Toxins

19 pages, 6405 KiB

Open AccessArticle

The Venom Proteome of the Ecologically Divergent Australian Elapid, Southern Death Adder Acanthophis antarcticus

by Theo Tasoulis, C. Ruth Wang, Shaun Ellis, Tara L. Pukala, Joanna Sumner, Kate Murphy, Nathan Dunstan and Geoffrey K. Isbister

Toxins 2025, 17(7), 352; https://doi.org/10.3390/toxins17070352 - 14 Jul 2025

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Abstract

The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland [...] Read more.

The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.8% of the venom, comprising twelve different toxin identification hits belonging to seven toxin families. The most abundant protein family was three-finger toxins (3FTxs; 59.8% whole venom), consisting mostly of one long-chain neurotoxin, alpha-elapitoxin-Aa2b making up 59% of the venom and two proteoforms of another long-chain neurotoxin. Phospholipase A₂s (PLA₂s) were the second most abundant, with four different toxins making up 22.5% of the venom. One toxin was similar to two previous non-neurotoxic PLA₂s, making up 16% of the venom. The remaining protein families present were CTL (3.6%), NGF (2.5%), CRiSP (1.8%), LAAO (1.4%), and AChE (0.8%). A. antarcticus is the first Australian elapid characterised that has a 3FTx dominant venom, a composition typical of elapids on other continents, particularly cobras Naja sp. The fact that A. antarcticus has a venom composition similar to cobra venom while having a viper-like ecology illustrates that similar venom expressions can evolve independently of ecology. The predominance of post-synaptic neurotoxins (3FTxs) and pre-synaptic neurotoxins (PLA₂) is consistent with the neurotoxic clinical effects of envenomation in humans. Full article

(This article belongs to the Section Animal Venoms)

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4 pages, 154 KiB

Open AccessEditorial

Assessing the Use of BotulinumtoxinA for Hyperactive Urinary Tract Dysfunction a Decade After Approval

by Heinrich Schulte-Baukloh

Toxins 2025, 17(7), 351; https://doi.org/10.3390/toxins17070351 - 13 Jul 2025

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Abstract

Botulinum toxin was approved by the Food and Drug Administration in 2011 for neurogenic bladder and in 2013 for idiopathic overactive bladder (OAB) [...] Full article

(This article belongs to the Special Issue Botulinum Toxin for Urinary Tract Disease: After a Decade from Approval)

15 pages, 264 KiB

Open AccessReview

Intramuscular Botulinum Toxin for Complex Regional Pain Syndrome: A Narrative Review of Published Cases

by Marc Klee, Nilkolaj la Cour Karottki and Bo Biering-Sørensen

Toxins 2025, 17(7), 350; https://doi.org/10.3390/toxins17070350 - 11 Jul 2025

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Abstract

Background: Since the 1980s, numerous case reports have explored the use of intramuscular botulinum toxin (BoNT) for Complex Regional Pain Syndrome (CRPS), with significant variation in rationale, dosing, guidance techniques, and outcome measures. This narrative review aims to summarize published evidence on the [...] Read more.

Background: Since the 1980s, numerous case reports have explored the use of intramuscular botulinum toxin (BoNT) for Complex Regional Pain Syndrome (CRPS), with significant variation in rationale, dosing, guidance techniques, and outcome measures. This narrative review aims to summarize published evidence on the use of intramuscular BoNT in patients with CRPS, including studies using earlier terminology such as reflex sympathetic dystrophy (RSD). Given the heterogeneous and largely anecdotal nature of the literature, this review is intended to map the existing landscape rather than conduct a formal analysis. Methods: The PubMed and EMBASE databases were searched in August 2024 using terms related to CRPS and botulinum toxin. Following abstract and full-text screening, 25 publications were included. Results: The included studies span single case reports, case series, and small cohorts, encompassing at least 96 individual CRPS patients treated with intramuscular BoNT. Reported outcomes were heterogeneous, and key treatment parameters—such as toxin type, target muscles, guidance technique, and dosing—were inconsistently reported. Conclusion: The evidence for intramuscular BoNT in CRPS remains limited and heterogeneous, preventing firm conclusions on its efficacy or safety. Its use may be considered in select cases, particularly those with disabling or painful focal dystonia or myofascial pain, but standardized prospective studies are needed to clarify its clinical role. Full article

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

17 pages, 10456 KiB

Open AccessArticle

Efficacy and Safety of Letibotulinum Toxin A for the Treatment of Melasma in Two Different Dilutions: A Randomized Double-Blind Split-Face Study

by Juthapa Pongklaokam, Woraphong Manuskiatti, Rungsima Wanitphakdeedecha, Pitchaya Maneeprasopchoke, Panwadee Thongjaroensirikul, Yanin Nokdhes, Rona Maria R. Abad-Constantino, Woramate Bhorntarakcharoen, Sariya Sittiwanaruk and Thanya Techapichetvanich

Toxins 2025, 17(7), 349; https://doi.org/10.3390/toxins17070349 - 11 Jul 2025

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Abstract

Background: Melasma is an acquired hyperpigmentation disorder with multifactorial etiologies and limited response to conventional therapies. Recent evidence suggests that Botulinum Toxin A (BoNT-A) may modulate ultraviolet (UV)-induced pigmentation and offer therapeutic benefits. Objective: We sought to evaluate the efficacy and safety of [...] Read more.

Background: Melasma is an acquired hyperpigmentation disorder with multifactorial etiologies and limited response to conventional therapies. Recent evidence suggests that Botulinum Toxin A (BoNT-A) may modulate ultraviolet (UV)-induced pigmentation and offer therapeutic benefits. Objective: We sought to evaluate the efficacy and safety of two intradermal dilutions of Letibotulinum toxin A (LetiBoNT-A) in Thai patients with melasma. Methods: In this randomized, double-blind, split-face study, 30 participants aged 32–62 years received a single intradermal injection of LetiBoNT-A, with 20 units administered per cheek. A 1:5 dilution was injected on one side of the face, and a 1:10 dilution was injected on the contralateral side. Outcomes were evaluated over a 6-month period using the Hemi-modified Melasma Area and Severity Index (Hemi-mMASI), VISIA^® brown spot analysis, and quantitative assessments of skin texture. Results: Both dilutions significantly improved Hemi-mMASI scores (1:5, p = 0.043; 1:10, p = 0.002) and brown spots (1:5, p = 0.002; 1:10, p < 0.001). The 1:10 dilution showed earlier and more sustained improvements. Subgroup analysis revealed greater reductions in Hemi-mMASI scores among patients with telangiectatic melasma, particularly with the 1:10 dilution, though they were not statistically significant. Additionally, the 1:10 dilution significantly reduced pore volume, pore area, and sebum levels. One case of transient facial asymmetry was reported with the 1:5 dilution. Conclusions: LetiBoNT-A is a safe and effective adjunct in melasma treatment. The 1:10 dilution offered superior clinical outcomes. Full article

(This article belongs to the Special Issue The Evolving Role of Botulinum Toxin in Clinical Therapeutics)

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46 pages, 3177 KiB

Open AccessReview

Recent Advancements in Lateral Flow Assays for Food Mycotoxin Detection: A Review of Nanoparticle-Based Methods and Innovations

by Gayathree Thenuwara, Perveen Akhtar, Bilal Javed, Baljit Singh, Hugh J. Byrne and Furong Tian

Toxins 2025, 17(7), 348; https://doi.org/10.3390/toxins17070348 - 11 Jul 2025

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Abstract

Mycotoxins are responsible for a multitude of diseases in both humans and animals, resulting in significant medical and economic burdens worldwide. Conventional detection methods, such as enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS), are highly effective, [...] Read more.

