Toxins

21 pages, 1503 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

10 pages, 826 KB

Open AccessReview

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

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

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

Abstract

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

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

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

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14 pages, 2042 KB

Open AccessArticle

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

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

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

Abstract

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

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

(This article belongs to the Section Mycotoxins)

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14 pages, 1385 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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19 pages, 1891 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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27 pages, 1328 KB

Open AccessReview

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

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

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

Abstract

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

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

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

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35 pages, 2573 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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20 pages, 4381 KB

Open AccessArticle

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

Abstract

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

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

(This article belongs to the Section Plant Toxins)

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19 pages, 6901 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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16 pages, 1454 KB

Open AccessReview

Prenatal Aflatoxin B₁ Exposure: A Review of Pathogenesis and Impact on Fetal Skeletal Development and Ossification

by Giovana Perez Montenegro, João Victor Batista da Silva, Sher Ali, Sana Ullah, Lucas Gabriel Dionisio Freire, Carlos Augusto Fernandes de Oliveira and Leandra Náira Zambelli Ramalho

Toxins 2026, 18(3), 122; https://doi.org/10.3390/toxins18030122 - 1 Mar 2026

Abstract

Prenatal exposure to aflatoxin B₁ (AFB₁) poses a significant risk to fetal development and is associated with reduced birth weight in humans. Experimental studies consistently show that AFB₁ induces fetal abnormalities, with skeletal malformations and ossification defects being the [...] Read more.

Prenatal exposure to aflatoxin B₁ (AFB₁) poses a significant risk to fetal development and is associated with reduced birth weight in humans. Experimental studies consistently show that AFB₁ induces fetal abnormalities, with skeletal malformations and ossification defects being the most common. However, the specific impact of AFB₁ on fetal osteogenesis remains unclear. Given this knowledge gap, this study aimed to review the existing literature concerning the pathogenesis of AFB₁ and its potential influence on bone development. The primary mechanisms implicated in AFB₁’s impact on bone include dysfunction in vitamin D and calcium metabolism, alterations in parathyroid hormone production and function, induction of inflammatory responses, and oxidative stress. Collectively, these mechanisms have the potential to impair osteoblast and osteoclast function and, consequently, compromise ossification. Based on these findings, studies should explore and elucidate the effects of AFB₁. Elucidating these mechanisms is crucial for mitigating the deleterious impacts of AFB₁ on fetal skeletal development. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 684 KB

Open AccessArticle

Should Every Symptomatic Patient with Mushroom Poisoning Be Monitored in the Intensive Care Unit?—A Retrospective Observational Study

by Duygu Kayar Calili, Demet Bolukbasi, Serife Gokbulut Bektas and Seval Izdes

Toxins 2026, 18(3), 121; https://doi.org/10.3390/toxins18030121 - 27 Feb 2026

Abstract

A rapid method for the early diagnosis of fatal mushroom poisoning is not available. Therefore, in our region, symptomatic patients are admitted to intensive care units (ICUs) for close monitoring and treatment. This retrospective study evaluated ICU patients with mushroom poisoning to assess [...] Read more.

A rapid method for the early diagnosis of fatal mushroom poisoning is not available. Therefore, in our region, symptomatic patients are admitted to intensive care units (ICUs) for close monitoring and treatment. This retrospective study evaluated ICU patients with mushroom poisoning to assess clinical and laboratory trends, treatment characteristics, and outcomes and determine the necessity of level 3 ICU admission. Fifty-four patients were included in this study, and the duration of ICU stay was 5.5 ± 3.9 days. Acute liver failure (ALF) was observed in 7% of patients. Eight patients (14.8%) only received symptomatic treatment, whereas two patients underwent liver transplantation, and one of whom died. The overall mortality rate was 5.6%. A significant decrease was observed in alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, creatinine, lactate dehydrogenase, international normalized ratio, and prothrombin time values on the day of discharge from the ICU compared with the day of admission (p < 0.05). Mushroom poisoning cases thought to be at risk of developing ALF can be transferred to transplant centers early to avoid wasting time. However, to ensure that ICU resources are used effectively, we believe that monitoring and treatment in a level 3 ICU should be reserved for patients progressing to liver failure rather than all symptomatic patients. Full article

