Toxins

17 pages, 2725 KiB

Open AccessReview

Botulinum Toxin for Bruxism: An Overview

by Manuella Salm Coelho, Júlia Meller Dias de Oliveira, Helena Polmann, Patrícia Pauletto, Cristine Miron Stefani, Lara Catarine De Luca Maciel and Graziela De Luca Canto

Toxins 2025, 17(5), 249; https://doi.org/10.3390/toxins17050249 - 16 May 2025

Abstract

This overview aimed at assessing botulinum toxin type A (BoNT-A)’s effectiveness in managing bruxism compared to a placebo, the absence of treatment, or other interventions in adults. Only systematic reviews (SRs), with or without a meta-analysis, were included. A comprehensive literature search was [...] Read more.

This overview aimed at assessing botulinum toxin type A (BoNT-A)’s effectiveness in managing bruxism compared to a placebo, the absence of treatment, or other interventions in adults. Only systematic reviews (SRs), with or without a meta-analysis, were included. A comprehensive literature search was conducted on 16 June 2024, encompassing seven databases and grey literature sources. Experts and reference lists of the included SRs were also consulted. Study selection was conducted in two phases by two independent authors. Methodological quality was evaluated using AMSTAR-2. Overlap was assessed using the corrected covered area. The 14 included SRs addressed several outcomes. In most studies, BoNT-A showed effectiveness in reducing pain (n = 10), the frequency of bruxism events (n = 7), and the maximum bite force (n = 5). None of the SRs effectively evaluated BoNT-A’s impact on functional movements. All of the included SRs scored “critically low” and “low” confidence rates in AMSTAR-2. Only one SR attempted to assess the certainty of the evidence, although unsuccessfully. The overlap across included SRs was rated as “high”, with a corrected covered area of 10.11%. The current systematic reviews on BoNT-A for bruxism lack methodological quality, limiting the reliability of their findings. Despite evidence indicating a potential reduction in pain, bruxism events, and the maximum bite force, methodological limitations prevent definitive conclusions from being drawn. High-quality research with standardized methodologies is essential to establish BoNT-A’s efficacy and support evidence-based clinical practice. Full article

(This article belongs to the Section Bacterial Toxins)

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19 pages, 3329 KiB

Open AccessArticle

Response Surface Methodology Optimization of Time-Resolved Fluorescence Immunoassay for Rapid Detection of AflatoxinB₁ in Yellow Rice Wine

by Mengjie Zhu, Dun Wang, Du Wang, Jing Dong, Xue Wang, Qi Zhang and Man Xiao

Toxins 2025, 17(5), 248; https://doi.org/10.3390/toxins17050248 - 16 May 2025

Abstract

Yellow rice wine is susceptible to aflatoxinB₁ (AFB₁) contamination, yet existing detection technologies suffer from limitations such as high false-positive rates, cumbersome operational protocols, or elevated costs, rendering them inadequate for large-scale screening requirements. Consequently, the development of a highly [...] Read more.

Yellow rice wine is susceptible to aflatoxinB₁ (AFB₁) contamination, yet existing detection technologies suffer from limitations such as high false-positive rates, cumbersome operational protocols, or elevated costs, rendering them inadequate for large-scale screening requirements. Consequently, the development of a highly sensitive and rapid detection method for AFB₁ is urgently needed to provide technical support for quality supervision and risk assessment of yellow rice wine. In this study, AFB₁ detection was performed using time-resolved fluorescence immunoassay technology, with quantitative analysis based on the ratio of the T signal value of the detection line to the C signal value of the quality control line and the natural logarithmic value of the standard solution concentration. Statistical experimental designs were used to optimize the process of this rapid detection of AFB₁ in yellow rice wine. The most important factors influencing recovery rate (p < 0.05), as identified by a two-level Plackett-Burman design with 11 variables, were methanol-water volume fraction, sample to extraction solvent ratio, heating temperature, and heating time. The steepest ascent method was employed to identify the optimal regions for these four key factors. Central composite design (CCD) coupled with response surface methodology (RSM) was subsequently utilized to further explore the interactive effects among variables and determine their optimal values that maximize the recovery rate. The analysis results indicated that interactions between methanol-water volume fraction and other three factors–sample to extraction solvent ratio, heating temperature, heating time–affected the response variable (recovery rate) significantly. The predicted results showed that the maximum recovery rate of AFB₁ (97.35%) could be obtained under the optimum conditions of a methanol-water volume fraction of 78%, a sample to extraction solvent ratio of 1:3.2, a heating temperature of 34 °C, and a heating time of 6.4 min. These predicted values were further verified by validation experiments. The excellent correlation between predicted and experimental values confirmed the validity and practicability of this statistical optimum strategy. Optimal conditions obtained in this experiment laid a good foundation for further use of time-resolved fluorescence immunoassay for rapid detection of AFB₁ in yellow rice wine, demonstrating broad application prospects. Full article

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12 pages, 1959 KiB

Open AccessArticle

Toxin Profiling of Amanita citrina and A. sinocitrina: First Report of Buiotenine Detection

by Yi-Zhe Zhang, Yi Yao, Kai-Ping Zhang, Jia-Qi Liang, Jia-Ju Zhong, Zhong-Feng Li, Hai-Jiao Li and Fei Xu

Toxins 2025, 17(5), 247; https://doi.org/10.3390/toxins17050247 - 16 May 2025

Abstract

Amanita species are widely distributed worldwide. Many of these species are poisonous and can cause health problems, resulting in morbidity and mortality. The toxins responsible for poisoning are amatoxins, aminohexadienoic acid, ibotenic acid, muscimol and muscarines, which damage the liver, kidney, central nervous [...] Read more.

Amanita species are widely distributed worldwide. Many of these species are poisonous and can cause health problems, resulting in morbidity and mortality. The toxins responsible for poisoning are amatoxins, aminohexadienoic acid, ibotenic acid, muscimol and muscarines, which damage the liver, kidney, central nervous system and parasympathetic nervous system. In recent years, several toxins have been discovered from different poisonous mushrooms. In this study, multiwalled carbon nanotube purification and ultrahigh-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used for the sensitive detection and targeted quantitative screening of 12 mushroom toxins (muscarine, two isoxazole derivatives, three tryptamine alkaloids, three amatoxins and three phallotoxins) from Amanita citrina, A. citrina var. grisea and A. sinocitrina. This study found that buiotenine, one of the tryptamine alkaloids, was detected in A. citrina and A. sinocitrina with an average content of 2.90 and 1.19–6.70 g/kg (n = 3) in the dried mushrooms, respectively. None of the 12 common toxins were discovered in A. citrina var. grisea. These results provide reference data for future research on the role of toxins in the evolution of Amanita mushrooms. Future studies should explore the biosynthetic pathways and ecological roles of these toxins in Amanita species. Full article

(This article belongs to the Special Issue Advances in Poisonous Mushrooms and Their Toxins)

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Graphical abstract

2 pages, 477 KiB

Open AccessCorrection

Correction: Di Paola et al. Impact of Mycotoxin Contaminations on Aquatic Organisms: Toxic Effect of Aflatoxin B1 and Fumonisin B1 Mixture. Toxins 2022, 14, 518

by Davide Di Paola, Carmelo Iaria, Fabiano Capparucci, Alessia Arangia, Rosalia Crupi, Salvatore Cuzzocrea, Nunziacarla Spanò, Enrico Gugliandolo and Alessio Filippo Peritore

Toxins 2025, 17(5), 246; https://doi.org/10.3390/toxins17050246 - 15 May 2025

Abstract

In the original publication [...] Full article

(This article belongs to the Section Mycotoxins)

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28 pages, 8296 KiB

Open AccessArticle

Survey of Microcystin-Producing Cyanobacteria in French Lakes of Various Trophic Status Using Environmental and Cyanobacterial Parameters and an Active Mussel Biomonitoring

by Emilie Lance, Alexandra Lepoutre, Luc Brient, Nicolas Maurin, Emmanuel Guillon, Alain Geffard and Dominique Amon-Moreau

Toxins 2025, 17(5), 245; https://doi.org/10.3390/toxins17050245 - 15 May 2025

Abstract

Microcystins (MCs), hepatotoxins produced by cyanobacteria, represent a potential threat to aquatic ecosystems and human health. Measuring various environmental and cyanobacterial parameters in water samples can be useful for monitoring water quality and assessing risk but remains a short-term approach. Beyond local risk [...] Read more.

