Toxins

13 pages, 3043 KiB

Open AccessArticle

Differential Retention and Loss of a Mycotoxin in Fungal Evolution

by Lin Chen, Ziying Yan, Bolei Yang, Bowen Tai, Weizhao Li, Erfeng Li, Gang Wang and Fuguo Xing

Toxins 2025, 17(6), 311; https://doi.org/10.3390/toxins17060311 - 19 Jun 2025

Viewed by 849

Abstract

Ochratoxin A (OTA) is designated as a mycotoxin and is regulated worldwide due to its harmful effects on humans and animals, but the evolutionary history and ecological significance of OTA in fungi remain poorly understood. Phylogenetic analysis suggested that Aspergillus and Metarhizium obtained [...] Read more.

Ochratoxin A (OTA) is designated as a mycotoxin and is regulated worldwide due to its harmful effects on humans and animals, but the evolutionary history and ecological significance of OTA in fungi remain poorly understood. Phylogenetic analysis suggested that Aspergillus and Metarhizium obtained an ancient OT cluster, which evolved independently, followed by horizontal OT transfer from Aspergillus to Penicillium. The varying presence of functional, absent and pseudogenized OT genes across Aspergillus species revealed that this cluster is undergoing a degeneration process in this genus. Furthermore, the cyclase OtaY in the OTA cluster is likely derived from bacteria, which was revealed by phylogenetic analysis. This is the first attempt to investigate the ecological significance of OTA in fungi, suggesting that it may be nonfunctional in Aspergillus spp. and has undergone multiple forms of loss during evolution. Full article

(This article belongs to the Section Mycotoxins)

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9 pages, 1664 KiB

Open AccessCommunication

Molecular Diagnosis in Hymenoptera Allergy: Comparison of Euroline DPA-Dx and ImmunoCAP

by Lluís Marquès, Arantza Vega, Federico de la Roca, Carmen Domínguez, Víctor Soriano-Gomis, Teresa Alfaya, Laia Ferré-Ybarz, José-María Vega, Mario Tubella and Berta Ruiz-León

Toxins 2025, 17(6), 310; https://doi.org/10.3390/toxins17060310 - 19 Jun 2025

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Abstract

The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the [...] Read more.

The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the limited availability of allergenic components (false negatives). In this study, we analyzed the discrepancies in the results obtained with Euroline^® DPA-Dx and ImmunoCAP^® in the diagnosis of allergic reactions due to Hymenoptera stings in 151 patients. The results (positive/negative) of ImmunoCAP^® and Euroline^® agreed in 77/151 (50.99%) cases; with 15/151 (9.93%) cases positive for the same insect, and 61/151 (40.4%) cases positive for multiple insects. When the results were used to decide which venom to use for immunotherapy, there was a statistically significant discrepancy for Polistes dominula (21.8% of cases with ImmunoCAP^® compared to only 8.4% with Euroline^®). The presence of Polistes venom phospholipase (Pol d 1) in Euroline^® did not increase its ability to differentiate double sensitization to wasps. ImmunoCAP^® and Euroline^® exhibited comparable diagnostic performance in bee venom allergy. For vespid venom allergy—particularly involving Polistes species—ImmunoCAP^® appeared to show a slight diagnostic advantage, although this finding should be interpreted with caution. Full article

(This article belongs to the Section Animal Venoms)

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20 pages, 1159 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

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Abstract

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

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

(This article belongs to the Section Mycotoxins)

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17 pages, 2956 KiB

Open AccessArticle

Comparative Efficacy of Ribosome-Inactivating Protein-Containing Immunotoxins in 2D and 3D Models of Sarcoma

by Giulia Calafato, Massimo Bortolotti, Letizia Polito and Andrea Bolognesi

Toxins 2025, 17(6), 308; https://doi.org/10.3390/toxins17060308 - 18 Jun 2025

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Abstract

Sarcomas are very complex and clinically challenging mesenchymal tumors. Although the standard therapeutic approach has improved the 5-year survival rate, many patients experience local relapses and/or distant metastases. To improve patient outcome, new strategies need to be investigated. Immunotoxins (ITs) based on rRNA [...] Read more.

Sarcomas are very complex and clinically challenging mesenchymal tumors. Although the standard therapeutic approach has improved the 5-year survival rate, many patients experience local relapses and/or distant metastases. To improve patient outcome, new strategies need to be investigated. Immunotoxins (ITs) based on rRNA N-glycosylases (also named ribosome-inactivating proteins, RIPs) are promising tools for cancer therapy because, by combining rRNA-glycosylase’s high cytotoxicity with carrier selectivity, they can specifically eliminate target neoplastic cells. In the last few years, 3D models have been extensively used in cancer research, particularly for target-specific drug screening. This study aimed to evaluate the possibility of utilizing ribosome-inactivating protein (RIP)-containing ITs to selectively target TfR1-, EGFR1- and Her2-expressing sarcoma adherent cells (ACs), spheroids (SSs) and organoids (ORs). To compare Its’ efficacy and ability to induce apoptosis, we performed dose–response viability and caspase 3/7 activation assays on rhabdomyosarcoma and osteosarcoma ACs, SSs and ORs treated with Tf-IT, αEGFR1-IT and αHer2-IT. Our results indicate that, compared to the corresponding unconjugated RIPs, all ITs showed increased cytotoxicity in sarcoma ACs. Despite the increased complexity characterizing 3D models, the higher IC₅₀ differences between ITs and unconjugated RIPs were obtained in ORs, which appeared more resistant to the nonspecific killing of the RIPs than either the ACs or SSs, thus augmenting the therapeutic window between unconjugated and conjugated RIPs. IT induced a more delayed apoptosis in 3D compared to 2D models. Our results provide essential outcomes for the potential use of these RIP-based ITs as a therapeutic strategy to treat sarcoma. Full article

(This article belongs to the Special Issue Plant Toxin Emergency)

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18 pages, 2415 KiB

Open AccessArticle

Growth Dynamics and Toxin Production of Pseudo-nitzschia Species Isolated from the Central Adriatic Sea

by Tina Tomašević, Jasna Arapov, Ivana Ujević, Tina Bonačić, Mia Bužančić, Antonija Bulić, Sanda Skejić, Romana Roje-Busatto and Živana Ninčević Gladan

Toxins 2025, 17(6), 307; https://doi.org/10.3390/toxins17060307 - 17 Jun 2025

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Abstract

The marine diatoms Pseudo-nitzschia spp. are globally distributed primary producers, with certain species capable of producing neurotoxin domoic acid (DA), causing amnesic shellfish poisoning (ASP). This study investigates the toxicity and growth rates of Pseudo-nitzschia species isolated from aquaculture areas in the Central [...] Read more.