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24 pages, 3546 KB

Open AccessReview

Stinging Salvation: Harnessing Scorpion Venom Peptides for Revolutionary Pain Relief

by Reza Mosaddeghi-Heris, Mojtaba Pandeh, Leila Ghorbi, Niloofar Taheri, Maedeh Shariat Zadeh, Kimia Bagheri and Paolo Martelletti

Toxins 2026, 18(3), 120; https://doi.org/10.3390/toxins18030120 - 26 Feb 2026

Abstract

Peptides from scorpion venom, mainly in species such as Olivierus martensii (formerly Olivierus martensii Karsch, often designated BMK) (BmK) and Tityus serrulatus from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and [...] Read more.

Peptides from scorpion venom, mainly in species such as Olivierus martensii (formerly Olivierus martensii Karsch, often designated BMK) (BmK) and Tityus serrulatus from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic–antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward. Full article

(This article belongs to the Special Issue Natural Toxin–Based Therapeutics from Animals, Plants, and Marine Organisms: Clinical Evidence and Drug Development Perspectives)

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18 pages, 5515 KB

Open AccessArticle

Interaction Between Bacillus subtilis and Trichoderma citrinoviride: Synergistic Inhibition of Aspergillus flavus Growth and Aflatoxin B₁ Production

by Guidong Li, Xianfeng Ren, Changying Guo, Baocheng Xu and Xinjing Dou

Toxins 2026, 18(3), 119; https://doi.org/10.3390/toxins18030119 - 26 Feb 2026

Abstract

Aspergillus flavus (A. flavus) and its potent carcinogenic metabolite, aflatoxin B₁ (AFB₁), pose severe threats to food safety and public health. This study explored the biocontrol potential of Bacillus and Trichoderma strains and their interactions. Through dual-culture assays, [...] Read more.

Aspergillus flavus (A. flavus) and its potent carcinogenic metabolite, aflatoxin B₁ (AFB₁), pose severe threats to food safety and public health. This study explored the biocontrol potential of Bacillus and Trichoderma strains and their interactions. Through dual-culture assays, Bacillus subtilis Bs92 and Trichoderma citrinoviride GC-T20 were identified as the most inhibitory among 15 isolates each, with their culture filtrates inhibiting A. flavus growth by 48.61% and 74%, respectively. Investigation of the inter-genus interaction revealed strong mutual inhibition: Trichoderma filtrate suppressed Bacillus growth by >90%, while Bacillus filtrate inhibited Trichoderma mycelial growth by 40–90%. To circumvent this antagonism and enhance efficacy, the culture filtrates of Bs92 and GC-T20 were combined. The combined treatment demonstrated superior performance, inhibiting A. flavus radial growth by 69.59% and AFB₁ production by 98.69%, significantly outperforming individual applications. These results indicate that the antifungal and anti-aflatoxigenic metabolites produced by Bs92 and GC-T20 are complementary. Their combined use presents a promising synergistic strategy for the biocontrol of A. flavus and AFB₁ contamination in food and agricultural products. Full article

(This article belongs to the Special Issue Advanced Detoxification Technologies for Mycotoxins)

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50 pages, 19473 KB

Open AccessArticle

In-Depth Multi-Assembler Venom-Gland Transcriptomics of Three Medically Important Colombian Snakes Highlights Diversity of Accessory, Low-Abundance Protein Families

by Mónica Saldarriaga-Córdoba, Claudia Clavero-León, Paola Rey-Suárez, Vitelbina Núñez-Rangel and Sebastián Estrada-Gómez

Toxins 2026, 18(3), 118; https://doi.org/10.3390/toxins18030118 - 25 Feb 2026

Abstract

Typically, most omics analysis (proteomic and transcriptomic) of snakes are focused on the dominant enzymatic proteins used for evolutionary analysis or those engaged in envenoming symptoms. This study presents a comprehensive multi-assembler transcriptomic analysis focused on the non-dominant and enzymatic or non-enzymatic putative [...] Read more.