Microcystins (MCs), hepatotoxins produced by cyanobacteria, represent a potential threat to aquatic ecosystems and human health. Measuring various environmental and cyanobacterial parameters in water samples can be useful for monitoring water quality and assessing risk but remains a short-term approach. Beyond local risk assessments, estimating global and medium-term levels of freshwater contamination by MC-producing cyanobacteria is challenging in large lakes due to the spatio-temporal variability of their proliferation and the need to multiply sampling dates and locations. In such conditions, a sentinel organism can be valuable for monitoring MCs in situ and providing a time-integrated picture of contamination levels at various stations. We previously assessed the ability of the freshwater bivalves Anodonta anatina and Dreissena polymorpha to act as biointegrators of MCs, even under low exposure levels to cyanobacteria. In this study, through a two-season investigation in several French lakes experiencing moderate cyanobacterial blooms, we evaluated the relevance of various parameters (cyanobacterial density and biovolume, chlorophyll-a, and phycocyanin) as well as the use of bivalves as indicators of medium-term freshwater contamination by MC-producing cyanobacteria. MC concentrations in cyanobacterial biomass (intracellular MCs) and in bivalves (free MCs, being unbound, and total free and protein-bound accumulated MCs) were measured alongside the characterization of phytoplankton communities. Both mussels integrated and highlighted the presence of intracellular MCs in the environment over the period between two successive water samplings, even at low contamination levels, demonstrating their suitability for in situ biomonitoring of MC-producing cyanobacteria. The results are discussed in terms of the strengths and limitations of different parameters for assessing MC contamination levels in waters depending on the objective (managing, preventing, or global evaluation) and the monitoring strategies used. Full article

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

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16 pages, 599 KiB

Open AccessArticle

Toxicity Assessment of Catechins on Representative Aquatic Organisms and Terrestrial Plant

by Khawaja Muhammad Imran Bashir, Hye-Ryeon An, Bertoka Fajar Surya Perwira Negara, Gabriel Tirtawijaya, Maria Dyah Nur Meinita, Jae-Hak Sohn, Dicky Harwanto and Jae-Suk Choi

Toxins 2025, 17(5), 244; https://doi.org/10.3390/toxins17050244 - 14 May 2025

Abstract

Catechins, renowned for their health benefits, have unexamined environmental impacts. This study assessed the toxicity of crude catechin and catechin hydrate on invertebrate larvae, plant, and microalgae. The survival rates of Daphnia magna Straus and Artemia salina L. were monitored every 24 h [...] Read more.

Catechins, renowned for their health benefits, have unexamined environmental impacts. This study assessed the toxicity of crude catechin and catechin hydrate on invertebrate larvae, plant, and microalgae. The survival rates of Daphnia magna Straus and Artemia salina L. were monitored every 24 h over a three-day period. The germination rate and radicle length of Lactuca sativa L. was measured every 24 h for four days. Inhibitory effects were evaluated in both freshwater and seawater cultures of Chlorella vulgaris Beijerinck, with cell density recorded every 24 h and yield inhibition calculated after 96 h. Results indicated that increasing catechin concentration and exposure duration decreased the survival rate of D. magna and A. salina. Daphnia magna was more sensitive to catechins than A. salina, with 24 h lethal concentration 50 (LC-50) values of 1174 µg/mL compared to 1895 µg/mL for crude catechin, and 54 µg/mL compared to 153 µg/mL for catechin hydrate. The germination rate and radicle length of L. sativa, along with the cell density of C. vulgaris, decreased with increasing catechin concentration, but remained higher even after prolonged exposure. At low catechin concentrations, C. vulgaris cell density exceeded control levels. This study demonstrates that catechins in aquatic environments can significantly impact ecosystems. At certain concentrations, catechins are toxic and potentially lethal to aquatic organisms. Conversely, at lower concentrations, catechins may promote microalgal growth, suggesting a fertilizing effect. Understanding these dynamics is crucial for maintaining the stability of aquatic ecosystems. Full article

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25 pages, 2812 KiB

Open AccessArticle

Dual Proteomics Strategies to Dissect and Quantify the Components of Nine Medically Important African Snake Venoms

by Damien Redureau, Fernanda Gobbi Amorim, Thomas Crasset, Imre Berger, Christiane Schaffitzel, Stefanie Kate Menzies, Nicholas R. Casewell and Loïc Quinton

Toxins 2025, 17(5), 243; https://doi.org/10.3390/toxins17050243 - 13 May 2025

Viewed by 146

Abstract

Snakebite envenoming constitutes a significant global health issue, particularly in Africa, where venomous species such as Echis vipers and Dendroaspis mambas pose substantial risks to human health. This study employs a standardized venomics workflow to comprehensively characterize and comparatively quantify the venom composition [...] Read more.

Snakebite envenoming constitutes a significant global health issue, particularly in Africa, where venomous species such as Echis vipers and Dendroaspis mambas pose substantial risks to human health. This study employs a standardized venomics workflow to comprehensively characterize and comparatively quantify the venom composition of nine medically relevant snake species chosen from among the deadliest in Africa. Utilizing shotgun venom proteomics and venom gland transcriptomics, we report detailed profiles of venom complexity, highlighting the relative abundance of dominant toxin families such as three-finger toxins and Kunitz-type proteins in Dendroaspis, and metalloproteinases and phospholipases A₂ in Echis. We delineate here the relative abundance and structural diversity of venom components. Key to our proteomic approach is the implementation of Multi-Enzymatic Limited Digestion (MELD), which improved protein sequence coverage and enabled the identification of rare toxin families such as hyaluronidases and renin-like proteases, by multiplying the overlap of generated peptides and enhancing the characterization of both toxin and non-toxin components within the venoms. The culmination of these efforts resulted in the construction of a detailed toxin database, providing insights into the biological roles and potential therapeutic targets of venom proteins and peptides. The findings here compellingly validate the MELD technique, reinforcing its reproducibility as a valuable characterization approach applied to venomics. This research significantly advances our understanding of venom complexity in African snake species, including representatives of both Viperidae and Elapidae families. By elucidating venom composition and toxin profiles, our study paves the way for the development of targeted therapies aimed at mitigating the morbidity and mortality associated with snakebite envenoming globally. Full article

(This article belongs to the Special Issue Toxins: From the Wild to the Lab)

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Graphical abstract

22 pages, 16972 KiB

Open AccessReview

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

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

Toxins 2025, 17(5), 240; https://doi.org/10.3390/toxins17050240 - 13 May 2025

Viewed by 109

Abstract

Ultrasound-guided botulinum toxin type A (BoNT-A) injections have become an essential tool in the management of lower limb spasticity. Following our previous work, which focused on upper limb muscles, this third part provides a detailed visual guide to the identification and injection of [...] Read more.

