Toxins

18 pages, 10242 KB

Open AccessArticle

Toxicity of Volatile Organic Compounds Produced by Pathogens Ewingella americana and Cedecea neteri Associated with Pleurotus pulmonarius

by Zhiyuan Wei, Yifan Wang, Jieheng Qiu, Yulu Nie, Lian Wang and Bin Liu

Toxins 2025, 17(9), 449; https://doi.org/10.3390/toxins17090449 - 5 Sep 2025

Abstract

Bacterial diseases of Pleurotus pulmonarius, caused by diverse pathogens and associated with a range of symptoms, reduce its commercial value and lead to substantial economic losses. While most research has focused on Pseudomonas tolaasii and its non-volatile toxin tolaasin, little is known [...] Read more.

Bacterial diseases of Pleurotus pulmonarius, caused by diverse pathogens and associated with a range of symptoms, reduce its commercial value and lead to substantial economic losses. While most research has focused on Pseudomonas tolaasii and its non-volatile toxin tolaasin, little is known about other bacterial pathogens and their volatile metabolites. In this study, two bacterial pathogens were isolated from symptomatic P. pulmonarius fruiting bodies in Guangxi, China, and identified as Ewingella americana and Cedecea neteri. Using headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC-MS), we identified 16 volatile organic compounds (VOCs) produced by these two species, seven of which exhibited toxicity-inducing sunken lesions, discoloration, and inhibition of mycelial growth. Symptom severity was quantified by colorimetric analysis. Among the toxic VOCs, 2,4-di-tert-butylphenol was the most potent, inducing sunken lesions and slight discoloration at concentrations as low as 0.5 mg/mL, and causing significant inhibition of mycelial growth at 5 μg/L. The remaining VOCs also caused varying degrees of sunken lesions, yellowing or browning, and suppression of mycelial growth. This study is the first to demonstrate the pathogenic potential of VOCs produced by bacterial pathogens in P. pulmonarius, underscoring their role as important virulence factors and providing a foundation for further investigation into their mechanisms and control strategies. Full article

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18 pages, 2325 KB

Open AccessArticle

Injection of Affibodies by a Self-Organizing Bacterial Syringe to Interfere with Intracellular Signaling

by Thomas Müller, Sophie Gieß, Fanny Maier, Lara Hofacker, Luca Stenger, Larissa Parker, Robert Grosse and Gudula Schmidt

Toxins 2025, 17(9), 448; https://doi.org/10.3390/toxins17090448 - 5 Sep 2025

Abstract

Photorhabdus luminescens produces a syringe-like toxin complex to inject toxic enzymes into cells. We demonstrated that the recombinant Photorhabdus toxin complex (PTC) can be engineered for translocation of foreign cargo proteins across cellular membranes. We showed that the system is suitable for injection [...] Read more.

Photorhabdus luminescens produces a syringe-like toxin complex to inject toxic enzymes into cells. We demonstrated that the recombinant Photorhabdus toxin complex (PTC) can be engineered for translocation of foreign cargo proteins across cellular membranes. We showed that the system is suitable for injection of trimeric affibodies into mammalian cells in order to influence crucial signaling pathways. As proof of principle, we inhibited Ras-driven tumor cell proliferation by injection of an affibody which interacts with the Ras binding domain of Raf kinase. The system described here could be applicable to target a wide range of signaling molecules for cell biological or therapeutic intervention. Full article

(This article belongs to the Section Bacterial Toxins)

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14 pages, 2477 KB

Open AccessArticle

Potential Linkage Between Zebra Mussel Establishment, Cyanobacterial Community Composition, and Microcystin Levels in United States Lakes

by Feng Zhang, Jayun Kim, Ozeas S. Costa, Jr., Song Liang and Jiyoung Lee

Toxins 2025, 17(9), 447; https://doi.org/10.3390/toxins17090447 - 5 Sep 2025

Abstract

Zebra mussel invasion of North American lakes during the last century may play an important role in the occurrence of toxic cyanobacterial blooms. However, empirical evidence quantifying their influence on cyanobacterial community dynamics at broad spatial scales remains limited. Here, we analyzed data [...] Read more.

