Toxins

14 pages, 809 KB

Open AccessReview

Botulinum Toxin Type A for Pediatric Torticollis: A Review of Clinical Research

by Na-Yoen Kwon, Soo-Hyun Sung and Hyun-Kyung Sung

Toxins 2025, 17(11), 543; https://doi.org/10.3390/toxins17110543 (registering DOI) - 1 Nov 2025

Pediatric torticollis, predominantly resulting from congenital muscular torticollis, is characterized by unilateral shortening of the sternocleidomastoid muscle, leading to head tilt and limited cervical mobility. Conventional management primarily involves physical therapy and repositioning strategies, with most infants achieving full recovery. However, a subset [...] Read more.

Pediatric torticollis, predominantly resulting from congenital muscular torticollis, is characterized by unilateral shortening of the sternocleidomastoid muscle, leading to head tilt and limited cervical mobility. Conventional management primarily involves physical therapy and repositioning strategies, with most infants achieving full recovery. However, a subset of patients exhibits persistent symptoms despite conservative treatment. Botulinum toxin type A (BoNT-A) has emerged as a minimally invasive adjunct intervention that targets muscular hypertonicity by inhibiting acetylcholine release at neuromuscular junctions. This scoping review synthesizes clinical evidence from six studies, including randomized controlled trials and case reports, assessing the efficacy and safety of BoNT-A in pediatric torticollis. Results indicate consistent improvements in range of motion, head posture correction, and patient satisfaction, with rare and mild adverse events such as local bruising and transient muscle weakness. Despite promising outcomes, variability in dosing, injection protocols, and follow-up durations underscores the need for standardized treatment guidelines and further high-quality research. These findings support BoNT-A as a valuable therapeutic option for refractory pediatric torticollis, warranting integration into multidisciplinary care frameworks. Full article

(This article belongs to the Special Issue Natural Toxin–Based Therapeutics from Animals, Plants, and Marine Organisms: Clinical Evidence and Drug Development Perspectives)

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14 pages, 855 KB

Open AccessArticle

Beyond Glycemic Control: Concurrent GLP-1 Receptor Agonist Use Is Associated with Reduced Urinary Adverse Events Following OnabotulinumtoxinA Treatment in Non-Diabetic Adults with Overactive Bladder

by Muhammed A. M. Hammad, Sophia G. Quesada, Aimee L. Belczyk and Gamal M. Ghoniem

Toxins 2025, 17(11), 542; https://doi.org/10.3390/toxins17110542 (registering DOI) - 1 Nov 2025

Abstract

Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, is widely prescribed for weight loss in non-diabetic populations. Given the link between obesity and overactive bladder (OAB), we explored whether GLP-1 use would improve adverse urinary events beyond its weight loss benefit for non-diabetic adults [...] Read more.

Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, is widely prescribed for weight loss in non-diabetic populations. Given the link between obesity and overactive bladder (OAB), we explored whether GLP-1 use would improve adverse urinary events beyond its weight loss benefit for non-diabetic adults undergoing onabotulinumtoxin A (BTX-A) treatment for OAB. Using the TriNetX database, we conducted a retrospective cohort study of non-diabetic OAB patients treated with BTX-A alone or with concurrent GLP-1 therapy. Propensity score matching (1:1) was adjusted for age, race, ethnicity, hypertension, and BMI/obesity. After matching, 992 patients were included in each group. GLP-1 use was associated with a lower incidence of urinary retention (8.6% vs. 4.9%, risk difference 3.66%, p = 0.0044) and urinary tract infection (13.3% vs. 8.8%, risk difference 4.54%, p = 0.00224), with corresponding improved one-year retention-free and UTI-free survival on Kaplan–Meier (KM) analysis. Antispasmodic initiation rates were similar (11.8% vs. 10.3%, risk difference 1.55%, p = 0.6921), and KM analysis showed no significant difference. These findings suggest that GLP-1 receptor agonist use may improve select urinary adverse events in non-diabetic adults undergoing BTX-A treatment for OAB and support further investigation into its potential adjunctive role in OAB management with longer follow-up. Full article

(This article belongs to the Special Issue Botulinum Toxins in Lower-Urinary-Tract Diseases and Dysfunctions)

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14 pages, 1112 KB

Open AccessArticle

Furosemide and the Symptom Burden: The Potential Mediating Role of Uremic Toxins in Patients with CKD

by Margaux Costes-Albrespic, Sophie Liabeuf, Islam-Amine Larabi, Solène M. Laville, Bénédicte Stengel, Abdou Y. Omorou, Luc Frimat, Jean-Claude Alvarez, Ziad A. Massy, Natalia Alencar de Pinho and the CKD-REIN Study Group

Toxins 2025, 17(11), 541; https://doi.org/10.3390/toxins17110541 (registering DOI) - 1 Nov 2025

Abstract

Furosemide appears to contribute to the accumulation of protein-bound uremic toxins (PBUTs) and to induce adverse drug reactions. We investigated the extent to which the association between the furosemide dose and serum PBUT concentrations mediates the relationship between the furosemide dose and the [...] Read more.

