Toxins

18 pages, 3255 KiB

Open AccessArticle

Growth Response and Cell Permeability of the Fish-Killing Phytoflagellate Heterosigma akashiwo Under Projected Climate Conditions

by Malihe Mehdizadeh Allaf and Charles G. Trick

Toxins 2025, 17(5), 259; https://doi.org/10.3390/toxins17050259 (registering DOI) - 21 May 2025

Abstract

Climate change and anthropogenic alterations in biogeochemical cycles are intensifying the frequency, duration, and potential toxicity of harmful algal blooms (HABs) in marine ecosystems. However, these effects are highly variable and depend on species identity, strain-specific traits, and local environmental conditions. Key drivers [...] Read more.

Climate change and anthropogenic alterations in biogeochemical cycles are intensifying the frequency, duration, and potential toxicity of harmful algal blooms (HABs) in marine ecosystems. However, these effects are highly variable and depend on species identity, strain-specific traits, and local environmental conditions. Key drivers include rising sea surface temperatures, changes in salinity resulting from altered precipitation patterns and runoff, and elevated CO₂ levels leading to ocean acidification. Heterosigma akashiwo, a euryhaline raphidophyte responsible for the widespread killing of fish, is particularly responsive to these changes. This study investigated the combined effects of temperature, salinity, and CO₂ concentration on the growth, yield, and cell membrane permeability of H. akashiwo using a Design of Experiment (DOE) approach. DOE facilitates a detailed and systematic analysis of multifactorial interactions, enabling a deeper understanding of complex relationships while maximizing efficiency and minimizing the use of experimental resources. The results revealed that growth and yield were maximized at higher temperatures and salinities, whereas cell permeability increased under cooler, less saline, and lower CO₂ conditions. These findings suggest that projected future ocean conditions may enhance biomass production while potentially reducing cellular permeability and, by extension, toxicity. This study highlights the value of the DOE framework in identifying key interactions among environmental drivers of HABs, offering a practical foundation for future predictive modeling under climate change scenarios. Full article

(This article belongs to the Special Issue Mechanisms Underlying Metabolic Regulation by Marine Toxins)

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13 pages, 1599 KiB

Open AccessReview

Botulinum Toxin in Pain-Related Post-Stroke Limb Spasticity: A Meta-Analysis of Early and Late Injections

by Frances Marie Tamayo, Raymond Rosales, Jörg Wissel, Bo Biering-Sørensen, Joshua Nathaniel Ellano and David Simpson

Toxins 2025, 17(5), 258; https://doi.org/10.3390/toxins17050258 (registering DOI) - 21 May 2025

Abstract

Spasticity is a common complication associated with stroke, and around 72% of stroke patients will develop pain during the disease. Botulinum toxin (BoNT) is a safe and efficacious treatment for spasticity and can improve associated complications, including pain. Hence, this meta-analysis aims to [...] Read more.

Spasticity is a common complication associated with stroke, and around 72% of stroke patients will develop pain during the disease. Botulinum toxin (BoNT) is a safe and efficacious treatment for spasticity and can improve associated complications, including pain. Hence, this meta-analysis aims to establish whether BoNT can reduce pain-related post-stroke spasticity (pPSS) in the early treatment period (<12 weeks post-stroke) or in the late period (>12 weeks post-stroke) based on the available evidence. This study also aims to establish the dose–response relationship of BoNT-A in pPSS. Based on pooled data from multiple studies, there is no significant difference in the scores measuring pPSS between patients who received early BoNT-A injections and those who received a placebo. This finding suggests that within the early treatment period, BoNT-A may not be more effective than a placebo in reducing pPSS. However, it is important to note that the data for early BoNT-A injections are limited, indicating that research is needed to draw definitive conclusions [z = 3.90 (p < 0.0001)]. While BoNT-A appears somewhat more effective than a placebo in the late phase, as indicated by the small to moderate positive z value, there is not enough evidence to confidently claim superiority over a placebo [z = 1.48 (p = 0.14)]. Full article

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

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16 pages, 1260 KiB

Open AccessReview

Clinical Evidence of Bee Venom Acupuncture for Ankle Pain: A Review of Clinical Research

by Soo-Hyun Sung, Hyein Jeong, Jong-Hyun Park, Minjung Park and Gihyun Lee

Toxins 2025, 17(5), 257; https://doi.org/10.3390/toxins17050257 - 21 May 2025

Abstract

The prevalence of ankle pain in adults is 9–15%, with up to 45% of sports-related injuries attributed to ankle pain and injuries. If ankle pain is not controlled in a timely manner, it can lead to ankle instability, resulting in further damage, recurrence [...] Read more.