Zebra mussel invasion of North American lakes during the last century may play an important role in the occurrence of toxic cyanobacterial blooms. However, empirical evidence quantifying their influence on cyanobacterial community dynamics at broad spatial scales remains limited. Here, we analyzed data from the U.S. EPA National Lakes Assessment (>1000 lakes) to examine potential linkages among zebra mussels, cyanobacterial community composition, and cyanotoxin levels. The analysis results showed significant differences in cyanobacterial communities between lakes located in areas with and without established zebra mussel populations. The lakes with established zebra mussels exhibited significantly higher microcystin levels and cyanobacterial abundance, but lower phosphorus concentrations. Structural equation modeling was used to confirm and estimate the effect of zebra mussels on microcystin concentrations via different pathways. The results suggest three potential pathways whereby zebra mussels influence microcystin production: (1) altering phosphorus concentration; (2) increasing cyanobacterial abundance; and (3) shifting cyanobacteria community structure. The total effect of zebra mussel establishment resulted in an overall 1.40-fold net increase in microcystin level, which presumably resulted from three contributing factors: (1) a 1.06-fold increase through an increased cyanobacterial abundance; (2) a 1.53-fold increase through a selective force, resulting in increased cyanobacteria toxicity; and (3) a 0.86-fold decrease in microcystin level through total phosphorus decrease. The study highlights the potential role of zebra mussel invasion in altering cyanobacterial composition and influencing microcystin levels in U.S. lakes. Full article

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

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16 pages, 2449 KB

Open AccessArticle

Comprehensive Insight into Microcystin-Degrading Mechanism of Sphingopyxis sp. m6 Based on Mlr Enzymes

by Qin Ding, Tongtong Liu, Zhuoxiao Li, Rongli Sun, Juan Zhang, Lihong Yin and Yuepu Pu

Toxins 2025, 17(9), 446; https://doi.org/10.3390/toxins17090446 - 5 Sep 2025

Abstract

Bacterial degradation is one important Microcystin (MC) removal method in the natural environment. The traditional MC-degrading pathway was proposed based on the functions of individual recombinant Mlr enzymes and the structures of the main MC-degrading products. However, the actual MC-degrading mechanism by Mlr [...] Read more.

Bacterial degradation is one important Microcystin (MC) removal method in the natural environment. The traditional MC-degrading pathway was proposed based on the functions of individual recombinant Mlr enzymes and the structures of the main MC-degrading products. However, the actual MC-degrading mechanism by Mlr enzymes in wild-type bacteria remains unclear. In this study, bioinformatic analysis, heterologous expression, and knockout mutation were performed to elaborate the MC-degrading mechanism by Mlr enzymes in Sphingopyxis sp. m6. The results showed that mlr gene cluster was initially acquired by horizontal gene transfer, followed by vertical inheritance within Alphaproteobacteria. Mlr enzymes exhibit distinct subcellular localizations and possess diverse conserved catalytic domains. The enzymatic cascade MlrA/MlrB/MlrC sequentially cleaves Microcystin-LR (MC-LR) via Adda-Arg, Ala-Leu, and Adda-Glu bonds, generating characteristic intermediates (linearized MC-LR, tetrapeptide, and Adda). Notably, recombinant MlrC demonstrated dual-targeting degrading capability (linearized MC-LR and tetrapeptide), while tetrapeptide specificity in endogenous processing of Sphingopyxis sp. m6. Marker-free knockout mutants of mlr genes were first constructed in MC-degrading bacteria, unveiling that mlrA was indispensable in initial MC cleavage, whereas mlrB/mlrC/mlrD displayed functional compensation through other enzymes with similar functions. This study promotes the mechanistic understanding of MC bacterial degradation and offers a theoretical basis for a bioremediation strategy targeting cyanotoxin pollution. Full article

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

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17 pages, 835 KB

Open AccessArticle

Application of Graphitized Multi-Walled Carbon Nanotubes Combined with Orbitrap High-Resolution Mass Spectrometry for the Rapid Detection of Ten Toxins in Wild Mushrooms

by Bo Zhang, Yang Liu, Shengnan Li, Ruonan Li, Yunhui Zhang and Hua Zhao

Toxins 2025, 17(9), 445; https://doi.org/10.3390/toxins17090445 - 4 Sep 2025

Abstract

Wild mushroom poisoning is an emerging global food safety issue, especially in subtropical regions like southwestern China, where incidents are geographically clustered. Current detection methods are often time-consuming and overlook region-specific toxins. We developed a rapid, sensitive, and accurate method for the simultaneous [...] Read more.