Ultrasound-guided botulinum toxin type A (BoNT-A) injections have become an essential tool in the management of lower limb spasticity. Following our previous work, which focused on upper limb muscles, this third part provides a detailed visual guide to the identification and injection of proximal lower limb muscles frequently involved in spastic gait and posture disorders. This guide presents the ultrasound anatomy, clinical relevance, and injection strategies for eleven key muscles: gluteus maximus, piriformis, psoas major, rectus femoris, sartorius, gracilis, adductor longus, adductor magnus, semimembranosus, semitendinosus, and biceps femoris. For each muscle, the Elias University Hospital (EUH) model is applied, highlighting the zones of maximum thickness and motor point density to ensure precise and effective BoNT-A delivery. Enhanced with high-resolution ultrasound images and dynamic scanning techniques, this visual guide supports clinicians in performing safe, targeted injections. It serves as both an educational and practical reference for the ultrasound-guided treatment of spasticity in the proximal lower limb, completing the series and offering a standardized framework for comprehensive BoNT-A management. By promoting accurate toxin delivery, this approach is expected to improve functional mobility, reduce spasticity-related complications, and optimize patient-centered outcomes in rehabilitation settings. Full article

(This article belongs to the Section Bacterial Toxins)

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20 pages, 2307 KiB

Open AccessArticle

Molecular Quantification of Total and Toxigenic Microcystis Using Digital-Droplet-Polymerase-Chain-Reaction-Based Multiplex Assay

by In-Su Kim and Hae-Kyung Park

Toxins 2025, 17(5), 242; https://doi.org/10.3390/toxins17050242 - 12 May 2025

Viewed by 109

Abstract

The proliferation of harmful cyanobacteria, particularly Microcystis, poses significant risks to drinking and recreational water resources, especially under the influence of climate change. Conventional monitoring methods based on microscopy for harmful cyanobacteria management systems are limited in detecting toxigenic genotypes, hindering accurate [...] Read more.

The proliferation of harmful cyanobacteria, particularly Microcystis, poses significant risks to drinking and recreational water resources, especially under the influence of climate change. Conventional monitoring methods based on microscopy for harmful cyanobacteria management systems are limited in detecting toxigenic genotypes, hindering accurate risk assessment. In this study, we developed a digital droplet PCR (ddPCR)-based method for the simultaneous quantification of total and toxigenic Microcystis in freshwater environments. We targeted the secA gene, specific to the Microcystis genus, and the mcyA gene, associated with microcystin biosynthesis. Custom-designed primers and probes showed high specificity and sensitivity, enabling accurate detection without cross-reactivity. The multiplex ddPCR assay allowed for concurrent quantification of both targets in a single reaction, reducing the analysis time and cost. Application to field samples demonstrated good agreement with microscopic counts and revealed seasonal shifts in toxigenic genotype abundance. Notably, ddPCR detected Microcystis at very low densities—down to 7 cells/mL in the mixed cyanobacterial communities of field samples—even when microscopy failed, highlighting its utility for early bloom detection. This approach provides a reliable and efficient tool for monitoring Microcystis dynamics and assessing toxin production potential, offering significant advantages for the early warning and proactive management of harmful cyanobacterial blooms. Full article

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

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14 pages, 2086 KiB

Open AccessArticle

Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity

by Lingchen Yang, Tristan Decas, Yuhang Zhang and Imourana Alassane-Kpembi

Toxins 2025, 17(5), 241; https://doi.org/10.3390/toxins17050241 - 12 May 2025

Viewed by 158

Abstract

The deoxynivalenol (DON) mycotoxin poses serious health risks, especially to swine, which are highly susceptible to intestinal damage. Existing strategies to counteract DON toxicity remain insufficient. This study aimed to evaluate the protective effects of cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, against [...] Read more.

The deoxynivalenol (DON) mycotoxin poses serious health risks, especially to swine, which are highly susceptible to intestinal damage. Existing strategies to counteract DON toxicity remain insufficient. This study aimed to evaluate the protective effects of cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, against DON-induced intestinal toxicity in porcine intestinal epithelial cells. Using differentiated and proliferating porcine intestinal epithelial cells (IPEC-J2), we evaluated CBD (2.5–5 μM) against DON (0.5–50 μM) through viability assays, apoptosis markers (Bax/Bcl-2 ratio), inflammatory mediators (NFκB, IL-6, COX-2), oxidative stress indicators (TXNIP, SOD1, CAT), tight junction gene expression (Claudin-1, Occludin), and barrier permeability. DON exhibited dose- and time-dependent cytotoxicity (IC₅₀ = 2.60 μM at 24 h; 1.07 μM at 48 h). Pre-treatment with 5 μM CBD restored cell viability at low DON concentrations (0.5–2 μM) but failed at ≥8 μM. In differentiated cells, CBD suppressed apoptosis (reduced Bax/Bcl-2 ratio), oxidative stress (downregulated TXNIP; restored CAT expression), and inflammation (decreased IL-6 and COX-2) under high-dose DON (50 μM), while enhancing tight junction protein expression and barrier integrity at 5 μM DON. Conversely, in proliferating cells, CBD exacerbated apoptosis (elevated Bax/Bcl-2 ratio) and inflammatory responses (upregulated IL-6 and COX-2) at subtoxic levels of DON (2 μM). CBD alone induced cytotoxicity at ≥10 μM. Our findings demonstrate that CBD exhibits context-dependent efficacy, providing protection in differentiated epithelia under moderate DON exposure (≤5 μM) but exhibiting detrimental effects in proliferating cells. Its narrow therapeutic window and paradoxical actions necessitate cautious application. These findings position CBD as a potential adjunctive therapy for DON detoxification but highlight critical limitations for standalone use. Full article

(This article belongs to the Section Mycotoxins)

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11 pages, 5158 KiB

Open AccessArticle

Fumonisin B₁ Exposure Causes Intestinal Tissue Damage by Triggering Oxidative Stress Pathways and Inducing Associated CYP Isoenzymes

by Changyu Cao, Weiping Hua, Runxi Xian and Yang Liu

Toxins 2025, 17(5), 239; https://doi.org/10.3390/toxins17050239 - 12 May 2025

Viewed by 145

Abstract

Fumonisin B₁ (FB₁) is considered the most toxic fumonisin produced by fungi and is commonly found in contaminated feed and crops. Fumonisin and its metabolites extensively exist in feed and crops, where FB₁-polluted crop ingestion can do harm [...] Read more.

