Toxins

26 pages, 1778 KB

Open AccessArticle

Phenotypic and Genotypic Characteristics of Staphylococcus aureus Nasal Strains Isolated from Students of the Pomeranian Medical University in Szczecin, Poland: A Cross-Sectional Study

by Paweł Kwiatkowski, Helena Masiuk, Agata Pruss, Stefania Giedrys-Kalemba, Piotr Baszuk, Iwona Wojciechowska-Koszko and Monika Sienkiewicz

Toxins 2026, 18(5), 237; https://doi.org/10.3390/toxins18050237 - 21 May 2026

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Abstract

Staphylococcus aureus nasal carriage contributes to asymptomatic transmission in both community and healthcare settings. This study aimed to characterize S. aureus strains isolated from students of the Pomeranian Medical University in Szczecin, Poland, using phenotypic and genotypic methods. A total of 175 S. [...] Read more.

Staphylococcus aureus nasal carriage contributes to asymptomatic transmission in both community and healthcare settings. This study aimed to characterize S. aureus strains isolated from students of the Pomeranian Medical University in Szczecin, Poland, using phenotypic and genotypic methods. A total of 175 S. aureus strains were isolated from the nasal vestibules of 800 students between 2014 and 2015. Species identification and antimicrobial susceptibility testing were performed using standard microbiological methods, while virulence-associated genes and agr groups were analyzed using Single-PCR and Multiplex-PCR assays. Genotypic diversity was assessed by pulsed-field gel electrophoresis (PFGE). The prevalence of S. aureus nasal carriage among students was 21.9% and did not differ according to faculty or year of study. Most isolates (84.0%) were susceptible to all tested antibiotics, and no methicillin-resistant S. aureus (MRSA) strains were detected. All strains carried the hla gene, whereas hld and hlg were identified in 93.7% and 93.1% of isolates, respectively. In addition, the tst gene was detected in 22.3% of strains, while the lukS-PV/lukF-PV genes were identified in only one isolate (0.6%). The most prevalent enterotoxin genes were sep (17.1%) and sea (13.7%), whereas genes of the egc cluster, including seg, sei, and seo, were detected in 53.7% of isolates. Significant associations were observed between specific egc gene combinations and superantigen gene profiles, including increased frequencies of sec, sel, and tst genes (p < 0.001). The predominant agr type was agr-1 (49.7%), followed by agr-3 (28.6%) and agr-2 (20.0%). Strains carrying agr-1 more frequently harbored the g i m n o cluster as well as the sec, sel, and sep genes, whereas agr-3-positive isolates were significantly associated with the g i m o u and g i o u clusters and with the presence of tst, sea, and seh genes (p < 0.05). PFGE analysis demonstrated substantial genetic heterogeneity among the isolates, with no evidence of a predominant clonal lineage. These findings indicate a heterogeneous, non-epidemic population structure of S. aureus strains circulating among university students and highlight the considerable diversity and interrelationships of virulence-associated genetic profiles within this population. Full article

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

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33 pages, 3545 KB

Open AccessReview

Biological Detoxification of Mycotoxins by Lactic Acid Bacteria: Safeguarding Food from Fungal Contaminants

by Nazia Tabassum, Minji Kim, Tae-Hee Kim, Du-Min Jo, Won-Kyo Jung, Young-Mog Kim and Fazlurrahman Khan

Toxins 2026, 18(5), 236; https://doi.org/10.3390/toxins18050236 - 20 May 2026

Cited by 2 | Viewed by 1807

Abstract

Mycotoxins are one of the biggest threats to global food safety, public health, and economic stability. More than 400 mycotoxins have been found to be secondary metabolites of toxigenic fungi, mostly from the genera Aspergillus, Fusarium, Penicillium, and Alternaria. [...] Read more.

Mycotoxins are one of the biggest threats to global food safety, public health, and economic stability. More than 400 mycotoxins have been found to be secondary metabolites of toxigenic fungi, mostly from the genera Aspergillus, Fusarium, Penicillium, and Alternaria. Aflatoxins (AFs), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEA), fumonisins (FBs), patulin (PAT), and T-2/HT-2 toxins are the most dangerous to the health of people and animals. Conventional physical and chemical decontamination methods are only partially effective and can reduce food quality, leave toxic residues, or be too expensive for smallholder food systems. Recent studies have shown that the application of lactic acid bacteria (LAB) as a biological detoxification method is a safe, cost-effective, and environmentally friendly option, and has a long history of safe use in fermented foods. Selected strains or taxonomic units have been granted GRAS status by the FDA or QPS (Qualified Presumption of Safety) status by EFSA. However, their use for mycotoxin detoxification still requires strain-level safety assessment and efficacy validation in the intended food matrix. There are several mechanisms by which LAB employ to reduce the bioavailability of mycotoxins in food systems: (i) physical adsorption via cell wall components such as peptidoglycan, teichoic acids, and exopolysaccharides; (ii) enzymatic biotransformation that may produce non-toxic or less-toxic metabolites, though the safety of degradation products requires case-by-case toxicological assessment; (iii) antifungal metabolite production that inhibits fungal growth and mycotoxin biosynthesis; and (iv) competitive exclusion of toxigenic fungi during fermentation. This comprehensive review examines the existing evidence on the detoxification of major food mycotoxins by LAB, with an emphasis on mechanisms, strain-specific efficacy, food-matrix applications, and factors that affect detoxification efficacy. Discussion has also been made of translating in vitro findings to in vivo settings and food-scale applications, alongside regulatory frameworks, current challenges, and future research directions. The review also suggests ways to combine LAB with new technologies, such as encapsulation, genetic engineering, and fermentation optimization, to make food systems safer by synergistically controlling mycotoxins. Full article

(This article belongs to the Special Issue Adverse Effects of Co-Contaminated Mycotoxins and Strategies for Their Mitigation)

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51 pages, 6769 KB

Open AccessArticle

A Comprehensive Structural and Functional Analysis of Saccharomyces Killer Toxins

by Jack W. Creagh, Lily L. Givens, David C. Reetz, Sarah A. Coss, Rodolfo Bizarria, Jr., Siti Aisyah Alias, Mohammed Rizman-Idid, Jagdish S. Patel, Andre Rodrigues, F. Marty Ytreberg and Paul A. Rowley

Toxins 2026, 18(5), 235; https://doi.org/10.3390/toxins18050235 - 20 May 2026

Cited by 3 | Viewed by 2070

Abstract

Antifungal killer toxins are cytotoxic proteins that have the potential to combat the growing threat of fungi to human health and agriculture. A lack of empirical tertiary structures has limited understanding of their mechanisms of action and their ability to target pathogens. In [...] Read more.

Antifungal killer toxins are cytotoxic proteins that have the potential to combat the growing threat of fungi to human health and agriculture. A lack of empirical tertiary structures has limited understanding of their mechanisms of action and their ability to target pathogens. In this study, AlphaFold and molecular dynamics simulations were used to generate tertiary structure models of all canonical Saccharomyces killer toxins and to place them in the context of historical empirical data. These models enabled the prediction of functional domains and posttranslational modifications, including proteolytic cleavage sites and disulfide bonds. They also revealed unexpected homology between Saccharomyces killer toxins, suggesting that all but K28 are likely ionophores. Structural homology to the well-studied killer toxins K1 and K2 enabled the prediction of the antifungal and immunity mechanisms of K1L, K21, K45, K74, and KHS. The understudied killer toxins Klus, KHR, and K62 were found to have homology to bacterial and plant toxins, including members of the aerolysin family and antifungal lectins. These structural similarities provide clues for the mechanisms of killer toxin carbohydrate binding, oligomerization, and membrane attack. This modeling approach will help guide the continued use of the model yeast S. cerevisiae to study killer toxins in the context of the wealth of functional data gathered in the decades since their first discovery. Full article

(This article belongs to the Special Issue Molecular Response of Hosts to Fungal Toxins)

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11 pages, 1783 KB

Open AccessArticle

New Furoisocoumarins with Phytotoxic Activity from the Fungus Aspergillus calidoustus VKM F-4916

by Tatiana V. Antipova, Vsevolod R. Dubovik, Anton N. Yurchenko, Olesya I. Zhuravleva, Valentina P. Zhelifonova, Elizaveta G. Lukina, Boris P. Baskunov, Oussama Abdelhamid Mammeri, Sergey N. Smirnov, Natalya E. Ivanushkina, Kirill V. Zaitsev, Qunfang Weng, Mikhail B. Vainshtein and Alexander O. Berestetskiy

Toxins 2026, 18(5), 234; https://doi.org/10.3390/toxins18050234 - 20 May 2026

Viewed by 765

Abstract

Aspergillus fungi are a source of low-molecular compounds of various structures possessing biological activities. We investigated the secondary metabolite profile of the soil fungus A. calidoustus VKM F-4916. The strain was found to synthesize new metabolites attributed to furoisocoumarins, which we named asperisocoumarin [...] Read more.