Wild mushroom poisoning is an emerging global food safety issue, especially in subtropical regions like southwestern China, where incidents are geographically clustered. Current detection methods are often time-consuming and overlook region-specific toxins. We developed a rapid, sensitive, and accurate method for the simultaneous detection of ten characteristic mushroom toxins prevalent in Guizhou, China. The method combines graphite multi-walled carbon nanotubes (G-MWCNTs) for sample preparation with Orbitrap high-resolution mass spectrometry (HRMS). Wild mushroom samples were extracted via ultrasonic-assisted methanol–water extraction, purified using G-MWCNTs, and separated on a Hypersil GOLD C18 column (100 mm × 2.1 mm, 1.9 μm). Gradient elution was performed with 0.1% formic acid + 0.01% ammonia and acetonitrile; quantification used the external standard method. The method achieved LODs of 0.005–0.2 mg/kg and LOQs of 0.015–0.6 mg/kg, with RSDs below 18.11% and excellent linearity (R² = 0.9936–0.9989). Among 45 wild mushroom samples, toxin levels ranged from 0.032 to 445.10 mg/kg, with a detection rate of 22.22%, suggesting notable poisoning risk. This method reduces pretreatment time while ensuring high analytical performance, offering a reliable tool for rapid toxin screening and supporting regional surveillance of wild mushroom poisoning. Full article

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

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8 pages, 415 KB

Open AccessArticle

Differences in Marine Toxin Poisonings Reported to US Poison Centers After Pandemic Restrictions

by Baylin J. Bennett, Cailee Hill, Hugh B. Roland, Lorraine C. Backer, Amy H. Schnall and Matthew O. Gribble

Toxins 2025, 17(9), 444; https://doi.org/10.3390/toxins17090444 - 4 Sep 2025

Abstract

This study investigated whether marine toxin poisonings reported to U.S. Poison Centers changed during the height of the pandemic period (April 2020 to December 2021). The National Poison Data System was queried for single-substance human exposure calls between 1 January 2000 and 31 [...] Read more.

This study investigated whether marine toxin poisonings reported to U.S. Poison Centers changed during the height of the pandemic period (April 2020 to December 2021). The National Poison Data System was queried for single-substance human exposure calls between 1 January 2000 and 31 March 2022 pertaining to ichthyosarcotoxins. Incidence rate ratios for exposure calls were calculated using mixed-effects negative binomial regression. Call counts were aggregated by year and regressed on a binary indicator for occurrence during pandemic restrictions. During the peak pandemic period, exposure calls decreased for several toxins: ciguatera poisoning: 0.57 (0.43, 0.76); clupeotoxic fish poisoning: 0.12 (0.04, 0.39); diarrhetic shellfish poisoning: 0.28 (0.16, 0.49); paralytic shellfish poisoning: 0.23 (0.17, 0.33); scombroid fish poisoning: 0.46 (0.36, 0.57). However, palytoxin poisoning (1.94 (1.32, 2.84)) and tetrodotoxin poisoning (1.73 (1.46, 2.04)) exposure calls appear to have increased. All results were Bonferroni-significant (p ≤ 0.0009). Sensitivity analyses suggest the PLTX increase began prior to pandemic restrictions, whereas the TTX increase appeared to be directly associated with the restrictions. Both men and women reported increases in TTX exposure calls. The TTX increase could be associated with potentially increased participation in outdoor activities, as TTX exposures are linked to amphibia, echinoderms, fish, and mollusks, among other animals. Full article

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

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11 pages, 1634 KB

Open AccessArticle

Botulinum Toxin Complex Serotype B-Okra Exerts Systemic Toxicity via the Oral Route by Disrupting the Intestinal Epithelial Barrier

by Chiyono Morimoto, Sho Amatsu, Takuhiro Matsumura, Masahiko Zuka and Yukako Fujinaga

Toxins 2025, 17(9), 443; https://doi.org/10.3390/toxins17090443 - 4 Sep 2025

Abstract

Botulinum toxin (BoNT) causes flaccid paralysis by blocking the release of neurotransmitters. BoNTs associate with neurotoxin-associated proteins to form medium and large progenitor toxin complexes. The large progenitor toxin complex serotype A-62A (L-PTC/A-62A) specifically targets intestinal M cells for invasion, whereas large progenitor [...] Read more.