Furosemide appears to contribute to the accumulation of protein-bound uremic toxins (PBUTs) and to induce adverse drug reactions. We investigated the extent to which the association between the furosemide dose and serum PBUT concentrations mediates the relationship between the furosemide dose and the symptom burden in patients with chronic kidney disease (CKD). This cross-sectional analysis included patients with CKD stages 2 to 5 from the CKD-REIN cohort and with data on the baseline serum concentrations of the free fractions of indoxyl sulphate (IS), kynurenine (KYN), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA), as measured by liquid chromatography–tandem mass spectrometry. The symptom burden was also assessed with a modified (8-item) symptom subscale from the Kidney Disease Quality of Life-36 (e.g., muscle soreness, cramps, itchy skin, dry skin, dizziness, appetite, numbness, and nausea). We used beta regressions to model the association between the furosemide dose and the symptom burden and used structural equation models to quantify the mediating effect of PBUT on this association. Among the 2053 included patients (males: 66%, median age: 68; mean estimated glomerular filtration rate: 35 mL/min/1.73 m²), those prescribed high-dose furosemide (>120 mg/day) had higher symptom burden than those not prescribed furosemide (i.e., a 5.67-point lower symptom score, 95%CI 1.41–9.93). The sum of PBUTs explained 3.78% (95%CI 0.10–18.01%) of this association. Similar results were observed for IS, KYN, and IAA, considered separately, but not for PCS, whose estimated mediation effect was nearly null. Although high-dose furosemide was associated with a greater symptom burden in patients with CKD, mediation by PBUT accumulation appeared to be minimal. Full article

(This article belongs to the Special Issue Uremic Toxins and Hemodialysis: Mechanisms, Challenges, and Therapeutic Advances)

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20 pages, 1479 KB

Open AccessArticle

Functional Effects of BoNT-A Application in Masseter Muscle in Patients with Symptoms of Bruxism

by Krystian Matusz, Artur Drużdż, Natalie Górna, Mariusz Glapiński, Małgorzata Gałczyńska-Rusin, Agata Czajka-Jakubowska, Michał Michalak and Agnieszka Przystańska

Toxins 2025, 17(11), 540; https://doi.org/10.3390/toxins17110540 (registering DOI) - 31 Oct 2025

Abstract

Bruxism, defined as a repetitive jaw-muscle activity characterized by clenching or grinding of teeth and/or by bracing or thrusting of the mandible, is a prevalent behavior affecting up to 22% of adults worldwide. While traditionally viewed as a disorder, current understanding recognizes bruxism [...] Read more.

Bruxism, defined as a repetitive jaw-muscle activity characterized by clenching or grinding of teeth and/or by bracing or thrusting of the mandible, is a prevalent behavior affecting up to 22% of adults worldwide. While traditionally viewed as a disorder, current understanding recognizes bruxism as a behavior that may have both positive and negative consequences. Objective assessment methods for evaluating the effectiveness of interventions in symptomatic patients remain limited. This article presents the first longitudinal study using myotonometry to quantify changes in masseter muscle following botulinum toxin type A (BoNT-A) treatment in patients with symptoms of bruxism. In total, 57 patients were recruited and their masseter muscle tone, stiffness, elasticity, relaxation time, and creep parameters were measured. Measurements were performed at baseline, 3 weeks, and 3 months post-injection during both rest and maximum voluntary contraction. BoNT-A treatment produced significant improvements in all biomechanical parameters, with the greatest effects observed in patients with the highest baseline muscle values. The objective biomechanical changes correlated with the duration of BoNT-A’s therapeutic effects. These findings establish myotonometry as a valuable tool for objective assessment of masticatory muscle function and demonstrate that BoNT-A produces measurable, long-lasting biomechanical changes in masseter muscle parameters, supporting its possible clinical application in this challenging condition. Full article

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

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11 pages, 2215 KB

Open AccessArticle

Aflatoxigenic Aspergillus Section Flavi Strains and Diverse Molds Isolated from California Almonds

by Barbara Szonyi, Guangwei Huang, Tim Birmingham and Dawit Gizachew

Toxins 2025, 17(11), 539; https://doi.org/10.3390/toxins17110539 (registering DOI) - 31 Oct 2025

Abstract

Almonds are an essential crop for the economy of California. However, mold and mycotoxin contamination of this commodity has a serious impact on food safety and international trade. The contamination levels of molds and the aflatoxigenic potential of Aspergillus section Flavi isolates were [...] Read more.

Almonds are an essential crop for the economy of California. However, mold and mycotoxin contamination of this commodity has a serious impact on food safety and international trade. The contamination levels of molds and the aflatoxigenic potential of Aspergillus section Flavi isolates were studied on almonds collected at a processing plant in California. The mean total fungal count for 80 samples was 1.0 × 10⁴ CFU/g, while 62 samples (77.5%) had a total mold count less than 1.0 × 10⁴ CFU/g. The most common fungal contaminants were Aspergillus section Nigri (100% of samples), followed by Penicillium (57.5%) and Cladosporium (52.5%) species. Rhizopus, Fusarium and Alternaria spp. were less frequent. A total of 26 A. section Flavi strains were identified, with most strains (23) belonging to the L morphotype of A. flavus. In addition, two S morphotypes of A. flavus, and one A. tamarii strain were observed. Other Aspergillus species, including A. terreus and A. ochraceus were rare. High Performance Liquid Chromatography (HPLC) analysis revealed that 9 out of 13 isolated A. flavus strains produced aflatoxin B₁ (AFB₁) on yeast extract sucrose media. The highest levels of AFB₁ were produced by two A. flavus isolates belonging to the S morphotype (78 and 260 µg/kg). Increasing temperatures and drought conditions may change the population dynamics of toxigenic mold strains on almonds, emphasizing the need to continue monitoring these fungal populations. Full article