The marine diatoms Pseudo-nitzschia spp. are globally distributed primary producers, with certain species capable of producing neurotoxin domoic acid (DA), causing amnesic shellfish poisoning (ASP). This study investigates the toxicity and growth rates of Pseudo-nitzschia species isolated from aquaculture areas in the Central Adriatic Sea. A total of 54 strains from eight species were analysed, with strains originating from four different study sites. Growth rates and toxin production were examined across different growth phases in other species and strains. Most species, including P. allochrona, P. calliantha, P. delicatissima, P. fraudulenta, P. galaxiae, P. mannii, and P. multistriata, did not produce DA at any growth phase. The only species that showed toxin production, at 18 °C was P. pseudodelicatissima (0.0007–0.0250 pg cell⁻¹). Notably, the majority of P. pseudodelicatissima strains were toxic in the decay phase and some strains showed continuous toxin production throughout all growth phases. The highest growth rates for the analysed species were recorded in strains of P. delicatissima, which also exhibited the highest cell abundance (8.19 × 10⁵ cell mL⁻¹), followed by the species P. allochrona, P. mannii and P. pseudodelicatissima. Full article

(This article belongs to the Special Issue Unraveling the Environmental Threat of Harmful Algae Blooms (HABs): Causes and Impacts)

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16 pages, 6694 KiB

Open AccessArticle

LL-37 Attenuates Sepsis-Induced Lung Injury by Alleviating Inflammatory Response and Epithelial Cell Oxidative Injury via ZBP1-Mediated Autophagy

by Hu Gao, Fajuan Tang, Bin Chen and Xihong Li

Toxins 2025, 17(6), 306; https://doi.org/10.3390/toxins17060306 - 17 Jun 2025

Viewed by 560

Abstract

Background: Sepsis-induced acute lung injury (ALI) is a serious disease constituting a heavy burden on society due to high mortality and morbidity. Inflammation and oxidative stress constitute key pathological mechanisms in ALI caused by sepsis. LL-37 can improve the survival of septic mice. [...] Read more.

Background: Sepsis-induced acute lung injury (ALI) is a serious disease constituting a heavy burden on society due to high mortality and morbidity. Inflammation and oxidative stress constitute key pathological mechanisms in ALI caused by sepsis. LL-37 can improve the survival of septic mice. Nevertheless, its function and underlying mechanism in sepsis-evoked ALI is elusive. Methods: The human A549 alveolar epithelial cell line was treated with LL-37 or ZBP1 recombinant vector under LPS exposure. Then, the effects on cell oxidative stress injury, inflammatory response, and autophagy were analyzed. RNA-seq analysis was performed to detect the differentially expressed genes (DEGs) between the LPS and LPS/LL-37 groups. Furthermore, the effects of LL-37 on cecal ligation and the puncture (CLP)-constructed ALI model were explored. Results: LL-37 attenuated LPS-evoked oxidative injury in human alveolar epithelial cells by increasing cell viability and suppressing ROS, malondialdehyde, and lactate dehydrogenase levels and apoptosis. Moreover, LPS-induced releases of pro-inflammatory IL-18, TNF-α, and IL-1β were suppressed by LL-37. Furthermore, LPS’s impairment of autophagy was reversed by LL-37. RNA-seq analysis substantiated 1350 differentially expressed genes between the LPS and LPS/LL-37 groups. Among them was ZBP1, a significantly down-regulated gene with the largest fold change. Moreover, LL-37 suppressed LPS-increased ZBP1 expression. Importantly, ZBP1 elevation restrained LL-37-induced autophagy in LPS-treated cells and abrogated LL-37-mediated protection against LPS-evoked oxidative injury and inflammation. LL-37 ameliorated abnormal histopathological changes, tissue edema, the lung injury score, oxygenation index (PaO2/FiO2), and glycemia contents in the CLP-constructed ALI model, which were offset through ZBP1 elevation via its activator CBL0137. Additionally, LL-37 suppressed inflammation and oxidative stress in lung tissues, concomitant with autophagy elevation and ZBP1 down-regulation. Conclusions: LL-37 may alleviate the progression of sepsis-evoked ALI by attenuating pulmonary epithelial cell oxidative injury and inflammatory response via ZBP1-mediated autophagy activation, indicating a promising approach for the therapy of ALI patients. Full article

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14 pages, 832 KiB

Open AccessReview

Biological Mechanisms of Enterotoxigenic Bacteroides fragilis Toxin: Linking Inflammation, Colorectal Cancer, and Clinical Implications

by Seyedesomaye Jasemi, Paola Molicotti, Milena Fais, Ilaria Cossu, Elena Rita Simula and Leonardo A. Sechi

Toxins 2025, 17(6), 305; https://doi.org/10.3390/toxins17060305 - 16 Jun 2025

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Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) has emerged as a gut microbiome pathogen that can promote intestinal inflammation and contribute to colorectal cancer (CRC). Its principal virulence factor, the Bacteroides fragilis toxin (BFT), is a zinc-dependent metalloprotease that disrupts epithelial barrier integrity, initiates inflammatory signaling [...] Read more.

Enterotoxigenic Bacteroides fragilis (ETBF) has emerged as a gut microbiome pathogen that can promote intestinal inflammation and contribute to colorectal cancer (CRC). Its principal virulence factor, the Bacteroides fragilis toxin (BFT), is a zinc-dependent metalloprotease that disrupts epithelial barrier integrity, initiates inflammatory signaling pathways, and enhances epithelial proliferation. Although growing evidence supports a link between ETBF and CRC, some inconsistencies across studies highlight the need for further investigation into the molecular mechanisms underpinning BFT-mediated pathogenesis. This review examines the biological structure and activity of BFT, with a focus on its role in epithelial injury, inflammatory responses, and tumorigenesis. In addition, we discuss current challenges in the detection and characterization of ETBF and BFT, including technical limitations in clinical diagnostics and methodological variability across studies. Recent advances in multi-omics technologies, molecular diagnostics, nanobody-based detection platforms, and probiotic intervention are also highlighted as promising avenues for improving ETBF identification and therapeutic targeting. Future research integrating systematic molecular profiling with clinical data is essential to enhance diagnostic accuracy, elucidate pathophysiological mechanisms, and develop effective interventions against ETBF-associated diseases. Full article

(This article belongs to the Special Issue Enterotoxigenic Bacteroides fragilis Toxin: Biological Properties and Pathogenesis)

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17 pages, 911 KiB

Open AccessArticle

Toxicodynamic Assessment of Aqueous Neem (Azadirachta indica A. Juss) Seed Extract on Mortality and Carboxylesterase Activity in Key Organs of Bombyx mori L. Larvae

by Ajin Rattanapan, Chuthep Phannasri, Chawiwan Phannasri, Patcharawan Sujayanont and Kattinat Sagulsawasdipan

Toxins 2025, 17(6), 304; https://doi.org/10.3390/toxins17060304 - 16 Jun 2025

Viewed by 404

Abstract

Botanical insecticides derived from neem (Azadirachta indica A. Juss.) seeds have gained significant interest due to their sustainable characteristics and low environmental impact. However, their use in sericulture remains contentious due to the heightened sensitivity of domesticated silkworms to environmental stressors. This [...] Read more.