Botulinum toxin (BoNT) causes flaccid paralysis by blocking the release of neurotransmitters. BoNTs associate with neurotoxin-associated proteins to form medium and large progenitor toxin complexes. The large progenitor toxin complex serotype A-62A (L-PTC/A-62A) specifically targets intestinal M cells for invasion, whereas large progenitor toxin complex serotype B-Okra (L-PTC/B-Okra) is mainly taken up by enterocytes and exhibits higher toxicity via the oral route. Hemagglutinin (HA) is a neurotoxin-associated protein that promotes BoNT absorption from the intestine and has carbohydrate-binding and barrier-disrupting activities. In this study, we established an in vitro reconstitution and purification system for recombinant L-PTC/B-Okra and created a recombinant L-PTC/B-Okra mutant rL-PTC/B-KA with carbohydrate-binding activity but not barrier-disrupting activity. rL-PTC/B-KA showed significantly reduced oral toxicity. Our results demonstrate that the B-Okra toxin disrupts the epithelial barrier of enterocytes and exerts oral toxicity. Full article

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

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17 pages, 939 KB

Open AccessReview

Intermittent Infusion Hemodiafiltration: A Narrative Review of an Emerging Dialysis Modality

by Xiaoxi Zhou, Jing Sun and Lining Miao

Toxins 2025, 17(9), 442; https://doi.org/10.3390/toxins17090442 - 3 Sep 2025

Abstract

The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) [...] Read more.

The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) is an emerging, hybrid dialysis technique that combines standard hemodialysis with the cyclic backfiltration of ultrapure dialysate. This approach enables dynamic blood volume control and periodic backflushing of the dialyzer membrane. Recent clinical studies demonstrate that I-HDF can reduce intradialytic hypotension incidence, improve systemic and microcirculatory perfusion, and enhance the clearance of middle molecules such as β₂-microglobulin, while minimizing albumin loss. These benefits are particularly relevant to toxin clearance and hemodynamic stabilization, key priorities in optimizing dialysis outcomes. Large-scale cohort data suggest that I-HDF may be linked to improved long-term survival in dialysis patients. Given its physiological advantages and operational flexibility, I-HDF may also offer a practical solution in healthcare systems with limited access to high-volume online hemodiafiltration or kidney transplantation. Further research is warranted to develop individualized infusion protocols and validate its broader applicability. 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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14 pages, 1252 KB

Open AccessArticle

Preliminary Assessment of Alkaloid Content in Cocoa (Theobroma cacao L.) Hulls for Safe Consumption as a Feed Ingredient

by Francesca Mercogliano, Corinne Bani, Marco Tretola, Carla Landolfi, Matteo Ottoboni, Federica Cheli, Patrizia Restani, Luciano Pinotti and Chiara Di Lorenzo

Toxins 2025, 17(9), 441; https://doi.org/10.3390/toxins17090441 - 3 Sep 2025

Abstract

The European Circular Economy Action Plan outlines a forward-looking strategy that emphasizes waste reduction and the acquisition of high-quality secondary resources. Previous research has shown that cocoa processing by-products contain compounds of interest for various industrial areas, making them an attractive matrix for [...] Read more.

The European Circular Economy Action Plan outlines a forward-looking strategy that emphasizes waste reduction and the acquisition of high-quality secondary resources. Previous research has shown that cocoa processing by-products contain compounds of interest for various industrial areas, making them an attractive matrix for reuse. However, a gap remains in our understanding of the safety of these by-products intended for feed. In this study, theobromine and caffeine were quantified by High-Performance Liquid Chromatography (HPLC-UV) in cocoa hulls for safety considerations, evaluating theobromine compliance with toxicological and safety levels, and considering their potential application as an ingredient in animal feed. In addition, the identification of phenolic components and associated antioxidant activity was conducted through High-Performance Thin-Layer Chromatography (HPTLC). This preliminary study indicates that theobromine content is a limiting factor for the inclusion of cocoa hulls in animal diets, as it restricts inclusion levels to remain within current regulatory limits. Examples of general estimates of dietary theobromine exposure at inclusion levels based on regulatory limits for dairy cows and veal calves confirmed a low risk for animal health. Furthermore, the detection of antioxidant activity linked to the presence of polyphenols highlights the potential of cocoa hulls as a sustainable food by-product for feed formulation. Full article

(This article belongs to the Section Plant Toxins)

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13 pages, 10491 KB

Open AccessArticle

Genetic Characterization of Staphylococcus aureus Isolates Associated with Toxic Shock Syndrome Toxin Production: An Epidemiological and Bioinformatics Approach

by J. R. Aguirre-Sánchez, C. Chaidez-Quiroz, Nohemi Castro-del Campo and Nohelia Castro-del Campo

Toxins 2025, 17(9), 440; https://doi.org/10.3390/toxins17090440 - 3 Sep 2025

Abstract

Staphylococcus aureus is an opportunistic pathogen, a member of the ESKAPE group, associated with nosocomial infections and foodborne illnesses due to its production of various toxins. This study conducted a comprehensive genomic characterization of S. aureus isolates producing toxic shock syndrome toxin (TSST-1) [...] Read more.