(This article belongs to the Special Issue Potential Risks and Analytical Challenges of Mycotoxins in Food and Feed)

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21 pages, 549 KB

Open AccessArticle

Optimisation of a One-Step Reusable Immuno-Affinity Purification Method for the Analysis and Detection of Fumonisin Mycotoxins in Foods and Feeds

by Christian Kosisochukwu Anumudu

Toxins 2025, 17(11), 538; https://doi.org/10.3390/toxins17110538 - 30 Oct 2025

Abstract

Fumonisins are among the most prevalent mycotoxins in maize and maize-based products, posing significant food safety and public health risks due to their hepatotoxic, nephrotoxic, and potential carcinogenic effects. Given the strict regulatory limits set by the European Commission and Codex Alimentarius, the [...] Read more.

Fumonisins are among the most prevalent mycotoxins in maize and maize-based products, posing significant food safety and public health risks due to their hepatotoxic, nephrotoxic, and potential carcinogenic effects. Given the strict regulatory limits set by the European Commission and Codex Alimentarius, the development of reliable, sensitive, and matrix–robust analytical methods remain a priority for routine monitoring in both food and feed systems. In this study, a reusable immuno-affinity purification methodology for the quantitative determination of fumonisin mycotoxins (FB1, FB2 and FB3) in foods and feeds (maize matrix) was developed. A single extraction protocol using 2% formic acid in water was employed, followed by cleanup with an immuno-affinity purification column and toxin elution by methanol/PBS (1:1, v/v). Detection and quantification of the mycotoxins was achieved by a normal phase ultra-high performance liquid chromatography coupled with electrospray ionisation triple quadrupole mass spectrometry (UHPLC/ESI-MS/MS). The chromatographic mobile phase utilised was a linear gradient of methanol/water containing 0.1% formic acid. The developed method has a limit of detection of 2.5 ng/g and a limit of quantification of 5 ng/g, all well below the European commission’s guidance values of 1000 ng/g for corn destined for human consumption and 800 ng/g for maize-based breakfast cereals and snacks. While the recovery rates of the method in this study ranged from 65–70% for the three fumonisin analogues in solutions, when tested in maize matrix, recoveries were markedly lower (~30%) due to pronounced matrix suppression. Good repeatability (standard deviation <10%) was achieved for all the fumonisin analogues. The developed method, although quick and effective in solvent systems, suffered limitations to its practical usage due to matrix suppression of the extracts derived from the immuno-affinity purification column, thus significantly reducing the application of the method in measuring fumonisin mycotoxins in food and feed samples. Overall, the method was effective in quantification of fumonisin mycotoxins in solvent solutions but not in food and feed matrices, thus necessitating further optimisation for practical usage. The performance of the developed method was compared to a commercial lateral flow immunochromatographic assay which proved to be better than the developed method in the quantification of toxins in food matrices, as the commercial lateral flow immunochromatographic assay outperformed the developed method in maize matrices. These findings highlight the need for matrix-based validation and further refinement of antibody stability to ensure robust application in regulatory monitoring of fumonisins using immunoaffinity purification methods. Full article

(This article belongs to the Special Issue Mycotoxin Contamination in Animal Nutrition and Its Mitigation Strategies)

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12 pages, 2254 KB

Open AccessArticle

Comprehensive Bibliometric Analysis of Uremic Toxin Research

by Marsuki Hardjo, Takuya Wakamatsu, Kazuki Watanabe, Shoko Yamazaki and Suguru Yamamoto

Toxins 2025, 17(11), 537; https://doi.org/10.3390/toxins17110537 - 30 Oct 2025

Abstract

Uremic toxins accumulate as kidney disease progresses, contributing to diverse systemic disorders. Despite numerous studies, no comprehensive mapping has been performed. In this study, keywords related to uremic toxins were quantitatively analyzed using bibliometric methods to clarify research trends, key molecules, and unresolved [...] Read more.

Uremic toxins accumulate as kidney disease progresses, contributing to diverse systemic disorders. Despite numerous studies, no comprehensive mapping has been performed. In this study, keywords related to uremic toxins were quantitatively analyzed using bibliometric methods to clarify research trends, key molecules, and unresolved challenges. Literature and molecular data on uremic toxins and chronic kidney disease were retrieved from the Web of Science and the European Uremic Toxin Work Group (EUTox) databases. Network, citation burst, and keyword frequency analyses were performed using KeyWords Plus. In total, 3302 articles were identified, showing an increasing trend. Citation burst analysis revealed a growing interest in gut microbiota-related topics (burst strength = 15.21), whereas keyword frequency analysis indicated that indoxyl sulfate (566 articles) and p-cresyl sulfate (537 articles) were the most studied toxins. Toxins such as trimethylamine-N-oxide have gained attention over the past 5 years. Analysis of the EUTox database identified 24 protein-bound uremic toxins; among the 94 toxins with unreported clinical toxicity, 15 molecules, including osteocalcin and quinolinic acid, were investigated in <5 studies. These findings suggest that the gut microbiota and related uremic toxins are current research focuses; however, further investigation of underreported uremic toxins is required to define their clinical significance. Full article