Botanical insecticides derived from neem (Azadirachta indica A. Juss.) seeds have gained significant interest due to their sustainable characteristics and low environmental impact. However, their use in sericulture remains contentious due to the heightened sensitivity of domesticated silkworms to environmental stressors. This study systematically investigates the toxicodynamic effects of aqueous neem seed extract (ANSE) on fifth instar larvae of Thai multivoltine Bombyx mori L., focusing on larval mortality and carboxylesterase (CarE) enzyme activity in essential detoxification organs. Larvae were exposed to ANSE concentrations ranging from 5 to 50 mg L⁻¹ for up to 72 h. Key findings highlight a pronounced dose- and time-dependent increase in mortality, with an accurately determined LC₅₀ value of 17 mg L⁻¹ at the longest time exposure, accompanied by mortality rates reaching approximately 83% at the highest concentration tested, indicating considerable susceptibility. Additionally, notable and distinct organ-specific responses were observed, with significant inhibition of CarE activity in the midgut contrasting with elevated activities in the fat body and Malpighian tubules. These differential enzymatic responses reveal previously undocumented adaptive detoxification mechanisms. Consequently, the study advocates cautious and regulated application of neem-based insecticides in sericulture, recommending precise management of concentrations and exposure durations according to silkworm strain sensitivities to ensure optimal silk production. Full article

(This article belongs to the Section Plant Toxins)

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18 pages, 4121 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 952

Abstract

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

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

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

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21 pages, 3474 KiB

Open AccessArticle

An Experimental Model of Acute Pulmonary Damage Induced by the Phospholipase A₂-Rich Venom of the Snake Pseudechis papuanus

by Daniela Solano, Alexandra Rucavado, Teresa Escalante, Edith Bastos Gandra Tavares, Suellen Karoline Moreira Bezerra, Clarice Rosa Olivo, Edna Aparecida Leick, Julio Alejandro Rojas Moscoso, Lourdes Dias, Iolanda de Fátima Lopes Calvo Tibério, Stephen Hyslop and José María Gutiérrez

Toxins 2025, 17(6), 302; https://doi.org/10.3390/toxins17060302 - 12 Jun 2025

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Abstract

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as [...] Read more.

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary–alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Full article

(This article belongs to the Section Animal Venoms)

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20 pages, 1582 KiB

Open AccessArticle

Bioaccumulation, Distribution and Biotransformation of Cylindrospermopsin in Potato (Solanum tuberosum) After Exposure by Surface or Sprinkler Irrigation

by Fredy Duque, Ana Isabel Prieto, Antonio Cascajosa-Lira, Luis Carlos Montenegro, Alexandre Campos, Angeles Jos and Ana M. Cameán

Toxins 2025, 17(6), 301; https://doi.org/10.3390/toxins17060301 - 12 Jun 2025

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Abstract

Cylindrospermopsin is an emerging cyanotoxin that can lead to phytotoxicity through different mechanisms. The presence of CYN in irrigation waters is of concern due to potential accumulation in plants, increasing the risk of human exposure by the consumption of vegetables. In this case, [...] Read more.

Cylindrospermopsin is an emerging cyanotoxin that can lead to phytotoxicity through different mechanisms. The presence of CYN in irrigation waters is of concern due to potential accumulation in plants, increasing the risk of human exposure by the consumption of vegetables. In this case, it is proposed to evaluate the effects of CYN on a crop considered staple food in Colombia, such as Solanum tuberosum, group Phureja var Criolla Colombia, known as “yellow potato”. This work evaluates for the first time the effects of CYN in potato plants exposed to this toxin using two different irrigation systems, surface and sprinkler irrigation. The parameters evaluated were CYN bioaccumulation and biotransformation in different parts of the potato plants irrigated with water containing CYN at environmentally relevant concentrations (84.65, 33.80, 3.05 and 3.05 µg/L after first, second, and third to fourth applications, respectively) and changes in nutritional mineral content in tubers. For this purpose, the concentrations of CYN and its potential metabolites in leaves, stem, roots, and tubbers of the plants exposed to the toxin were determined by Ultra-high Performance Liquid Chromatography–MS/MS (UHPLC-MS/MS). Mineral content was determined by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). CYN bioaccumulation was detected only in aerial parts of plants with sprinkler irrigation. A total of 57 CYN metabolites were found, and the main differences obtained in CYN biotransformation are linked to tissues and exposure conditions. There are significant differences in levels of Ca, K, Mg, Na, P, Cu, Fe, Mn, and Zn in tubers depending on CYN treatment, with higher contents after surface irrigation, and lower content with sprinkler application. These results demonstrate that the exposure conditions are an important factor for the potential presence and effects of CYN in potato plants. Full article

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

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13 pages, 5517 KiB

Open AccessArticle

Subchronic Exposure to Microcystin-LR Induces Hepatic Inflammation, Oxidative Stress, and Lipid Metabolic Disorders in Darkbarbel Catfish (Tachysurus vachelli)

by Huaxing Zhou, Tong Li, Huan Wang, Ye Zhang, Yuting Hu, Amei Liu and Guoqing Duan

Toxins 2025, 17(6), 300; https://doi.org/10.3390/toxins17060300 - 12 Jun 2025

Viewed by 369

Abstract

Microcystin-leucine arginine (MC-LR) is a prominent water pollutant known for its potent hepatic toxicity. However, the effects of subchronic exposure to environmentally relevant concentrations of MC-LR on the fish liver remain poorly understood. This study aimed to systematically evaluate the impact of subchronic [...] Read more.