Aspergillus fungi are a source of low-molecular compounds of various structures possessing biological activities. We investigated the secondary metabolite profile of the soil fungus A. calidoustus VKM F-4916. The strain was found to synthesize new metabolites attributed to furoisocoumarins, which we named asperisocoumarin J and K, and a known siderophore desferritriacetylfusigen. The structure of asperisocoumarin J and K were determined by mass spectrometry and NMR spectroscopy. Asperisocoumarins J, K and desferritriacetylfusigen possessed a phytotoxicity, inhibiting the lettuce root growth. Sow thistle leaf and wheat leaf cuttings were sensitive to the action of asperisocoumarin J and K at a concentration of 5 mg/mL. Analysis of the structures of furoisocoumarins (asperisocoumarins J and K) using the online resource Pesti-DGI-Net showed that compounds had the physico-chemical properties favorable for pesticide development, in particular, fungicides and herbicides. An in-depth study of the phytotoxic properties of furoisocoumarins and their natural analogs is of interest in the context of the search for new herbicide compounds. Full article

(This article belongs to the Special Issue Fungal Phytotoxins: A Themed Issue in Honor of Prof. Antonio Evidente)

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10 pages, 3768 KB

Open AccessArticle

Differential Thermal Inactivation Enables Simultaneous Quantitation of Ricin and Abrin

by Woo-Hyeon Jeong

Toxins 2026, 18(5), 233; https://doi.org/10.3390/toxins18050233 - 19 May 2026

Viewed by 654

Abstract

Ricin and abrin are highly lethal Type II ribosome-inactivating proteins. They depurinate the same site of the 28S rRNA to inhibit protein synthesis. Consequently, standard molecular-level activity assays used to detect the toxic activity of ricin or abrin do not distinguish between the [...] Read more.

Ricin and abrin are highly lethal Type II ribosome-inactivating proteins. They depurinate the same site of the 28S rRNA to inhibit protein synthesis. Consequently, standard molecular-level activity assays used to detect the toxic activity of ricin or abrin do not distinguish between the two in mixed samples without prior physical separation or specially designed substrates. This study proposes a novel, cost-effective method to separately and simultaneously quantify the activities of ricin and abrin in mixtures by exploiting their distinct thermal stabilities. Thermal inactivation was used to demonstrate that heating samples at 80 °C for 5 min maximized the difference in their activities; while ricin retained most of its activity, abrin activity dropped to 20% after thermal treatment. This thermal treatment yielded 4 standard curves—ricin or abrin, thermally treated or not treated—in the 0.3 to 50 µg/mL range. By applying Cramer’s rule, the individual concentrations of active ricin and abrin in mixed samples were successfully calculated. However, this method should be used with a method detecting presence of ricin/abrin, to avoid unexpected reactivity due to contaminating RIPs. Full article

(This article belongs to the Collection Ribosome-Inactivating Proteins)

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13 pages, 271 KB

Open AccessPerspective

Beyond Wrinkle Efficacy: Toward a Broader Assessment of Longitudinal Compatibility in Routine Upper-Face Aesthetic BoNT-A

by Andrea Felice Armenti

Toxins 2026, 18(5), 232; https://doi.org/10.3390/toxins18050232 - 19 May 2026

Viewed by 633

Abstract

Botulinum toxin A (BoNT-A) is well established for the esthetic treatment of upper-face dynamic lines, and long-term adult studies suggest that repeated treatment may remain effective and acceptable over time in many patients. However, wrinkle efficacy and patient satisfaction do not by themselves [...] Read more.

Botulinum toxin A (BoNT-A) is well established for the esthetic treatment of upper-face dynamic lines, and long-term adult studies suggest that repeated treatment may remain effective and acceptable over time in many patients. However, wrinkle efficacy and patient satisfaction do not by themselves determine whether repeated treatment remains acceptable in broader morphologic, dynamic–expressive, and longitudinal terms. At the same time, the toxin’s pharmacology entails finite presynaptic blockade followed by active synaptic and architectural recovery, and imaging, histological, and neurophysiological studies indicate that repeated chemodenervation cannot be assumed to be biologically neutral at the muscle level. The resulting problem is not whether BoNT-A works, but whether current outcome frameworks are sufficient to judge repeated-treatment compatibility in full. Here, structural tolerance is proposed as a provisional clinical lens for an underdescribed boundary: whether repeated-treatment compatibility is fully captured by wrinkle reduction and patient acceptability alone. The paper organizes this problem across morphologic, dynamic–expressive, and longitudinal domains, outlines candidate warning signs, and develops a pragmatic tiered approach to assessment spanning routine care, structured clinical follow-up, and research-oriented evaluation. The aim is to support more complete longitudinal thinking in upper-face aesthetic BoNT-A, to clarify what current outcome frameworks remain unaddressed, and to identify priorities for future empirical study. Full article

(This article belongs to the Section Bacterial Toxins)

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12 pages, 1587 KB

Open AccessArticle

In Vivo Model of Short-Term Efficacy and Favorable Safety of Botulinum Toxin Type E Compared with Type A

by Jeong-Sun Nam, Daewon Yoon, Yujin Kim, Su-Young Kim, Jae-Young Kim, Yoonkyoung Cha, Joon Seok and Beom Joon Kim

Toxins 2026, 18(5), 231; https://doi.org/10.3390/toxins18050231 - 16 May 2026

Viewed by 1273

Abstract

Botulinum toxin suppresses neurotransmitter release, thereby inhibiting muscle contraction and inducing flaccid paralysis. Botulinum toxin type A (BoNT/A) is widely used for neuromuscular blockade but, upon repeated administration, may cause long-lasting muscle atrophy, fibrosis, and inflammation. It is produced as a single peptide [...] Read more.

Botulinum toxin suppresses neurotransmitter release, thereby inhibiting muscle contraction and inducing flaccid paralysis. Botulinum toxin type A (BoNT/A) is widely used for neuromuscular blockade but, upon repeated administration, may cause long-lasting muscle atrophy, fibrosis, and inflammation. It is produced as a single peptide chain that becomes activated through cleavage into a heavy and light chain. BoNT/E, like BoNT/A, is produced as a single-chain polypeptide and requires cleavage to generate the active dichain form. Although BoNT/E is known to have a faster onset and shorter duration of action compared with BoNT/A, its efficacy and safety have not been thoroughly investigated. We compared BoNT/E and BoNT/A in SKH-1 hairless mice. Neuromuscular blockade, recovery pattern, and changes in muscle weight, volume, fiber size, fibrosis, mast cell infiltration, and diffusion to adjacent muscles were evaluated over time. BoNT/E induced maximal neuromuscular blockade on day 3 and fully recovered by day 35, whereas BoNT/A reached maximal effect on day 7 and showed only 20% recovery of the vehicle group by day 35. BoNT/E caused transient, dose-dependent reductions in muscle weight, volume, fiber size, and fibrosis, which largely normalized by day 35. In contrast, BoNT/A, administered at a dose of 0.5 U per injection site, induced persistent muscle atrophy, fibrosis, and significantly increased mast cell infiltration under the experimental conditions used in this study. Neither BoNT/E nor BoNT/A showed diffusion to adjacent muscles or changes in body weight. These findings suggest that BoNT/E provides rapid onset, short duration, and favorable safety, supporting its potential as an alternative therapeutic option for indications requiring temporary muscle relaxation with minimized long-term adverse effects. Full article

(This article belongs to the Section Bacterial Toxins)

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22 pages, 384 KB

Open AccessArticle

Multi-Mycotoxin Occurrence and Health Risk Assessment in Early Post-Harvest Durum Wheat, Barley, and Maize from Tunisia

by Khouloud Ben Hassouna, Jalila Ben Salah-Abbès, Samir Abbès, Ferjeni Zouidi, Mourad Jridi, Albert Sebastià, Noelia Pallarés and Houda Berrada

Toxins 2026, 18(5), 230; https://doi.org/10.3390/toxins18050230 - 16 May 2026

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Abstract

The contamination of cereals by mycotoxins represents a major concern due to their harmful effects on human health and food quality. The current study investigated the occurrence of major mycotoxins (AFB1, AFB2, AFG1, AFG2, OTA, ENA, ENA1, ENB, and ENB1) in 158 raw [...] Read more.