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

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15 pages, 2967 KB

Open AccessArticle

Biological Control of Microcystis aeruginosa Through Sequestration in Pseudofaeces Produced by the Freshwater Gastropod, Sinotaia aeruginosa

by Barry N. Madison, Mingzhi Qu, Elliot Gavrin, Wenwei Ren, Yuxiang Wang and Daniel D. Lefebvre

Toxins 2025, 17(11), 536; https://doi.org/10.3390/toxins17110536 - 30 Oct 2025

Abstract

Cyanobacteria harmful algal blooms (CHABs) are most commonly caused by the proliferation of the toxic species, Microcystis aeruginosa. It is therefore of considerable interest to develop biological control processes which are economically feasible and scalable for this cyanobacteria that produces the cyanotoxin, [...] Read more.

Cyanobacteria harmful algal blooms (CHABs) are most commonly caused by the proliferation of the toxic species, Microcystis aeruginosa. It is therefore of considerable interest to develop biological control processes which are economically feasible and scalable for this cyanobacteria that produces the cyanotoxin, microcystin. Some gastropods that are abundant in freshwater ecosystems can filter feed on floating planktonic microphytes. We investigated this in the freshwater snail, Sinotaia aeruginosa which indiscriminately accumulated M. aeruginosa, Chlorella vulgaris, and Trichormus variabilis (syn. Anabaena variabilis) The initial filtration rates were approx. 44 and 19 mL · g_wwt⁻¹ · h⁻¹ for unicellular and colony-forming M. aeruginosa, respectively. The pseudofaeces that were formed directly by filtration possessed a limited period of stability, and the bulk of the M. aeruginosa from pseudofaeces was eventually released back to the water column as undigested cyanobacteria. Nevertheless, the rate of sequestration of colonial M. aeruginosa into pseudofaeces was greater than its rate of release, thereby indicating that the temporary stability of pseudofaeces alone would be adequate to impede bloom formation. Therefore, these results provide evidence for using this gastropod in an effective preventative strategy for CHABs formation. Our results highlight the importance of understanding the impact of feeding mechanisms on ecosystem structure when proposing their use in biomanipulative processes aimed at correcting cyanobacteria impacted ecosystems. Full article

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

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20 pages, 1877 KB

Open AccessArticle

Photobiomodulation with Combined Wavelengths Results in Improved Clinical Recovery in a Murine Model of Bothrops leucurus Venom Envenomation

by Gisele Dias da Silva, Fabiana Lessa Silva, Anaiá da Paixão Sevá, Juneo Freitas Silva, Danilo Machado Deorce, Nerildo de Jesus da Costa Junior, Fernanda Amaral Silva and Fernando Alzamora Filho

Toxins 2025, 17(11), 535; https://doi.org/10.3390/toxins17110535 - 30 Oct 2025

Abstract

Snakebite envenomation by Bothrops species is a neglected tropical disease and a major cause of local tissue damage and disability in Latin America. Antivenom therapy is effective against systemic effects but fails to prevent local myonecrosis, inflammation, and pain. This study evaluated photobiomodulation [...] Read more.

Snakebite envenomation by Bothrops species is a neglected tropical disease and a major cause of local tissue damage and disability in Latin America. Antivenom therapy is effective against systemic effects but fails to prevent local myonecrosis, inflammation, and pain. This study evaluated photobiomodulation therapy (PBMT) using infrared (808 nm) alone or in combination with red (660 nm) laser in a murine model of Bothrops leucurus envenomation. A single PBMT session was applied, and animals were evaluated at 24 and 72 h. Combined treatment significantly reduced edema, hyperthermia, plasma CK and LDH, restored nociceptive thresholds, and improved motor recovery compared with infrared alone. Principal component analysis demonstrated clustering of combined-treatment animals with negative controls, supporting a synergistic therapeutic effect. These findings highlight dual-wavelength PBMT as a promising adjunctive approach to antivenom, directly targeting local venom-induced pathology. Full article

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16 pages, 356 KB

Open AccessReview

Mycotoxins and the Intestinal Epithelium: From Barrier Injury to Stem Cell Dysfunction

by Wenying Huo, Yingying Qiao, Xiangru He, Cailing Wang, Ruiqing Li, Long Che and Enkai Li

Toxins 2025, 17(11), 534; https://doi.org/10.3390/toxins17110534 - 30 Oct 2025

Abstract

Mycotoxins are toxic secondary metabolites produced by filamentous fungi that contaminate agricultural commodities, posing risks to food safety, animal productivity, and human health. The gastrointestinal tract is the first and most critical site of exposure, where the intestinal epithelium functions as both a [...] Read more.