Mycotoxins are responsible for a multitude of diseases in both humans and animals, resulting in significant medical and economic burdens worldwide. Conventional detection methods, such as enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS), are highly effective, but they are generally confined to laboratory settings. Consequently, there is a growing demand for point-of-care testing (POCT) solutions that are rapid, sensitive, portable, and cost-effective. Lateral flow assays (LFAs) are a pivotal technology in POCT due to their simplicity, rapidity, and ease of use. This review synthesizes data from 78 peer-reviewed studies published between 2015 and 2024, evaluating advances in nanoparticle-based LFAs for detection of singular or multiplex mycotoxin types. Gold nanoparticles (AuNPs) remain the most widely used, due to their favorable optical and surface chemistry; however, significant progress has also been made with silver nanoparticles (AgNPs), magnetic nanoparticles, quantum dots (QDs), nanozymes, and hybrid nanostructures. The integration of multifunctional nanomaterials has enhanced assay sensitivity, specificity, and operational usability, with innovations including smartphone-based readers, signal amplification strategies, and supplementary technologies such as surface-enhanced Raman spectroscopy (SERS). While most singular LFAs achieved moderate sensitivity (0.001–1 ng/mL), only 6% reached ultra-sensitive detection (<0.001 ng/mL), and no significant improvement was evident over time (ρ = −0.162, p = 0.261). In contrast, multiplex assays demonstrated clear performance gains post-2022 (ρ = −0.357, p = 0.0008), largely driven by system-level optimization and advanced nanomaterials. Importantly, the type of sample matrix (e.g., cereals, dairy, feed) did not significantly influence the analytical sensitivity of singular or multiplex lateral LFAs (Kruskal–Wallis p > 0.05), confirming the matrix-independence of these optimized platforms. While analytical challenges remain for complex targets like fumonisins and deoxynivalenol (DON), ongoing innovations in signal amplification, biorecognition chemistry, and assay standardization are driving LFAs toward becoming reliable, ultra-sensitive, and field-deployable platforms for high-throughput mycotoxin screening in global food safety surveillance. Full article

(This article belongs to the Special Issue Advances in Contamination, Detection and Risk Assessment of Mycotoxins)

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15 pages, 1732 KiB

Open AccessArticle

Differentiating Zeranol Implant Abuse and Fusarium spp. Toxin-Contaminated Corn Intake by Detection and Quantification of Resorcylic Acid Lactones in Bovine Urine

by Rafael Silva Gomes, Vanessa Gonçalves dos Santos, Carlos Juliano da Silva, Amanda Martinez Nagato Simões, Eliene Alves dos Santos, Mary Ane Gonçalves Lana, Kelly Moura Keller, Marco Blokland, Ane Arrizabalaga-Larrañaga, Rafael Romero Nicolino, Marcelo Resende de Souza, Tadeu Chaves de Figueiredo, Saskia Sterk and Silvana de Vasconcelos Cançado

Toxins 2025, 17(7), 347; https://doi.org/10.3390/toxins17070347 - 11 Jul 2025

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Abstract

Resorcylic acid lactones (RALs) are fungal metabolites with known biological activity. Zeranol, a synthetic RAL, has been used as an estrogenic growth promoter in cattle; however, its use is prohibited in several countries. Zearalenone, a mycotoxin produced by Fusarium spp., is commonly found [...] Read more.

Resorcylic acid lactones (RALs) are fungal metabolites with known biological activity. Zeranol, a synthetic RAL, has been used as an estrogenic growth promoter in cattle; however, its use is prohibited in several countries. Zearalenone, a mycotoxin produced by Fusarium spp., is commonly found in contaminated animal feed and can be metabolized into other RALs, which are subsequently excreted in urine. To differentiate between natural contamination from feed and the illegal administration of zeranol, the European Union Reference Laboratory for Growth Promoters (EURL) developed a mathematical equation. This study aims to evaluate the detection and quantification of RALs in bovine urine from animals fed zearalenone-contaminated diets, implanted with zeranol, or subjected to both conditions. RALs were detected and quantified in the urine of cattle consuming contaminated corn, while zeranol and taleranol were identified in the urine of implanted animals. The EURL equation proved to be a valuable tool for determining the origin of RALs in bovine urine and holds significant potential for monitoring and enforcing regulations regarding the illegal use of zeranol. Full article

(This article belongs to the Section Mycotoxins)

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17 pages, 5008 KiB

Open AccessArticle

Biodegradation of Microcystins by Aquatic Bacteria Klebsiella spp. Isolated from Lake Kasumigaura

by Thida Lin, Kazuya Shimizu, Tianxiao Liu, Qintong Li and Motoo Utsumi

Toxins 2025, 17(7), 346; https://doi.org/10.3390/toxins17070346 - 10 Jul 2025

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Abstract

Microcystins (MCs) are the most toxic and abundant cyanotoxins found in natural waters during harmful cyanobacterial blooms. These toxins pose a significant threat to plant, animal, and human health due to their toxicity. Degradation of MCs by MC-degrading bacteria is a promising method [...] Read more.

Microcystins (MCs) are the most toxic and abundant cyanotoxins found in natural waters during harmful cyanobacterial blooms. These toxins pose a significant threat to plant, animal, and human health due to their toxicity. Degradation of MCs by MC-degrading bacteria is a promising method for controlling these toxins, demonstrating safety, high efficiency, and cost-effectiveness. In this study, we isolated potential MC-degrading bacteria (strains TA13, TA14, and TA19) from Lake Kasumigaura in Japan and found that they possess a high capacity for MC degradation. Based on 16S rRNA gene sequencing, all three isolated strains were identified as belonging to the Klebsiella species. These bacteria effectively degraded MC-RR, MC-YR, and MC-LR under various temperature and pH conditions within 10 h, with the highest degrading activity and degradation rate observed at 40 °C. Furthermore, the isolated strains efficiently degraded MCs not only under neutral pH conditions, but also in alkaline environments. Additionally, we detected the MC-degrading gene (mlrA) in all three isolated strains, marking the first report of the mlrA gene in Klebsiella species. The copy number of the mlrA gene in the strains increased after exposure to MCs. These findings indicate that strains TA13, TA14, and TA19 significantly contribute of MC bioremediation in Lake Kasumigaura during cyanobacterial blooms. Full article

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

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20 pages, 1188 KiB

Open AccessReview

Increased Cardiovascular Mortality in Hemodialysis: The Role of Chronic Inflammation, Complement Activation, and Non-Biocompatibility

by Ákos Géza Pethő, Tibor Fülöp, Petronella Orosz, Gábor Szénási, Mihály Tapolyai and László Dézsi

Toxins 2025, 17(7), 345; https://doi.org/10.3390/toxins17070345 - 10 Jul 2025

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Abstract

Background: Chronic kidney disease (CKD) is an established global health problem, with the increased prevalence of vascular inflammation, accelerated atherogenesis, and thrombotic risk all contributing to overall cardiovascular risk. The major CKD-specific risk factor is presumed to be the accumulation of uremic toxins [...] Read more.