The contamination of cereals by mycotoxins represents a major concern due to their harmful effects on human health and food quality. The current study investigated the occurrence of major mycotoxins (AFB1, AFB2, AFG1, AFG2, OTA, ENA, ENA1, ENB, and ENB1) in 158 raw cereal samples (durum wheat, barley, and maize) collected from two Tunisian regions: Beja (continental region) and Mahdia (coastal region). Mycotoxins were extracted using the QuEChERS method and quantified by UHPLC–MS/MS. Several mycotoxins were detected at high levels across all the cereals. In the Beja region, durum wheat was contaminated with AFB1, AFG1, ENA, ENA1, ENB, and ENB1, with ENB being the most frequent (70%). Mahdia durum wheat was contaminated only with ENA, ENA1, ENB, and ENB1, with ENB1 being the most prevalent (22.6%). Barley from both regions was contaminated only with ENs. The ENB was the most frequent (Beja 66%, Mahdia 28.6%). Maize from Beja was contaminated by OTA and ENs, with ENA1 being the most frequent (22.5%), while maize from Mahdia was contaminated by AFB1, AFB2, AFG2, and ENs (AFB1 was the most frequent, 35%). All wheat samples contaminated with AFG1 (6.55%) exceeded the European Union maximum limit for AFs in cereals (4 µg/kg). Similarly, maize samples contaminated with AFB1 (17.5%), AFB2 (10%), and AFG2 (2.5%) exceeded the EU maximum limit for aflatoxins in maize (10 µg/kg). Additionally, maize samples contaminated with OTA (5%) exceeded the EU maximum limit for OTA in unprocessed cereals (5 µg/kg). The co-occurrence of multiple mycotoxins was observed in all cereal types, with up to six different mycotoxins detected in a single sample. Dietary risk assessment revealed high EDIs of AFB1, AFG1, and ENs through the consumption of wheat and barley by Tunisian adults. The calculated MOE values for AFB1 and AFG1 in wheat were below 10,000 (MOE = 1190 for AFB1 and 2.5 for AFG1), suggesting a potential health concern associated with dietary exposure. Despite this potential risk, AFB1 and AFG1 were detected in only 3% and 7% of the analyzed samples, respectively. These results highlight the need for regular monitoring and the establishment of regulations to control mycotoxins in Tunisian cereals. Full article

(This article belongs to the Section Mycotoxins)

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19 pages, 2256 KB

Open AccessArticle

Efficient Biotransformation of Zearalenone in Acidic Food Matrices by Alkaline Enzyme–Inorganic Hybrid Nanoflower

by Ping Ding, Wenchao Liao, Chenyu Chen, Xincheng Chen, Chengfei Wang and Xiaoyang Li

Toxins 2026, 18(5), 229; https://doi.org/10.3390/toxins18050229 - 13 May 2026

Viewed by 932

Abstract

Zearalenone (ZEN) is a pervasive mycotoxin contaminating global food and feed. While enzymatic degradation offers a promising, specific, and eco-friendly strategy for mycotoxin mitigation, the biotransformation of ZEN within acidic food matrices remains challenging due to the intrinsically low activity of zearalenone lactonase [...] Read more.

Zearalenone (ZEN) is a pervasive mycotoxin contaminating global food and feed. While enzymatic degradation offers a promising, specific, and eco-friendly strategy for mycotoxin mitigation, the biotransformation of ZEN within acidic food matrices remains challenging due to the intrinsically low activity of zearalenone lactonase (ZENG). In this work, we synthesized a ZENG–hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂) hybrid nanoflower (CaNF) via biomineralization under alkaline conditions. Compared to free ZENG, the as-prepared biohybrid nanoflower exhibited markedly enhanced acid tolerance and catalytic activity, achieving a 12-fold increase in ZEN degradation efficiency at pH 5.0. Furthermore, the biohybrid nanoflower demonstrated robust performance in various acidic food matrices, including corn juice, wort, beer, and corn steep liquor. This study presents a powerful enzymatic tool for the efficient biotransformation of ZEN in acidic food-related systems. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 639 KB

Open AccessArticle

Early Intervention of Hemiplegic Shoulder Pain in the Context of Post-Stroke Shoulder Spasticity: A Canadian Cross-Sectional Survey

by Farris Kassam, Fraser MacRae, Linden Lechner, Heather Dow, Ève Boissonnault, Fiona Huang and Paul Winston

Toxins 2026, 18(5), 228; https://doi.org/10.3390/toxins18050228 - 12 May 2026

Viewed by 1522

Abstract

Objectives: To investigate current Canadian physicians’ practice patterns of treating upper limb post-stroke spasticity (PSS) and hemiplegic shoulder pain (HSP) acutely after a stroke. In addition, by examining Canadian physicians’ diagnostic capabilities, time till treatment, minimum criteria to begin treatment, mechanisms of treatment, [...] Read more.

Objectives: To investigate current Canadian physicians’ practice patterns of treating upper limb post-stroke spasticity (PSS) and hemiplegic shoulder pain (HSP) acutely after a stroke. In addition, by examining Canadian physicians’ diagnostic capabilities, time till treatment, minimum criteria to begin treatment, mechanisms of treatment, targeting of muscles, and benefits and adverse effects of treatment, we aim to learn about areas of improvement to optimize PSS management for Canadians. Design: The present study was a cross-sectional survey, polling practicing Canadian physicians. Results: A total of 17 physicians completed the survey, all PM&R specialists, save one neurologist. Four provinces were represented in the responses. Participants had, on average, over ten years of experience managing post-stroke spasticity in outpatient and inpatient clinics. All 17 perform botulinum neurotoxin A (BoNT-A) injections for HSP associated with PSS. Most participants reported that they will begin BoNT-A treatments 2–3 weeks post-stroke, most commonly targeting the pectoralis major, subscapularis, and latissimus dorsi. Participants reported the mean median dosage they use as onabotulinum toxin A (169.12 units, SD = 73.70), incobotulinum toxin A (178.13 units, SD = 65.75), and abobotulinum toxin A (470.83 units, SD = 171.17). For injection guidance, participants responded that they use ultrasound for the largest percentage of their caseload, followed by electromyography, then electrical stimulation, then palpation. Very seldom did participants use palpation alone. Conclusions: From the limited sample included in analyses, the Canadian physicians respondents seem to be treating HSP and associated PSS with variable strategies. Further research is required to align dosages, targets, and guidance strategies as they vary considerably. Full article

(This article belongs to the Special Issue Botulinum Toxin: Advancing Treatments for Spasticity)

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21 pages, 2752 KB

Open AccessArticle

Nicotinamide Ameliorates Deoxynivalenol-Induced Injury in Renal Cells via Inhibiting PARP1 Hyperactivation and Restoring NAD⁺ Homeostasis

by Chao Chen, Yifan Qin, Zijun Luo, Peiqiang Mu, Jikai Wen and Yiqun Deng

Toxins 2026, 18(5), 227; https://doi.org/10.3390/toxins18050227 - 10 May 2026

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Abstract

Deoxynivalenol (DON) is a globally prevalent mycotoxin that threatens food and feed safety via severe multi-organ toxicity. Previous studies indicate that DON induces cellular energy metabolism dysregulation by triggering oxidative stress and impairing mitochondrial function. During this process, nicotinamide adenine dinucleotide (NAD⁺ [...] Read more.