Mycotoxins are toxic secondary metabolites produced by filamentous fungi that contaminate agricultural commodities, posing risks to food safety, animal productivity, and human health. The gastrointestinal tract is the first and most critical site of exposure, where the intestinal epithelium functions as both a physical and immunological barrier against luminal toxins and pathogens. While extensive research has demonstrated that mycotoxins disrupt epithelial integrity through tight junction impairment, oxidative stress, apoptosis, and inflammation, their effects on the intestinal stem cell (ISC) compartment and epithelial regeneration remain insufficiently understood. This review integrates recent findings from in vivo, cell culture, and advanced 3D intestinal organoid and gut-on-chip models to elucidate how mycotoxins such as deoxynivalenol and zearalenone impair ISC proliferation, alter Wnt/Notch signaling, and compromise mucosal repair. We also discuss dose relevance, species differences, and the modulatory roles of the microbiome and short-chain fatty acids, as well as emerging evidence of additive or synergistic toxicity under co-exposure conditions. By bridging well-established mechanisms of barrier disruption with the emerging concept of ISC-driven regenerative failure, this review identifies a critical knowledge gap in mycotoxin toxicology and highlights the need for integrative models that link epithelial damage to impaired regeneration. Collectively, these insights advance understanding of mycotoxin-induced intestinal dysfunction and provide a foundation for developing nutritional, microbial, and pharmacological strategies to preserve gut integrity and repair. Full article

(This article belongs to the Special Issue Mycotoxin Contamination in Animal Nutrition and Its Mitigation Strategies)

14 pages, 1032 KB

Open AccessReview

Anthrax Toxin: A Pioneer of Targeted Protein Toxins

by Sandy Richter and Gudula Schmidt

Toxins 2025, 17(11), 533; https://doi.org/10.3390/toxins17110533 - 29 Oct 2025

Abstract

With anthrax toxin as a pioneer, several bacterial toxins have been engineered to deliver proteins of interest into the cytosol of specific mammalian cells. Such targeted protein toxins combine the ability to deliver cargo molecules into cells with designed receptor interaction for targeting [...] Read more.

With anthrax toxin as a pioneer, several bacterial toxins have been engineered to deliver proteins of interest into the cytosol of specific mammalian cells. Such targeted protein toxins combine the ability to deliver cargo molecules into cells with designed receptor interaction for targeting selected cells. This review summarizes the actual knowledge of modified anthrax toxin. Moreover, the significant efforts which have been made to utilize other bacterial toxins are discussed. The targeted protein toxins described in this review include single-chain toxins, pore-forming toxins, and injection machineries. Full article

(This article belongs to the Special Issue Anthrax Toxin Chronicles: Celebrating 70 Years of Scientific Breakthroughs in Chemistry, Biology, and Toxicology)

28 pages, 2223 KB

Open AccessArticle

Peanut and Peanut-Based Foods Contamination by Toxigenic Fungi and Mycotoxins: Potential Risks for Beninese Consumers

by Christin Sogbossi Gbétokpanou, Camille Jonard, Ornella Anaïs Mehinto, Sébastien Gofflot, Mawougnon Jaurès Martial Adjéniya, Ogouyôm Herbert Iko Afe, Dona Gildas Anihouvi, Samiha Boutaleb, Claude Bragard, Paulin Azokpota, Jacques Mahillon, Marianne Sindic, Marie-Louise Scippo, Yann Eméric Madodé and Caroline Douny

Toxins 2025, 17(11), 532; https://doi.org/10.3390/toxins17110532 - 29 Oct 2025

Abstract

This study assessed mycotoxin contamination in roasted peanut snacks and kluiklui (fried pressed peanut cake), and consumer exposure in southern Benin. Roasted peanut snacks and kluiklui were sampled from markets across six municipalities, and their production follow-up was conducted on two sites using [...] Read more.

This study assessed mycotoxin contamination in roasted peanut snacks and kluiklui (fried pressed peanut cake), and consumer exposure in southern Benin. Roasted peanut snacks and kluiklui were sampled from markets across six municipalities, and their production follow-up was conducted on two sites using different processing methods. Mycotoxins were quantified using UPLC-MS/MS, while fungal species were identified via culture-based methods. Exposure to aflatoxin B1, total aflatoxins and ochratoxin A was estimated. Aflatoxin B1 predominated, reaching 169 µg/kg in roasted peanut snacks and 2144.64 µg/kg in marketed kluiklui. In contrast, just-produced kluiklui contained much lower levels (11.73–37.78 µg/kg). Aspergillus flavus and Aspergillus niger predominated in kluiklui from the first processing site, while Aspergillus chevalieri dominated in kluiklui from the second processing site. The grinding step (using public grinder) was identified as the main contamination point. The significative higher mycotoxin levels in kluiklui sampled on markets compared to just-produced kluiklui are probably due to poor storage conditions. Dietary exposure estimates revealed that margins of exposure for aflatoxins were far below the safety threshold of 10,000, and liver cancer risk estimates were particularly high for kluiklui consumers. Kluiklui consumption poses a significant health risk in Benin. Improved hygiene in public grinders and better storage practices are urgently needed to reduce contamination and protect consumers’ health. Full article

(This article belongs to the Special Issue Aflatoxins: Contamination, Analysis and Control)

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25 pages, 1786 KB

Open AccessReview

Aflatoxins in Mexican Maize Systems: From Genetic Resources to Agroecological Resilience and Co-Occurrence with Fumonisins

by Carlos Muñoz-Zavala, Obed Solís-Martínez, Jessica Berenice Valencia-Luna, Kai Sonder, Ana María Hernández-Aguiano and Natalia Palacios-Rojas

Toxins 2025, 17(11), 531; https://doi.org/10.3390/toxins17110531 - 29 Oct 2025

Abstract

Aflatoxins (AFs) and fumonisins (FUMs) are among the most prevalent and toxic mycotoxins affecting maize production globally. In Mexico, their co-occurrence poses a significant public health concern, as maize is not only a dietary staple but also predominantly grown and consumed at the [...] Read more.