Fumonisin B₁ (FB₁) is considered the most toxic fumonisin produced by fungi and is commonly found in contaminated feed and crops. Fumonisin and its metabolites extensively exist in feed and crops, where FB₁-polluted crop ingestion can do harm to livestock and poultry, causing poultry intestinal toxicity in the latter. For investigating FB₁-mediated intestinal toxicity, we assessed the function of FB₁ exposure in quail intestines and explored its possible molecular mechanisms. In total, 120 quail pups were classified into two groups, where those in the control group were given a typical control diet, and those in the experimental group were given a typical diet that contained 30 mg/kg FB₁. We evaluated the histopathological and ultrastructural changes in quails’ intestines on days 14, 28, and 42, and studied the molecular mechanisms by assessing oxidative stress, inflammation, and nuclear xenobiotic receptors (NXRs). Our results suggest that FB₁ exposure causes intestinal inflammation by triggering oxidative stress pathways and modulating NXRs to induce Cytochrome P450 proteins (CYP) isoforms, leading to intestinal histopathological damage. The results of this study shed novel light on the molecular mechanism underlying FB₁-induced intestinal injury in juvenile quails. Full article

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32 pages, 3654 KiB

Open AccessReview

Potential of Venom-Derived Compounds for the Development of New Antimicrobial Agents

by Esraa Yasser Rabea, Esraa Dakrory Mahmoud, Nada Khaled Mohamed, Erada Rabea Ansary, Mahmoud Roushdy Alrouby, Rabab Reda Shehata, Youssef Yasser Mokhtar, Prakash Arullampalam, Ahmed M. Hegazy, Ahmed Al-Sabi and Tarek Mohamed Abd El-Aziz

Toxins 2025, 17(5), 238; https://doi.org/10.3390/toxins17050238 - 11 May 2025

Viewed by 593

Abstract

The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa pose significant public health threats, as they are increasingly resistant to common [...] Read more.

The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa pose significant public health threats, as they are increasingly resistant to common antibiotics, leading to more severe and difficult-to-treat infections. These pathogens are part of the ESKAPE group, which includes Enterococcus faecium, Staphylococcus aureus, and Enterobacter species. Animal venoms, derived from a wide range of species such as snakes, scorpions, spiders, bees, wasps, and ants, represent a rich source of bioactive peptides. Venoms have been a valuable source for drug discovery, providing unique compounds with therapeutic potential. Venom-derived drugs are known for their increased bioactivity, specificity, and stability compared to synthetic alternatives. These compounds are being investigated for various conditions, including treatments for diabetes, pain relief, cancer, and infections, showcasing their remarkable antimicrobial efficacy. In this review, we provide a comprehensive investigation into the potential of venom-derived compounds for developing new antimicrobial agents, including antibacterial, antifungal, antiviral, and antiparasitic therapeutics. Key venom components, including melittin from bee venom, phospholipase A₂ from snake venom, and chlorotoxin from scorpion venom, exhibit potent antimicrobial effects through mechanisms such as membrane disruption, enzymatic inhibition, and immune modulation. We also explore the challenges related to the development and clinical use of venom-derived antimicrobials, including toxicity, stability, and delivery mechanisms. These compounds hold immense promise as transformative tools against resistant pathogens, offering a unique avenue for groundbreaking advancements in antimicrobial research and therapeutic development. Full article

(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)

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4 pages, 172 KiB

Open AccessEditorial

Snake Venom: Toxicology and Associated Countermeasures

by Nicholas J. Youngman

Toxins 2025, 17(5), 237; https://doi.org/10.3390/toxins17050237 - 10 May 2025

Viewed by 150

Abstract

This Special Issue aims to provide insight into the understudied toxicological effects induced by snakebite envenoming, as well as to highlight current and future countermeasures for reducing the extreme morbidity and mortality associated with this globally neglected tropical disease [...] Full article

(This article belongs to the Special Issue Snake Venom: Toxicology and Associated Countermeasures)

15 pages, 3111 KiB

Open AccessArticle

The Impact of Biocontrol Agents on the Metabolome of Penicillium nordicum Strains and Its Relation to Ochratoxin A Production on Dry-Cured Ham

by Eva Cebrián, Elia Roncero, João Luz, Mar Rodríguez, Marta Sousa Silva, Carlos Cordeiro and Félix Núñez

Toxins 2025, 17(5), 236; https://doi.org/10.3390/toxins17050236 - 9 May 2025

Viewed by 179

Abstract

Throughout the process of dry-cured ham, moulds such as P. nordicum, a producer of ochratoxin A (OTA), grow on its surface. The use of combined biocontrol agents (BCAs) is a promising strategy for controlling this hazard. The goal of this study is [...] Read more.

Throughout the process of dry-cured ham, moulds such as P. nordicum, a producer of ochratoxin A (OTA), grow on its surface. The use of combined biocontrol agents (BCAs) is a promising strategy for controlling this hazard. The goal of this study is to assess the effect of D. hansenii, S. xylosus, and P. chrysogenum as BCAs on the metabolome of two strains of P. nordicum and to understand the differences between both strains. Each ochratoxigenic strain was inoculated both individually and in combination with the BCAs onto ham for 30 days under the environmental conditions experienced during traditional ripening. Untargeted metabolomics was performed through mass spectrometry using a Q-Exactive Plus Orbitrap. The BCAs caused alterations in the metabolomes of both ochratoxigenic moulds, mainly in phenylalanine catabolism and the valine, leucine, and isoleucine biosynthesis pathways, although with some differences. In the absence of the BCAs, the metabolomes of both types of P. nordicum were globally changed, despite these being moulds of the same species. In conclusion, these data help us to understand the differences between OTA-producing strains in dry-cured ham and confirm the need to demonstrate the efficacy of BCAs against a wide range of toxigenic moulds before they can be used to minimise OTA contamination in the meat industry. Full article

(This article belongs to the Special Issue Occurrence, Toxicity, Metabolism, Analysis and Control of Mycotoxins)

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21 pages, 2835 KiB

Open AccessArticle

Extensive Variation in Thermal Responses and Toxin Content Among 40 Strains of the Cold-Water Diatom Pseudo-nitzschia seriata—In a Global Warming Context

by Caroline Weber, Anna Junker Olesen, Robert G. Hatfield, Bernd Krock and Nina Lundholm

Toxins 2025, 17(5), 235; https://doi.org/10.3390/toxins17050235 - 9 May 2025

Viewed by 238

Abstract

Phytoplankton are single-celled microorganisms with short generation times that may comprise high diversity in genetic and phenotypic traits, allowing them to acclimate to changes rapidly. High intraspecific genetic variation is well known in phytoplankton, but less is known about variation in physiological traits. [...] Read more.

Phytoplankton are single-celled microorganisms with short generation times that may comprise high diversity in genetic and phenotypic traits, allowing them to acclimate to changes rapidly. High intraspecific genetic variation is well known in phytoplankton, but less is known about variation in physiological traits. To investigate variability and plasticity in genetic, morphological, and physiological traits of the toxigenic diatom genus Pseudo-nitzschia in a global warming scenario, we exposed 40 strains of the cold-water P. seriata to different temperatures (2 °C, 6 °C and 10 °C). The maximum growth rate and cellular toxin content showed extensive intraspecific variation, whereas morphological and genetic variation was minor. Thermal reaction norms showed a general increase in growth rate with increasing temperature; however, three distinct types of thermal responses were found among the 40 strains. All 40 strains contained toxins (domoic acid) in both exponential and stationary growth phase, and toxin content increased significantly with temperature. Most strains (>87%) contained measurable levels of domoic acid at all three temperatures. In conclusion, P. seriata shows extensive intraspecific variation in measured physiological traits like growth and toxin content, a variation exceeding the response of each strain to increases in temperature. Intraspecific variation in harmful species thus needs attention for the future understanding of food web dynamics, as well as the management and forecasting of harmful blooms. Full article

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16 pages, 1699 KiB

Open AccessArticle

Development and Preclinical Testing of a Novel Neurodenervant in the Rat: C3 Transferase Mitigates Botulinum Toxin’s Adverse Effects on Muscle Mechanics

by Cemre Su Kaya Keles, Zeynep D. Akdeniz Dogan and Can A. Yucesoy

Toxins 2025, 17(5), 234; https://doi.org/10.3390/toxins17050234 - 9 May 2025

Viewed by 169

Abstract

Spasticity, characterized by elevated muscle tone, is commonly managed with botulinum toxin type A (BTX-A). However, BTX-A can paradoxically increase passive muscle forces, narrow muscles’ length range of force exertion (l_range), and elevate extracellular matrix (ECM) stiffness. C3 transferase, known to [...] Read more.