Deoxynivalenol (DON) is a globally prevalent mycotoxin that threatens food and feed safety via severe multi-organ toxicity. Previous studies indicate that DON induces cellular energy metabolism dysregulation by triggering oxidative stress and impairing mitochondrial function. During this process, nicotinamide adenine dinucleotide (NAD⁺), a central coenzyme in cellular energy metabolism, frequently exhibits significantly decreased intracellular levels or even complete depletion. However, the molecular mechanisms underlying the disruption of NAD⁺ homeostasis by DON exposure, as well as the development of targeted countermeasures, remain elusive. Using human embryonic kidney 293T (HEK293T) cells as an in vitro renal toxicity model, we dissected DON-induced NAD⁺ dysregulation and evaluated the protective potential of nicotinamide (NAM). DON caused significant NAD⁺ depletion in porcine serum (in vivo) and HEK293T cells (in vitro), which was confirmed as a key driver of cytotoxicity. Mechanistically, although DON binds and inhibits nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD⁺ salvage pathway, neither NAMPT knockdown and overexpression nor nicotinamide mononucleotide (NMN) supplementation rescued DON-induced toxicity. Instead, DON dose-dependently activated poly(ADP-ribose) polymerase 1 (PARP1), the primary intracellular NAD⁺-consuming enzyme, to accelerate NAD⁺ depletion. PARP1 knockdown markedly attenuated DON-induced cytotoxicity, identifying PARP1 hyperactivation as the core toxic mechanism. NAM dose-dependently suppressed PARP1 activity, replenished NAD⁺ pools, and reversed cell injury. These findings establish PARP1-driven NAD⁺ depletion as an important mechanism of DON-induced renal toxicity, providing a promising intervention candidate for mitigating DON toxicity in food safety. Full article

(This article belongs to the Special Issue Adverse Effects of Co-Contaminated Mycotoxins and Strategies for Their Mitigation)

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21 pages, 2725 KB

Open AccessArticle

Response of Hemolytic and Photosynthetic Activity of Chattonella marina Complex Under Variable N:P Stoichiometry

by Xinyi Wang, Kehan Yi, Yongjun Jiang and Mengmeng Tong

Toxins 2026, 18(5), 226; https://doi.org/10.3390/toxins18050226 - 9 May 2026

Cited by 1 | Viewed by 558

Abstract

Chattonella marina is an ichthyotoxic, bloom-forming raphidophyte known for its hemolytic activity. However, the mechanisms by which nitrogen (N) and phosphorus (P) limitation influence this hemolytic toxicity remain poorly understood. In this study, both N and P limitation reduced growth, photosynthetic efficiency (F [...] Read more.

Chattonella marina is an ichthyotoxic, bloom-forming raphidophyte known for its hemolytic activity. However, the mechanisms by which nitrogen (N) and phosphorus (P) limitation influence this hemolytic toxicity remain poorly understood. In this study, both N and P limitation reduced growth, photosynthetic efficiency (F_v/F_m, Y_II, rETR_max), and the expression of nutrient-uptake, tetrapyrrole/chlorophyll biosynthesis genes. Nevertheless, the two nutrients produced opposite effects on toxicity: N limitation lowered hemolytic activity and ROS levels to near zero, whereas P limitation kept both relatively high, similar to nutrient-replete controls. The addition of the antioxidant NAC (N-Acetyl-L-cysteine) reduced hemolytic activity, confirming that ROS contributes to toxicity. Transcriptome data showed that under N limitation, genes for nitrogen uptake and initial reduction (NRT, NR, glnA) were upregulated, while downstream assimilation genes (nirA, GLT1) were downregulated. In contrast, under P limitation, all the nitrogen-metabolism-related genes (NRT, NR, glnA, nirA, GLT1) were downregulated. In the tetrapyrrole pathway, most genes were downregulated under both nutrient-limited conditions, except for HemD, suggesting a bottleneck that may result in the accumulation of porphyrin intermediates within the tetrapyrrole/chlorophyll biosynthesis pathway. Together, the secondary products derived primarily from the reaction of ROS with tetrapyrrole-based compounds appear to be the main contributors to hemolytic toxicity. Consequently, high levels of both ROS and porphyrin intermediates under P-limited conditions, as well as high ROS levels but low porphyrin intermediates under nutrient-sufficient conditions, may both contribute to the high hemolytic toxicity of C. marina. In contrast, under N limitation, despite the accumulation of porphyrin intermediates, the strong suppression of photosynthetic electron transport limits both ROS production and the synthesis of nitrogen-containing toxins, resulting in low hemolytic activity. These findings demonstrate that nutrient conditions regulate hemolytic activity in C. marina in a nutrient-specific manner. Full article

(This article belongs to the Special Issue Harmful Algal Toxins: Structure, Function, and Taxonomic Insights)

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25 pages, 8811 KB

Open AccessArticle

Plasma Metabolomics Reveals a Shared Metabolomic Profile in Experimental and Human Chronic Kidney Disease

by Søren H. Elsborg, Jasmine C. L. Atay, Johan Palmfeldt, Christian Daugaard Peters, Krista Dybtved Kjærgaard, Henricus A. M. Mutsaers and Rikke Nørregaard

Toxins 2026, 18(5), 225; https://doi.org/10.3390/toxins18050225 - 9 May 2026

Viewed by 1634

Abstract

Chronic kidney disease (CKD) affects nearly 10% of the global population, yet diagnosis and disease monitoring still rely primarily on plasma creatinine. Because creatinine levels are strongly influenced by non–renal factors, such as age, sex, muscle mass, and diet, its accuracy as a [...] Read more.

Chronic kidney disease (CKD) affects nearly 10% of the global population, yet diagnosis and disease monitoring still rely primarily on plasma creatinine. Because creatinine levels are strongly influenced by non–renal factors, such as age, sex, muscle mass, and diet, its accuracy as a kidney function marker is limited. To identify plasma biomarkers that reflect kidney injury, we applied untargeted and targeted metabolomics in the adenine-induced CKD mouse model, a well-known tubular damage model, and validated the findings in plasma from patients with advanced CKD and healthy controls. We identified five metabolites that showed altered plasma levels in both experimental and human CKD, of which galactonic acid, pipecolic acid, and N-acetylneuraminic acid were significantly associated with measured glomerular filtration rate (GFR). As a proof-of-concept, we demonstrated that integrating these metabolites into a biomarker panel alongside creatinine could improve GFR estimation compared with creatinine alone. Our study introduces a promising metabolite-based biomarker panel that might enhance the accuracy of kidney function assessment and could potentially support diagnosis, risk stratification, and monitoring of disease progression; however, validation in a broader CKD cohort is needed. Full article

(This article belongs to the Section Uremic Toxins)

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17 pages, 543 KB

Open AccessArticle

Carry-Over Factor of Zearalenone in the Roof of the Third Ventricle of the Brain and Selected Skeletal Muscles During Low-Dose Zearalenone Mycotoxicosis in Prepubertal Gilts

by Magdalena Gajęcka, Łukasz Zielonka and Maciej T. Gajęcki

Toxins 2026, 18(5), 224; https://doi.org/10.3390/toxins18050224 - 8 May 2026

Viewed by 898

Abstract

The aim of this study was to determine whether exposure to low doses of zearalenone (ZEN) over a period of six weeks affects the values of the carry-over factor (COF) of ZEN in the roof of the third cerebral ventricle (RTCV) and in [...] Read more.

The aim of this study was to determine whether exposure to low doses of zearalenone (ZEN) over a period of six weeks affects the values of the carry-over factor (COF) of ZEN in the roof of the third cerebral ventricle (RTCV) and in selected skeletal muscles (longissimus and quadriceps) in prepubertal gilts. The study was conducted on 60 clinically healthy prepubertal gilts with an initial body weight (BW) of 14.5 ± 2 kg. Gilts were randomly assigned to a control group (group C; n = 15) and three experimental groups (ZEN5, ZEN10, and ZEN15; n = 15 each). Groups ZEN5, ZEN10, and ZEN15 were administered ZEN per os at doses of 5 µg/kg BW, 10 µg/kg BW, and 15 µg/kg BW, respectively. Group C animals were orally administered a placebo. Tissue samples (brain and skeletal muscles) were collected post-mortem for toxicological analyses on exposure days 7 (D1), 21 (D2), and 42 (D3). The concentrations of ZEN and its metabolites, α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL), were determined in the collected samples. All examined tissues contained the parent compound, but ZEN metabolites were not detected in any of the samples. The absence of ZEN metabolites may have resulted from a physiological deficit of estradiol (E₂) and, consequently, testosterone (T) and progesterone (P₄) in prepubertal gilts. Low-dose ZEN mycotoxicosis led to a persistent presence of ZEN in the RTCV (COF from 1 × 10⁻⁶ on D1 to 7 × 10⁻⁷ on D3) and somewhat lower ZEN levels in skeletal muscles (COF from 8 × 10⁻⁶ on D1 to 6 × 10⁻⁷ on D3). The presence of ZEN in the RTCV confirms that it crosses the blood–brain barrier and may therefore participate in the hormonal homeostasis of the brain. Full article

(This article belongs to the Section Mycotoxins)

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24 pages, 882 KB

Open AccessReview

Nutritional Factors Affecting Uremic Toxin Production

by Fanny Jouve, Christophe O. Soulage and Laetitia Koppe

Toxins 2026, 18(5), 223; https://doi.org/10.3390/toxins18050223 - 8 May 2026

Viewed by 1530

Abstract

Chronic kidney disease (CKD) is characterized by persistent exposure to uremic toxins (UTs), many of which originate from gut microbial metabolism and contribute to renal, cardiovascular, and metabolic complications. Current evidence indicates that CKD is associated with dysbiosis and the enrichment of microbial [...] Read more.