Microcystin-leucine arginine (MC-LR) is a prominent water pollutant known for its potent hepatic toxicity. However, the effects of subchronic exposure to environmentally relevant concentrations of MC-LR on the fish liver remain poorly understood. This study aimed to systematically evaluate the impact of subchronic MC-LR exposure on the liver of darkbarbel catfish (Tachysurus vachelli). A total of 270 one-year-old fish were exposed to MC-LR (0, 2, and 5 μg/L) for 28 days and sampled on days 14 (D14) and 28 (D28). Histopathological analysis revealed marked hepatic inflammation in the MC-LR treatment groups, manifested as cellular degeneration, hyperemia, and inflammation. MC-LR exposure induced oxidative stress, evidenced by elevated malondialdehyde (MDA) levels and compensatory upregulation of superoxide dismutase (SOD) activity on D28. While hepatic lipid profiles were not altered by low-dose MC-LR, significant elevation of low-density lipoprotein cholesterol (LDL-C) specifically on D28 indicated incipient lipid metabolic disorder. Metabolomic analysis demonstrated a higher sensitivity, highlighting the stress response of the liver to low-dose MC-LR exposure. The results suggest MC-LR exposure disrupted hepatic phosphatidylcholine (PC) biosynthesis and inhibited lipoprotein formation, thereby impairing lipid transport and contributing to lipid metabolic disorders. In summary, subchronic exposure to environmentally relevant concentrations of MC-LR-induced hepatic tissue inflammation, oxidative stress, and lipid metabolic disorders in darkbarbel catfish. Full article

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9 pages, 1635 KiB

Open AccessCommunication

Dual-Toxin-Producing Clostridium botulinum Strain Isolated from a Foodborne Botulism Case in Korea: Genomic and Functional Insights

by Eun-Sun Choi, Chi-Hwan Choi, Jun-Ho Jeon, So-Hyeon Kim, Hyun-Ju Song, Hwajung Yi, Gi-eun Rhie and Yoon-Seok Chung

Toxins 2025, 17(6), 299; https://doi.org/10.3390/toxins17060299 - 12 Jun 2025

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Abstract

Clostridium botulinum produces one of the most potent biological toxins and causes botulism, a rare but potentially fatal neuroparalytic disease. In 2014, a foodborne botulism case was reported in Korea, and a strain (CB-2014001) was isolated. Initial characterization identified it as a BoNT/B-producing [...] Read more.

Clostridium botulinum produces one of the most potent biological toxins and causes botulism, a rare but potentially fatal neuroparalytic disease. In 2014, a foodborne botulism case was reported in Korea, and a strain (CB-2014001) was isolated. Initial characterization identified it as a BoNT/B-producing strain based on mouse bioassay and conventional PCR. However, subsequent genomic analysis revealed the presence of dual BoNT gene clusters, bont/B and bont/F, corresponding to subtypes B5 and F2, respectively. Therefore, we aimed to analyze the genetic characteristics and toxin expression profiles of the isolated strain. The strain showed high sequence identity with Bf-type strains such as CDC 3281 and An436. Functional assays confirmed simultaneous expression of both BoNT/B and /F toxins at 35 °C, and temperature-dependent assays revealed predominant expression of BoNT/F at 30 °C and BoNT/B at 37 °C, indicating that toxin expression is influenced by environmental temperature. These findings highlight the potential for differential pathogenicity based on culture conditions and underscore the importance of developing diagnostic tools capable of detecting multiple bont genes. To our knowledge, this is the first report of a dual-toxin-producing C. botulinum strain associated with foodborne botulism in Korea, providing important insights into botulism diagnosis, treatment strategies, and public health preparedness. Full article

(This article belongs to the Section Bacterial Toxins)

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16 pages, 2935 KiB

Open AccessArticle

Cladoceran Chydorus sphaericus and Colonial Cyanobacteria: Potentially a Toxic Relationship?

by Helen Agasild, Ilmar Tõnno, Margarita E. Gonzales Ferraz, Peeter Nõges, Priit Zingel, Lea Tuvikene, René Freiberg, Tiina Nõges and Kristel Panksep

Toxins 2025, 17(6), 298; https://doi.org/10.3390/toxins17060298 - 12 Jun 2025

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Abstract

Chydorus sphaericus is often a dominant cladoceran zooplankton species in water bodies experiencing harmful cyanobacterial blooms. However, its relationship with toxin-producing algae remains largely unexplored. In this study, the feeding behavior of C. sphaericus on colonial cyanobacteria and potentially toxic Microcystis was investigated [...] Read more.

Chydorus sphaericus is often a dominant cladoceran zooplankton species in water bodies experiencing harmful cyanobacterial blooms. However, its relationship with toxin-producing algae remains largely unexplored. In this study, the feeding behavior of C. sphaericus on colonial cyanobacteria and potentially toxic Microcystis was investigated in a temperate, shallow, eutrophic lake. Liquid chromatographic analyses of phytoplankton marker pigments in C. sphaericus gut content revealed that pigments characteristic of cyanobacteria (identified a zeaxanthin, echinenone, and canthaxanthin) comprised the majority of its diet. Among them, colonial cyanobacteria (marked by the pigment canthaxanthin) were the highly preferred food source despite their minor contribution to phytoplankton biomass. qPCR targeting Microcystis genus-specific mcyE synthase genes, which are involved in microcystin biosynthesis, indicated that potentially toxic strains of Microcystis were present in C. sphaericus gut content throughout its temporal and spatial presence in the lake. The results suggest that the common small cladoceran in eutrophic waters, C. sphaericus, has a close trophic interaction with colonial cyanobacteria (including Microcystis) and may represent an important vector for transferring toxigenic Microcystis to the food web, even under conditions of low Microcystis biomass in the lake water. Full article

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

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10 pages, 260 KiB

Open AccessReview

Calcimimetics and Vascular Calcification

by Avinash Chandu, Carolt Arana, Juan Daniel Díaz-García, Mario Cozzolino, Paola Ciceri and José-Vicente Torregrosa

Toxins 2025, 17(6), 297; https://doi.org/10.3390/toxins17060297 - 12 Jun 2025

Viewed by 578

Abstract

In patients with chronic kidney disease (CKD), cardiovascular events (CVA) are the main cause of morbidity and mortality. Vascular calcification, linked to bone mineral metabolism disorders such as elevated serum phosphate, parathyroid hormone (PTH), and FGF23, well-known uremic toxins, aggravate this risk. Calcimimetics [...] Read more.

In patients with chronic kidney disease (CKD), cardiovascular events (CVA) are the main cause of morbidity and mortality. Vascular calcification, linked to bone mineral metabolism disorders such as elevated serum phosphate, parathyroid hormone (PTH), and FGF23, well-known uremic toxins, aggravate this risk. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR), a G protein-coupled receptor that regulates PTH secretion and synthesis in response to changes in extracellular calcium in the parathyroid glands. Through direct and indirect mechanisms, they have demonstrated their efficacy in reducing the progression of vascular, valvular, and soft tissue calcification in experimental studies. Although clinical studies in dialysis patients did not achieve statistical significance in their primary objectives, positive results in subgroup analyses suggest that the lack of significance may be attributable to the short follow-up period. This finding highlights the need to consider early treatment strategies, especially in advanced stages of chronic kidney disease, to more effectively address the progression of vascular calcification through serum uremic toxins control. Full article

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

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16 pages, 3327 KiB

Open AccessReview

Cyanobacterial Blooms and the Presence of Cyanotoxins in the Brazilian Amazon

by Maria Paula Cruz Schneider, Elane Cunha, Lucas Silva, James Leão, Vanessa Costa Tavares, Eliane Brabo de Sousa and Silvia Faustino

Toxins 2025, 17(6), 296; https://doi.org/10.3390/toxins17060296 - 11 Jun 2025

Viewed by 639

Abstract

The records of blooms and cyanotoxins in the Brazilian Legal Amazon are scarce and do not represent the reality observed in recent years when there was an increase in notifications and studies carried out in this region. In this article, we carefully analyzed [...] Read more.