Background: Chronic kidney disease (CKD) is an established global health problem, with the increased prevalence of vascular inflammation, accelerated atherogenesis, and thrombotic risk all contributing to overall cardiovascular risk. The major CKD-specific risk factor is presumed to be the accumulation of uremic toxins in circulation and tissues, further accelerating the progression of CKD and its co-morbidities, including those of bone mineral disorders and cardiovascular diseases. Materials and Methods: In our narrative review, we focused on non-traditional cardiovascular risk factors, as they evolve with declined kidney function and are potentially further modulated by the choice of kidney replacement therapy. Results: Based on the data from the literature to date, the pre-eminent role of non-traditional risk factors emerges to mediate inflammation and increased cardiovascular mortality. In particular, patients receiving hemodialysis (HD) display dramatically increased CVD-mediated mortality. This intensified state of inflammation may be linked to the direct exposure of the bloodstream to a bio-incompatible environment in HD; for both complement-mediated and non-complement-mediated reactions, the possible contribution of neutrophil extracellular traps and complement activation-related pseudoallergy are reviewed in detail. Conclusions: Our narrative review emphasizes key elements of a bio-incompatible HD environment that may contribute to increased cardiovascular mortality in patients receiving HD. Summarizing these results may provide conceptual opportunities to develop new therapeutic targets. Full article

(This article belongs to the Section Uremic Toxins)

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27 pages, 768 KiB

Open AccessReview

Pre-Harvest Aflatoxin Contamination in Crops and Climate Change Factors: A European Overview

by Ainhoa Bereziartua, Anke Huss, Jannigje G. Kers, Lidwien A. M. Smit, Roel Vermeulen and Daniel Martins Figueiredo

Toxins 2025, 17(7), 344; https://doi.org/10.3390/toxins17070344 - 8 Jul 2025

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Abstract

Aflatoxin (AF) contamination of crops during the pre-harvest period is a significant global concern for food and feed safety (FFS). In Europe, climate change presents a growing threat to agricultural products by increasing the risk of AF contamination. This umbrella review evaluates the [...] Read more.

Aflatoxin (AF) contamination of crops during the pre-harvest period is a significant global concern for food and feed safety (FFS). In Europe, climate change presents a growing threat to agricultural products by increasing the risk of AF contamination. This umbrella review evaluates the scope and quality of pre-harvest data on climate-related AF contamination in Europe, addressing key questions: What insights do researchers provide on the relationship between climate change and pre-harvest AF contamination, and what data are lacking? Which crops are the focus of current research, and where in Europe are these studies concentrated? How is the data presented, and is it standardized? We conducted an umbrella literature review, extracting relevant studies from PubMed and Scopus up to 14 October 2024. Our findings indicate that rising temperatures, droughts, and shifting rainfall patterns increasingly favor the growth of aflatoxigenic fungi and pre-harvest AF contamination in European crops, posing risks to FFS and agricultural stability. However, inconsistencies in data collection and reporting limit cross-regional comparisons and hinder the development of effective mitigation strategies. Standardizing methodologies and improving data accessibility will enhance predictive modeling, strengthen risk assessments, and support targeted adaptation efforts, providing actionable insights for policymakers and agricultural stakeholders. Full article

(This article belongs to the Section Mycotoxins)

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19 pages, 1475 KiB

Open AccessArticle

Chemical and Morphological Constitutive Defensive Traits of Cyanobacteria Have Different Effects on the Grazing of a Small Tropical Cladoceran

by Luciana Machado Rangel, Marcella Coelho Berjante Mesquita, Shara Rosa de Barros, Vinicius Neres-Lima, Michael Ribas Celano, Mauro Cesar Palmeira Vilar, Sandra Maria Feliciano de Oliveira e Azevedo and Marcelo Manzi Marinho

Toxins 2025, 17(7), 343; https://doi.org/10.3390/toxins17070343 - 5 Jul 2025

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Abstract

Antipredator defenses of bloom-forming cyanobacteria species maximize their fitness but can reduce carbon and energy transfer efficiency to higher trophic levels, making them a key regulator of plankton communities in eutrophic waters. We investigated the grazing responses of the tropical cladoceran Moina micrura [...] Read more.

Antipredator defenses of bloom-forming cyanobacteria species maximize their fitness but can reduce carbon and energy transfer efficiency to higher trophic levels, making them a key regulator of plankton communities in eutrophic waters. We investigated the grazing responses of the tropical cladoceran Moina micrura to different strains of the cyanobacteria Microcystis aeruginosa and Planktothrix isothrix, using a good food source (green algae Mono-raphidium capricornutum) as a control. Both Microcystis strains grow as unicellular and are microcystins producers; however, this cyanotoxin was not detected on the filamentous Planktothrix strains. M. micrura ingested all cyanobacteria at reduced rates compared to single diets with Monoraphidium. In mixed diets, food type had a significant effect on grazing responses, which differed interspecifically. Planktothrix was more grazed than Microcystis strains. Feeding selectivity on Monoraphidium was negatively affected by the increase of cyanobacteria in the diet. We observed varied responses across treatments, ranging from feeding inhibition to different degrees of tolerance toward cyanobacteria, particularly in non-microcystin-producing species. We also highlight the selectivity of small tropical cladocerans, a pattern that is not yet well documented. These findings emphasize that studies incorporating phyto- and zooplankton with a history of coexistence can provide more meaningful insights into natural ecosystem dynamics. Full article

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

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20 pages, 3269 KiB

Open AccessArticle

Immunomodulatory Effect of a Cysteine-Rich Secretory Protein from an Entomopathogenic Nematode with Sterol-Binding Activity

by Jorge Frias, Duarte Toubarro, Tiago Paiva and Nelson Simões

Toxins 2025, 17(7), 342; https://doi.org/10.3390/toxins17070342 - 5 Jul 2025

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Abstract

The Steinernema carpocapsae nematode is known to release several excretory/secretory products (ESPs) in its venom upon contact and during the parasitic infection process of insect hosts. A recurrent family of proteins found in this nematode’s venom is the CAP (cysteine-rich secretory protein/antigen 5/pathogenesis-related [...] Read more.

The Steinernema carpocapsae nematode is known to release several excretory/secretory products (ESPs) in its venom upon contact and during the parasitic infection process of insect hosts. A recurrent family of proteins found in this nematode’s venom is the CAP (cysteine-rich secretory protein/antigen 5/pathogenesis-related 1) protein, but the functional role of these proteins remains unknown. To elucidate the biological function, this study focused on characterising the secreted protein, first identified in the venom of the nematode’s parasitic stage, and the sequence retrieved from transcriptomic analysis. The structural comparisons of the Sc-CAP protein model, as determined by AlphaFold2, revealed related structures from other parasitic nematodes of vertebrates. Some of these closely related proteins are reported to have sterol-binding ability. The Sc-CAP recombinant protein was successfully produced in Escherichia coli in conjunction with a chaperone protein. The results showed that the Sc-CAP protein binds to cholesterol, and docking analyses of sterols on the protein revealed potential molecular interactions. Immunoassays performed in Galleria mellonella larvae revealed that this venom protein has an inhibitory effect against phenoloxidase and the antimicrobial response of insects. This suggests that the venom protein has an immunomodulatory function against insects, emphasising its importance during the parasite–host interaction. Full article

(This article belongs to the Section Animal Venoms)

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15 pages, 881 KiB

Open AccessArticle

Economic Evaluation of the InTENSE Program of Therapy Alongside Botulinum Neurotoxin a for the Rehabilitation of Chronic Upper Limb Spasticity

by Rachel Milte, Jia Song, Sean Docking, Julie Ratcliffe, Ian D. Cameron, Maria Crotty, Louise Ada, Coralie English and Natasha A. Lannin

Toxins 2025, 17(7), 341; https://doi.org/10.3390/toxins17070341 - 4 Jul 2025

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Abstract

Spasticity is a persistent and debilitating consequence of stroke and effective rehabilitation is a healthcare priority. Botulinum neurotoxin A (BoNT-A) with supportive therapy has increasingly been embedded within clinical practice for treatment of post-stroke spasticity. But the evidence for this approach has hitherto [...] Read more.