Spasticity, characterized by elevated muscle tone, is commonly managed with botulinum toxin type A (BTX-A). However, BTX-A can paradoxically increase passive muscle forces, narrow muscles’ length range of force exertion (l_range), and elevate extracellular matrix (ECM) stiffness. C3 transferase, known to inhibit myofibroblast and fascial tissue contractility, may counteract ECM stiffening. This study investigated whether combining BTX-A with C3 transferase reduces active forces without altering passive forces or l_range. Additionally, we examined the isolated effects of C3 transferase on muscle levels. Male Wistar rats received injections into the tibialis anterior (TA): Control (n = 7, saline) and C3 + BTX-A (n = 7, 2.5 µg C3 + 0.1U BTX-A). TA forces were measured one month post-injection, and isolated C3 transferase effects were assessed in separate groups (Control and C3, n = 6 each). Active forces were 43.5% lower in the C3 + BTX-A group compared to the Control group. No differences between groups in passive forces (p = 0.33) or l_range (p = 0.19) were observed. C3 transferase alone had no significant effect on relative muscle mass (p = 0.298) or collagen content (p = 0.093). Supplementing BTX-A with C3 transferase eliminates BTX-A’s adverse effects at the muscle level. C3 transferase alone causes no atrophy or collagen increase, which are key factors in BTX-A-induced ECM stiffening. This novel neurodenervant formula shows promise for advancing spasticity management. Full article

(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)

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19 pages, 1900 KiB

Open AccessReview

Structure, Toxicity, Prevalence, and Degradation of Six Understudied Freshwater Cyanopeptides

by Blake B. Stringer, Regina G. Szlag Silva, Jeremy J. Kodanko and Judy A. Westrick

Toxins 2025, 17(5), 233; https://doi.org/10.3390/toxins17050233 - 8 May 2025

Viewed by 441

Abstract

Anthropogenic influences have increased global warming and eutrophication, escalating the frequency and severity of harmful cyanobacterial blooms (cHABs) in freshwater ecosystems. These blooms release cyanopeptides, a diverse class of bioactive compounds with varying acute and chronic toxicities upon ingestion. To date, research has [...] Read more.

Anthropogenic influences have increased global warming and eutrophication, escalating the frequency and severity of harmful cyanobacterial blooms (cHABs) in freshwater ecosystems. These blooms release cyanopeptides, a diverse class of bioactive compounds with varying acute and chronic toxicities upon ingestion. To date, research has prioritized acutely toxic cyanopeptides like microcystins. As a result, significantly less is known about other freshwater cyanopeptides. This review highlights six understudied cyanopeptide classes, anabaenopeptins, cyanopeptolins, aeruginosamides, aeruginosins, microginins, and cyclamides, and provides a comprehensive overview of their molecular structures, toxicological profiles, environmental concentrations, and known degradation pathways. Given the potential toxicity, increased environmental abundance, and environmental stability of many cyanopeptides in freshwater sources, further research is needed to understand if degraded cyanopeptides are still biologically active prior to entering drinking water to ensure public health. Full article

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11 pages, 1985 KiB

Open AccessArticle

BLF1 Affects ATP Hydrolysis Catalyzed by Native and Mutated eIF4A1 and eIF4A2 Proteins

by Min An, Xin Cheng, Yu Zhang, Jiang Gu and Xuhu Mao

Toxins 2025, 17(5), 232; https://doi.org/10.3390/toxins17050232 - 7 May 2025

Viewed by 117

Abstract

Burkholderia lethal factor 1 (BLF1), a toxin derived from Burkholderia pseudomallei, reacts with eukaryotic initiation factor (eIF) 4A to inhibit protein synthesis. eIF4A1 and eIF4A2 are involved in translation initiation and share over 90% sequence similarity. However, they exert distinct effects on [...] Read more.

Burkholderia lethal factor 1 (BLF1), a toxin derived from Burkholderia pseudomallei, reacts with eukaryotic initiation factor (eIF) 4A to inhibit protein synthesis. eIF4A1 and eIF4A2 are involved in translation initiation and share over 90% sequence similarity. However, they exert distinct effects on cancer treatment outcomes. To understand the molecular mechanism by which BLF1 modulates eIF4A isoforms in cancer cells, we investigated its effects on eIF4A-mediated adenosine 5′-triphosphate (ATP) hydrolysis. We found that eIF4A1 has a higher ATP-binding affinity compared to eIF4A2 (K_m = 6.55 ± 0.78 μM vs. K_m = 11.61 ± 2.33 μM). Meanwhile, we also found that eIF4A1 is more sensitive to changes in temperature, pH, and Mg²⁺ concentration. Through N-terminal swapping and single amino acid mutations, we found that leucine 98 (L98) and alanine 100 (A100) play important roles in the ATPase activities of eIF4A isoforms. Moreover, BLF1 treatment significantly enhanced eIF4A2-mediated ATP hydrolysis at all tested ATP concentrations. These differences in BLF1-regulated eIF4A isoforms may explain its selective cytotoxicity against cancer cells. Our findings provide molecular insights into the functional difference between eIF4A isoforms and suggest that BLF1 might be of promising value for anticancer therapies. Full article

(This article belongs to the Special Issue Novel Technologies for the Detection and Identification of Natural Toxins)

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55 pages, 3842 KiB

Open AccessReview

New Strategies and Artificial Intelligence Methods for the Mitigation of Toxigenic Fungi and Mycotoxins in Foods

by Fernando Mateo, Eva María Mateo, Andrea Tarazona, María Ángeles García-Esparza, José Miguel Soria and Misericordia Jiménez

Toxins 2025, 17(5), 231; https://doi.org/10.3390/toxins17050231 - 7 May 2025

Viewed by 242

Abstract

The proliferation of toxigenic fungi in food and the subsequent production of mycotoxins constitute a significant concern in the fields of public health and consumer protection. This review highlights recent strategies and emerging methods aimed at preventing fungal growth and mycotoxin contamination in [...] Read more.

The proliferation of toxigenic fungi in food and the subsequent production of mycotoxins constitute a significant concern in the fields of public health and consumer protection. This review highlights recent strategies and emerging methods aimed at preventing fungal growth and mycotoxin contamination in food matrices as opposed to traditional approaches such as chemical fungicides, which may leave toxic residues and pose risks to human and animal health as well as the environment. The novel methodologies discussed include the use of plant-derived compounds such as essential oils, classified as Generally Recognized as Safe (GRAS), polyphenols, lactic acid bacteria, cold plasma technologies, nanoparticles (particularly metal nanoparticles such as silver or zinc nanoparticles), magnetic materials, and ionizing radiation. Among these, essential oils, polyphenols, and lactic acid bacteria offer eco-friendly and non-toxic alternatives to conventional fungicides while demonstrating strong antimicrobial and antifungal properties; essential oils and polyphenols also possess antioxidant activity. Cold plasma and ionizing radiation enable rapid, non-thermal, and chemical-free decontamination processes. Nanoparticles and magnetic materials contribute advantages such as enhanced stability, controlled release, and ease of separation. Furthermore, this review explores recent advancements in the application of artificial intelligence, particularly machine learning methods, for the identification and classification of fungal species as well as for predicting the growth of toxigenic fungi and subsequent mycotoxin production in food products and culture media. Full article

(This article belongs to the Special Issue Mitigation and Detoxification Strategies of Mycotoxins)

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9 pages, 1156 KiB

Open AccessArticle

Preclinical Evaluation of Botulinum Toxin Type E (TrenibotulinumtoxinE) Using the Mouse Digit Abduction Score (DAS) Assay

by Gregory S. Nicholson, David Canty, Annemarie Southern, Kevin Whelan, Amy D. Brideau-Andersen and Ron S. Broide

Toxins 2025, 17(5), 230; https://doi.org/10.3390/toxins17050230 - 6 May 2025

Viewed by 289

Abstract

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological [...] Read more.