Chronic kidney disease (CKD) is characterized by persistent exposure to uremic toxins (UTs), many of which originate from gut microbial metabolism and contribute to renal, cardiovascular, and metabolic complications. Current evidence indicates that CKD is associated with dysbiosis and the enrichment of microbial taxa carrying genes involved in UT precursor production. Diet is a major modulator of the gut microbiota and therefore represents a promising lever to reduce UT generation in synergy with current nephroprotective therapies. Beyond simple protein restriction, more specific dietary approaches, particularly plant-based low-protein diets, appear especially relevant. Additional factors, including amino acid composition, lipid quality, food processing, constipation, transit time, meal timing, and circadian rhythms, may also influence microbial metabolism and UT production. This review examines the role of nutrition in shaping the gut microbiota–UT–kidney axis and discusses how dietary modulation may support precision nutrition in the context of CKD. It also highlights future directions based on multidimensional phenotyping and robust biomarkers to capture interindividual variability, guide personalized interventions, and ultimately improve renal and cardiovascular outcomes in CKD. Full article

(This article belongs to the Special Issue New Insights in Uremic Toxins and Toxin-Related Outcomes in Chronic Kidney Disease)

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17 pages, 3039 KB

Open AccessArticle

Optimized SPE–UPLC–MS/MS Method for Sensitive Determination of Cereulide in Complex InfantFormula Matrices

by Zixiao Zhou, Ziyi Wang, Chundi Mu, Yan Qi, Jing Zhang, Xia Cui, Sai Fan, Jing Xiao and Rong Zhao

Toxins 2026, 18(5), 222; https://doi.org/10.3390/toxins18050222 - 8 May 2026

Cited by 4 | Viewed by 1573

Abstract

Cereulide is a heat-stable cyclic depsipeptide toxin produced by Bacillus cereus and is responsible for foodborne emetic syndrome. Recent reports of Bacillus cereus contamination and cereulide occurrence in infant formula have raised increasing food safety concerns. Due to the immature immune and metabolic [...] Read more.

Cereulide is a heat-stable cyclic depsipeptide toxin produced by Bacillus cereus and is responsible for foodborne emetic syndrome. Recent reports of Bacillus cereus contamination and cereulide occurrence in infant formula have raised increasing food safety concerns. Due to the immature immune and metabolic systems of infants, exposure to cereulide through contaminated formula may lead to potential health risks. However, direct application of existing cereulide analytical methods to infant formula remains challenging because of the unique processing technologies, encapsulated nutrients, and variable matrix composition of this product category, which may hinder toxin release and cause significant matrix interference. In practical analysis, inter-laboratory comparisons revealed that existing methods exhibited relatively large deviations and insufficient sensitivity, making them not specifically optimized for infant formula matrices. The present study was motivated by the need for a matrix-specific, sensitive, and reliable analytical method for cereulide determination in infant formula. In this study, a method based on solid-phase extraction coupled with ultra-performance liquid chromatography–tandem mass spectrometry (SPE–UPLC–MS/MS) was developed and validated. To improve the applicability of cereulide analysis to infant formula, this method incorporates a hydration-assisted extraction step tailored to infant formula, which increased the detected cereulide response by approximately fourfold, together with optimized SPE clean-up and improved chromatographic conditions to reduce matrix effects and enhance quantitative reproducibility. The method showed good linearity (0.1–10 μg·L⁻¹, R² > 0.999), low values for limit of detection (LOD) (0.03 μg·kg⁻¹) and limit of quantification (LOQ) (0.1 μg·kg⁻¹), and acceptable recoveries (94.4–110.3%) with RSDs below 3.7%. The developed method was successfully applied to commercial infant formula samples, and cereulide-positive samples were identified. This method provides a reliable analytical tool for the monitoring of cereulide in infant formula and contributes to improved food safety surveillance and exposure risk assessment. Full article

(This article belongs to the Special Issue Detection and Risk Assessment of Microbial Toxins in Food)

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19 pages, 8001 KB

Open AccessArticle

Preliminary Insights into Geographic Variation in Venom Profiles and Functional Activities of Nigerian Snakes, Bitis arietans and Naja nigricollis

by Akindele Oluwatosin Adeyi, Oluwatimilehin Stephen Emmanuel, Samuel Itang Itang, Babafemi Siji Ajisebiola, Mihir Kumar, Gotravalli V. Rudresha, Prasad Gopalkrishna Gond, Thomas Crasset, Damien Redureau, Fernanda Gobbi Amorim, Kartik Sunagar and Loïc Quinton

Toxins 2026, 18(5), 221; https://doi.org/10.3390/toxins18050221 - 7 May 2026

Cited by 1 | Viewed by 1976

Abstract

Snakebite envenoming is a major yet neglected tropical disease in sub-Saharan Africa, where antivenom efficacy is critically limited by intraspecific venom variation shaped by local ecological pressures. Nigeria’s sharply contrasting Sudan Savanna (North) and Lowland Rainforest (South) provide an ideal natural system to [...] Read more.

Snakebite envenoming is a major yet neglected tropical disease in sub-Saharan Africa, where antivenom efficacy is critically limited by intraspecific venom variation shaped by local ecological pressures. Nigeria’s sharply contrasting Sudan Savanna (North) and Lowland Rainforest (South) provide an ideal natural system to investigate this variation, yet a comparative analysis of its medically important snakes has been lacking. We conducted an integrated proteomic and functional characterization of venoms from the puff adder (Bitis arietans) and black-necked spitting cobra (Naja nigricollis) collected in Kaduna (North) and Ibadan (South). Using high-resolution LC-MS/MS, SDS-PAGE, and biochemical assays (phospholipase A₂, protease, fibrinogenolytic, hemolytic, and coagulation activities), we mapped region-specific venom compositions and characterized their functional activities. Bitis arietans displayed region-associated divergence: southern venom was enriched in serine proteases, whereas northern venom was dominated by lectins and distinct snake venom metalloproteinase isoforms. Naja nigricollis showed a conserved phospholipase A₂/three-finger toxins backbone, yet southern venoms exhibited elevated snake venom metalloproteinase III and L-amino acid oxidase. These molecular differences manifested functionally, with southern B. arietans venom showing higher protease activity than northern B. arietans, whereas southern and northern N. nigricollis venom exhibited similar protease activity but enhanced phospholipase A₂ activity in southern N. nigricollis. This work provides the first integrated proteomic and functional comparison of venoms from northern and southern Nigerian venom sample of B. arietans and N. nigricollis. While based on a limited number of individuals, the observed differences should be considered preliminary and indicative of potential regional trends rather than population-level characteristics. Full article

(This article belongs to the Special Issue Unlocking the Deep Secrets of Toxins)

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14 pages, 2217 KB

Open AccessArticle

Clinical Effectiveness of IncobotulinumtoxinA Using a Standardized Protocol in the Management of Myogenous Temporomandibular Disorders: A 12-Month Retrospective Study

by David Faustino Ângelo, Henrique José Cardoso, Marcella Sarkis, Kelly Santos, Francesco Maffia, David Sanz and Francisco Salvado

Toxins 2026, 18(5), 220; https://doi.org/10.3390/toxins18050220 - 7 May 2026

Viewed by 946

Abstract

Background: Myogenous temporomandibular disorders (TMDs) are a common subtype of orofacial pain. Evidence regarding treatment with botulinum toxin type A (BoNT-A) remains heterogeneous, and its use is generally limited to refractory cases. This study evaluated 12-month clinical outcomes following an incobotulinumtoxinA protocol (the [...] Read more.

