), its main metabolite alpha-zearalenol (aZOL), and aflatoxin M1 (AfM1), and examined their relationship with oxidative stress markers (MDA, SOD, GPx, CAT, and TAOC) and hormones (cortisol, estradiol, and anti-Müllerian hormone). Higher mycotoxin levels were associated with increased oxidative stress, particularly elevated MDA levels, and disrupted antioxidant enzyme activity. Notably, DON showed a positive correlation with SOD and estradiol levels, indicating a compensatory antioxidant response, while AfM1 served as a negative predictor. The metabolite aZOL was strongly linked to cortisol, with effects influenced by estradiol levels, implying endocrine-disrupting activity. Importantly, the interaction between DON and AMH appeared to impact dominant follicle development, suggesting a potential mechanism by which environmental toxins impair fertility without directly reducing oocyte or embryo counts. These results highlight the complex, dose-dependent effects of mycotoxins on oxidative and hormonal balances within the follicular environment, with implications for oocyte quality and reproductive success. Better understanding these mechanisms could help develop early diagnostic markers and targeted interventions to improve fertility outcomes in women exposed to changing environmental conditions. Full article

(This article belongs to the Special Issue The Effects of Mycotoxins on Reproductive Physiology and Other Health in Animals and Humans)

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Graphical abstract

12 pages, 254 KB

Open AccessCommunication

Artificial Intelligence in Managing Spasticity with Botulinum Toxin Type A—Insights from an Exploratory Pilot Investigation: The AIMS Study

by Mirko Filippetti, Rita Di Censo, Lyria Arcari, Maria Concetta Schiavariello, Marco Battaglia, Salvatore Facciorusso, Stefania Spina, Laura Antonucci, Andrea Santamato, Alessio Baricich, Nicola Smania and Alessandro Picelli

Toxins 2025, 17(12), 573; https://doi.org/10.3390/toxins17120573 - 27 Nov 2025

Abstract

This study aimed to explore the potential role of artificial intelligence in optimizing botulinum toxin type A treatment for spasticity and to evaluate its alignment with expert clinical decisions. A comparative analysis was conducted using thirty hypothetical clinical cases involving individuals with spasticity [...] Read more.

This study aimed to explore the potential role of artificial intelligence in optimizing botulinum toxin type A treatment for spasticity and to evaluate its alignment with expert clinical decisions. A comparative analysis was conducted using thirty hypothetical clinical cases involving individuals with spasticity resulting from various neurological conditions. Five rehabilitation physicians, each with more than five years of experience, participated in the study. An artificial intelligence model trained on scientific literature and clinical guidelines generated treatment recommendations, including target muscles and dosages, which were compared with those proposed independently by the physicians. The primary outcome was the level of agreement in muscle selection and dosage. The model demonstrated consistency and adherence to guidelines but showed limited adaptability in complex presentations, such as an adducted thigh and equinovarus foot. It generally recommended lower dosages and differed significantly from physicians in both muscle selection and treatment strategies. Artificial intelligence shows promise as a clinical support tool in spasticity management, offering standardized and reproducible recommendations. However, its limited capacity to interpret clinical subtleties currently restricts its practical application. Future models should integrate multimodal clinical data and real-time clinician feedback to better emulate expert decision-making processes. Full article

(This article belongs to the Special Issue Botulinum Toxin in Spasticity Management—from Established Practices to Emerging Frontiers)

14 pages, 1561 KB

Open AccessSystematic Review

Impact of Protein Concentrate Production on Mycotoxin Mitigation: A Systematic Review

by Caroline Senna, Marianna Cruz, Larine Kupski and Eliana Badiale-Furlong

Toxins 2025, 17(12), 572; https://doi.org/10.3390/toxins17120572 - 26 Nov 2025

Abstract

The plant-based protein industry has explored new material sources, such as agro-industrial by-products and extraction techniques based on chemical properties assisted by ultrasound, high pressure and other tools to improve the yield and functionality of protein concentrates. However, promising by-products from vegetable processing [...] Read more.