Spasticity is a persistent and debilitating consequence of stroke and effective rehabilitation is a healthcare priority. Botulinum neurotoxin A (BoNT-A) with supportive therapy has increasingly been embedded within clinical practice for treatment of post-stroke spasticity. But the evidence for this approach has hitherto been limited to the findings of a limited number of small trials. The InTENSE trial was undertaken specifically to provide high-quality clinical trial evidence focusing on the effect of BoNT-A and adjunctive therapy on upper limb spasticity. While the clinical trial did not detect a significant impact upon clinical outcomes, there remains a need to evaluate any impact on the broader use of healthcare resources and overall cost-effectiveness. A detailed cost–utility analysis of the InTENSE trial was undertaken. The costs over the 12-month follow-up period were compared with quality-adjusted life years (QALY) gained using utilities generated from the EQ-5D three level (EQ-5D-3L) instrument. There were no significant differences in QALY gained between the intervention and control groups identified, or in the majority of health and community care costs. The Incremental Cost-Effectiveness Ratio per QALY gained was estimated at AU $63,947.11 (Australian dollars), which is well above accepted thresholds for cost-effectiveness in Australia. The study was unable to identify evidence for the cost-effectiveness of treatment approaches combining BoNT-A with adjunctive therapy. Full article

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23 pages, 2062 KiB

Open AccessReview

Potential Compounds as Inhibitors of Staphylococcal Virulence Factors Involved in the Development of Thrombosis

by Anna Lichota, Krzysztof Gwozdzinski and Monika Sienkiewicz

Toxins 2025, 17(7), 340; https://doi.org/10.3390/toxins17070340 - 4 Jul 2025

Viewed by 237

Abstract

For many years, staphylococci have been detected mainly in infections of the skin and soft tissues, organs, bone inflammations, and generalized infections. Thromboembolic diseases have also become a serious plague of our times, which, as it turns out, are closely related to the [...] Read more.

For many years, staphylococci have been detected mainly in infections of the skin and soft tissues, organs, bone inflammations, and generalized infections. Thromboembolic diseases have also become a serious plague of our times, which, as it turns out, are closely related to the toxic effects of staphylococci. Staphylococcus aureus, because of the presence of many different kinds of virulence factors, is capable of manipulating the host’s innate and adaptive immune responses. These include toxins and cofactors that activate host zymogens and exoenzymes, as well as superantigens, which are highly inflammatory and cause leukocyte death. Coagulases and staphylokinases can control the host’s coagulation system. Nucleases and proteases inactivate various immune defense and surveillance proteins, including complement components, peptides and antibacterial proteins, and surface receptors that are important for leukocyte chemotaxis. On the other hand, secreted toxins and exoenzymes are proteins that disrupt the endothelial and epithelial barrier as a result of cell lysis and disintegration of linking proteins, which ultimately increases the risk of thromboembolism. In this review, we discuss various virulence factors and substances that may inhibit their activity. Full article

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15 pages, 4607 KiB

Open AccessArticle

Transcriptome Analysis of Dimethyl Fumarate Inhibiting the Growth of Aspergillus carbonarius

by Siruo Wang, Bowen Tai, Xifan Yu, Erfeng Li, Gang Wang, Jing Jin and Fuguo Xing

Toxins 2025, 17(7), 339; https://doi.org/10.3390/toxins17070339 - 4 Jul 2025

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Abstract

Aspergillus carbonarius is one of the main pathogens responsible for postharvest diseases in fruits and is also one of the main ochratoxin A-producing strains. It not only causes significant economic losses but also poses a risk to human health. We found an inhibitory [...] Read more.

Aspergillus carbonarius is one of the main pathogens responsible for postharvest diseases in fruits and is also one of the main ochratoxin A-producing strains. It not only causes significant economic losses but also poses a risk to human health. We found an inhibitory effect of dimethyl fumarate fumigation on the growth of A. carbonarius. To further explore its antifungal mechanism, this study elucidated the functions of key pathway-related genes through a transcriptomics analysis. A total of 1402 differentially expressed genes (DEGs) were identified, including 987 up-regulated and 415 down-regulated genes. Dimethyl fumarate was found to significantly inhibit the growth of A. carbonarius by disrupting cell integrity and obstructing mycelium growth and secondary metabolism. These findings provide a basis for the potential application of dimethyl fumarate in the food industry to inhibit A. carbonarius and subsequent ochratoxin A contamination. Full article

(This article belongs to the Section Mycotoxins)

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20 pages, 10410 KiB

Open AccessArticle

Modeling Algal Toxin Dynamics and Integrated Web Framework for Lakes

by Özlem Baydaroğlu, Serhan Yeşilköy, Anchit Dave, Marc Linderman and Ibrahim Demir

Toxins 2025, 17(7), 338; https://doi.org/10.3390/toxins17070338 - 3 Jul 2025

Viewed by 392

Abstract

Harmful algal blooms (HABs) are one of the major environmental concerns, as they have various negative effects on public and environmental health, recreational services, and economics. HAB modeling is challenging due to inconsistent and insufficient data, as well as the nonlinear nature of [...] Read more.

Harmful algal blooms (HABs) are one of the major environmental concerns, as they have various negative effects on public and environmental health, recreational services, and economics. HAB modeling is challenging due to inconsistent and insufficient data, as well as the nonlinear nature of algae formation data. However, it is crucial for attaining sustainable development goals related to clean water and sanitation. From this point of view, we employed the sparse identification nonlinear dynamics (SINDy) technique to model microcystin, an algal toxin, utilizing dissolved oxygen as a water quality metric and evaporation as a meteorological parameter. SINDy is a novel approach that combines a sparse regression and machine learning method to reconstruct the analytical representation of a dynamical system. The model results indicate that MAPE values of approximately 2% were achieved in three out of four lakes, while the MAPE value of the remaining lake is 11%. Moreover, a model-driven and web-based interactive tool was created to develop environmental education, raise public awareness on HAB events, and produce more effective solutions to HAB problems through what-if scenarios. This interactive and user-friendly web platform allows tracking the status of HABs in lakes and observing the impact of specific parameters on harmful algae formation. Full article

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

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18 pages, 3265 KiB

Open AccessArticle

Nymphoides peltata Alleviates Patulin-Induced Glutamine Metabolic Stress and Epithelial Toxicity in Small Intestinal Epithelial Cells

by Chae Hyun Lee, Sangsu Shin, Tae Hyun Kim and Sang In Lee

Toxins 2025, 17(7), 337; https://doi.org/10.3390/toxins17070337 - 3 Jul 2025

Viewed by 366

Abstract

Patulin (PAT) is a mycotoxin commonly found in fruits and contaminated feedstuffs, known for its gastrointestinal and systemic toxicity. However, the mechanisms underlying PAT-induced damage to intestinal epithelial cells remain poorly understood. In this study, we demonstrated that 6.5 µM PAT exposure for [...] Read more.