Background: Myogenous temporomandibular disorders (TMDs) are a common subtype of orofacial pain. Evidence regarding treatment with botulinum toxin type A (BoNT-A) remains heterogeneous, and its use is generally limited to refractory cases. This study evaluated 12-month clinical outcomes following an incobotulinumtoxinA protocol (the Ângelo Botulinum Toxin Protocol^®) in adults with DC/TMD-confirmed myogenous TMD unresponsive to conservative therapy. Methods: This retrospective observational study reviewed records from 98 adults treated with incobotulinumtoxinA following the predefined injection protocol. All patients had failed ≥ 3 months of conservative management and completed ≥ 12 months of follow-up. Outcomes included myalgia severity (0–3), patient-reported orofacial pain intensity (VAS 0–10), and maximum mouth opening (MMO). Favorable outcome criteria required myalgia 0–1 or VAS ≤ 2 and MMO ≥ 35 mm. Results: Myalgia significantly decreased at 12 months (2.69 ± 0.64 to 0.43 ± 0.85; p < 0.001). Patient-reported orofacial pain intensity also improved (2.44 ± 2.54 to 0.37 ± 1.33; p < 0.001). MMO remained stable, indicating preserved mandibular mobility. Overall, 79.6% of patients met the predefined favorable outcome criteria. Reintervention was required in 12 patients; 7 received additional incobotulinumtoxinA injections, and 5 underwent TMJ arthrocentesis. No complications were observed. Conclusion: This protocol was associated with improvements in muscular pain and orofacial discomfort while preserving mandibular mobility. However, given the retrospective design and absence of a control group, these findings should be interpreted as hypothesis generating. Full article

(This article belongs to the Special Issue Botulinum Toxin for the Pain Management in Musculoskeletal and Temporomandibular Disorders)

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19 pages, 5560 KB

Open AccessArticle

Development of a Sensitive UPLC-MS/MS Method for the Simultaneous Quantification of Mycotoxins in Wheat Products and Human Urine

by Bin Gao, Jialin Sun, Zechao Xu, Xiaohui Li, Jianxin Ma, Xiaomin Han and Shuo Wang

Toxins 2026, 18(5), 219; https://doi.org/10.3390/toxins18050219 - 6 May 2026

Cited by 2 | Viewed by 969

Abstract

Mycotoxin contamination in wheat products has consistently been a key issue of concern in food safety, and urinary biomonitoring provides an effective approach for assessing internal human exposure. In this study, a sensitive ultra-performance liquid chromatography–tandem mass spectrometry method was developed and validated [...] Read more.

Mycotoxin contamination in wheat products has consistently been a key issue of concern in food safety, and urinary biomonitoring provides an effective approach for assessing internal human exposure. In this study, a sensitive ultra-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of 28 mycotoxins in wheat products and human urine. For the two matrices, the extraction solvent, acid concentration, solid-phase extraction cartridge type, and enzymatic hydrolysis parameters were optimized. Under the optimized conditions, all target compounds showed excellent linear relationships within the tested concentration ranges (R² > 0.99). In wheat products, the spiked recoveries ranged from 70.2% to 120%, the repeatabilities ranged from 1.6% to 9.1%, and the limits of detection and limits of quantification were 0.001~8.3 μg/kg and 0.002~25.0 μg/kg, respectively. In urine, the spiked recoveries ranged from 79.3% to 120%, the repeatabilities ranged from 0.7% to 9.4%, and the limits of detection and limits of quantification were 0.0001~1.0 μg/L and 0.0002~3.0 μg/L, respectively. Analysis of real samples showed that at least seven mycotoxins were detected in wheat product samples, and at least five were detected in urine samples. In wheat products, the detection rates of deoxynivalenol, enniatin B, enniatin A₁, enniatin B₁, tenuazonic acid, and tentoxin were all 100%, whereas in urine, the detection rate of fumonisin B₁ reached 100%, and tenuazonic acid showed the highest mean concentration in both matrices. In conclusion, the developed ultra-performance liquid chromatography–tandem mass spectrometry method is suitable for the simultaneous quantification of 28 mycotoxins in wheat products and human urine, and its preliminary application demonstrates good practical applicability. Full article

(This article belongs to the Special Issue Detection and Risk Assessment of Microbial Toxins in Food)

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10 pages, 465 KB

Open AccessArticle

Alternaria Mycotoxins in the Hemp (Cannabis sativa L.) Food Chain

by Terenzio Bertuzzi, Lorena Schiavi, Federico Siboni, Roberta Battaglia, Paola Giorni, Domenica Iraci Capuccinello and Massimo Montanari

Toxins 2026, 18(5), 218; https://doi.org/10.3390/toxins18050218 - 5 May 2026

Viewed by 946

Abstract

Hemp seeds and derived products were recently re-evaluated in the food sector, thanks to their high nutritional value and absence of gluten. This increasing diffusion required to investigate the occurrence of mycotoxins, in particular of Alternaria toxins (ALTs), has been uncovered at high [...] Read more.

Hemp seeds and derived products were recently re-evaluated in the food sector, thanks to their high nutritional value and absence of gluten. This increasing diffusion required to investigate the occurrence of mycotoxins, in particular of Alternaria toxins (ALTs), has been uncovered at high levels in previous work. An integrated approach was involved in this study. First, Alternaria spp. incidence and ALTs were determined in hemp seeds harvested in different fields during 2024 and 2025 and the influence of meteorological conditions and of varieties was evaluated. Then, their distribution in hemp oil and defatted flour was studied after a cold pressing process of naturally contaminated hemp seeds, finding a high percentage, over 85%, in hemp cake. Finally, a small survey was conducted on different hemp products intended for direct human consumption, confirming the risk of contamination in seeds, flour and derived bakery products. Full article

(This article belongs to the Special Issue Mycotoxins Along the Food Chain: Detection, Contamination and Control)

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8 pages, 1348 KB

Open AccessCase Report

Subcutaneous Incobotulinumtoxin-A for Refractory Central Post-Stroke Neuropathic Pain: A Report of Two Cases

by Stefano Carda and Elisa Grana

Toxins 2026, 18(5), 217; https://doi.org/10.3390/toxins18050217 - 3 May 2026

Viewed by 1107

Abstract

Background: Post-stroke neuropathic pain, particularly central post-stroke pain and facial pain syndromes, continues to be challenging to manage with conventional pharmacological approaches. While botulinum toxin A (BoNT-A) is well established for treating spasticity after stroke, its use in the management of central neuropathic [...] Read more.

Background: Post-stroke neuropathic pain, particularly central post-stroke pain and facial pain syndromes, continues to be challenging to manage with conventional pharmacological approaches. While botulinum toxin A (BoNT-A) is well established for treating spasticity after stroke, its use in the management of central neuropathic pain remains less well established. Methods: This report presents two cases of patients with refractory neuropathic pain following ischemic cerebrovascular accidents who achieved significant pain relief through subcutaneous botulinum toxin administration, after failure of multiple conventional and intramuscular BoNT-A approaches. Results: Case 1 involves a 66-year-old patient with 18 years of post-stroke hemicorporeal pain who responded dramatically to subcutaneous BoNT-A injections after extensive prior treatment failures. Case 2 describes a 54-year-old with trigeminal-region and mandibular pain following ICA dissection who achieved complete pain resolution at facial sites with subcutaneous administration of BoNT-A. Conclusions: These cases demonstrate the potential efficacy of subcutaneous botulinum toxin for managing post-stroke neuropathic pain in selected patients and suggest a mechanism of action related to peripheral pain sensitization rather than motor denervation. Our findings support further investigation of subcutaneous administration techniques for pain management in specialized centers. Full article

(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)

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32 pages, 422 KB

Open AccessReview

Amatoxin Intoxication and Wild Mushroom Poisoning: Current Advances in Diagnosis, Risk Stratification, and Clinical Management

by Tsonka Dimitrova, Djeni Cherneva, Kaloyan Mihalev, Ivelin Iliev, Galina Yaneva and Svetlana Georgieva

Toxins 2026, 18(5), 216; https://doi.org/10.3390/toxins18050216 - 3 May 2026

Viewed by 2292

Abstract

Wild mushroom poisoning remains a major medical and toxicological challenge worldwide because of the diversity of toxic compounds, the broad spectrum of clinical manifestations, and the risk of severe hepatic or renal injury. Early differentiation between self-limiting gastrointestinal syndromes and potentially fatal intoxications [...] Read more.