Typically, most omics analysis (proteomic and transcriptomic) of snakes are focused on the dominant enzymatic proteins used for evolutionary analysis or those engaged in envenoming symptoms. This study presents a comprehensive multi-assembler transcriptomic analysis focused on the non-dominant and enzymatic or non-enzymatic putative proteins of the venom glands of three medically significant Colombian snake species. Together, these results highlight how continued improvements in modern omics workflows, coupled with extensive manual curation, enable more complete putative protein variants discovery when multiple assemblers are integrated. Here, we reconstructed the toxinomes of the viperids Bothrops asper and Crotalus durissus cumanensis, and the elapid Micrurus mipartitus, by comparing four assemblers (Trinity, SPAdes, SOAPdenovo-Trans k = 31 and k = 97) and integrating them into a non-redundant meta-assembly. Protein-candidate alignments were extensively inspected, and validation of conserved domains and functional motifs are discussed. The curated toxinomes revealed substantial diversity across major and accessory families, and assembler choice strongly affected transcript variant recovery. Together, these results provide a more comprehensive view of venom-gland transcriptome analysis and diversity, expanding the set of candidate venom components for future functional and proteomic validation, with potential implications for venom composition studies and antivenom development. Full article

(This article belongs to the Section Animal Venoms)

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17 pages, 925 KB

Open AccessReview

The Dark Side of Grasslands: Endophyte Toxicosis in Horses—Exposure Risks, Health Consequences, and Management

by Qendrim Zebeli, Lena Lindner and Barbara U. Metzler-Zebeli

Toxins 2026, 18(3), 117; https://doi.org/10.3390/toxins18030117 - 24 Feb 2026

Abstract

Grasslands are the cornerstone of horse feeding, used for grazing and to produce roughages and their products. However, improper grassland management hides several threats for equine health. In this context, grasslands contaminated with toxin-producing endophytes are considered an increasing threat for horses in [...] Read more.

Grasslands are the cornerstone of horse feeding, used for grazing and to produce roughages and their products. However, improper grassland management hides several threats for equine health. In this context, grasslands contaminated with toxin-producing endophytes are considered an increasing threat for horses in many parts of the world. Endophytes are fungi that may grow in a mutualistic relationship in a range of grasses, including fescue grass and perennial ryegrass, two foliage species commonly found in European and American meadows and pastures. The endophytes produce alkaloids that are highly toxic to insects and animals, including horses. Among the four types of endophyte alkaloids, namely peramine, loline, indole diterpene, and ergot alkaloids, the latter two are known to be (neuro)toxic to horses. Recent research indicates that increasing concentrations and co-occurrence of ergot alkaloids and indole diterpene in horse pastures and meadows, especially during hot and arid summer months, increase the risk of endophyte toxicosis in horses. The main aim of this review article is to summarize the most recent knowledge on endophytic alkaloids of grasslands and products thereof, and the resulting endophyte toxicosis in horses, focusing mainly on the exposure risks, symptoms and management strategies. Full article

(This article belongs to the Collection Editorial Board Members’ Collection Series: Fungal Metabolites: From Toxins to Therapeutics)

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12 pages, 1524 KB

Open AccessReview

From Gut to Systemic Circulation: Molecular Strategies of Botulinum Neurotoxin Complexes

by Juliette Mondy and Emmanuel Lemichez

Toxins 2026, 18(3), 116; https://doi.org/10.3390/toxins18030116 - 24 Feb 2026

Abstract

Botulinum neurotoxins (BoNTs), among the most potent biological toxins, rely on co-produced nontoxic proteins to survive harsh gastrointestinal conditions and achieve efficient systemic dissemination after oral exposure. Recent structural and functional studies have revealed how BoNTs bind to the nontoxic non-hemagglutinin (NTNH) factors [...] Read more.