Patulin (PAT) is a mycotoxin commonly found in fruits and contaminated feedstuffs, known for its gastrointestinal and systemic toxicity. However, the mechanisms underlying PAT-induced damage to intestinal epithelial cells remain poorly understood. In this study, we demonstrated that 6.5 µM PAT exposure for 24 h reduced glutamine (GLN) uptake and altered the expression of GLN transporters and related metabolic enzymes in IPEC-J2 cells. This concentration was selected based on previous in vitro studies that reported PAT-induced cytotoxicity in porcine intestinal epithelial cells. Moreover, PAT also upregulated ER stress markers (DDIT3, EIF2AK3, ERN1, and HSPA5) and inflammatory cytokines (IL-8, IL-1β, and TNF-α), while decreasing ZO-1 localization, indicating disrupted epithelial barrier integrity. Although 6 mM GLN supplementation only partially mediated ER stress and inflammatory responses, it more effectively restored ZO-1 localization. A high-throughput screening of 324 natural products was conducted to identify potential protective agents, identifying Nymphoides peltata extract as a promising candidate. Co-treatment with 80 ng/μL N. peltata extract improved GLN uptake, partially alleviated ER stress and inflammation, and significantly restored tight junction structure in PAT-exposed cells. Collectively, these findings suggest that N. peltata could serve as a novel natural therapeutic for enhancing intestinal resilience against PAT-induced toxicity. Specifically, this study highlights the potential use of N. peltata extract as a natural feed additive to protect intestinal health in livestock under mycotoxin stress. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 1948 KiB

Open AccessArticle

Establishing a 3D Spheroid Model of Cholinergic Neurons from SH-SY5Y Cells for Neurotoxicity Assessment

by Felipe Franco-Campos, Mónica Fernández-Franzón, Yelko Rodríguez-Carrasco and María-José Ruiz

Toxins 2025, 17(7), 336; https://doi.org/10.3390/toxins17070336 - 2 Jul 2025

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Abstract

The nervous system maintains homeostasis and coordinated behavior through complex neuronal and glial cells. Traditional models, such as primary rodent neurons and human-induced pluripotent stem cell (hIPSC)-derived neurons, have advanced our understanding of neuronal function and neurotoxic damage; however, they are costly and [...] Read more.

The nervous system maintains homeostasis and coordinated behavior through complex neuronal and glial cells. Traditional models, such as primary rodent neurons and human-induced pluripotent stem cell (hIPSC)-derived neurons, have advanced our understanding of neuronal function and neurotoxic damage; however, they are costly and labor-intensive. SH-SY5Y cells, an immortalized human neuroblastoma cell line, provide a more accessible alternative for studying neuronal processes and neurotoxicity. However, their limited capacity to differentiate into specific neuronal phenotypes remains a challenge. To address this limitation, differentiation protocols using neuronal factors and vitamins have been developed, primarily in two-dimensional (2D) cultures, which reduces physiological relevance. Here, we present a novel three-dimensional (3D) SH-SY5Y model incorporating 2D differentiation protocols to generate cholinergic neurons (ChAT+). This model enhances neurotoxicity studies related to pesticides and mycotoxins. Our protocol produces homogeneous spheroids differentiated into cholinergic neurons using serum restriction and specific factors, maintaining viability and circularity for up to 22 days. Differentiation was validated by immunofluorescence and Western blot by Choline acetyltransferase (ChAT) expression. This scalable and reproducible 3D model provides a valuable in vitro tool for neurotoxicological research, improving physiological relevance and enabling the study of cholinergic neuron differentiation and function. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Determination: From Risk Assessment to Global Management Strategies)

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25 pages, 3047 KiB

Open AccessArticle

Fate of Pyrrolizidine Alkaloids in Soil: Insights from Myosotis arvensis L. and Senecio vulgaris L.

by Ilva Nakurte, Gundars Skudriņš and Ieva Mežaka

Toxins 2025, 17(7), 335; https://doi.org/10.3390/toxins17070335 - 2 Jul 2025

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Abstract

Pyrrolizidine alkaloids are plant-derived toxins with environmental persistence and the potential to contaminate soil, water, and adjacent crops. This study investigated the leaching behavior and environmental fate of PAs from two PA-producing weeds—Myosotis arvensis L. (Boraginaceae) and Senecio vulgaris L. (Asteraceae)—in two [...] Read more.

Pyrrolizidine alkaloids are plant-derived toxins with environmental persistence and the potential to contaminate soil, water, and adjacent crops. This study investigated the leaching behavior and environmental fate of PAs from two PA-producing weeds—Myosotis arvensis L. (Boraginaceae) and Senecio vulgaris L. (Asteraceae)—in two Latvian agricultural soils: sandy loam and loam. Hot- and cold-water plant extracts were applied to soil columns (10 cm and 20 cm), and leachates were analyzed over a 14-day period using QuEChERS purification and LC-HRMS detection. Leaching varied by plant species, extract type, and soil. M. arvensis showed significantly higher cumulative leaching (77–84% for cold, 65–71% for hot extracts), attributed to the higher solubility of N-oxides. In contrast, S. vulgaris extracts leached minimally (<0.84% from sandy loam) and were undetectable in loam. The presence of cyclic diester PAs in S. vulgaris and the higher cation exchange capacity of loam favored retention or degradation. PANO-to-PA conversion occurred in both soils, indicating redox activity. The fate of PAs was influenced by structural type (diesters showing higher persistence), extraction method (hot extraction releasing more pyrrolizidine alkaloids), and soil properties such as pH, organic matter, and cation exchange capacity, which affected sorption and mobility. These findings underscore the significance of soil composition in controlling PA mobility and associated environmental risks. Future research should focus on long-term PA persistence across diverse soil types and investigate crop uptake potential and microbial degradation pathways under field conditions. Full article

(This article belongs to the Special Issue Toxic Plant-Derived Metabolites)

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19 pages, 2150 KiB

Open AccessArticle

Associations Between Uraemic Toxins and Gut Microbiota in Adults Initiating Peritoneal Dialysis

by Philippa James, Jordan Stanford, Ojas V. A. Dixit, Mary Ann Nicdao, Brett McWhinney, Kamal Sud, Michele Ryan, Scott Read, Golo Ahlenstiel, Kelly Lambert, Claire O’Brien and Katrina Chau

Toxins 2025, 17(7), 334; https://doi.org/10.3390/toxins17070334 - 1 Jul 2025

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Abstract

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis [...] Read more.

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m²) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into ‘high’ (n = 18) and ‘low’ (n = 26) uraemic toxin groups using K-means clustering. The ‘high’ group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The ‘high’ group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions. Full article

(This article belongs to the Section Uremic Toxins)

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17 pages, 1034 KiB

Open AccessArticle

Monitoring of Vitamin C Plasma Levels in a Reversible Model of Malabsorption Generated in Mice by Ebulin-f

by Daniel Arranz-Paraiso, M. Angeles Rojo, Cristina Martin-Sabroso, Manuel Cordoba-Diaz, Tomás Girbés, Manuel Garrosa and Damian Cordoba-Diaz

Toxins 2025, 17(7), 333; https://doi.org/10.3390/toxins17070333 - 30 Jun 2025

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Abstract

The development of reversible animal models for the study of intestinal pathologies is essential to reduce the number of animals used in research and to better understand disease mechanisms. In this study, we present a reversible model of intestinal malabsorption through the administration [...] Read more.