Wild mushroom poisoning remains a major medical and toxicological challenge worldwide because of the diversity of toxic compounds, the broad spectrum of clinical manifestations, and the risk of severe hepatic or renal injury. Early differentiation between self-limiting gastrointestinal syndromes and potentially fatal intoxications with progressive organ failure remain a central clinical challenge. This review examines recent advances in the diagnosis, risk stratification, and therapeutic management of wild mushroom poisoning, with amatoxin intoxication serving as the principal clinical focus. Selected evidence from other mushroom toxic syndromes is also included to support differential diagnosis, highlight syndrome-specific variability, and provide comparative clinical and methodological context. The recent literature indicates a shift from predominantly symptom-based diagnosis toward integrated models combining clinical evaluation, laboratory biomarkers, toxicological testing, and analytical and molecular methods. Liquid chromatography, mass spectrometry, immunoassays, and the molecular identification of fungal species have improved diagnostic precision, particularly in cases with uncertain exposure history or delayed presentation. Current management relies on early multimodal strategies including intensive supportive care, targeted pharmacological interventions, extracorporeal detoxification, and, in selected severe cases, liver transplantation. Overall, clinical outcome depends not only on toxin profile, but also on timely diagnosis, accurate early risk stratification, and prompt coordinated treatment. Future research should prioritize standardized diagnostic pathways, validated prognostic models, and clinically applicable treatment algorithms that support earlier escalation of care in severe mushroom intoxication. Full article

(This article belongs to the Section Mycotoxins)

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24 pages, 3956 KB

Open AccessArticle

Efficacy of Acid-Treated Mangosteen Peel as a Broad-Spectrum Mycotoxin Binder

by Warissara Kasikonsunthonchai, Saowalak Adunphatcharaphon, Chris Elliott, Doris Marko, Dino Grgic, Florian Call and Awanwee Petchkongkaew

Toxins 2026, 18(5), 215; https://doi.org/10.3390/toxins18050215 - 2 May 2026

Cited by 1 | Viewed by 1173

Abstract

Multiple mycotoxins in feed threaten animal health and food safety, demanding sustainable mitigation strategies. This study evaluated acid-modified mangosteen peel (AMP), an agricultural by-product, as a potential multi-mycotoxin adsorbent. Physicochemical characterization using scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) surface area analysis, and Fourier [...] Read more.

Multiple mycotoxins in feed threaten animal health and food safety, demanding sustainable mitigation strategies. This study evaluated acid-modified mangosteen peel (AMP), an agricultural by-product, as a potential multi-mycotoxin adsorbent. Physicochemical characterization using scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) surface area analysis, and Fourier transform infrared spectroscopy (FTIR) analyses demonstrated that acid modification increased surface area (1.9 to 9.03 m²/g), pore volume (0.005 to 0.027 cm³/g), and surface negativity, indicating enhanced adsorption properties. In vitro binding experiments assessed adsorption of aflatoxin B₁ (AFB₁), zearalenone (ZEA), ochratoxin A (OTA), T-2 toxin, deoxynivalenol (DON) and fumonisin B₁ (FB₁) under different pH conditions. AMP exhibited high adsorption efficiencies for AFB₁, ZEA, OTA, and T-2 toxin, particularly at pH 3, whereas DON and FB₁ showed limited binding. Adsorption behavior was dose-dependent and best described by Langmuir and Freundlich isotherm models. Simulated gastrointestinal digestion indicated stable binding of AFB₁ and ZEA under gastric conditions, with partial release of some toxins at neutral pH. Cytotoxicity assessment in porcine intestinal epithelial cells (IPEC J2) showed no apparent cytotoxic effects at 0.25–1 mg/mL. Therefore, AMP demonstrated improved multi-mycotoxin adsorption compared to the untreated material and showed no apparent cytotoxic effects in vitro within the tested concentration range, indicating its potential as a promising feed additive candidate. Full article

(This article belongs to the Special Issue Mitigation and Detoxification Strategies of Mycotoxins: 2nd Edition)

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16 pages, 8638 KB

Open AccessArticle

In Vitro Reduction of Extractable Zearalenone and Screening of Tentative Transformation Products by Metschnikowia pulcherrima KKP 1368 Under Selected Buffered pH Conditions Relevant to the Porcine Gastrointestinal Tract

by Krzysztof Waśkiewicz, Michał Dąbrowski, Michał Łuczyński, Marcin Wróbel and Łukasz Zielonka

Toxins 2026, 18(5), 214; https://doi.org/10.3390/toxins18050214 - 1 May 2026

Viewed by 623

Abstract

Zearalenone (ZEN) is an estrogenic mycotoxin produced by Fusarium spp. and commonly found in cereals and feed materials. This study evaluated the ability of Metschnikowia pulcherrima KKP 1368 biomass to reduce extractable ZEN under controlled buffered pH conditions (pH 3.50 and 7.00) selected [...] Read more.

Zearalenone (ZEN) is an estrogenic mycotoxin produced by Fusarium spp. and commonly found in cereals and feed materials. This study evaluated the ability of Metschnikowia pulcherrima KKP 1368 biomass to reduce extractable ZEN under controlled buffered pH conditions (pH 3.50 and 7.00) selected as simplified conditions relevant to the porcine gastrointestinal environment. ZEN was quantified by LC-MS/MS, whereas LC-MS-QTOF was used as a qualitative/semi-quantitative screening approach for tentatively assigned transformation-related features. In the presence of yeast biomass, extractable ZEN was already lower than in the corresponding controls at the first sampling point, indicating a rapid biomass-associated effect. After 12 h, reductions relative to the corresponding controls reached 63.0% at pH 3.50 (p < 0.0001) and 51.6% at pH 7.00 (p = 0.0001). ZEN remained stable in control samples, and the strain remained viable under both pH conditions throughout incubation. LC-MS-QTOF detected several tentatively assigned features consistent with zearalanone, zearalenone-14-glucuronide, and zearalenol O-glucoside; these assignments require confirmation with authentic standards. Overall, M. pulcherrima KKP 1368 reduced extractable ZEN in a simplified buffered in vitro system, probably through rapid adsorption/reduced extractability and possible biotransformation. Further studies using biomass fractions or inactivated biomass, mass-balance experiments, authentic standards, and toxicological assays are needed to clarify the relative contribution of adsorption and transformation and to assess the practical relevance of this approach. Full article

(This article belongs to the Special Issue Mycotoxins and Animal Health: Mechanisms, Impacts, and Mitigation Strategies)

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4 pages, 212 KB

Open AccessEditorial

Transcriptomic and Proteomic Study on Animal Venom: Looking Forward

by Paulo Lee Ho

Toxins 2026, 18(5), 213; https://doi.org/10.3390/toxins18050213 - 1 May 2026

Cited by 1 | Viewed by 832

Abstract

Transcriptomic and proteomic studies concerning venom and venom glands have provided major breakthroughs in the characterization and knowledge of global crude venom compositions and have also allowed for the identification of new toxins and activities [...] Full article

(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)

18 pages, 2348 KB

Open AccessArticle

Botulinum Neurotoxin-A Inhibits Tumor Growth in a Triple-Negative Breast Cancer Preclinical Model

by Evoli N. Lopez, Guadalupe Delgado-López, Paola Maycotte, Pablo Hernández-Jáuregui, Irma Herrera-Camacho, Nora Hilda Rosas-Murrieta, Eunice López-Muñoz, Claudia Teresita Gutiérrez-Quiroz, Uriel Ramírez-Carrera, Cindy Bandala, Lourdes Millán-Pérez-Peña and Maricruz Anaya-Ruiz

Toxins 2026, 18(5), 212; https://doi.org/10.3390/toxins18050212 - 30 Apr 2026

Viewed by 1627

Abstract

Triple-negative breast cancer (TNBC) continues to be a medical challenge requiring multiple treatment options. SV2A, a protein involved in vesicular release, has emerged as a promising biomarker for various cancers. Research shows that botulinum neurotoxin type A (BoNT/A), which binds to SV2A, the [...] Read more.