Botulinum neurotoxins (BoNTs), among the most potent biological toxins, rely on co-produced nontoxic proteins to survive harsh gastrointestinal conditions and achieve efficient systemic dissemination after oral exposure. Recent structural and functional studies have revealed how BoNTs bind to the nontoxic non-hemagglutinin (NTNH) factors to engage in interactions with either OrfXs/P47 or hemagglutinins (HAs) components for systemic dissemination. This review synthesizes recent findings that elucidate the molecular basis of NTNH-specific anchoring to the HA70 triskelion-like element or to the host protease-activated form of OrfX2, thereby highlighting divergent pathways that enhance oral toxicity. We also discuss current perspectives on the molecular mechanisms through which BoNTs, in cooperation with associated nontoxic proteins, are absorbed from the intestine. Full article

(This article belongs to the Special Issue Toxin–Host Interaction of Clostridium Toxins: 2nd Edition)

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19 pages, 307 KB

Open AccessArticle

From Muscular Hypertonus to Equilibrium: A Conceptual Framework for Aesthetic Neuromodulation Based on the Index of Muscular Equilibrium (IME)

by Andrea Felice Armenti

Toxins 2026, 18(2), 115; https://doi.org/10.3390/toxins18020115 - 23 Feb 2026

Abstract

Facial neuromodulation with botulinum toxin has traditionally been approached from the perspective of wrinkle correction. However, facial expressions primarily arise from coordinated muscular interactions that convey both positive and negative emotional valence. A conceptual framework focused on muscular equilibrium rather than wrinkle severity [...] Read more.

Facial neuromodulation with botulinum toxin has traditionally been approached from the perspective of wrinkle correction. However, facial expressions primarily arise from coordinated muscular interactions that convey both positive and negative emotional valence. A conceptual framework focused on muscular equilibrium rather than wrinkle severity may therefore offer a more comprehensive, reproducible, and clinically meaningful approach. In this article, we propose the Index of Muscular Equilibrium (IME) Framework, a conceptual model for aesthetic neuromodulation that integrates functional muscle mapping, validated severity scales, and a composite IME score to support personalized treatment planning and outcome assessment. The framework is derived from a narrative review of PubMed-indexed literature on facial muscle activity, emotional expression, and validated clinical assessment tools. It combines a Valence Map to classify positive- and negative-valence muscle groups, a standardized evaluation of static and dynamic hypertonus, a conceptual Plan Score to guide selective neuromodulation, and a feedback-based longitudinal workflow (the IME Loop). Together, these components enable structured assessment of muscular imbalance, integration of established wrinkle severity scales, and translation into individualized, function-oriented treatment strategies, with intended benefits including improved objectivity, reproducibility, and patient communication. By reframing treatment success from the duration of muscle blockade to the duration of expressive harmony, the IME Framework introduces testable constructs for future validation and offers a functional perspective on facial neuromodulation aligned with contemporary affective science. Full article

(This article belongs to the Special Issue Study on Botulinum Toxin in Facial Diseases and Aesthetics)

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15 pages, 1434 KB

Open AccessArticle

New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A₂ from Bothrops diporus Venom

by Daniela J. Sasovsky, Ana K. Oliveira, Dilza Trevisan Silva, Gonzalo A. Ojeda, Cristopher Almarza, Bruno Lomonte, Jay W. Fox, Félix A. Urra and Soledad Bustillo

Toxins 2026, 18(2), 114; https://doi.org/10.3390/toxins18020114 - 23 Feb 2026

Abstract

Phospholipases A₂ (PLA₂s) are key mediators of the cytotoxic and inflammatory activities of snake venoms. While PLA₂ isoforms from Bothrops diporus venom have been characterized and shown to possess antimetastatic and antiangiogenic properties, their impact on mitochondrial bioenergetics and [...] Read more.