The development of reversible animal models for the study of intestinal pathologies is essential to reduce the number of animals used in research and to better understand disease mechanisms. In this study, we present a reversible model of intestinal malabsorption through the administration of sublethal doses of ebulin-f, a ribosome-inactivating protein, and validate its usefulness by monitoring vitamin C absorption. The scientific community increasingly recognizes the importance of rationalizing experimental designs, optimizing treatment protocols, and minimizing the use of animals in research models. Thus, new methodologies are needed to minimize invasive sampling and to develop reversible animal models that recover physiologically post-study. Such models are essential for in vivo studies of human pathologies. Sublethal doses of ebulin-f (2.5 mg/kg) administered intraperitoneally to female Swiss CD1 mice (n = 6 per group) can cause reversible intestinal alterations in the small intestine, which offer the possibility of having a valuable reversible study model of malabsorption for the investigation of this syndrome. To verify whether nutrient absorption is altered, we used vitamin C as a traceable nutrient that can be quantified in the blood. Peripheral blood samples were collected through the retro-orbital area at 30, 80, 120, 180, and 1440 min post-administration, treated with DTT and MPA, and analyzed using a validated UV/Vis–HPLC method to indirectly determine vitamin C absorption by enterocytes. Pharmacokinetic analysis revealed significantly increased vitamin C absorption on days 1 and 3 post-treatment (AUC values of 3.65 × 10⁴ and 7.10 × 10⁴, respectively) compared to control (0.94 × 10⁴), with partial recovery by day 22 (3.27 × 10⁴). Blood concentration profiles indicate that intestinal damage peaks at day 3, followed by significant regeneration by day 22, establishing this as a viable reversible model for inflammatory bowel disease research. Full article

(This article belongs to the Special Issue Ribosome-Inactivating Proteins: From Plant Toxins to Drug Applications)

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16 pages, 5492 KiB

Open AccessArticle

Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines

by Camila R. Ferraz, Marília F. Manchope, Mariana M. Bertozzi, Telma Saraiva-Santos, Ketlem C. Andrade, Anelise Franciosi, Tiago H. Zaninelli, Julia Bagatim-Souza, Sergio M. Borghi, Denise M. Cândido, Thiago M. Cunha, Rubia Casagrande, Fábio H. Kwasniewski and Waldiceu A. Verri

Toxins 2025, 17(7), 332; https://doi.org/10.3390/toxins17070332 - 30 Jun 2025

Viewed by 320

Abstract

For centuries, researchers have been fascinated by the composition of scorpion venom and its local and systemic effects on humans. During a sting, scorpions inject peptides and proteins that can affect immune cells and neurons. While the immune and nervous systems have been [...] Read more.

For centuries, researchers have been fascinated by the composition of scorpion venom and its local and systemic effects on humans. During a sting, scorpions inject peptides and proteins that can affect immune cells and neurons. While the immune and nervous systems have been studied independently in the context of scorpion stings, here we reveal part of the mechanism by which Tityus serrulatus venom induces hyperalgesia in mice. Through behavioral, immune, imaging assays, and mice genetics, we demonstrate evidence of neuroimmune crosstalk during scorpion stings. Tityus serrulatus venom induced mechanical and thermal hyperalgesia in a dose-dependent manner, as well as overt pain-like behavior. The venom directly activated dorsal root ganglia neurons and increased the recruitment of macrophages and neutrophils, releasing pro-inflammatory cytokines TNF-α and IL-1β. Blocking TRPV1⁺ neurons, TNF-α, IL-1β, and NFκB reduced the mechanical and thermal hyperalgesia, overt pain-like behavior, and the migration of macrophages and neutrophils induced by Tityus serrulatus venom. Collectively, Tityus serrulatus venom targets primary afferent nociceptive TRPV1⁺ neurons to induce hyperalgesia through the recruitment of macrophages and neutrophils and the release of pro-inflammatory cytokines. Full article

(This article belongs to the Section Animal Venoms)

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27 pages, 2201 KiB

Open AccessReview

Toxicity, Mitigation, and Chemical Analysis of Aflatoxins and Other Toxic Metabolites Produced by Aspergillus: A Comprehensive Review

by Habtamu Fekadu Gemede

Toxins 2025, 17(7), 331; https://doi.org/10.3390/toxins17070331 - 30 Jun 2025

Viewed by 512

Abstract

Aflatoxins, toxic secondary metabolites produced primarily by Aspergillus flavus and Aspergillus parasiticus, pose significant risks to food safety, public health, and global trade. These mycotoxins contaminate staple crops such as maize and peanuts, particularly in warm and humid regions, leading to economic [...] Read more.

Aflatoxins, toxic secondary metabolites produced primarily by Aspergillus flavus and Aspergillus parasiticus, pose significant risks to food safety, public health, and global trade. These mycotoxins contaminate staple crops such as maize and peanuts, particularly in warm and humid regions, leading to economic losses and severe health effects, including hepatocellular carcinoma, immune suppression, and growth impairment. In addition to aflatoxins, Aspergillus species produce other toxic metabolites such as ochratoxin A, sterigmatocystin, and cyclopiazonic acid, which are associated with nephrotoxic, carcinogenic, and neurotoxic effects, respectively. This review provides a comprehensive analysis of aflatoxin toxicity, mitigation strategies, and chemical detection methods. The toxicity of aflatoxins is discussed in relation to their biochemical mechanisms, carcinogenicity, and synergistic effects with other mycotoxins. Various mitigation approaches, including pre-harvest biocontrol, post-harvest storage management, and novel detoxification methods such as enzymatic degradation and nanotechnology-based interventions, are evaluated. Furthermore, advances in aflatoxin detection, including chromatographic, immunoassay, and biosensor-based methods, are explored to improve regulatory compliance and food safety monitoring. This review underscores the need for integrated management strategies and global collaboration to reduce aflatoxin contamination and its associated health and economic burdens. Future research directions should focus on genetic engineering for resistant crop varieties, climate adaptation strategies, and improved risk assessment models. Full article

(This article belongs to the Special Issue Toxicity, Mitigation and Chemical Analysis of Aflatoxins and Other Toxic Metabolites Produced by Aspergillus)

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14 pages, 368 KiB

Open AccessArticle

Long-Term Effectiveness of Onabotulinum Toxin-A in a Combined Total Endoscopic Management of Pediatric Vesicoureteral Reflux in Neurogenic Bladder Dysfunction

by Claudio Paratore, Chiara Pellegrino, Noemi Deanesi, Rebecca Pulvirenti, Maria Luisa Capitanucci and Giovanni Mosiello

Toxins 2025, 17(7), 330; https://doi.org/10.3390/toxins17070330 - 29 Jun 2025

Viewed by 237

Abstract

Vesicoureteral reflux (VUR) management in children with neurogenic bladder dysfunction (NBD) remains a clinical challenge. Total endoscopic management (TEM), combining intradetrusor Onabotulinum Toxin-A (BTX-A) and subureteric dextranomer/hyaluronic acid (Deflux^(R)) injection, offers a minimally invasive alternative. The aim of this retrospective study [...] Read more.