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24–27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule. Full article

(This article belongs to the Special Issue Biological and Pharmacological Properties of Botulinum Neurotoxins)

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17 pages, 690 KiB

Open AccessReview

Therapeutic Potential of Scolopendra subspinipes: A Comprehensive Scoping Review of Its Bioactive Compounds, Preclinical Pharmacology, and Clinical Applications

by Ye-Seul Lee, Yoon Jae Lee and In-Hyuk Ha

Toxins 2025, 17(5), 229; https://doi.org/10.3390/toxins17050229 - 5 May 2025

Viewed by 253

Abstract

Scolopendra subspinipes, commonly known as the Chinese red-headed centipede, has been utilized in traditional East Asian medicine for centuries to treat conditions such as chronic pain, inflammation, convulsions, and infections. Recent pharmacological investigations have uncovered a wide array of bioactive molecules—including peptides, [...] Read more.

Scolopendra subspinipes, commonly known as the Chinese red-headed centipede, has been utilized in traditional East Asian medicine for centuries to treat conditions such as chronic pain, inflammation, convulsions, and infections. Recent pharmacological investigations have uncovered a wide array of bioactive molecules—including peptides, alkaloids, and polysaccharide–protein complexes—from both venom and whole-body extracts. This review synthesizes findings from 45 in vitro, in vivo, and clinical studies investigating the pharmacological effects of venom-derived and whole-body-derived compounds from S. subspinipes across multiple domains, including analgesic, anti-inflammatory, antimicrobial, antifungal, antioxidant, antitumor, antithrombotic, anti-fibrotic, and neuroprotective activities, along with a brief scoping review of clinical practice guidelines. Key venom-derived compounds such as the peptide SsmTX-I, immunomodulatory antimicrobial peptide scolopendrasin IX, and antitumor peptide scolopentide exhibit strong mechanistic rationale and preclinical efficacy, positioning them as lead candidates for clinical development. Compounds derived from whole-body extracts, including alkaloids and polysaccharide–protein complexes, also demonstrate promising therapeutic potential. Mechanistic studies suggest these compounds operate via distinct pathways—such as ion-channel inhibition, NF-κB suppression, and apoptosis induction—offering potential advantages over existing therapies. However, current evidence remains primarily preclinical, and challenges such as extract variability, immunogenicity, and lack of standardized dosing must be addressed. Future research should prioritize isolation and structural optimization of key peptides, standardized formulation development, toxicological profiling, and early-phase human trials. The integration of traditional knowledge and modern pharmacological insights underscores the potential of venom- and whole-body-derived S. subspinipes agents to enrich the drug discovery, particularly for conditions with unmet therapeutic needs. Full article

(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)

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24 pages, 1940 KiB

Open AccessReview

Toxin Accumulation, Distribution, and Sources of Toxic Xanthid Crabs

by Yuchengmin Zhang, Hongchen Zhu, Tomohiro Takatani and Osamu Arakawa

Toxins 2025, 17(5), 228; https://doi.org/10.3390/toxins17050228 - 5 May 2025

Viewed by 197

Abstract

Several species of crabs from the Xanthidae family are recognized as dangerous marine organisms due to their potent neurotoxins, including paralytic shellfish toxin (PST), tetrodotoxin (TTX), and palytoxin (PLTX). However, the mechanisms of toxin accumulation and transport and the origin of these toxins [...] Read more.

Several species of crabs from the Xanthidae family are recognized as dangerous marine organisms due to their potent neurotoxins, including paralytic shellfish toxin (PST), tetrodotoxin (TTX), and palytoxin (PLTX). However, the mechanisms of toxin accumulation and transport and the origin of these toxins in toxic xanthid crabs remain unknown. The identification of toxic crab species, their toxicity and toxin composition, and toxin profiles have been studied thus far. To date, more than ten species of xanthid crabs have been confirmed to possess toxins. Recently, several new studies on crabs, including the geographic distribution of toxin profiles and the ecological role of crabs, have been reported. Therefore, this review provides a summary of global research on toxic xanthid crabs, containing new findings and hypotheses on the toxification in and the origins of these crabs. Furthermore, the challenges and future perspectives in this field are also discussed. Full article

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

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27 pages, 6630 KiB

Open AccessArticle

Multi-Mycotoxin Contamination in Serbian Maize During 2021–2023: Climatic Influences and Implications for Food and Feed Safety

by Felipe Penagos-Tabares, Anastasija Todorov, Jog Raj, Hunor Farkaš, Goran Grubješić, Zdenka Jakovčević, Svetlana Ćujić, Jelena Nedeljković-Trailović and Marko Vasiljević

Toxins 2025, 17(5), 227; https://doi.org/10.3390/toxins17050227 - 4 May 2025

Viewed by 344

Abstract

Mycotoxin contamination in maize poses significant food and feed safety risks, particularly in regions with variable climatic conditions like Serbia. This study investigated the occurrence of regulated mycotoxins in maize harvested across the Republic of Serbia from 2021 to 2023, emphasizing the impact [...] Read more.

Mycotoxin contamination in maize poses significant food and feed safety risks, particularly in regions with variable climatic conditions like Serbia. This study investigated the occurrence of regulated mycotoxins in maize harvested across the Republic of Serbia from 2021 to 2023, emphasizing the impact of climatic factors. A total of 548 samples of unprocessed maize grains were analysed for the presence of key mycotoxins, including aflatoxins, ochratoxin A, zearalenone, deoxynivalenol, fumonisins, and trichothecenes type A (T-2 and HT-2 toxins), using validated analytical methods. The results revealed high contamination frequencies, with aflatoxins and fumonisins being the most prevalent. The results revealed substantial temporal variability and frequent co-contamination of mycotoxins. Aflatoxin B₁ (AFB₁) was the most concerning contaminant, with 73.2% of the samples in 2022 exceeding the European regulatory limit for human consumption (5 µg/kg) for un processed maize grains, reaching peak concentrations of 527 µg/kg, which is 105.4 times higher than the allowed limit. For animal feed, the limit of 20 µg/kg was exceeded in 40.5% of the samples, with the highest concentration being 26.4 times greater than the maximum allowable level. In 2021, the non-compliance rates for AFB₁ in food and feed were 8.3% and 2.3%, respectively, while in 2023, they were 23.2% and 12.2%, respectively. Fumonisins contamination was also high, particularly in 2021, with fumonisin B₁ (FB₁) detected in 87.1% of samples and average concentrations reaching 4532 µg/kg. Although levels decreased in 2023 (70.7% occurrence, average 885 µg/kg), contamination remained significant. Deoxynivalenol (DON) contamination was consistently high (>70% of samples), with peak concentrations of 606 µg/kg recorded in 2021. Zearalenone (ZEN) and ochratoxin A (OTA) occurred less frequently, but ZEN levels peaked in 2022 at 357.6 µg/kg, which is above the regulatory limit of 350 µg/kg for food. Trichothecenes (HT-2 and T-2 toxins) were detected sporadically, with concentrations well below critical thresholds. Co-occurrence of mycotoxins was frequent, with significant mixtures detected, particularly between aflatoxins and fumonisins, as well as other fusarial toxins. The analysis demonstrated that temperature, humidity, and rainfall during both the growing and harvest seasons strongly influenced mycotoxin levels, with the most severe contamination occurring under specific climatic conditions. Notably, the highest mycotoxin levels, like aflatoxins, were linked to warmer temperatures and lower rainfall. The high non-compliance rates for aflatoxins and fumonisins and co-contamination pose significant food and feed safety risks. From a public health perspective, chronic exposure to contaminated maize increases the likelihood of carcinogenesis and reproductive disorders. Reduced productivity and bioaccumulation in animal tissues/products represent serious economic and safety concerns for livestock. This study provides insights into the potential risks to food and feed safety and the need for enhanced regulatory frameworks, continuous monitoring, and mitigation strategies in Serbia as well as other geographical regions. Full article