The prevalence of ankle pain in adults is 9–15%, with up to 45% of sports-related injuries attributed to ankle pain and injuries. If ankle pain is not controlled in a timely manner, it can lead to ankle instability, resulting in further damage, recurrence of pain, and secondary injuries. The present study aimed to assess the therapeutic potential and safety profile of bee venom acupuncture (BVA) in the management of ankle pain. Ten electronic databases were searched for articles published up to March 2025. We included clinical studies that utilized BVA for the treatment of ankle pain and studies that included pain- and function-related assessment tools. The safety of bee venom acupuncture (BVA) was assessed by extracting adverse events from the included studies and categorizing them according to the Common Terminology Criteria for Adverse Events (CTCAE). A total of 14 clinical studies were selected, of which 9 were case reports, 2 were case-controlled clinical trials (CCTs), and 3 were randomized controlled trials (RCTs). The conditions causing ankle pain were mostly traumatic (42.9%), followed by inflammatory (21.4%) and neuropathic disorders (14.3%). BVA was applied at concentrations ranging from 0.05 to 0.5 mg/mL, with a per-session volume ranging from 0.04 to 2.5 mL. In most studies, BVA was reported to improve both ankle pain and function simultaneously. Among the 14 studies, four participants reported adverse events following BVA treatment, all of which were classified as grade 1 or grade 2, indicating mild to moderate severity. This review suggests that BVA may be recommended for controlling ankle pain based on clinical evidence. However, the number of high-quality RCTs is limited, and half of the studies did not report side effects, indicating the need for further clinical research to verify its safety and efficacy. Full article

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

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25 pages, 1538 KiB

Open AccessSystematic Review

Effect of Ochratoxin A (OTA) on the Immune System: A Systematic Review

by Yusif Mubarik, Shadrach Tetteh Boyetey, Anastasia Rosebud Aikins and Mohamed Mutocheluh

Toxins 2025, 17(5), 256; https://doi.org/10.3390/toxins17050256 - 20 May 2025

Abstract

Ochratoxin A (OTA) is a mycotoxin with different adverse health effects. The authors conducted a systematic review to evaluate the effects of OTA on the immune system, with more emphasis on its effects on immune system organs, innate and adaptive immunity and related [...] Read more.

Ochratoxin A (OTA) is a mycotoxin with different adverse health effects. The authors conducted a systematic review to evaluate the effects of OTA on the immune system, with more emphasis on its effects on immune system organs, innate and adaptive immunity and related signaling pathways. Studies have demonstrated that exposure to OTA disrupts the functions of immune system organs, resulting in weight loss, histological lesions and a decrease in antibody-secreting cells. There is evidence that OTA impairs epithelial barrier integrity and macrophage function and induces elevated secretion of pro-inflammatory cytokines. In adaptive immunity, OTA regulates T-cell differentiation, particularly Th1 and Th17 subsets, and adversely impacts humoral immunity, ultimately leading to immune suppression. Full article

(This article belongs to the Special Issue Mycotoxins in Food and Feeds: Human Health and Animal Nutrition)

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25 pages, 723 KiB

Open AccessSystematic Review

Systematic Review on CyanoHABs in Central Asia and Post-Soviet Countries (2010–2024)

by Kakima Kastuganova, Galina Nugumanova and Natasha S. Barteneva

Toxins 2025, 17(5), 255; https://doi.org/10.3390/toxins17050255 - 20 May 2025

Abstract

Cyanobacterial harmful blooms (CyanoHABs) in lakes, estuaries, and freshwater reservoirs represent a significant risk to water authorities worldwide due to their cyanotoxins and economic impacts. The duration, spread, and severity of CyanoHABs have markedly increased over the past decades. The article addresses CyanoHABs, [...] Read more.