Vesicoureteral reflux (VUR) management in children with neurogenic bladder dysfunction (NBD) remains a clinical challenge. Total endoscopic management (TEM), combining intradetrusor Onabotulinum Toxin-A (BTX-A) and subureteric dextranomer/hyaluronic acid (Deflux^(R)) injection, offers a minimally invasive alternative. The aim of this retrospective study is to evaluate the long-term effectiveness of TEM. Inclusion criteria: symptomatic II–V grade VUR (also I in bilateral VUR) in NBD children with follow-up ≥12 months. Nineteen patients were enrolled, 24 ureters (grade I–II: 2, grade III–V: 22); 5 patients (20.8%) had bilateral VUR. Mean age at surgery: 7.6 years (1.3–17). No complications were reported. TEM was effective in 11 patients (57.9%), 3/11 requiring a second TEM treatment. VUR resolution appeared in 14 ureters (58.3%), downgrading in 6 (42.9%), persistence in 4 (28.6%). Among non-responders’ patients (8/19, 42.1%), five (26.3%) required bladder augmentation (one combined with ureteral reimplantation), one (5.3%) underwent reimplantation, and two (10.5%) continued conservative management. At bladder biopsy, 11 patients (57.9%) had chronic inflammation, 8 (42.1%) showed fibrosis; no difference in success rate was recorded. All responders required repeated BTX-A injections. Mean follow-up: 3.2 years (range 1–4.7). In selected patients, TEM appears to be a safe and effective strategy, potentially delaying or avoiding major reconstructive surgery. Full article

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18 pages, 2349 KiB

Open AccessArticle

Comparing Computational Peritoneal Dialysis Models in Pigs and Patients

by Sangita Swapnasrita, Joost C. de Vries, Joanna Stachowska-Piętka, Carl M Öberg, Karin G. F. Gerritsen and Aurélie Carlier

Toxins 2025, 17(7), 329; https://doi.org/10.3390/toxins17070329 - 28 Jun 2025

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Abstract

Computational models of peritoneal dialysis (PD) are increasingly useful for optimizing treatment in patients with kidney disease requiring dialysis (KDRD). However, although several mathematical models have been developed in the past few decades, a direct comparison of the models’ accuracy with respect to [...] Read more.

Computational models of peritoneal dialysis (PD) are increasingly useful for optimizing treatment in patients with kidney disease requiring dialysis (KDRD). However, although several mathematical models have been developed in the past few decades, a direct comparison of the models’ accuracy with respect to predicting in vivo data is needed to further create robust personalized models. Here, we used a dataset obtained in a previous in vivo experimental model of PD in pigs (23 sessions of 4 h 2 L dwells in four pigs) and humans (20 sessions in 20 patients) to compare six computational models of PD: the Graff model (UGM), the three-pore model (TPM), the Garred model (GM), and the Waniewski model (WM), as well as two variations of these (UGM-18, SWM). We conducted this comparison to predict the dialysate concentrations of key uremic toxins and electrolytes (four in humans) throughout a 4 h dwell. The model predictions can provide insight into inter-individual differences in ultrafiltration, which are critical for tailoring PD regimens in KDRD. While TPM offered improved physiological reality, its computational cost suggests a trade-off between model complexity and clinical applicability for real-time or portable kidney support systems. In future applications, such models could provide adaptive PD regimens for tailored care based on patient-specific toxin kinetics and fluid dynamics. 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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20 pages, 3412 KiB

Open AccessArticle

Snake Venom Metalloproteinases from Puff Adder and Saw-Scaled Viper Venoms Cause Cytotoxic Effects in Human Keratinocytes

by Keirah E. Bartlett, Adam Westhorpe, Mark C. Wilkinson and Nicholas R. Casewell

Toxins 2025, 17(7), 328; https://doi.org/10.3390/toxins17070328 - 28 Jun 2025

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Abstract

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The puff adder (Bitis arietans) and saw-scaled viper (Echis romani) have cytotoxic venoms that cause permanent injury via dermonecrosis around the bite site. Identifying the [...] Read more.

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The puff adder (Bitis arietans) and saw-scaled viper (Echis romani) have cytotoxic venoms that cause permanent injury via dermonecrosis around the bite site. Identifying the cytotoxic toxins within these venoms will allow for the development of targeted treatments to prevent snakebite morbidity. In this study, venoms from both species were fractionated using gel filtration chromatography, and a combination of cytotoxicity approaches, SDS-PAGE gel electrophoresis, and enzymatic assays were applied to identify the venom cytotoxins in the resulting fractions. Our results indicate that snake venom metalloproteinase (SVMP) toxins are responsible for causing cytotoxic effects across both venoms. The PI subclass of SVMPs is likely the main driver of cytotoxicity following envenoming by B. arietans, while the structurally distinct PIII subclass of SVMPs is mostly responsible for conveying this effect in E. romani venom. Identifying distinct SVMPs as cytotoxicity-causing toxins in these two African viper venoms will facilitate the future design and development of novel therapeutics targeting these medically important venoms, which in turn could help to mitigate the severe life- and limb-threatening consequences of tropical snakebites. Full article

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21 pages, 1391 KiB

Open AccessArticle

Botulinum Neurotoxin A-Induced Muscle Morphology Changes in Children with Cerebral Palsy: A One-Year Follow-Up Study

by Charlotte Lambrechts, Nathalie De Beukelaer, Ines Vandekerckhove, Ineke Verreydt, Anke Andries, Francesco Cenni, Ghislaine Gayan-Ramirez, Kaat Desloovere and Anja Van Campenhout

Toxins 2025, 17(7), 327; https://doi.org/10.3390/toxins17070327 - 27 Jun 2025

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Abstract

Botulinum neurotoxin type A (BoNT-A) is widely used to reduce spasticity in children with cerebral palsy. Despite its therapeutic benefits, incomplete muscle recovery has been observed post-treatment. This study evaluated longitudinal BoNT-A effects on muscle morphology over one year in children with CP [...] Read more.

Botulinum neurotoxin type A (BoNT-A) is widely used to reduce spasticity in children with cerebral palsy. Despite its therapeutic benefits, incomplete muscle recovery has been observed post-treatment. This study evaluated longitudinal BoNT-A effects on muscle morphology over one year in children with CP (n = 26, mean age: 5.19 years ± 3.26). Three-dimensional freehand ultrasound assessed medial gastrocnemius muscle volume (MV), muscle belly length (ML), cross-sectional area (CSA), and echo intensity (EI) at baseline and at 3, 6, and 12 months post-BoNT-A. Z-score normalization accounted for natural muscle growth. Linear mixed models analyzed muscular changes over time, and repeated-measures ANOVA compared muscle parameters to an age- and severity-matched control group (n = 26, mean age: 4.98 ± 2.15) at one-year follow-up. MV exhibited a declining trend at 3 (p = 0.005), 6 (p = 0.003), and 12 months (p = 0.007), while ML remained unchanged throughout follow-up (p = 0.95). The initially reduced CSA at 6 months (p = 0.0005) recovered at one year, and EI increased only at 3 months post-BoNT-A (p < 0.0001). At one-year follow-up, there was a trend for reduced growth rate (MV/month) (p = 0.035) in the intervention group, whereas the control group exhibited an increased muscle growth (p = 0.029). These findings suggest distinct recovery timelines for CSA and ML, which may explain the incomplete MV recovery and highlight substantial interindividual variation in recovery processes. Full article