The records of blooms and cyanotoxins in the Brazilian Legal Amazon are scarce and do not represent the reality observed in recent years when there was an increase in notifications and studies carried out in this region. In this article, we carefully analyzed 48 studies to identify the locations where the blooms occurred, the most frequent species, and the tests performed to detect cyanotoxins within the territory of the Brazilian Legal Amazon. The analyzed studies identified approximately 145 taxa of cyanobacteria, and the most frequent species belong to the genera Microcystis and Planktothrix. The most frequently detected cyanotoxin was microcystin, and, in some locations, even with a low cell density, there was the production of toxins. In most cases, Microcystis and Dolichospermum were the major genera associated with blooms and toxin production. The state of Pará had the highest number of records of toxin-producing cyanobacteria, including records of seasonal events, while Acre had no records. This work contributes to our knowledge of the geographic distribution and occurrence of cyanobacteria and cyanotoxins in the Brazilian Amazon and proposes new strategies for improving the monitoring of cyanotoxins in the Amazon region. Full article

(This article belongs to the Special Issue New Reports of Toxigenic Cyanobacteria and Cyanotoxins in Understudied Regions)

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20 pages, 335 KiB

Open AccessReview

From Physicochemical Classification to Multidimensional Insights: A Comprehensive Review of Uremic Toxin Research

by Mario Cozzolino, Lorenza Magagnoli and Paola Ciceri

Toxins 2025, 17(6), 295; https://doi.org/10.3390/toxins17060295 - 10 Jun 2025

Viewed by 609

Abstract

Chronic kidney disease (CKD) is a global health burden, with uremic toxins (UTs) playing a central role in its pathophysiology. In this review, we systematically examined the evolution of UT classification from the 2003 European Uremic Toxin Work Group (EUTox) system based on [...] Read more.

Chronic kidney disease (CKD) is a global health burden, with uremic toxins (UTs) playing a central role in its pathophysiology. In this review, we systematically examined the evolution of UT classification from the 2003 European Uremic Toxin Work Group (EUTox) system based on molecular weight and protein-binding properties to the 2023 multidimensional framework integrating clinical outcomes, clearance technologies, and artificial intelligence. We highlighted the toxicity mechanisms of UTs across the cardiovascular, immune, and nervous systems and evaluated traditional (e.g., low-/high-flux hemodialysis) and advanced (e.g., high-cutoff dialysis and hemoadsorption) clearance strategies. Despite progress, challenges persist in toxin detection, clearance efficiency, and personalized therapy. Future directions include multi-omics-based biomarker discovery, optimized dialysis membranes, advanced adsorption technology, and AI-driven treatment personalization. This synthesis aims to bridge translational gaps and guide precision medicine in nephrology. Full article

(This article belongs to the Special Issue Contemporary and Emerging Modalities of Kidney Assistance Therapy for Patients with Kidney Dysfunction Requiring Dialysis)

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21 pages, 1915 KiB

Open AccessArticle

CYP1B1 Knockout in a Bovine Hepatocyte-like Cell Line (BFH12) Unveils Its Role in Liver Homeostasis and Aflatoxin B1-Induced Hepatotoxicity

by Silvia Iori, Ludovica Montanucci, Caterina D’Onofrio, Maija Lahtela-Kakkonen, Lorena Lucatello, Anisa Bardhi, Andrea Barbarossa, Francesca Capolongo, Anna Zaghini, Marianna Pauletto, Mauro Dacasto and Mery Giantin

Toxins 2025, 17(6), 294; https://doi.org/10.3390/toxins17060294 - 10 Jun 2025

Viewed by 626

Abstract

CYP1B1 is a key enzyme involved in xenobiotic and endogenous metabolism, yet its physiological role in bovine liver homeostasis remains unclear. In this study, we generated a CYP1B1 knockout (CYP1B1^KO) bovine hepatocyte-like cell line to indirectly investigate its role in [...] Read more.

CYP1B1 is a key enzyme involved in xenobiotic and endogenous metabolism, yet its physiological role in bovine liver homeostasis remains unclear. In this study, we generated a CYP1B1 knockout (CYP1B1^KO) bovine hepatocyte-like cell line to indirectly investigate its role in liver function. Transcriptomic analysis revealed alterations in immune regulation, epithelial barrier integrity, and detoxification pathways, with concurrent compensatory CYP1A1 upregulation. Beyond its physiological role, CYP1B1 was found to actively participate in Aflatoxin B1 (AFB1) metabolism, a mycotoxin posing significant health risks to humans and livestock. Molecular docking suggested that CYP1B1 facilitates the conversion of AFB1 into AFM1 and AFBO. In agreement with these predictions, CYP1B1^KO cells exposed to AFB1 showed reduced AFM1 production and decreased cytotoxicity. Further transcriptomic analysis indicated that CYP1B1^KO cells exhibited mitigated oxidative stress and inflammatory responses, along with downregulation of CYP3A74, a key enzyme in AFB1 bioactivation. This suggests that CYP1B1 KO reduces AFB1 toxicity by directly limiting AFB1 bioactivation and indirectly modulating the broader hepatic CYP network, further limiting the formation of toxic intermediates. These findings provide novel insights into CYP1B1’s function in bovine hepatocytes, highlighting its dual role in maintaining liver homeostasis and mediating AFB1 metabolism. The observed interplay between CYP1B1, CYP1A1, and CYP3A74 underscores the complexity of AFB1 biotransformation and warrants further investigation into the coordinated regulation of xenobiotic metabolism in cattle. Full article

(This article belongs to the Section Mycotoxins)

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18 pages, 3009 KiB

Open AccessArticle

Lipopolysaccharide Induces Mitochondrial Fragmentation and Energetic Shift in Reactive Microglia: Evidence for a Cell-Autonomous Program of Metabolic Plasticity

by Marcelle Pereira dos Santos, Vitor Emanuel Leocadio, Lívia de Sá Hayashide, Mariana Marques, Clara Fernandes Carvalho, Antonio Galina and Luan Pereira Diniz

Toxins 2025, 17(6), 293; https://doi.org/10.3390/toxins17060293 - 9 Jun 2025

Viewed by 745

Abstract

Microglia, the resident immune cells of the central nervous system (CNS), play essential roles in maintaining brain homeostasis. While transient activation is protective, chronic microglial reactivity contributes to neuroinflammatory damage and neurodegeneration. The mitochondrial mechanisms underlying this shift remain poorly understood. Here, we [...] Read more.