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

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58 pages, 6780 KiB

Open AccessReview

A Comprehensive Review of Hypotheses About the Biological Function of Zearalenone, and a New Hypothesis for the Function of Resorcylic and Dihydroxyphenylacetic Macrolactones in Fungi

by María Viñas and Petr Karlovsky

Toxins 2025, 17(5), 226; https://doi.org/10.3390/toxins17050226 - 3 May 2025

Viewed by 241

Abstract

The special metabolite of Fusarium spp. zearalenone (ZEN) exerts estrogenic effects on mammals, stimulates plant growth, stimulates sexual development in fungi, and inhibits fungal growth. These activities inspired hypotheses about the biological function of ZEN. We briefly review the discovery of ZEN and [...] Read more.

The special metabolite of Fusarium spp. zearalenone (ZEN) exerts estrogenic effects on mammals, stimulates plant growth, stimulates sexual development in fungi, and inhibits fungal growth. These activities inspired hypotheses about the biological function of ZEN. We briefly review the discovery of ZEN and its implications. The main subject of this review is a critical assessment of the hypotheses that ZEN is a fungal hormone, a plant hormone, a virulence factor, or a fungal defense metabolite. Conceptual and technical issues related to testing these hypotheses, such as inadequate analytical methods, confusion of incidental effects with biological functions, and lack of normalization, are illuminated. Based on these considerations, gene knockout experiments, and on the effects of biotic interactions on ZEN synthesis, we argue that ZEN is a defense metabolite protecting Fusarium spp. against mycoparasites and competitors. Similar reasoning and published data suggest that the Fusarium metabolite fusaristatin A fulfils the same function. Fungi produce many macrolactones of resorcylic acid (RALs) and dihydroxyphenylacetic acid (DHPLs) with properties similar to ZEN. Their widespread occurrence, antifungal activity, and further considerations prompt us to hypothesize that the fundamental function of fungal RALs and DHPLs lies in defense and interference competition. Full article

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11 pages, 1370 KiB

Open AccessCommunication

Ultrasound-Guided Botulinum Toxin Injections for Hand Spasticity: A Technical Guide for the Dorsal Approach

by Calogero Malfitano, Antonio Robecchi Majnardi, Arianna Pesaresi and Vincenzo Ricci

Toxins 2025, 17(5), 225; https://doi.org/10.3390/toxins17050225 - 3 May 2025

Viewed by 369

Abstract

Spasticity often occurs following neurological disorders such as traumatic brain injury, cerebral palsy, and stroke. Botulinum toxin (BTX) injections, especially when paired with rehabilitation, are among the most effective interventions for these patients. Various techniques for administering BTX injections to the upper limb [...] Read more.

Spasticity often occurs following neurological disorders such as traumatic brain injury, cerebral palsy, and stroke. Botulinum toxin (BTX) injections, especially when paired with rehabilitation, are among the most effective interventions for these patients. Various techniques for administering BTX injections to the upper limb muscles have been described. However, a standardized method for ultrasound-guided injections in the intrinsic muscles of the hand remains quite scant in the literature. The authors suggest a novel dorsal approach to treat the most common abnormal postural patterns in hand spasticity, thumb-in-palm, and intrinsic plus. This approach facilitates access to the muscles while minimizing patient discomfort, as it avoids the need to open forcibly the spastic hand. The adductor pollicis, flexor pollicis brevis, lumbrical, and interosseus muscles have been identified as primary anatomical targets to improve hand posture and function. Standardized sonographic scans are leveled with anatomical illustrations and probe/patient positioning images for interventional procedures. Additionally, tips and techniques for promptly identifying vascular bundles are included to enhance the safety of the procedures. This technical report aims to provide an easy and ready-to-use tool in clinical practice for injecting intrinsic hand muscles in spastic patients, utilizing a novel dorsal approach. Full article

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

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11 pages, 4941 KiB

Open AccessArticle

Consistent Killers: Conservation of Thrombin-Like Action on Fibrinogen by Bushmaster (Lachesis Species) Venoms Underpins Broad Antivenom Cross-Reactivities

by Lee Jones and Bryan G. Fry

Toxins 2025, 17(5), 224; https://doi.org/10.3390/toxins17050224 - 2 May 2025

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Abstract

Snakebite represents a significant public health challenge in Central and South America, with Lachesis (Bushmaster) species posing unique clinical challenges due to their severe envenomation effects arising from a combination of potent venom and copious venom yields. Using in vitro coagulation assays, we [...] Read more.

Snakebite represents a significant public health challenge in Central and South America, with Lachesis (Bushmaster) species posing unique clinical challenges due to their severe envenomation effects arising from a combination of potent venom and copious venom yields. Using in vitro coagulation assays, we analyzed the coagulotoxic venom effects from four distinct localities: L. muta from Surinam and French Guiana and L. stenophrys from Costa Rica and Panama. This study examined the venom’s impact on human plasma and fibrinogen and evaluated the efficacy of two regionally available antivenoms (PoliVal-ICP and Antivipmyn-Tri) in neutralizing the pathophysiological effects. Our results demonstrated a remarkable consistency in the pseudo-procoagulant venom activity (also known as: thrombin-like) across different species and localities. Antivenom efficacy testing revealed that both the PoliVal-ICP and Antivipmyn-Tri antivenoms effectively neutralized the venom effects across localities for both species, with the ICP antivenom showing the highest neutralization capacity. These toxicology findings highlight the biochemical conservation of venom composition across Lachesis species which underpins effective cross-neutralization in antivenom treatment. Full article

(This article belongs to the Section Animal Venoms)

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20 pages, 5467 KiB

Open AccessArticle

Bongkrekic Acid and Its Novel Isomers: Separation, Identification, and Determination in Food Matrices

by Suhe Dong, Danli Liu, Runfeng Lin, Yingjie Zhu, Peihong Zhu, Xin Jiang, Jie Mao, Yanqing Cao, Jing Peng, Tianyue Zhao, Danning Shen, Tao Li, Kun He and Na Wang

Toxins 2025, 17(5), 223; https://doi.org/10.3390/toxins17050223 - 2 May 2025

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Abstract

The toxicity associated with bongkrekic acid (BKA) is severe due to its chemical structure, which also facilitates high mortality rates; however, its isomer, isobongkrekic acid (iBKA), with only minor structural variance, demonstrates marked differences in toxicity. This discrepancy in structural properties and toxicity [...] Read more.