Phospholipases A₂ (PLA₂s) are key mediators of the cytotoxic and inflammatory activities of snake venoms. While PLA₂ isoforms from Bothrops diporus venom have been characterized and shown to possess antimetastatic and antiangiogenic properties, their impact on mitochondrial bioenergetics and immune modulation has not yet been investigated. In this study, we examined the bioenergetic and immunomodulatory effects of B. diporus PLA₂s using integrated biochemical, metabolic, and multiplex cytokine analyses. In MDA-MB-231 breast cancer cells, pooled PLA₂s induced a dose-dependent decrease in MTT-reducing activity, increased mitochondrial ROS, caused Δψm hyperpolarization, and decreased NADH autofluorescence, collectively indicating sustained mitochondrial stress. Real-time impedance measurements further revealed a marked inhibition of cell proliferation. In human PBMCs, pooled PLA₂s elicited a dynamic cytokine program, inducing early cytotoxic (Granzyme B) and chemotactic (CCL2, CCL3, CCL4) mediators, followed by late pro-inflammatory and regulatory factors such as IL-6, TNF-β, IL-10 and IL-15. Analysis of a single purified PLA₂ isoform (Fraction 6) confirmed activation of the canonical IL-6/TNF-α/IL-1β axis but uniquely induced IL-10 and CCL20, revealing isoform-specific immunomodulatory properties. Altogether, these findings provide the first integrated characterization of mitochondrial and immune perturbations induced by B. diporus PLA₂s, expanding their recognized biological scope and underscoring their potential as molecular templates for novel pharmacological strategies targeting mitochondrial vulnerabilities or modulating the tumor immune microenvironment. Full article

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

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17 pages, 834 KB

Open AccessArticle

Role of Serum IL-33 in Bothrops Snakebite Victims: Linking Inflammation and Endothelial Dysfunction

by Nicole Coelho Lopes, Ranieri Sales de Souza Santos, Gdayllon Cavalcante Meneses, Leticia Machado de Araújo, Bruna Viana Barroso Martins, Katarina Maria dos Reis Araújo, Marina Coelho Feitosa, Yury Pifano Varela, Fathima Shihana, Sandra Mara Brasileiro Mota, Geraldo Bezerra da Silva Junior, Elizabeth De Francesco Daher, Polianna Lemos Moura Moreira Albuquerque and Alice Maria Costa Martins

Toxins 2026, 18(2), 113; https://doi.org/10.3390/toxins18020113 - 23 Feb 2026

Abstract

Bothrops snakebites pose a significant public health challenge in low- and middle-income regions, often resulting in inflammation, coagulopathy, and renal complications even after antivenom therapy. This study investigated the role of interleukin-33 (IL-33) and endothelial biomarkers in patients with Bothrops envenoming to better [...] Read more.

Bothrops snakebites pose a significant public health challenge in low- and middle-income regions, often resulting in inflammation, coagulopathy, and renal complications even after antivenom therapy. This study investigated the role of interleukin-33 (IL-33) and endothelial biomarkers in patients with Bothrops envenoming to better understand the mechanisms associated with bleeding and kidney dysfunction. In a prospective cohort of 31 patients from Northeast Brazil, serum levels of IL-33, von Willebrand factor A2 (vWF-A2), angiopoietin-1, angiopoietin-2, syndecan-1, and VCAM-1 were measured at admission and at 10 and 20 h after antivenom administration. Fourteen patients (45%) presented with bleeding at baseline. Traditional clinical and laboratory parameters did not differ between the bleeding and non-bleeding groups on admission; however, IL-33 levels were significantly higher in patients with bleeding. Elevated IL-33 on admission correlated positively with vWF-A2 and estimated glomerular filtration rate, and negatively with angiopoietin-1, suggesting links between inflammation, endothelial dysfunction, and early renal involvement. IL-33 showed a good performance in bleeding patients (AUC = 0.739; IC 95% 0.562–0.917). These findings identified the link between IL-33, early hemorrhage, endothelial dysfunction, and renal involvement in acute Bothrops envenoming. After antivenom therapy, IL-33 levels presented dynamic changes in all patients and require further studies. Full article

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