Microglia, the resident immune cells of the central nervous system (CNS), play essential roles in maintaining brain homeostasis. While transient activation is protective, chronic microglial reactivity contributes to neuroinflammatory damage and neurodegeneration. The mitochondrial mechanisms underlying this shift remain poorly understood. Here, we investigated whether lipopolysaccharide (LPS) induces coordinated mitochondrial and metabolic alterations in BV-2 microglial cells. LPS stimulation (100 ng/mL, 24 h) induced a reactive phenotype, with increased Iba1 (+82%), F4/80 (+132%), and Cd68 (+44%), alongside elevated hydrogen peroxide (~6-fold) and nitrite (~45-fold). Cytotoxicity increased by 40% (LDH assay), and cell viability dropped to ~80% of the control (MTT). Extracellular lactate increased, indicating glycolytic reprogramming. However, LPS-primed cells showed greater ATP depletion under antimycin A challenge, reflecting impaired metabolic flexibility. Hoechst staining revealed a ~4-fold increase in pyknotic nuclei, indicating apoptosis. Mitochondrial dysfunction was confirmed by a 30–40% reduction in membrane potential (TMRE, JC-1), a ~30% loss of Tomm20, and changes in dynamics: phospho-Drp1 increased (+23%), while Mfn1/2 decreased (33%). Despite a ~70% rise in Lamp2 signal, Tomm20–Lamp2 colocalization decreased, suggesting impaired mitophagy. High-resolution respirometry revealed decreased basal (−22%), ATP-linked (24%), and spare respiratory capacity (41%), with increased non-mitochondrial oxygen consumption. These findings demonstrate that LPS induces mitochondrial dysfunction, loss of metabolic adaptability, and increased apoptotic susceptibility in microglia. Mitochondrial quality control and energy flexibility emerge as relevant targets to better understand and potentially modulate microglial responses in neuroinflammatory and neurodegenerative conditions. Full article

(This article belongs to the Section Bacterial Toxins)

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13 pages, 3351 KiB

Open AccessArticle

Patient Satisfaction with Aesthetic Outcomes Following OnabotulinumtoxinA Treatment for Chronic Migraine: A Cross-Sectional Study

by Magdalena Boczarska-Jedynak, Marta Bott-Karoń, Karol Marschollek, Mariola Antolak, Maciej Świat and Marta Waliszewska-Prosół

Toxins 2025, 17(6), 292; https://doi.org/10.3390/toxins17060292 - 8 Jun 2025

Viewed by 700

Abstract

OnabotulinumtoxinA (OnaBoNT-A) is approved for chronic migraine prevention and follows the PREEMPT protocol with injections in the glabellar and forehead regions. While aesthetic changes are considered a side effect, their effect on patient satisfaction has not been thoroughly assessed. This study evaluated patient [...] Read more.

OnabotulinumtoxinA (OnaBoNT-A) is approved for chronic migraine prevention and follows the PREEMPT protocol with injections in the glabellar and forehead regions. While aesthetic changes are considered a side effect, their effect on patient satisfaction has not been thoroughly assessed. This study evaluated patient satisfaction with facial aesthetic outcomes after repeated OnaBoNT-A treatment for chronic migraine. Conducted at specialist headache centers, it included adult patients with chronic migraine who had received at least three OnaBoNT-A cycles. Participants completed a structured questionnaire on demographics, migraine history, facial wrinkles and age perception, appearance satisfaction, psychological impact, treatment satisfaction, and adverse aesthetic events. A total of 124 patients (92.7% female; median age 42.5 years) participated. OnaBoNT-A reduced wrinkle severity (p < 0.0001). Most patients (74.2%) reported aesthetic improvement post-treatment. The majority of patients (76.7%) declared that treatment met or exceeded expectations. 32% reported looking younger post-treatment, with a median perceived age difference of 5 years. Adverse event frequency was similar to pivotal trial outcomes, mostly mild, with no treatment discontinuations. OnaBoNT-A for chronic migraine, following the PREEMPT protocol, provides significant therapeutic benefits and high patient satisfaction regarding aesthetic outcomes. Although aesthetic side effects were generally mild, they were not uncommon. Full article

(This article belongs to the Special Issue Botulinum Neurotoxins for the Treatment of Chronic Pain and Headaches)

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21 pages, 7088 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Viewed by 1276

Abstract

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

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

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

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16 pages, 7887 KiB

Open AccessArticle

The Ghost of Predator Past: Interaction of Past Predator Exposure and Resource Availability on Toxin Retention and Cell Growth in a Dinoflagellate

by Gihong Park, Christina Batoh and Hans G. Dam

Toxins 2025, 17(6), 290; https://doi.org/10.3390/toxins17060290 - 7 Jun 2025

Viewed by 702

Abstract

The non-consumptive effects of past predator exposure on phytoplankton have gained recognition, but how these effects are modulated by resource availability requires further study. We examined the simultaneous effects of past predator exposure (direct, indirect, and no exposure) and nutrient regime (combinations of [...] Read more.

The non-consumptive effects of past predator exposure on phytoplankton have gained recognition, but how these effects are modulated by resource availability requires further study. We examined the simultaneous effects of past predator exposure (direct, indirect, and no exposure) and nutrient regime (combinations of N- and P-repletion and limitation) on the paralytic shellfish toxin retention and cell growth rate of a toxic dinoflagellate, Alexandrium catenella (strain BF-5), under a laboratory-simulated bloom condition (exponential, stationary, and declining phases). Within a past predator exposure treatment, cell toxin retention was generally higher under N-replete than N-limited conditions. The cells of past direct predator exposure treatment retained or produced more toxin than those in the indirect-exposure or no-exposure treatments regardless of nutrient regime in the exponential and stationary phase. By contrast, cells directly exposed to predators showed lower growth rates than the other two treatments, and also showed a tradeoff between toxin retention rate and growth rate. Separate experiments also showed that the effect of past predator exposure on reducing cell growth is stronger under N repletion than N limitation. These results imply that the interactions of past predator exposure and resource availability impact bloom dynamics and toxin transfer in the food web. Full article

(This article belongs to the Special Issue Ecology and Evolution of Harmful Algal Blooms)

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10 pages, 653 KiB

Open AccessArticle

Clinical Efficacy of Bladder Neck Injection of Botulinum Toxin A in Treating Neurogenic and Non-Neurogenic Voiding Dysfunctions Due to Bladder Neck Dysfunction

by Yu-Shuang Lee, Yu-Khun Lee, Tien-Lin Chang, Cheng-Ling Lee, Sheng-Fu Chen, Jia-Fong Jhang, Yuan-Hong Jiang and Hann-Chorng Kuo

Toxins 2025, 17(6), 289; https://doi.org/10.3390/toxins17060289 - 6 Jun 2025

Viewed by 554

Abstract

Bladder neck dysfunction (BND) is a pathophysiology associated with voiding dysfunction in patients with neurogenic or non-neurogenic voiding dysfunction. Botulinum toxin A (BoNT-A) injection is a minimally invasive alternative for treating bladder outlet dysfunction; however, its efficacy for BND has not been well [...] Read more.