Cyanobacterial harmful blooms (CyanoHABs) in lakes, estuaries, and freshwater reservoirs represent a significant risk to water authorities worldwide due to their cyanotoxins and economic impacts. The duration, spread, and severity of CyanoHABs have markedly increased over the past decades. The article addresses CyanoHABs, cyanotoxins, and monitoring methodologies in post-Soviet and Central Asian countries. This particular region was selected for this systematic review due to its relative lack of representation in global CyanoHABs reporting, particularly in the Central Asian region. The main aim of this systematic review was to analyze the primary literature available from the period of 2010–2024 to examine the current situation of CyanoHAB detection, monitoring, and management in Central Asia and post-Soviet countries. Following a detailed database search in a number of selected databases (Google Scholar, Pubmed, Web of Science (WOS), Scopus, Elibrary, ENU, and KazNU) along with additional hand searching and citation searching, 121 primary articles reporting 214 local cyanobacterial bloom cases were selected for this review. Aquatic cyanotoxins were reported in water bodies of eight countries, including high concentrations of microcystins that often exceeded reference values established by the World Health Organization (WHO). Advancing monitoring efforts in Baltic countries, Belarus, and the Russian Federation differed from only a few Central Asian reports. However, Central Asian aquatic ecosystems are especially threatened by rising anthropogenic pressures (i.e., water use, intensive agriculture, and pollution), climate change, and the lack of adequate ecological surveillance. We hypothesize that recent Caspian seal mass mortality events have been caused by a combination of infection (viral or bacterial) and exposure to algal neurotoxins resulting from harmful algal blooms of Pseudo-nitzschia. We conclude that there is an urgent need to improve the assessment of cyanobacterial blooms in Central Asia and post-Soviet countries. Full article

(This article belongs to the Special Issue Managing and Preventing Harmful Algal Blooms (HABs): Do We Know Enough? (2nd Edition))

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30 pages, 5676 KiB

Open AccessReview

Insecticidal Activities of Diterpene Alkaloids in Plants of the Genera Aconitum and Delphinium

by Jinqiu Wang, Luchuan Zheng, Wenxi Huang, Linxuan Li, Jialian Yuan and Lin Chen

Toxins 2025, 17(5), 254; https://doi.org/10.3390/toxins17050254 - 20 May 2025

Abstract

As the global population grows, food security and agricultural productivity face challenges, and insect pests cause significant losses to crops. The effectiveness of traditional chemical pesticides is declining, and eco-friendly pesticides need to be developed. Diterpenoid alkaloids (DAs), natural products of plant origin, [...] Read more.

As the global population grows, food security and agricultural productivity face challenges, and insect pests cause significant losses to crops. The effectiveness of traditional chemical pesticides is declining, and eco-friendly pesticides need to be developed. Diterpenoid alkaloids (DAs), natural products of plant origin, have attracted attention due to their low environmental risks. Here we review the classification, structure, insecticidal and anti-feeding activities of diterpenoid alkaloids, as well as the current state of research on these chemicals. Studies have shown that C₁₉- and C₂₀-diterpenoid alkaloids show significant activity against a variety of insects, but there are still limited studies on C₁₈-diterpenoid alkaloids. Therefore, through in-depth research on diterpenoid alkaloids, we have discovered that there are various compounds with high efficiency and specificity in insecticidal and antifeedant activities among C₁₉- and C₂₀-diterpenoid alkaloids, which exhibit high selectivity and efficiency towards target pests. This paper emphasizes the potential of diterpenoid alkaloids as novel biopesticides and highlights the need to combine new technologies to conduct further systematic evaluation and screening of these compounds. This work provides new ideas for the development of environmentally friendly pesticides and contributes to sustainable agricultural practices. Full article

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17 pages, 3704 KiB

Open AccessArticle

Heterologous Overexpression of Cytochrome P450BM3 from Bacillus megaterium and Its Role in Gossypol Reduction

by Wenpeng Fan, Jingjing Cui, Tongxiang Xu, Shiheng Xu, Zulibina Ainiwaer, Qiyu Luo and Caidie Wang

Toxins 2025, 17(5), 253; https://doi.org/10.3390/toxins17050253 - 20 May 2025

Abstract

Gossypol is a polyphenolic toxic compound present in cotton plants. To determine whether the candidate cytochrome P450BM3 enzymes could reduce gossypol in vitro, functional recombinant cytochrome P450BM3 enzymes were successfully expressed in E. coli. Site-directed mutagenesis generated mutants (R162H, R162K, Q129H, Q129N) [...] Read more.