Staphylococcus aureus is an opportunistic pathogen, a member of the ESKAPE group, associated with nosocomial infections and foodborne illnesses due to its production of various toxins. This study conducted a comprehensive genomic characterization of S. aureus isolates producing toxic shock syndrome toxin (TSST-1) using a comparative genomics and bioinformatics approach. A total of 166, including 3 bovine mastitis isolates and 163 public genomes, were analyzed. Twenty-eight distinct sequence types (STs) were identified, with ST30 and ST5 being the most prevalent, corresponding to the clonal complexes CC30 and CC5, respectively. Phylogenetic reconstruction revealed two major clades aligned with these complexes, each exhibiting unique virulence factor profiles. Notably, TSST-1 was detected in bovine mastitis genomes, alongside a broad repertoire of virulence markers, such as enterotoxins and secretion system components, posing a potential risk to public health. Additionally, genes related to environmental information processing systems, including ABC transporters and phosphotransferase systems, were prevalent. These results underscore the need for strengthened genomic surveillance and the implementation of both preventive and corrective measures in dairy herds to mitigate zoonotic transmission and ensure food safety. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins：Presence and Detection in Human, Animals and Food)

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14 pages, 4137 KB

Open AccessArticle

Neurotoxicity of Sri Lankan Krait (Bungarus ceylonicus) and Common Krait (Bungarus caeruleus) Venoms and Their Neutralisation by Commercial Antivenoms In Vitro

by Jithmi Galappaththige, Geoffrey K. Isbister, Kalana Maduwage, Wayne C. Hodgson and Anjana Silva

Toxins 2025, 17(9), 439; https://doi.org/10.3390/toxins17090439 - 2 Sep 2025

Abstract

The common krait (Bungarus caeruleus) and the endemic Sri Lankan krait (B. ceylonicus) are two species of krait responsible for envenomings in Sri Lanka that result in progressive neuromuscular paralysis. We characterised the in vitro neurotoxicity of B. ceylonicus [...] Read more.

The common krait (Bungarus caeruleus) and the endemic Sri Lankan krait (B. ceylonicus) are two species of krait responsible for envenomings in Sri Lanka that result in progressive neuromuscular paralysis. We characterised the in vitro neurotoxicity of B. ceylonicus and B. caeruleus venoms and studied their neutralisation by two commercially available Indian polyvalent antivenoms (i.e., VINS and BHARAT), Thai banded krait antivenom and Australian polyvalent antivenom using the chick biventer cervicis nerve-muscle preparation. Both venoms displayed concentration-dependent neurotoxicity, showing equipotent pre-synaptic neurotoxicity at 0.03 μg/mL. At a higher concentration (1 μg/mL), both venoms showed post-synaptic neurotoxicity, with B. ceylonicus venom being more potent. VINS was unable to neutralise the neurotoxicity of B. ceylonicus venom, but neutralised both pre- and post-synaptic neurotoxicity of B. caeruleus venom. BHARAT neutralised in vitro pre- and post-synaptic activity of both B. ceylonicus and B. caeruleus venoms. Banded krait antivenom and Australian polyvalent antivenoms were unable to fully neutralise the neurotoxicity of either venom at tested concentrations. In conclusion, B. ceylonicus venom shows pre- and post-synaptic neurotoxicity similar to B. caeruleus venom. BHARAT effectively neutralises both pre- and post-synaptic neurotoxicity of B. ceylonicus venom. Both Indian polyvalent antivenoms effectively neutralise neurotoxicity induced by B. caeruleus venom. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 2239 KB

Open AccessArticle

Biocatalytic Detoxification of Ochratoxins A/B by a Fungal Dye-Decolorizing Peroxidase: Mechanistic Insights and Toxicity Assessment

by Wenjing Xia, Nianqing Zhu, Jie Mei, Yueqin Peng, Fanglin Song, Shuai Ding, Fei Li and Xue Zhou

Toxins 2025, 17(9), 438; https://doi.org/10.3390/toxins17090438 - 2 Sep 2025

Abstract

Mycotoxin contamination in agricultural products poses severe global health risks, with ochratoxins (particularly OTA and OTB) exhibiting marked nephrotoxicity and classified as Group 2B carcinogens by IARC. Conventional physical/chemical detoxification methods often impair food nutritional quality, highlighting the need for enzymatic alternatives. Herein, [...] Read more.