The plant-based protein industry has explored new material sources, such as agro-industrial by-products and extraction techniques based on chemical properties assisted by ultrasound, high pressure and other tools to improve the yield and functionality of protein concentrates. However, promising by-products from vegetable processing are susceptible to incidental and natural contaminants, mainly mycotoxins. Adopting sustainable strategies and understanding how they affect mycotoxin fate during processing remains a challenge to ensure food security. In this study, a systematic literature review and bibliometric analysis were conducted to identify reliable pre-treatments and treatments for producing protein concentrates and evaluate the efficiency of technologies to mitigate mycotoxin bioaccessibility. Searching for research in Scopus, Web of Science and ScienceDirect (2010–2024) identified 3688 scientific articles on techniques to improve the yield and functionality of recovered proteins, but only three studies addressed mycotoxin fate. Aflatoxin, the most prevalent mycotoxin in raw materials, was the only one considered, highlighting that chemical and enzymatic treatments may help mitigate mycotoxicological risks in protein concentrates. Results indicate a gap in plant-based food security regarding mycotoxin contamination, which must be addressed through mitigation strategies aligned with efficient processes to ensure sustainable and safe plant protein-based foods. Full article

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

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18 pages, 5407 KB

Open AccessArticle

Differential Effects of Marimastat and Prinomastat on the Metalloprotease Activity of Various Snake Venoms

by Mahtab Khatibi, José R. Almeida, Soheil Gilabadi, David Ramírez, Paulina Valenzuela-Hormazábal, Ketan Patel and Sakthivel Vaiyapuri

Toxins 2025, 17(12), 571; https://doi.org/10.3390/toxins17120571 - 26 Nov 2025

Abstract

Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary [...] Read more.

Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary component of venoms, are mainly accountable for haemotoxic and myotoxic effects. Although predominantly found in viper venoms, these enzymes are also present in varying levels in elapid snake venoms. Marimastat and prinomastat are matrix metalloprotease inhibitors initially developed as cancer therapies. Recently, extensive research has focused on these inhibitors to neutralise venom metalloproteases. However, their effects on different viper and elapid snake venoms remain unclear. Here, we report the sensitivity of seven elapid venoms (specifically, cobras) and 12 viper venoms to marimastat and prinomastat, utilising selective in vitro experiments and molecular docking analyses performed using representative metalloprotease (VAP2, a viper metalloprotease from the venom of Crotalus atrox and an elapid metalloprotease from the venom of Naja atra) structures. Both compounds inhibited the metalloprotease, fibrinogenolytic, and caseinolytic activities of most viper venoms. While prinomastat displayed prominent inhibitory effects on cobra venoms in these assays, marimastat demonstrated limited inhibitory effects on these venoms. These findings illustrate the role of matrix metalloprotease inhibitors in modulating metalloprotease activities across a range of viper and cobra venoms. Collectively, this study establishes the differential effects of marimastat and prinomastat on various levels of metalloproteases present in viper and elapid venoms. This will enhance understanding of the abundance of metalloproteases in snake venoms and their sensitivity to different matrix metalloprotease inhibitors. Full article

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

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18 pages, 2187 KB

Open AccessArticle

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

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

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13 pages, 1185 KB

Open AccessSystematic Review

Botulinum Toxin Combined with Robot-Assisted Therapy for Post-Stroke Spasticity: A Systematic Review

by Salvatore Facciorusso, Stefania Spina, Mirko Filippetti, Rajiv Reebye, Gerard E. Francisco and Andrea Santamato

Toxins 2025, 17(12), 569; https://doi.org/10.3390/toxins17120569 - 25 Nov 2025

Abstract

(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical [...] Read more.

(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively. (3) Results: Seven trials (n = 229) were included. Across all studies, toxin treatment reduced spasticity within groups, whereas additional spasticity reduction with RAT versus conventional rehabilitation was inconsistent. In contrast, several lower-limb trials reported greater improvements in walking capacity and balance when RAT was added, while upper-limb trials showed comparable motor recovery across treatment arms with occasional advantages in strength and movement quality. A pilot four-arm study suggested that starting RAT around four weeks after injection may maximize upper-limb motor gains. (4) Conclusions: The combination of BoNT-A with RAT appears safe and is particularly promising for gait rehabilitation, but further research is needed to define optimal timing and protocols. Full article

(This article belongs to the Section Bacterial Toxins)

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16 pages, 1365 KB

Open AccessArticle

Dose-Dependent but Non-Interactive Effects of Ochratoxin A and Selenomethionine on Hepatic Lipid Metabolism and Oxidative Stress in Broiler Chickens

by Szabina Kulcsár, Krisztián Balogh, Erika Zándoki, Edward Agyarko, Omeralfaroug Ali, Benjámin Kövesi, Ágnes Freiler-Nagy, András Szabó and Miklós Mézes

Toxins 2025, 17(12), 568; https://doi.org/10.3390/toxins17120568 - 25 Nov 2025

Abstract

This study examined the effects of ochratoxin A (OTA) exposure and graded dietary selenium (Se) supplementation on fatty acid (FA) composition and oxidative stress markers in the liver of broiler chickens. OTA is known to generate oxidative stress, promote lipid peroxidation, and affect [...] Read more.