Gossypol is a polyphenolic toxic compound present in cotton plants. To determine whether the candidate cytochrome P450BM3 enzymes could reduce gossypol in vitro, functional recombinant cytochrome P450BM3 enzymes were successfully expressed in E. coli. Site-directed mutagenesis generated mutants (R162H, R162K, Q129H, Q129N) to explore structural determinants of catalytic efficiency. Both wild-type P450BM3 and mutants exhibited significant ability to reduce gossypol levels, with R162H and R162K showing 33.4% and 24.2% reduced catalytic efficiency compared with the wild-type enzyme, respectively. Q129H and Q129N mutants maintained comparable catalytic efficiency to the wild type. Metabolomic profiling revealed two distinct reducing pathways catalyzed by wild-type P450BM3 and its mutants (R162H/Q129H), involving decarboxylation, hydroxylation, and C-C bond cleavage. This study demonstrated the feasibility of P450BM3 as a highly efficient biocatalyst for reducing gossypol levels, speculated that Arg162 might be a critical active residue, and hypothesized the potential pathways by which P450BM3 catalyzes the reduction of gossypol content, thereby providing a theoretical foundation for the enzymatic reduction of gossypol. Full article

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13 pages, 1836 KiB

Open AccessArticle

A Comprehensive Probabilistic Risk Assessment Strategy of Aflatoxin B1 Exposure from Medical Areca Nuts Consumption

by Tian-Tian Zuo, Ya-Zhong Zhang, Hong-Yan Zhai, Rong-Yao Chen, Jing-Zhe Pu, Hong-Yu Jin, Jing Liu, Xian-Long Cheng and Feng Wei

Toxins 2025, 17(5), 252; https://doi.org/10.3390/toxins17050252 - 19 May 2025

Abstract

Aflatoxin B₁ (AFB₁) is widely found and substantially impends public health. The current work aimed to assess AFB₁ in medical areca nuts in China. The average content of AFB₁ was 13.0 μg/kg, and the maximum content was 146.0 [...] Read more.

Aflatoxin B₁ (AFB₁) is widely found and substantially impends public health. The current work aimed to assess AFB₁ in medical areca nuts in China. The average content of AFB₁ was 13.0 μg/kg, and the maximum content was 146.0 μg/kg. Furthermore, a comprehensive probabilistic risk assessment approach considering combined utilization of a Monte Carlo simulation with the margin of exposure (MOE) and quantitative liver cancer risk (HCC) strategies was developed for assessing the human health risk of AFB₁ from consuming medical areca nuts for the first time. The MOE values of AFB₁ in samples for no more than the 75th percentile were less than the threshold of 10,000 for both men and women. The estimated 90th percentile to the maximum of the HCC values for males and the estimated 75th percentile to the maximum of the HCC values for females were higher than one in a million upon exposure to medical areca nuts, indicating an unacceptable liver cancer risk. Sensitivity analysis demonstrated that for both MOE and HCC approaches, AFB₁ content was the parameter with the greatest effects on the results, followed by the exposure frequency (EF) and daily intake rate (IR). This study is the first of this kind, demonstrating the applicability of stochastic exposure evaluation techniques for the precise and scientific assessment of the health risk of AFB₁ in medical areca nuts, with the main purpose of minimizing human cancer risk. Full article

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23 pages, 3679 KiB

Open AccessArticle

Impact of Low-Level Ergot Alkaloids and Endophyte Presence in Tall Fescue Grass on the Metabolome and Microbiome of Fall-Grazing Steers

by Ignacio M. Llada, Jeferson M. Lourenco, Madison M. Dycus, Jessica M. Carpenter, Zachery R. Jarrell, Dean P. Jones, Garret Suen, Nicholas S. Hill and Nikolay M. Filipov

Toxins 2025, 17(5), 251; https://doi.org/10.3390/toxins17050251 - 17 May 2025

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Abstract

Fescue toxicosis (FT) is a mycotoxin-related disease caused by the ingestion of tall fescue, naturally infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. Some grazing on endophyte-free (E−) or non-toxic (NT), commercial endophyte-infected pastures takes place in the US as well. [...] Read more.