Mycotoxin contamination in agricultural products poses severe global health risks, with ochratoxins (particularly OTA and OTB) exhibiting marked nephrotoxicity and classified as Group 2B carcinogens by IARC. Conventional physical/chemical detoxification methods often impair food nutritional quality, highlighting the need for enzymatic alternatives. Herein, we systematically investigated the degradation mechanisms of ochratoxin A (OTA) and ochratoxin B (OTB) using Pleurotus ostreatus dye-decolorizing peroxidase (PoDyP4) coupled with redox mediators. Remarkably, hydroxybenzotriazole (HBT) enhanced degradation efficiency 26.7-fold for OTA and 10.6-fold for OTB compared to mediator-free systems, establishing it as the optimal catalytic enhancer. Through LC-MS/MS analysis, we identified five key degradation products, including 6-OH-OTA and OTB-quinone, elucidating a putative oxidative degradation pathway. In vitro cytotoxicological evaluation in HK-2 cells demonstrated that PoDyP4-treated ochratoxins significantly attenuated cytotoxicity, reducing malondialdehyde (MDA) levels by 48.7% (OTA) and 42.3% (OTB) (p < 0.01) and suppressing ROS generation. Molecular docking revealed strong binding affinities between PoDyP4 and ochratoxins, with calculated binding energies of −7.6 kcal/mol (OTA) and −8.6 kcal/mol (OTB), stabilized by hydrogen bond networks (1.9–3.4 Å). These findings position PoDyP4 as a promising biocatalyst for mycotoxin mitigation in food systems, offering a sustainable alternative to traditional detoxification methods. Full article

(This article belongs to the Section Mycotoxins)

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9 pages, 1915 KB

Open AccessArticle

Ultrasound-Guided Multi-Branch Rectus Femoris Nerve Block for Spasticity Assessment

by Stefano Carda, Elisa Grana, Thierry Deltombe and Rajiv Reebye

Toxins 2025, 17(9), 437; https://doi.org/10.3390/toxins17090437 - 1 Sep 2025

Abstract

Background: Stiff-knee gait commonly involves rectus femoris spasticity in patients with central nervous system lesions. Diagnostic nerve blocks aid in predicting treatment outcomes; however, current techniques may overlook multiple nerve branches that innervate the rectus femoris muscle, potentially resulting in an incomplete [...] Read more.

Background: Stiff-knee gait commonly involves rectus femoris spasticity in patients with central nervous system lesions. Diagnostic nerve blocks aid in predicting treatment outcomes; however, current techniques may overlook multiple nerve branches that innervate the rectus femoris muscle, potentially resulting in an incomplete assessment of treatment outcomes. Methods: We present an ultrasound-guided approach that we currently use in our practice, using anatomical landmarks, including the femoral artery, the sartorius muscle, and the rectus femoris’ characteristic “J-shaped” internal tendon. The technique employs an “elevator” scanning method to identify all motor nerve branches (typically 2–3) entering the proximal third of the rectus femoris muscle. Each branch is blocked using an in-plane needle approach with 1–2 mL of 2% lidocaine. Results: The technique enables the visualization of hyperechoic nerve branches entering the rectus femoris muscle from medial to lateral, sometimes accompanied by small vascular branches that are identifiable with a Doppler ultrasound. Optimal ultrasound settings include probes >8 MHz, appropriate focus positioning, and dynamic range < 60 dB. The multi-branch approach produces rapid-onset motor weakness (5–10 min). Conclusions: This comprehensive multi-branch rectus femoris nerve block technique may enhance diagnostic accuracy for spasticity assessment, potentially leading to more informed treatment selection for stiff-knee gait. Full article

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

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25 pages, 3243 KB

Open AccessArticle

Toxicity Profiling and In Vivo Metabolism of Danshensu-Derived Novel Antihypertensive Candidate 221s (2,9)

by Yunmei Chen, Kuan Yang, Lili Yu, Rong Wang, Shaojing Liu and Bei Qin

Toxins 2025, 17(9), 436; https://doi.org/10.3390/toxins17090436 - 1 Sep 2025

Abstract

Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and [...] Read more.

Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and long-term toxicity study and to elucidate the in vivo metabolic pathways of 221s (2,9) in order to provide critical insights into the observed toxicity. In the acute toxicity study, a single oral dose of 221s (2,9) at 3000 mg/kg in mice produced no clinical signs of toxicity or mortality, indicating an MTD of 3000 mg/kg. In a subsequent 12-week repeated-dose toxicity study in rats, doses of 20, 40, and 80 mg/kg were well tolerated, with no adverse clinical observations or deaths. Notably, organ coefficient analysis revealed transient lung injury, which resolved following a 4-week recovery period. The metabolite identification study indicated that metabolism in rats is predominated by Phase II metabolites, potentially contributing to the low toxicity of 221s (2,9). Further investigation into the impact of the drug metabolic enzyme–transporter interplay on the in vivo disposition of 221s (2,9) is warranted. Full article

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2 pages, 164 KB

Open AccessCorrection

Correction: Sławek et al. Case Series and Literature Review on Botulinum Toxin Efficacy in Axial Extensor Truncal Dystonia. Toxins 2025, 17, 375

by Jarosław Sławek, Iga Alicja Łobińska, Michał Schinwelski, Joanna Kopcewicz-Wiśniewska and Anna Castagna

Toxins 2025, 17(9), 435; https://doi.org/10.3390/toxins17090435 - 1 Sep 2025

Abstract

The authors wish to make the following corrections to this paper [...] Full article

(This article belongs to the Special Issue Advances in the Treatment of Movement Disorders with Botulinum Toxins)

23 pages, 7818 KB

Open AccessArticle

From Uremic Toxins to Hemodialysis Access Failure: IL-8 and MCP-1 Chemokines as a Link Between Endothelial Activation and AV Access Complications

by Rania Chermiti, Stanislas Bataille, Philippe Giaime, Justine Solignac, Nathalie Pedinielli, Nathalie McKay, Dorian Bigey-Frau, Guillaume Lano, Hamza Benjelloun, Tawfik Addi, Julien Mancini, Stéphane Burtey and Laetitia Dou

Toxins 2025, 17(9), 434; https://doi.org/10.3390/toxins17090434 - 31 Aug 2025

Abstract

Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) [...] Read more.

Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by indolic uremic toxins, as well as their association with AV access complications in hemodialysis patients. In cultured human endothelial cells, IL-8 and MCP-1 were upregulated by indolic uremic toxins through activation of their receptor, the aryl hydrocarbon receptor (AHR), and non-canonical TGF-β pathway involving TAK1/p38 MAPK/AP-1 signaling. In a retrospective observational study of 204 hemodialysis patients, baseline serum IL-8 or MCP-1 were positively correlated with indolic uremic toxins and TGFβ1. Additionally, serum IL-8 ≥ 40.26 pg/mL and serum MCP-1 were independently associated with an increased risk of AV access complications over a 2-year period. In conclusion, we demonstrated that indolic uremic toxins promote endothelial inflammation by inducing IL-8 and MCP-1 expression via AHR activation and non-canonical TGF-β signaling. Clinically, elevated serum IL-8 and MCP-1 were independently associated with an increased risk of AV access complications in hemodialysis patients. Full article

(This article belongs to the Section Uremic Toxins)

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18 pages, 2090 KB

Open AccessArticle

Regulation of FpvelC on Conidiation, Pathogenicity and Secondary Metabolism in Fusarium proliferatum

by Ling Wang, Shaoqing Tang, Weiyang Liao, Zhonghua Sheng, Shikai Hu, Gui’ai Jiao, Gaoneng Shao, Lihong Xie and Peisong Hu

Toxins 2025, 17(9), 433; https://doi.org/10.3390/toxins17090433 - 30 Aug 2025

Abstract

The velvet complex is a master regulator of multiple physiological processes in filamentous fungi. In this study, we characterized the functions of velvet gene FpvelC in Fusarium proliferatum, which was the causative agent of rice spikelet rot disease. Compared with the wild-type [...] Read more.