Aflatoxins (AFs) and fumonisins (FUMs) are among the most prevalent and toxic mycotoxins affecting maize production globally. In Mexico, their co-occurrence poses a significant public health concern, as maize is not only a dietary staple but also predominantly grown and consumed at the household level. This review examines the multifactorial nature of AFs and FUMs contamination in Mexican maize systems, considering the roles of maize germplasm, agricultural practices, environmental conditions, and soil microbiota. Maize landraces, well-adapted to diverse agroecological zones, exhibit potential resistance to AFs contamination and should be prioritized in breeding programs. Sustainable agricultural practices and biocontrol strategies, including the use of atoxigenic Aspergillus flavus strains, are presented as promising interventions. Environmental factors and soil characteristics further influence fungal proliferation and mycotoxin biosynthesis. Advances in microbiome engineering, biological breeding approaches, and predictive modeling offer novel opportunities for prevention and control. The synergistic toxicity of AFs and FUMs significantly increases health risks, particularly for liver cancer, highlighting the urgency of integrated mitigation strategies. While Mexico has regulatory limits for AFs, the lack of legal thresholds for FUMs remains a critical gap in food safety legislation. This comprehensive review underscores the need for biomarker-based exposure assessments and coordinated national policies, alongside multidisciplinary strategies to reduce mycotoxin exposure and enhance food safety in maize systems. Full article

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

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17 pages, 3170 KB

Open AccessArticle

Perillaldehyde-Elicited Inhibition of Ochratoxin A Production by Aspergillus carbonarius

by Dongmei Jiang, Liuqing Wang, Nan Jiang, Jiaqi Yan, Jingzhi Mei and Meng Wang

Toxins 2025, 17(11), 530; https://doi.org/10.3390/toxins17110530 - 29 Oct 2025

Abstract

Ochratoxin A (OTA) is a major mycotoxin contaminant in grapes and their products, and Aspergillus carbonarius is its main producer. Controlling the growth of A. carbonarius is therefore critical for mitigating OTA contamination. Plant-derived perillaldehyde, with good antifungal activity and safety, has garnered [...] Read more.

Ochratoxin A (OTA) is a major mycotoxin contaminant in grapes and their products, and Aspergillus carbonarius is its main producer. Controlling the growth of A. carbonarius is therefore critical for mitigating OTA contamination. Plant-derived perillaldehyde, with good antifungal activity and safety, has garnered growing attention. However, current understanding of how perillaldehyde affects A. carbonarius growth and OTA production remains poorly characterized. In this study, we systematically investigated the antifungal and antimycotoxigenic effects of perillaldehyde against A. carbonarius and explored the underlying mechanisms. The results showed that perillaldehyde could alter the mycelial morphology and damage the cell integrity of A. carbonarius. Additionally, perillaldehyde could diminish the total antioxidant capacity and impair the energy metabolism of A. carbonarius. Transcriptome analysis showed that the expressions of all the known conserved OTA biosynthetic genes and two OTA transport-related genes were significantly down-regulated, indicating that perillaldehyde could directly inhibit their expression. In conclusion, perillaldehyde can significantly inhibit OTA production by directly disrupting OTA biosynthesis and transport and inhibiting the growth of A. carbonarius. Thus, perillaldehyde has the potential to be used as a natural fungicide or alternative food preservative in grapes and their products, owing to its strong antifungal and antimycotoxigenic effects on A. carbonarius. Full article

(This article belongs to the Special Issue Mycotoxins and Spoilage Fungi in Agricultural Products and Foods: Current Status and Future Perspectives)

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15 pages, 1970 KB

Open AccessArticle

Hemolysis of Human Erythrocytes by Methicillin-Resistant Staphylococcus aureus Is Primarily Caused by PSMα Peptides

by Tyler K. Nygaard, Annika Gao, Eliot LaTray and Jovanka M. Voyich

Toxins 2025, 17(11), 529; https://doi.org/10.3390/toxins17110529 - 29 Oct 2025

Abstract

Staphylococcus aureus (S. aureus) is a major cause of human morbidity and mortality worldwide. Hemolysis caused by S. aureus cytotoxins is important for the acquisition of iron and subsequent bacterial survival during infection. S. aureus can express numerous hemolysins that have [...] Read more.

Staphylococcus aureus (S. aureus) is a major cause of human morbidity and mortality worldwide. Hemolysis caused by S. aureus cytotoxins is important for the acquisition of iron and subsequent bacterial survival during infection. S. aureus can express numerous hemolysins that have been shown to target human erythrocytes. However, the relative importance of each of these for causing hemolysis during pathogenesis in humans is not clear. In this study, we have examined the hemolytic capacity of different methicillin-resistant S. aureus (MRSA) deletion mutants against human erythrocytes in suspension using two separate assays. The first assay measured hemolysis caused by extracellular factors produced by MRSA, while the second measured hemolysis following co-culture of MRSA with human erythrocytes. Results from both assays demonstrated that phenol-soluble modulin-α peptides (PSMα) play a dominant role in causing hemolysis of human erythrocytes, highlighting a prominent target for novel therapeutic strategies designed to limit S. aureus iron acquisition and survival during human disease. Full article

(This article belongs to the Section Bacterial Toxins)

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16 pages, 316 KB

Open AccessArticle

Detection of Mycotoxigenic Fungi and Residual Mycotoxins in Cannabis Buds Following Gamma Irradiation

by Mamta Rani, Mohammad Jamil Kaddoura, Jamil Samsatly, Guy Chamberland, Suha Jabaji and Saji George

Toxins 2025, 17(11), 528; https://doi.org/10.3390/toxins17110528 - 28 Oct 2025

Abstract

Cannabis plants are susceptible to microbial contamination, including fungi capable of producing harmful mycotoxins. The presence of these toxins in cannabis products poses serious health risks, especially when used for medical purposes in immunocompromised people. This study evaluated the presence of fungi and [...] Read more.