Fescue toxicosis (FT) is a mycotoxin-related disease caused by the ingestion of tall fescue, naturally infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. Some grazing on endophyte-free (E−) or non-toxic (NT), commercial endophyte-infected pastures takes place in the US as well. Earlier, we found that grazing on toxic fescue with low levels of EAs during fall affects thermoregulation, behavior, and weight gain. Building on these findings, the current study aimed to investigate how the presence of low EA-producing E+ or NT endophytes can influence animal metabolome, microbiome, and, ultimately, overall animal health. Eighteen Angus steers were placed on NT, E+, and E− fescue pastures for 28 days. Urine, rumen fluid (RF), rumen solid (RS), and feces were collected pre-exposure, and on days 2, 7, 14, 21, and 28. An untargeted high-resolution metabolomics approach was used to analyze urine and RF, while 16S rRNA-based next-generation sequencing (NGS) was used to examine RF, RS, feces, and fescue plant microbiomes. While alpha- or beta-microbiota diversity across all analyzed matrices were unaffected, there were specific effects of E+ on the relative abundance of some taxa (i.e., Prevotellaceae). Additionally, E+ grazing impacted aromatic amino acid metabolism in the urine and the metabolism of lipids in both the RF and urine. In both matrices, trace amine-related metabolic features differed markedly between E+ and the other groups. Compared to the endophyte-free group, endophyte presence, whether novel or toxic, influenced amino acid and carbohydrate metabolism, as well as unsaturated fatty acid biosynthesis. These findings suggest that low-EA-producing and non-toxic endophytes in fescue have more prominent effects on the metabolome than the microbiome, and this metabolome perturbation might be associated with decreased performance and reported physiological signs of FT. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 2172 KiB

Open AccessArticle

Ustilaginoidin D Induces Acute Toxicity and Hepatotoxicity in Mice

by Bo Wang, Xiaolong Bai, Min Zhang, Xiangxiang Liu, Muhammad Zulqar Nain Dara, Lingjing Liu, Mingming Ou, Dayong Li, Jiyang Wang, Ling Liu and Wenxian Sun

Toxins 2025, 17(5), 250; https://doi.org/10.3390/toxins17050250 - 17 May 2025

Viewed by 143

Abstract

Ustilaginoidin D is a type of bis-naphtho-γ-pyrone mycotoxin produced by Ustilaginoidea virens, the causal agent of rice false smut. Although previous studies have demonstrated the inhibitory effect of ustilaginoidin D on ATP synthesis and cancer cell growth in mice, its specific health risks [...] Read more.

Ustilaginoidin D is a type of bis-naphtho-γ-pyrone mycotoxin produced by Ustilaginoidea virens, the causal agent of rice false smut. Although previous studies have demonstrated the inhibitory effect of ustilaginoidin D on ATP synthesis and cancer cell growth in mice, its specific health risks remain unclear. Here, we reveal that ustilaginoidin D is highly toxic to mice with an LD₅₀ value of 213 mg /kg·bw. Dose-dependent weight loss and liver damage were observed, accompanied by altered markers of liver cell damage, including the enzyme activities of alanine aminotransferase and aspartate aminotransferase and the content of glutathione in mouse liver. RNA-seq analysis of liver tissues from mice treated with 150 mg of ustilaginoidin D/kg·bw identified significant changes in gene expression profiles, with differentially expressed genes enriched in cancer-related pathways, hypertrophic cardiomyopathy, and metabolic pathways. RT-qPCR data are highly consistent with transcriptome analysis in expression profiles of 22 chemical-carcinogenesis-associated genes. These findings indicate that ustilaginoidin D induces acute toxicity and liver dysfunction in mice, raising serious concerns about its threat to human health. Full article

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

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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

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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

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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

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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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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

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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

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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

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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 289

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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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 166

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 150

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 204

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 177

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 715

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 193

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 208

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 277

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 202

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 634

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 144

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

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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 314

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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