This study examined the effects of ochratoxin A (OTA) exposure and graded dietary selenium (Se) supplementation on fatty acid (FA) composition and oxidative stress markers in the liver of broiler chickens. OTA is known to generate oxidative stress, promote lipid peroxidation, and affect the antioxidant system. Se, an essential trace element with antioxidant properties, may help counteract OTA-induced toxicity. In this short-term (5-day) in vivo feeding experiment, 21-day-old broiler chickens were divided into six groups, each with six birds: Control (diet free from Se), 0.3 mg/kg Se, 0.5 mg/kg Se, 2 mg/kg OTA, 2 mg/kg OTA + 0.3 mg/kg Se, 2 mg/kg OTA + 0.5 mg/kg Se. Our findings show that supplementing 0.3 mg/kg (p < 0.01) or 0.5 mg/kg Se (p < 0.001) in OTA-exposed birds significantly reduced the early oxidative stress markers (conjugated dienes and trienes) and significantly increased (0.3 mg/kg p < 0.01; 0.5 mg/kg p < 0.001) glutathione levels, indicating enhanced glutathione-dependent antioxidant protection. The treatments also significantly altered the ratio of monounsaturated and n6/n3 polyunsaturated FAs. OTA with 0.3 mg/kg Se supplementation significantly (p ˂ 0.05) reduced total unsaturation and FA average chain length. At a dose of 0.3 mg/kg, the interaction of Se and OTA altered the PUFA composition, while 0.5 mg/kg Se supplementation enhanced antioxidant defense and reduced lipid peroxidation. These results highlight the dual but separate role of Se, where inadequate doses may enhance OTA toxicity, while optimal supplementation may have a protective effect on hepatic lipid homeostasis. These findings can be used in the future progress of the mitigation strategy against OTA exposure in poultry nutrition. Full article

(This article belongs to the Special Issue Mycotoxins—Biomonitoring and Exposure)

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17 pages, 2236 KB

Open AccessReview

Updates on the Proposed Botulinum Toxin A Mechanisms of Action in Orofacial Pain: A Review of Animal Studies

by Jaime Fabillar Jr, Yumiko Yamamoto, Kazuyuki Koike, Daisuke Ikutame and Yoshizo Matsuka

Toxins 2025, 17(12), 567; https://doi.org/10.3390/toxins17120567 - 23 Nov 2025

Abstract

Experimental animal models of orofacial pain have been instrumental in elucidating biological pathways underlying the antinociceptive effect of botulinum neurotoxin type A (BoNT/A). Although several mechanisms have been proposed to explain how BoNT/A relieves pain, the precise modes of action, particularly in the [...] Read more.

Experimental animal models of orofacial pain have been instrumental in elucidating biological pathways underlying the antinociceptive effect of botulinum neurotoxin type A (BoNT/A). Although several mechanisms have been proposed to explain how BoNT/A relieves pain, the precise modes of action, particularly in the oral and maxillofacial areas, remain elusive. The purpose of this review was to synthesize and assess the latest proposed mechanisms of action through which BoNT/A attenuates orofacial pain in established animal models. A comprehensive search was conducted using the terms “botulinum neurotoxin,” “mechanism,” and “orofacial pain” or “trigeminal neuralgia.” Only animal studies involving the establishment of an orofacial pain model were selected. Additional relevant studies were identified through manual screening of cited references. Over the past five years, several animal pain models have been established to decipher the mechanisms underlying the BoNT/A-mediated antinociception in orofacial pain. The proposed mechanisms include retrograde transport, neuronal excitability regulation, neuropeptide inhibition, inflammatory modulation, and opioid system stimulation in both the peripheral and central nervous systems. Despite the insubstantial number of investigations and findings, BoNT/A exhibits multidimensional modulation of nociceptive responses and, therefore, remains a promising therapeutic agent for managing orofacial pain conditions, with animal studies consistently providing insights into the mechanism of its antinociceptive action. Full article

(This article belongs to the Special Issue Botulinum Toxin Therapy for Diseases in the Oral and Maxillofacial Regions)

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