Cannabis plants are susceptible to microbial contamination, including fungi capable of producing harmful mycotoxins. The presence of these toxins in cannabis products poses serious health risks, especially when used for medical purposes in immunocompromised people. This study evaluated the presence of fungi and mycotoxins in dried cannabis buds following gamma irradiation, using culture-based techniques, PCR/qPCR, and ELISA. Irradiation significantly reduced fungal and bacterial loads, eliminating culturable bacteria but did not achieve complete sterilization. Viable spores of toxigenic fungal genera, such as Aspergillus, Penicillium, and Fusarium, persisted. Sequencing of ITS amplicons revealed dominant mycotoxigenic fungi in non-irradiated (NR), irradiated (IR) and licensed producer (LP) samples, while next-generation sequencing (NGS) revealed additional non-culturable toxigenic species. PCR/qPCR detected biosynthetic genes for aflatoxins, trichothecenes, ochratoxins, and deoxynivalenol across all samples, with gene copy numbers remaining stable post-irradiation, suggesting DNA damage without full degradation. ELISA confirmed aflatoxin, ochratoxin, DON, and T2 toxins in both IR and LP samples at variable concentrations. While LP samples showed lower microbial counts and gene abundance, residual DNA and toxins were still detected. Our study shows that while irradiation decreases microbial loads, it does not completely remove toxigenic fungi or their metabolites. Ensuring the safety of cannabis products necessitates a multifaceted assessment that incorporates cultural, molecular, and immunological techniques, in parallel with more stringent microbial standards during production stage. Full article

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

20 pages, 2182 KB

Open AccessArticle

Nixtamalization of Maize to Reduce Mycotoxin Exposure: A Human Biomonitoring Intervention Study in Soweto, South Africa

by Elias Maris, Palesa Ndlangamandla, Oluwasola A. Adelusi, Oluwakamisi F. Akinmoladun, Julianah O. Odukoya, Richard T. Fagbohun, Samson A. Oyeyinka, Palesa Sekhejane, Roger Pero-Gascon, Marthe De Boevre, Siska Croubels, Patrick B. Njobeh and Sarah De Saeger

Toxins 2025, 17(11), 527; https://doi.org/10.3390/toxins17110527 - 26 Oct 2025

Abstract

Mycotoxin contamination is a global threat to food safety and human health, especially in regions facing food insecurity, such as Sub-Saharan Africa. This intervention study evaluates the effectiveness of nixtamalization, a traditional alkaline cooking method, in reducing mycotoxin levels in maize and corresponding [...] Read more.

Mycotoxin contamination is a global threat to food safety and human health, especially in regions facing food insecurity, such as Sub-Saharan Africa. This intervention study evaluates the effectiveness of nixtamalization, a traditional alkaline cooking method, in reducing mycotoxin levels in maize and corresponding urinary biomarkers of exposure. Forty adult healthy volunteers from an informal settlement in Kliptown, Soweto (South Africa), were randomly assigned to consume control maize or visibly moldy maize subjected to nixtamalization. Nixtamalization achieved a reduction in fumonisin B3 and deoxynivalenol (DON) to unquantifiable or undetectable levels in maize, while reducing fumonisin B1 (FB1), fumonisin B2, and zearalenone (ZEN) by 95%, 95%, and 89%, respectively. Aflatoxin B1 was unquantifiable before and eliminated after treatment. Biomarker analysis revealed that after consumption of either control or nixtamalized maize, urinary levels of FB1, ZEN, and its metabolites α- and β-zearalenol (α- and β-ZEL) did not show significant differences between groups (p > 0.05). DON and tenuazonic acid levels were not affected by the intervention (p > 0.05), with urinary detection frequencies remaining above 90%. These results demonstrate nixtamalization effectively lowers mycotoxin levels in maize, resulting in exposure levels comparable to control maize, and highlight human biomonitoring as a sensitive tool for evaluating food safety interventions. Full article

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

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29 pages, 2538 KB

Open AccessArticle

A General Food Chain Model for Bioaccumulation of Ciguatoxin into Herbivorous Fish in the Pacific Ocean Suggests Few Gambierdiscus Species Can Produce Poisonous Herbivores, and Even Fewer Can Produce Poisonous Higher Trophic Level Fish

by Michael J. Holmes and Richard J. Lewis

Toxins 2025, 17(11), 526; https://doi.org/10.3390/toxins17110526 - 25 Oct 2025

Abstract

We adapt previous conceptual and numerical models of ciguateric food chains for the bioaccumulation of Pacific-ciguatoxin-1 (P-CTX-1) to a general model for bioaccumulation of P-CTX3C by parrotfish (Scarus frenatus, S. niger, and S. psittacus) that feed by scraping turf [...] Read more.