Bladder neck dysfunction (BND) is a pathophysiology associated with voiding dysfunction in patients with neurogenic or non-neurogenic voiding dysfunction. Botulinum toxin A (BoNT-A) injection is a minimally invasive alternative for treating bladder outlet dysfunction; however, its efficacy for BND has not been well established. In this retrospective study, 41 patients with videourodynamic study-confirmed BND who failed medical therapy received a transurethral bladder neck injection of 100-U BoNT-A. Treatment outcomes were assessed using the Global Response Assessment. After BoNT-A injection, the patients were followed up and subsequent urological management was recorded. At 6 months, 65.9% of the patients reported satisfactory outcomes (26.8% successful and 39.0% improved). Patients with non-neurogenic BND had the highest satisfaction rate, higher than those with neurogenic BND (NBND) with and without detrusor sphincter dyssynergia (DSD). Among patients without detrusor acontractility (DA), a higher bladder outlet obstruction index predicted treatment failure. Patients with pure BND confirmed by urodynamics may benefit more from BoNT-A injections, whereas those with high baseline voiding detrusor pressure or spinal cord injury with detrusor sphincter dyssynergia may have less favorable results. Bladder neck BoNT-A injections for treating BND-associated voiding dysfunction did not achieve very successful outcomes. Only 26.8% of the patients had successful treatment outcomes, while 39.0% had improved outcomes and 34.1% failed the treatment. Full article

(This article belongs to the Special Issue Application of Botulinum Neurotoxin in Lower Urinary Tract Dysfunctions: Where Are We Now? II)

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41 pages, 3831 KiB

Open AccessArticle

Significance of the Stability of Fusarium Head Blight Resistance in the Variety Registration, Breeding, and Genetic Research of Winter Wheat Using Disease Index, Fusarium-Damaged Kernels, and Deoxynivalenol Contamination

by Ákos Mesterhazy, Beata Tóth, Attila Berényi, Katalin Ács and Tamas Meszlényi

Toxins 2025, 17(6), 288; https://doi.org/10.3390/toxins17060288 - 6 Jun 2025

Viewed by 560

Abstract

Fusarium head blight is one of the greatest threats to global wheat production. Despite the special attention paid by researchers to resistance genetics, the stability of resistance and the expression of its epidemiological relationships have not been tested in depth. As most studies [...] Read more.

Fusarium head blight is one of the greatest threats to global wheat production. Despite the special attention paid by researchers to resistance genetics, the stability of resistance and the expression of its epidemiological relationships have not been tested in depth. As most studies only present data on visual symptoms, in this study, we present data from four experiments. Here, 15–40 genotypes were tested with four and eight isolates (inocula) in 3–4-year experiments, with 32, 24, 36, and 12 epidemic situations used to determine the disease index (DI), Fusarium-damaged kernels (FDKs), and DON. All genotypes were tested for stability by the variance across epidemics, and the b value of the linear function was considered. Both indices were suitable for measuring stability/instability, but the variance results were more closely correlated with the experimental data than the b value, known as the stability index (SI). The use of variance is recommended due to its simplicity and reliability. In the first test, the rate of maximum/minimum variance for DI, FDK, and DON differed 15-, 20-, and 120-fold, respectively. In the second test, the same rates were 200, 400, and over 4000, with the other tests exhibiting similar tendencies. The traits differ, the epidemics vary, and a dependence on resistance level can be proven. The genotype ranking varies strongly in different epidemics, with approximately 50% of the correlations between variety responses being insignificant. Therefore, many epidemics are needed to obtain a reliable picture of the adaptation ability of the resistance traits and their stability. Approximately 25% of the genotypes tested belong to the most stable group. About 35% were discarded, and in the 40% medium, we observed both highly unstable and moderately stable genotypes. Principal component analysis (PCA) of the three traits in the experiments showed a confirmatory, nearly uniform distribution of genotypes, with a different footprint or “identity card” present for each genotype. The genotypes for the traits belong to one or two groups, although sometimes individual genotypes seem to be independent. No strict rule was found. This underlines the necessity of considering the plant’s traits (Di, FDK, and DON) in resistance testing. Highly resistant winter wheat lines could also be bred with very low variance and SI values and very high stability (SI values lower than 0.3). Of the traits, DON is the most important. With this methodology, variety registration also becomes possible. The epidemiological aspect has a decisive role in resistance studies, and without identifying stability in FHB resistance, no food safety estimates can be made. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 263 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 522

Abstract

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

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

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

15 pages, 2495 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 576

Abstract

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

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

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

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14 pages, 760 KiB

Open AccessArticle

Hydroculture Cultivation of Strawberries as Potential Reference Material for Microcystin Analysis: Approaches and Pitfalls

by Wannes Hugo R. Van Hassel, Benoît Guillaume and Julien Masquelier

Toxins 2025, 17(6), 285; https://doi.org/10.3390/toxins17060285 - 6 Jun 2025

Viewed by 493

Abstract

Toxic cyanobacterial blooms are prevalent in surface waters. Depending on several conditions, these blooms produce cyanotoxins. Human exposure to these toxins can occur through multiple routes, including contaminated crops through irrigation with contaminated water. Analytical methods have been developed for cyanotoxin quantification to [...] Read more.