Triple-negative breast cancer (TNBC) continues to be a medical challenge requiring multiple treatment options. SV2A, a protein involved in vesicular release, has emerged as a promising biomarker for various cancers. Research shows that botulinum neurotoxin type A (BoNT/A), which binds to SV2A, the BoNT/A receptor, can inhibit the growth of prostate and breast cancer cells, suggesting its potential as an alternative treatment for breast cancer. The purpose of this study was to determine the potential of BoNT/A to inhibit tumor growth in a mouse preclinical model. BoNT/A was evaluated for its effects in an in vitro model employing 4T1 cells and in an in vivo model of orthotopically inoculated 4T1 cells in BALB/c mice. BoNT/A inhibited the proliferation of 4T1 cells, which express the SV2A protein; decreased tumor growth in the preclinical model; and decreased inflammation, associated with fewer blood neutrophils and monocytes, suggesting an immunomodulatory and anti-inflammatory effect. The effect of BoNT/A on the TNBC model supports its use as a repurposed drug for this type of aggressive cancer. Our results emphasize the significance of the SV2A receptor and its interaction with BoNT/A as promising therapeutic targets, particularly for TNBC. Full article

(This article belongs to the Section Bacterial Toxins)

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22 pages, 3114 KB

Open AccessArticle

Effects of Cape Cobra (Naja nivea) Venom and Its Isolated Protein on the Modulation of Platelet Activation

by Mahtab Khatibi, José R. Almeida, Ashifa Al Juwaiser, Soheil Gilabadi, Ketan Patel and Sakthivel Vaiyapuri

Toxins 2026, 18(5), 211; https://doi.org/10.3390/toxins18050211 - 30 Apr 2026

Viewed by 1364

Abstract

The Cape cobra (Naja nivea), one of Africa’s most lethal snakes, can cause rapid, life-threatening paralysis. However, the impact of this venom on platelet function and blood coagulation remains poorly understood. To address this gap, we investigated the enzymatic profiles and [...] Read more.

The Cape cobra (Naja nivea), one of Africa’s most lethal snakes, can cause rapid, life-threatening paralysis. However, the impact of this venom on platelet function and blood coagulation remains poorly understood. To address this gap, we investigated the enzymatic profiles and the impacts of N. nivea venom on multiple aspects of haemostasis using human whole blood. Our results illustrate that Cape cobra venom significantly increases clotting time in rotational thromboelastometry without affecting other coagulation parameters. This venom significantly inhibits platelet aggregation and activation yet does not exert cytotoxic effects on platelets. The venom was subsequently fractionated using reverse-phase high-performance liquid chromatography, and the most potent purified fraction was identified as a cytotoxin (three-finger toxin) through mass spectrometry. This purified fraction showed an inhibitory effect on platelet activity. These findings highlight that N. nivea venom can induce haemotoxicity in addition to neurotoxicity. Moreover, three-finger toxins may be promising candidates for bioprospecting to develop novel antithrombotic agents. Full article

(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)

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18 pages, 4351 KB

Open AccessArticle

Spider Venom Peptides as Potential Allosteric Inhibitors of Undecaprenyl Diphosphatase (UppP) from Acinetobacter baumannii: In Silico Identification and Structural Analysis

by Yamil Liscano, Juan M. Álvarez-Caballero and Alberto Aragón-Muriel

Toxins 2026, 18(5), 210; https://doi.org/10.3390/toxins18050210 - 30 Apr 2026

Viewed by 1051

Abstract

The antimicrobial resistance of Acinetobacter baumannii necessitates the development of novel therapeutic strategies targeting essential enzymes such as Undecaprenyl Pyrophosphate Phosphatase (UppP). This study explored spider venom peptides in silico as potential allosteric inhibitors of A. baumannii UppP. A systematic literature review was [...] Read more.

The antimicrobial resistance of Acinetobacter baumannii necessitates the development of novel therapeutic strategies targeting essential enzymes such as Undecaprenyl Pyrophosphate Phosphatase (UppP). This study explored spider venom peptides in silico as potential allosteric inhibitors of A. baumannii UppP. A systematic literature review was conducted to select eight α-helical peptides with reported anti-A. baumannii activity, followed by their computational physicochemical characterization. Three-dimensional models of A. baumannii UppP and the candidate peptides were generated, and a putative allosteric binding site was validated through molecular docking of a known inhibitor of the BacA homolog. The eight peptides were subsequently docked to this validated site using HADDOCK. Results revealed variable binding affinities; peptides LC-AMP-I1, Lycosin-II, and GK37 exhibited the most favorable HADDOCK scores and extensive interaction networks, consistent with their reported high antimicrobial potency. Other candidates, notably Lt-MAP2, showed low binding affinity but high predicted synergistic potential. These findings identify promising spider venom peptide candidates, suggesting dual (membrane disruption/UppP inhibition) or synergistic mechanisms of action, and validate UppP as a viable pharmacological target for peptide-based inhibitors. Full article

(This article belongs to the Section Animal Venoms)

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17 pages, 761 KB

Open AccessReview

Enniatins and Beauvericin as Emerging Mycotoxins in the Context of Climate Change in Europe

by Francesca De Battistis, Chiara Civitelli, Valentina Prota, Francesca Caloni, Alberto Mantovani and Olimpia Vincentini

Toxins 2026, 18(5), 209; https://doi.org/10.3390/toxins18050209 - 30 Apr 2026

Cited by 3 | Viewed by 1849

Abstract

Emerging mycotoxins are unregulated natural toxins, often detected in small-grain cereal crops. They are produced by various Fusarium molds and have been reported in surveys conducted across Europe. Many Fusarium species that produce mycotoxins thrive and exhibit greater pathogenicity under relatively warm and [...] Read more.

Emerging mycotoxins are unregulated natural toxins, often detected in small-grain cereal crops. They are produced by various Fusarium molds and have been reported in surveys conducted across Europe. Many Fusarium species that produce mycotoxins thrive and exhibit greater pathogenicity under relatively warm and humid conditions. Environmental conditions that promote fungal growth often also enhance mycotoxin accumulation. Various abiotic factors influence both Fusarium growth and mycotoxin biosynthesis, and several studies have associated these environmental conditions with the occurrence of enniatins (ENNs) and beauvericin (BEA) in cereal crops. Ongoing climate change in Europe may further support the spread and development of Fusarium species, potentially increasing the production of emerging mycotoxins. Following recent updates on the occurrence of these mycotoxins, this review evaluates the scientific literature concerning Fusarium species responsible for ENNs and BEA production. Full article

(This article belongs to the Special Issue Detection, Biosynthesis and Control of Mycotoxins (4th Edition))

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Open AccessReview

The Battle Against Pertussis: Discovery of Endogenous Human Proteins and Peptides as Toxin-Inhibitors

by Stefanie Lietz and Holger Barth

Toxins 2026, 18(5), 208; https://doi.org/10.3390/toxins18050208 - 29 Apr 2026

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Abstract

The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of [...] Read more.

The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of pertussis. After infection with B. pertussis, PT is released and binds to its human target cells, which internalize PT. The enzyme subunit of PT is then taken up into the cytosol, where it catalyzes the ADP-ribosylation of the α-subunit of inhibitory GTP-binding proteins from the Gαi type. This ultimately leads to the development of the characteristic clinical symptoms associated with pertussis. Pertussis is a vaccine-preventable but highly infectious respiratory disease, and especially younger children are prone to develop severe pertussis. Despite the vaccination, over the past few years, increasing case numbers have been reported globally. Moreover, treatment options are strongly limited to antibiotics and symptomatic treatment. Therefore, novel therapies against toxin-mediated diseases are urgently required, while AB-type toxins such as PT are promising pharmacological targets to combat these associated diseases. To identify novel pharmacological inhibitors for AB-type toxins, huge potential lies within the human proteome/peptidome. Endogenous protein or peptide inhibitors for bacterial toxins might have evolved as part of the innate immunity and are awaited to be discovered. The scientific community is committed to identify potential candidates through targeted screening or explorative hypothesis-driven approaches. This review summarizes the recent efforts in the identification and characterization of the human body’s own proteins and peptides that inhibit PT. PT-inhibiting peptides were found by unbiased screening of peptide libraries from human hemofiltrate or hypothesis-driven evaluation, and PT-neutralizing mechanisms were discovered in cell-based approaches. The identification of endogenous peptides and proteins, e.g., defensins and α₁-antitrypsin, as potent inhibitors of PT paves the way towards the development of novel therapeutic options against pertussis. Full article

(This article belongs to the Special Issue Bacterial Toxins and Immune System)

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Toxins, Volume 18, Issue 5 (May 2026) – 45 articles

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