We adapt previous conceptual and numerical models of ciguateric food chains for the bioaccumulation of Pacific-ciguatoxin-1 (P-CTX-1) to a general model for bioaccumulation of P-CTX3C by parrotfish (Scarus frenatus, S. niger, and S. psittacus) that feed by scraping turf algae, and surgeonfish (Naso unicornis) that mostly feed on macroalgae. We also include the Indian Ocean parrotfish Chlorurus sordidus as a model for an excavator feeding parrotfish and include comparisons with the detritivorous surgeonfish Ctenochaetus striatus that brush-feeds on turf algae. Our food chain model suggests that, of the Gambierdiscus and Fukuyoa species so far analysed for ciguatoxin (CTX) production from the Pacific, only G. polynesiensis produces sufficient P-CTX3C to consistently produce parrotfish or N. unicornis with poisonous flesh. Our model suggests that insufficient CTX would accumulate into the flesh of parrotfish or N. unicornis to become poisonous from ingesting benthic dinoflagellates producing ≤0.03 pg P-CTX3C eq./cell, except from extended feeding times on high-density blooms and in the absence of significant depuration of CTX. Apart from G. polynesiensis, only G. belizeanus and possibly G. silvae and G. australes are thought to produce >0.03 pg P-CTX3C eq./cell in the Pacific. However, with relatively low maximum concentrations of ≤0.1 pg P-CTX3C eq./cell it is likely that their contribution is minimal. Our model also suggests that the differences between the area of turf algae grazed by parrotfish and similar sized C. striatus results in greater accumulation of CTX by this surgeonfish. This makes C. striatus a higher ciguatera risk than similar sized parrotfish, either directly for human consumption or as prey for higher trophic level fishes, consistent with poisoning data from Polynesia. It also suggests the possibility that C. striatus could bioaccumulate sufficient CTX to become mildly poisonous from feeding on lower toxicity Gambierdiscus or Fukuyoa species known to produce ≥0.02 P-CTX3C eq./cell. This indicates the potential for at least two food chain pathways to produce ciguateric herbivorous fishes, depending on the CTX concentrations produced by resident Gambierdiscus or Fukuyoa on a reef and the grazing capacity of herbivorous fish. However, only G. polynesiensis appears to produce sufficient P-CTX3C to consistently accumulate in food chains to produce higher trophic level fishes that cause ciguatera in the Pacific. We incorporate CTX depuration into our model to explore scenarios where mildly poisonous parrotfish or N. unicornis ingest CTX at a rate that is balanced by depuration to estimate the Gambierdiscus/Fukuyoa densities and CTX concentrations required for these fish to remain poisonous on a reef. Full article

(This article belongs to the Collection Ciguatoxin)

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15 pages, 534 KB

Open AccessArticle

Leptin and Adiponectin as Uremic Adipokines: Associations with Survival in a Prospective Hemodialysis Cohort

by Thuy-Anh V. Bui, Amy S. You, Sara S. Kalantar, Jihoon Yoon, Yoko Narasaki, John Sy, Ramy Hanna, Andrea Daza, Yalitzi Guerrero, Anyssa Dang, Ria Arora, Danh V. Nguyen, Kamyar Kalantar-Zadeh and Connie M. Rhee

Toxins 2025, 17(11), 525; https://doi.org/10.3390/toxins17110525 - 25 Oct 2025

Abstract

Background: While experimental models show that leptin and adiponectin have inverse effects on the cardiovascular system, it has been suggested that the leptin-to-adiponectin (L/A) ratio may be an important predictor of cardiovascular disease and death. Higher circulating leptin and adiponectin levels are observed [...] Read more.

Background: While experimental models show that leptin and adiponectin have inverse effects on the cardiovascular system, it has been suggested that the leptin-to-adiponectin (L/A) ratio may be an important predictor of cardiovascular disease and death. Higher circulating leptin and adiponectin levels are observed in uremia due to decreased renal degradation and/or clearance and increased production. We sought to examine the association between the L/A ratio and mortality in a prospective hemodialysis cohort. Methods: Among a prospective cohort of 448 hemodialysis patients from the NIH “Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (CKD) (MADRAD) study who underwent leptin and adiponectin measurements, we examined characteristics associated with high leptin and adiponectin (defined as the highest tertile) using logistic regression. We then examined the association of L/A ratio levels (categorized as tertiles) with all-cause mortality using Cox regression. Results: Multivariable logistic regression analyses showed female sex, diabetes, presence of an arteriovenous fistula/graft, and lower serum albumin, IL-6, and adiponectin were associated with high leptin, whereas female sex, longer vintage, Black race, higher IL-6, and lower leptin were associated with high adiponectin. When examining L/A ratios, the highest tertile was associated with lower mortality in case-mix Cox models (ref: lowest tertile): HR (95% CI) 0.14 (0.06–0.35). These associations were robust in analyses that additionally adjusted for laboratory covariates: (HR 95% CI) 0.18 (0.07–0.46). Conclusions: In a prospective cohort of hemodialysis patients, inflammation and malnutrition markers were associated with lower leptin and higher adiponectin levels. Additionally, high L/A ratio levels were associated with lower mortality. Further studies are needed to determine the mechanisms relating adipocytokines, inflammation and nutrition, and survival in this population. 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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