Toxic cyanobacterial blooms are prevalent in surface waters. Depending on several conditions, these blooms produce cyanotoxins. Human exposure to these toxins can occur through multiple routes, including contaminated crops through irrigation with contaminated water. Analytical methods have been developed for cyanotoxin quantification to investigate these exposures. Yet, proper comparisons between different labs via proficiency tests or interlaboratory comparison tests, as well as method quality assurance, are impossible. Developing reference materials for cyanotoxins in plants would help resolve these problems. Therefore, a novel liquid hydroculture setup was optimized to grow and contaminate strawberries. During fruit ripening, these plants were exposed to growth medium contaminated with pure microcystin-LR or freeze-dried cyanobacterial biomass containing different microcystin congeners. Afterwards, fruits, greens, and roots were harvested. Validated UHPLC-MS/MS methods were used to quantify the microcystin congeners in the growth medium and the plants. Furthermore, both contamination conditions resulted in the accumulation of toxin(s) in the roots and the greens. Yet in the contamination models, no toxin(s) accumulated in the fruits. Therefore, this contamination approach, combined with strawberries as a berry plant model, is only suitable for reference material production for limited matrices. Our cultivation model to produce reference material could be evaluated for other berry producers. Full article

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

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24 pages, 7044 KiB

Open AccessArticle

Genomics and Transcriptomics of 3ANX (NX-2) and NX (NX-3) Producing Isolates of Fusarium graminearum

by Philip L. Walker, Sean Walkowiak, Srinivas Sura, E. RoTimi Ojo and Maria A. Henriquez

Toxins 2025, 17(6), 284; https://doi.org/10.3390/toxins17060284 - 5 Jun 2025

Viewed by 567

Abstract

Fusarium head blight (FHB) is an important fungal disease caused by Fusarium graminearum and other Fusarium spp., resulting in significant yield losses across cereal grains. Recently identified F. graminearum isolates in Canada, capable of producing type A trichothecene mycotoxins 3ANX (NX-2, 7-α hydroxy,15-deacetylcalonectrin) [...] Read more.

Fusarium head blight (FHB) is an important fungal disease caused by Fusarium graminearum and other Fusarium spp., resulting in significant yield losses across cereal grains. Recently identified F. graminearum isolates in Canada, capable of producing type A trichothecene mycotoxins 3ANX (NX-2, 7-α hydroxy,15-deacetylcalonectrin) and NX (NX-3, 7-α hydroxy, 3,15-dideacetylcalonectrin), demonstrated high levels of genetic diversity. While recent studies have detected this genetic and chemical diversity, little is known of the underlying molecular mechanisms and processes influenced by these distinct chemotypes and regional populations. In the current study, we used an -omics approach coupled with high-resolution mass spectrometry to characterize twenty F. graminearum isolates collected from five distinct regions across Manitoba. These data identified regional F. graminearum populations within Manitoba that demonstrate distinct genomic variation and patterns of gene expression, particularly within pathogenicity-associated processes. Further, we identified genetic variation and differential expression between isolates showing high and low levels of pathogenicity, allowing for the identification of previously characterized and novel putative pathogenicity factors. Lastly, we detected the production of 3ANX and/or NX mycotoxins within the majority of our twenty characterized F. graminearum isolates, suggesting the 3ANX chemotype may be more prevalent than previously expected in Canada. Ultimately, these findings highlight the diversity of F. graminearum across Manitoba and, more importantly, uncover specific genomic regions and candidate pathogenicity factors influenced by this diversity. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 322 KiB

Open AccessArticle

Serum Indoxyl Sulfate as a Potential Biomarker of Peripheral Arterial Stiffness in Patients with Non-Dialysis Chronic Kidney Disease Stages 3 to 5

by Yahn-Bor Chern, Jen-Pi Tsai, Chin-Hung Liu, Yu-Li Lin, Chih-Hsien Wang and Bang-Gee Hsu

Toxins 2025, 17(6), 283; https://doi.org/10.3390/toxins17060283 - 5 Jun 2025

Viewed by 583

Abstract

Indoxyl sulfate (IS), which is a protein-bound uremic toxin, is involved in vascular dysfunction and cardiovascular risk in subjects with chronic kidney disease (CKD). However, its role in peripheral arterial stiffness (PAS) remains unclear. This cross-sectional study evaluated the relationship between IS and [...] Read more.

Indoxyl sulfate (IS), which is a protein-bound uremic toxin, is involved in vascular dysfunction and cardiovascular risk in subjects with chronic kidney disease (CKD). However, its role in peripheral arterial stiffness (PAS) remains unclear. This cross-sectional study evaluated the relationship between IS and PAS in patients diagnosed with CKD stages 3 through 5 who are not undergoing dialysis. Patients with CKD from a single center were enrolled. High-performance liquid chromatography analyzed the serum IS levels. PAS was evaluated using brachial–ankle pulse wave velocity (baPWV). IS was independently associated with PAS (odds ratio [OR]: 1.389 for 1 μg/mL increase in IS, 95% confidence interval [CI]: 1.086–1.775, p = 0.009) in a multivariable analysis after adjustment for age, hypertension, diabetes mellitus, blood pressure, lipid profiles, renal function, albumin, and proteinuria. Moreover, the mean baPWV (p = 0.010), left baPWV (p = 0.009), and right baPWV (p = 0.015) levels significantly correlated with the log-transformed IS (log-IS) levels. The area under the receiver operating characteristic curve for serum IS as a predictor of PAS was determined to be 0.667 (95% CI: 0.580−0.754; p = 0.0002). IS was associated with PAS in non-dialysis CKD stages 3–5, suggesting that IS may be a possible vascular risk marker. Future studies should address the nature of the relationship between IS and vascular dysfunction and assess therapeutic strategies to reduce IS. Full article

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

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22 pages, 3496 KiB

Open AccessReview

INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome

by Marta Rivas, Mariana Pichel, Vanesa Zylberman, Mariana Colonna, Marina Valerio, Carolina Massa, Romina Pardo, Andrés E. Ciocchini, Santiago Sanguineti, Ian Roubicek, Linus Spatz and Fernando Alberto Goldbaum

Toxins 2025, 17(6), 282; https://doi.org/10.3390/toxins17060282 - 5 Jun 2025

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Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing Escherichia coli-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children [...] Read more.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing Escherichia coli-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children die during the acute phase, and about 30% experience long-term renal sequelae. Argentina has the highest incidence of STEC-HUS globally. Given the prominent role of Stx in its pathophysiology, STEC-HUS is considered more of a toxemia than a bacterial disease. Stx transport occurs before and after the STEC-HUS onset, allowing for the distinction between an early toxemia phase and an advanced toxemia phase. In this review, we present our efforts to develop INM004, an anti-Stx treatment aimed at ameliorating or preventing the clinical consequences of STEC-HUS. We describe the protein engineering that facilitated this development and the clinical path to demonstrate the safety and efficacy of INM004. This immunotherapy could represent a new step in the treatment of STEC-HUS, which could potentially prevent long-term damage. If phase 3 trials are successful, earlier and broader use of INM004 is envisioned. We also discuss the potential impact of INM004 therapy, targeted vaccination strategies, and new diagnostic tools for this disease. Full article

(This article belongs to the Special Issue Antibodies for Innovative Studies of Bacterial Toxins)

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Toxins, Volume 17, Issue 6 (June 2025) – 52 articles

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