The toxicity associated with bongkrekic acid (BKA) is severe due to its chemical structure, which also facilitates high mortality rates; however, its isomer, isobongkrekic acid (iBKA), with only minor structural variance, demonstrates marked differences in toxicity. This discrepancy in structural properties and toxicity highlights that risks have been potentially underestimated within current detection standards for BKAs. In this study, a novel BKA trans isomer at the C8 and C9 double carbon bonds (E-configuration), termed iBKA-neo, was successfully separated and identified. Subsequently, the multiple reaction monitoring parameters and chromatographic conditions for three BKA isomers were optimized, enabling effective separation within 15 min via UHPLC-MS/MS, among which the ammonium positive adduct ions yielded significantly higher response intensities for all BKA isomers than traditional deprotonated molecules. Additionally, distinct differences in the ion ratios between iBKA-neo and BKA were utilized for preliminary screening. On this basis, the extraction and enrichment strategies for BKAs were optimized in food matrices and validated comprehensively with good linearity (0.25–500 μg/kg), a superior limit of quantification (0.25 μg/kg), acceptable recoveries (82.32–114.84%), and stable intraday and interday precision (an RSD less than 12.67%). These findings significantly contribute to ecotoxicology and the formulation of safety standards concerning BKAs. Full article

(This article belongs to the Special Issue Novel Technologies for the Detection and Identification of Natural Toxins)

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18 pages, 1815 KiB

Open AccessReview

Against Clostridioides difficile Infection: An Update on Vaccine Development

by Jingyao Wang, Qianquan Ma and Songhai Tian

Toxins 2025, 17(5), 222; https://doi.org/10.3390/toxins17050222 - 1 May 2025

Viewed by 409

Abstract

Clostridioides difficile (C. difficile) is a major pathogen responsible for antibiotic-associated diarrhea, frequently observed in hospital settings. Due to the widespread use of antibiotics, the incidence and severity of C. difficile infection (CDI) are rising across the world. CDI is primarily [...] Read more.

Clostridioides difficile (C. difficile) is a major pathogen responsible for antibiotic-associated diarrhea, frequently observed in hospital settings. Due to the widespread use of antibiotics, the incidence and severity of C. difficile infection (CDI) are rising across the world. CDI is primarily driven by two homologous protein exotoxins, toxin A (TcdA) and toxin B (TcdB). Other putative virulence factors include binary toxin CDT, surface layer proteins, phosphorylated polysaccharides, and spore coat proteins. These C. difficile virulence factors are potential targets for vaccine development. Although several C. difficile vaccines have entered clinical trials, there is currently no approved vaccine on the market. This review outlines the intoxication mechanism during CDI, emphasizing the potential antigens that can be used for vaccine development. We aim to provide a comprehensive overview of the current status of research and development of C. difficile vaccines. Full article

(This article belongs to the Section Bacterial Toxins)

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28 pages, 2126 KiB

Open AccessReview

Snake Venom Compounds: A New Frontier in the Battle Against Antibiotic-Resistant Infections

by Barathan Muttiah and Alfizah Hanafiah

Toxins 2025, 17(5), 221; https://doi.org/10.3390/toxins17050221 - 1 May 2025

Viewed by 486

Abstract

The occurrence of antibiotic-resistant bacteria is a serious global health issue, and it emphasizes the need for novel antimicrobial agents. This review explores the potential of snake venom as another alternative strategy against antimicrobial resistance. Snake venoms are complex combinations of bioactive peptides [...] Read more.

The occurrence of antibiotic-resistant bacteria is a serious global health issue, and it emphasizes the need for novel antimicrobial agents. This review explores the potential of snake venom as another alternative strategy against antimicrobial resistance. Snake venoms are complex combinations of bioactive peptides and proteins, including metalloproteases (MPs), serine proteases (SPs), phospholipase A₂ (PLA₂) enzymes, three-finger toxins (3FTXs), cysteine-rich secretory proteins (CRISPs), L-amino acid oxidases (LAAOs), and antimicrobial peptides (AMPs). The antibacterial products possess wide-spectrum antibacterial activity against resistant microbes via diverse mechanisms such as cell membrane disruption, enzymatic hydrolysis of microbial structures, generation of oxidative stress, inhibition of biofilms, and immunomodulation. Strong antimicrobial activity is reported by most studies, but these are mostly restricted to in vitro testing with low translational use. Although preliminary insights into molecular targets and physiological effects exist, further studies are needed to clarify long-term safety and therapeutic potential. Special attention is given to snake venom-derived extracellular vesicles (SVEVs), which enhance the therapeutic potential of venom toxins by protecting them from degradation, improving bioavailability, and facilitating targeted delivery. Furthermore, innovative delivery strategies such as PEGylation, liposomes, hydrogels, microneedle patches, biopolymer films, and nanoparticles are discussed for their role in reducing systemic toxicity and enhancing antimicrobial efficacy. The rational modification of venom-derived peptides further expands their therapeutic utility by improving pharmacokinetics and minimizing off-target effects. Together, these approaches highlight the translational potential of snake venom-based therapies as next-generation antimicrobials in the fight against resistant infections. By outlining these challenges and directions, this review positions snake venom as an overlooked but fertile resource in the battle against antibiotic resistance. Full article

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18 pages, 4890 KiB

Open AccessArticle

Is There a Correlation Between Masticatory Muscle Thickness and Pain After Botulinum Toxin Injections in Myogenic TMD Patients?: A Pilot Study

by Hye-Ji Park, Hee-Jin Kim and Sung Ok Hong

Toxins 2025, 17(5), 220; https://doi.org/10.3390/toxins17050220 - 28 Apr 2025

Viewed by 469

Abstract

Botulinum toxin type A (BoNT-A), a potent neurotoxin, is increasingly used to treat myogenic temporomandibular disorders (TMDs); however, the interplay between muscle atrophy and pain relief remains incompletely understood. This pilot study investigated how masseter and temporalis muscle thickness and pain intensity change [...] Read more.

Botulinum toxin type A (BoNT-A), a potent neurotoxin, is increasingly used to treat myogenic temporomandibular disorders (TMDs); however, the interplay between muscle atrophy and pain relief remains incompletely understood. This pilot study investigated how masseter and temporalis muscle thickness and pain intensity change over 12 weeks following BoNT-A injections in 15 patients (mean age 51.42 years) with myogenic TMD. Muscle thickness was measured via ultrasonography across multiple anatomical positions under both clenching and resting conditions at baseline and at 2, 4, 8, and 12 weeks post-injection. Significant thinning of both muscles occurred within 2 weeks, lasting until 12 weeks, but became less pronounced after the first month. Pain intensity showed parallel decreases, most notably early on, but these reductions were not consistently statistically significant. Correlation analyses revealed no strong persistent association between muscle thickness and pain except for a moderately positive correlation in the anterior temporalis at two weeks (r = 0.61, p = 0.04). BoNT-A induces rapid masticatory muscle atrophy and modest pain relief; however, these outcomes do not coincide. Pain relief was observed earlier than the full development of muscle atrophy and should be considered during TMD pain management. Full article

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

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Toxins, Volume 17, Issue 5 (May 2025) – 41 articles

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