The velvet complex is a master regulator of multiple physiological processes in filamentous fungi. In this study, we characterized the functions of velvet gene FpvelC in Fusarium proliferatum, which was the causative agent of rice spikelet rot disease. Compared with the wild-type Fp9 strain, deletion of FpvelC hindered conidiation, leading to a low level of trehalose content but excessive accumulation of chitin in conidia. Lack of FpvelC resulted in increased sensitivity to oxidative stress and decreased expression of antioxidant genes. Notably, ΔFpvelC exhibited attenuated pathogenicity on rice and maize, failure to produce invasive hyphae, and downregulation of genes encoding xylanases and xyloglucanases during infection processes. Nevertheless, disruption of FpvelC enhanced production of fumonisin B1 (FB1) and fusaric acid concomitantly; transcripts of the clustering genes responsible for the two mycotoxins’ biosynthesis were significantly increased. Additionally, the absence of FpvelC was displayed as more sensitive to rapamycin than the Fp9 strain, accompanied with less intracellular glutamine. Overall, FpvelC played versatile roles in conidiation, response to oxidative stress, pathogenicity and mycotoxins production in F. proliferatum. Full article

(This article belongs to the Special Issue Occurrence, Toxicity, Metabolism, Analysis Methods and Control Strategies of Mycotoxins (2nd Edition))

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18 pages, 1966 KB

Open AccessFeature PaperArticle

Modification of Closed-State Inactivation in Voltage-Gated Sodium Channel Na_v1.7 by Two Novel Arachnid Toxins

by John W. Johnson, Hillary G. Rikli and Stephen R. Johnson

Toxins 2025, 17(9), 432; https://doi.org/10.3390/toxins17090432 - 29 Aug 2025

Abstract

Venomous invertebrates have provided a large diversity of toxins that selectively and potently modulate ion channels that are indispensable tools for elucidating the structure and underlying mechanisms of these channels. Voltage-gated sodium channels (VGSC) are responsible for the initiation and propagation of action [...] Read more.

Venomous invertebrates have provided a large diversity of toxins that selectively and potently modulate ion channels that are indispensable tools for elucidating the structure and underlying mechanisms of these channels. Voltage-gated sodium channels (VGSC) are responsible for the initiation and propagation of action potentials in excitable cells and represent an important target for a variety of diseases. The Na_v1.7 isoform, located in the peripheral nervous system, is central to pain signaling and is under intense investigation as a target for the treatment of pain. Closed-state inactivation (CSI) has been implicated in various disease states, such as arrhythmias and neuropathic pain. The investigation of venom toxins and VGSC CSI is poorly understood. However, many scorpion and spider toxins bind to site 3, characterized by a delay in steady-state inactivation, and interact with domain IV of the channel alpha subunit. In this study, two novel toxins were isolated from the venoms of Heteroctenus junceus and Poecilotheria regalis that demonstrated similar activity to site 3 modulators. Both toxins were shown to inhibit CSI while enhancing the rate at which CSI can occur. Taken together, this study demonstrates the need for additional investigation in CSI as well as the ability for toxins to modulate this phenomenon. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 2338 KB

Open AccessArticle

Extract of Indigofera spicata Exerts Antiproliferative Effects on Human Colorectal and Ovarian Carcinoma Cells

by Galyna Shuvayeva, Mykola Tupychak, Olena Vovk, Dmytro Demash, Svitlana Chernyshuk, Yaroslav Bobak, Andriy Prokopiv, Nazariy Pokhodylo, Leoni A. Kunz-Schughart, Mary T. Fletcher and Oleh Stasyk

Toxins 2025, 17(9), 431; https://doi.org/10.3390/toxins17090431 - 29 Aug 2025

Abstract

Metabolic anticancer therapy based on enzymatic arginine (Arg) deprivation (ADT) is currently being evaluated in clinical trials. The combination of ADT with low doses of the plant cytotoxic analogs of Arg, canavanine (Cav) or indospicine (Isp), have been proposed as being more efficient [...] Read more.

Metabolic anticancer therapy based on enzymatic arginine (Arg) deprivation (ADT) is currently being evaluated in clinical trials. The combination of ADT with low doses of the plant cytotoxic analogs of Arg, canavanine (Cav) or indospicine (Isp), have been proposed as being more efficient and selective against malignant cells. The leguminous plant Indigofera spicata contains one of the highest known amounts of Isp. Here we demonstrate for the first time that the Isp-containing ethanolic extract from I. spicata is growth-inhibiting and toxic for cultured human colorectal and ovarian carcinoma cells. The extract reduces the viability of colorectal carcinoma cells two-fold under Arg-deficient conditions and entirely abrogates their residual proliferative potential (growth recovery) after the treatment. Pre-exposure of the extract to recombinant human arginase I (rhARGI) as a therapeutic Arg-depleting agent did not impact the extract’s efficacy. Further development of Isp as a component of combinatorial anticancer metabolic targeting strategies is discussed. Full article

(This article belongs to the Section Plant Toxins)

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