(This article belongs to the Special Issue Botulinum Toxin in Neuro-Rehabilitation: Expanding Horizons in Spasticity and Beyond)

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7 pages, 232 KiB

Open AccessEditorial

Aspergillus flavus and Aflatoxins (3rd Edition)

by Tanvir Ahmad, Shihua Wang and Yang Liu

Toxins 2025, 17(7), 326; https://doi.org/10.3390/toxins17070326 - 25 Jun 2025

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Abstract

Aspergillus flavus is a saprophytic fungus commonly found in grain crops [...] Full article

(This article belongs to the Special Issue Aspergillus flavus and Aflatoxins (3rd Edition))

14 pages, 1057 KiB

Open AccessArticle

Antibacterial Activity of Jelleine-I, a Peptide Isolated from Royal Jelly of Apis mellifera, Against Colistin-Resistant Klebsiella pneumoniae

by William Gustavo Lima, Rayssa Maria Rodrigues Laia, Julio Cesar Moreira Brito, Daniel Augusto Guedes Reis Michel, Rodrigo Moreira Verly, Jarbas Magalhães Resende and Maria Elena de Lima

Toxins 2025, 17(7), 325; https://doi.org/10.3390/toxins17070325 - 25 Jun 2025

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Abstract

Klebsiella pneumoniae can acquire resistance mechanisms to colistin and present a pan-resistant phenotype. Therefore, new alternative agents are imperative to control this pathogen, and the peptide Jelleine-I stands out as a promising prototype. Here, the antibacterial activity of Jelleine-I against clinical isolates of [...] Read more.

Klebsiella pneumoniae can acquire resistance mechanisms to colistin and present a pan-resistant phenotype. Therefore, new alternative agents are imperative to control this pathogen, and the peptide Jelleine-I stands out as a promising prototype. Here, the antibacterial activity of Jelleine-I against clinical isolates of colistin-resistant K. pneumoniae (CRKP) was investigated. Antimicrobial activity was assessed by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time kill-curve assay. The release of 260 nm-absorbing materials (DNA/RNA) and the release of proteins were used in the lysis assay. Anti-biofilm activity was studied in microplates. In vivo activity was determined by the lethality assay using Tenebrio molitor larvae. The results show that the MIC of Jelleine-I ranged from 16 to 128 µM and the MBC was on average 128 µM. Jelleine-I at 200 µM killed all CRKP cells in suspension (10⁶ colony-forming units (CFU)/mL) after 150 min of incubation. Jelleine-I acts on the CRKP cell membrane inducing lysis. Biomass and viability of CRKP-induced biofilms are reduced after treatment with Jelleine-I, and the use of this peptide in T. molitor larvae infected with CRKP reduces lethality and improves overall larval health. In conclusion, Jelleine-I is a potential prototype for the development of new antimicrobial agents. Full article

(This article belongs to the Section Animal Venoms)

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19 pages, 318 KiB

Open AccessArticle

First Total Diet Study of Aflatoxins in Singapore: Exposure Risk, High-Risk Foods, and Public Health Implications

by Ker Lew, Yu Lee Leyau, Ping Shen, Xin Li, Sherine Liew, Joachim Chua, Hui Yi Lim, Yuansheng Wu, Kern Rei Chng and Sheot Harn Chan

Toxins 2025, 17(7), 324; https://doi.org/10.3390/toxins17070324 - 25 Jun 2025

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Abstract

Dietary exposure of Singapore population to foodborne and natural toxins was estimated through Total Diet Study (TDS) approach. Among the common mycotoxins and plant toxins studied, such as aflatoxins, ochratoxin A, zearalenone, deoxynivalenol, and fumonisins, aflatoxins were identified with food safety concerns. Aflatoxin [...] Read more.

Dietary exposure of Singapore population to foodborne and natural toxins was estimated through Total Diet Study (TDS) approach. Among the common mycotoxins and plant toxins studied, such as aflatoxins, ochratoxin A, zearalenone, deoxynivalenol, and fumonisins, aflatoxins were identified with food safety concerns. Aflatoxin occurrence was determined in 642 commonly consumed foods, with a detection rate of 4%, and a mean concentration of 0.01–0.07 µg/kg. Dietary exposure and risk assessment of aflatoxins for the general population revealed a mean estimated daily intake (EDI) of 0.0002–0.002 ng/kg bw/day, a margin of exposure (MOE) of 2819–7101, cancer risk of 0.002–0.004 additional cases per 100,000 person per year, and a hazard quotient (HQ) of 0.19–0.20. Despite the low overall estimated exposure risk for the general population, elevated exposure was observed among the eaters-only group, with the highest upper-bound (UB) exposure reaching 3.4 ng/kg bw/day for high consumers (95th percentile) of satay sauce, a popular Asian delicacy. The corresponding cancer risk of 0.23 additional cases per 100,000 individuals, or 14 additional cases annually, contributes to an estimation of 1% of the 1442 liver cancer cases reported in Singapore in 2022. These findings highlight the importance of continuous monitoring and call for appropriate mitigation strategies for further reduction in aflatoxin exposure in the Singapore population. Full article

(This article belongs to the Special Issue Advances in Contamination, Detection and Risk Assessment of Mycotoxins)

38 pages, 660 KiB

Open AccessReview

Toxic Shock Syndrome Toxin-1 (TSST-1) in Staphylococcus aureus: Prevalence, Molecular Mechanisms, and Public Health Implications

by Rahima Touaitia, Nasir Adam Ibrahim, Eman Abdullah Almuqri, Nosiba S. Basher, Takfarinas Idres and Abdelaziz Touati

Toxins 2025, 17(7), 323; https://doi.org/10.3390/toxins17070323 - 24 Jun 2025

Viewed by 740

Abstract

Staphylococcus aureus is a significant pathogen responsible for various infections, with its production of toxic shock syndrome toxin-1 (TSST-1) being a central factor in the pathogenesis of toxic shock syndrome (TSS). This study investigates the prevalence, molecular mechanisms, and public health implications of [...] Read more.

Staphylococcus aureus is a significant pathogen responsible for various infections, with its production of toxic shock syndrome toxin-1 (TSST-1) being a central factor in the pathogenesis of toxic shock syndrome (TSS). This study investigates the prevalence, molecular mechanisms, and public health implications of TSST-1-producing S. aureus. This study reviews methods for detecting TSST-1, focusing on PCR-based molecular techniques and immunological methods like ELISA, as well as the challenges in accurately diagnosing TSST-1 due to antibiotic resistance and strain variability. The findings reveal that TSST-1 is widely distributed across clinical, foodborne, and zoonotic sources, with significant prevalence in both healthcare and agricultural settings. This study also discusses the regulatory networks controlling TSST-1 production, including the agr system and other environmental cues like glucose, iron, and pH levels, which influence toxin expression. The results underline the need for improved surveillance and diagnostic approaches, as well as the development of targeted therapies to mitigate the impact of TSST-1 in both hospital and community settings. The conclusions highlight the importance of understanding TSST-1’s molecular mechanisms for developing effective public health strategies to control its spread. Full article

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

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