Toxins

34 pages, 4764 KB

Open AccessArticle

Algicidal Monoterpenes Against Toxin-Producing Microcystis aeruginosa with Reduced Toxicity Toward Chlorella sorokiniana: In Vitro, Molecular Docking, and ADMET Study

by El Mehdi Darrag, Yasser Essadki, Saad Zekri, Halima Chernane, Abderrahmane Romane, Ismail Hdoufane, Driss Cherqaoui, Brahim Oudra, Abdelilah Meddich, Vitor Vasconcelos and Abdelaziz Baçaoui

Toxins 2026, 18(6), 258; https://doi.org/10.3390/toxins18060258 (registering DOI) - 5 Jun 2026

Abstract

Harmful algal blooms pose a persistent threat to the integrity of freshwater ecosystems and public health. However, there are no selective chemical control agents available to suppress cyanobacterial growth without damaging beneficial phytoplankton. In this study, ten structurally diverse monoterpenes were assessed in [...] Read more.

Harmful algal blooms pose a persistent threat to the integrity of freshwater ecosystems and public health. However, there are no selective chemical control agents available to suppress cyanobacterial growth without damaging beneficial phytoplankton. In this study, ten structurally diverse monoterpenes were assessed in vitro for their differential activity against the potent toxin-producing cyanobacterium Microcystis aeruginosa and the ecologically valuable microalga Chlorella sorokiniana using disc diffusion (DDM) and minimum inhibitory concentration (MIC) assays. Inhibition zones against M. aeruginosa ranged from 6.9 to 43.6 mm, with thymol recording the largest zone (43.6 mm). MIC values ranged from 0.25 to >1 mg/mL for both organisms, and selectivity indices identified camphor and carvone as the most cyanobacterium-preferential compounds, while carene and α-pinene showed the inverse selectivity pattern. Molecular docking against six AlphaFold2-predicted target proteins, photosynthetic complexes, Adenosine Triphosphate (ATP) synthase subunits, and superoxide dismutase (SOD) from both organisms, revealed binding affinities between −3.9 and −6.2 kcal/mol. Phenolic monoterpenes consistently engaged active-site glutamate and aspartate residues via hydrogen bonds and Pi–Anion interactions, most strikingly in the M. aeruginosa ATP synthase, whereas the M. aeruginosa SOD represented the least amenable target for all compounds. Computational ADMET profiling confirmed favorable pharmacokinetic properties and low predicted toxicity for the full panel. Full article

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

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18 pages, 4411 KB

Open AccessArticle

Recombinant Human Fab Antibodies Differentially Neutralize Shiga Toxin in Renal Epithelial and Endothelial Cells

by Fernando D. Gómez, Daniela Luz, Isabel Chinen, Daniel Girón, Raissa L. Ferreira, Camila Henrique, Ariela O. P. Bom, Izabella M. Henrique, Wanderson Marques da Silva, Flavia Sacerdoti, Elizabeth S. Miliwebsky, Gang Chen, Claudia C. Carbonari, Sachdev S. Sidhu, Roxane M. F. Piazza and María Marta Amaral

Toxins 2026, 18(6), 257; https://doi.org/10.3390/toxins18060257 (registering DOI) - 5 Jun 2026

Abstract

Hemolytic Uremic Syndrome (HUS) is a severe clinical manifestation primarily triggered by Shiga toxin-producing Escherichia coli (STEC). While Shiga toxins (Stx) are central to the development of systemic endothelial damage, current recombinant antibody developments have overwhelmingly focused on neutralizing the Stx2 subtype. However, [...] Read more.

Hemolytic Uremic Syndrome (HUS) is a severe clinical manifestation primarily triggered by Shiga toxin-producing Escherichia coli (STEC). While Shiga toxins (Stx) are central to the development of systemic endothelial damage, current recombinant antibody developments have overwhelmingly focused on neutralizing the Stx2 subtype. However, numerous STEC isolates produce Stx1 either independently or alongside Stx2, revealing a critical need to diversify the antibody repertoire for comprehensive antitoxin therapies. To address this, we characterized two novel, fully human recombinant Fabs targeting Stx1 (FabB6:Stx1 and FabC8:Stx1) selected from a synthetic library via phage display. We evaluated their binding specificity and neutralizing activity in Vero and human proximal tubular epithelial (HK-2) cells, as well as in primary human glomerular endothelial cells (HGEC exposed to HUS-derived STEC supernatants. Both Fabs exhibited high specificity and nanomolar affinity for Stx1. Notably, they displayed cell-type-dependent neutralization profiles, with FabC8:Stx1 demonstrating superior and more consistent neutralization in HK-2 cells. Crucially, when evaluated alongside previously characterized anti-Stx2 antibodies (FabC11:Stx1/Stx2 and FabF8:Stx2), the Stx1-specific Fabs conferred complementary protection against clinical STEC isolates. These findings support the inclusion of Stx1-targeting recombinant antibodies into broader multi-toxin neutralization strategies, thereby expanding the therapeutic potential against STEC-associated diseases. Full article

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

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17 pages, 6662 KB

Open AccessArticle

Qualitative and Quantitative Proteomic Analysis of Venoms from Mexican Rattlesnakes

by Lizbeth Hernández-Ancheyta, Víctor Hugo Reynoso, Juan Carlos López-Vidal, Javier Hernández-Sánchez, Karen Delgadillo-Gutiérrez, María Lilia Domínguez-López and Julieta Luna-Herrera

Toxins 2026, 18(6), 256; https://doi.org/10.3390/toxins18060256 (registering DOI) - 5 Jun 2026

Abstract

Despite the vast biodiversity of Mexican vipers, venom of endemic species has been barely studied. Here we analyzed the venom composition of three endemic species of rattlesnakes: Crotalus aquilus, C. triseriatus, and C. ravus. We used quantitative chromato-mass-spectrometry and compared [...] Read more.

Despite the vast biodiversity of Mexican vipers, venom of endemic species has been barely studied. Here we analyzed the venom composition of three endemic species of rattlesnakes: Crotalus aquilus, C. triseriatus, and C. ravus. We used quantitative chromato-mass-spectrometry and compared venoms with C. molossus, a species commonly found in North America, in a comparative and phylogenetic framework. In total, we identified 165 proteins grouped in 19 main protein families, consistent with previous reports for viperid venoms. In C. aquilus and C. triseriatus, the most predominant protein-family type was Serine Proteases, and in C. triseriatus and C. molossus it was Snake Venom Metalloproteases. The Label-free quantification revealed a high proportion of Snake Venom Metalloproteases in C. aquilus, C. triseriatus, and C. molossus, reaching 28–47% of the total venom. In contrast, in C. ravus 47% of the venom was composed of Phospholipases A₂. Among the four species analyzed, C. triseriatus and C. aquilus were most similar in compositional profiles and their profiles are highly correlated. Venom composition in terminal clades and taxa were better explained by protein losses than evolution of new proteins. The triseriatus group share seven proteins, while the clade C. aquilus + C. triseriatus share seven derived protein features, of which six are protein losses. Full article

(This article belongs to the Section Animal Venoms)

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20 pages, 865 KB

Open AccessArticle

Unveiling Hidden Aconitum Alkaloids in a Poisoning-Implicated Tincture by Untargeted Screening and Molecular Networking

by Qian He, Micong Jin, Jing Zhou, Hongshun Zhang and Chengye Sun

Toxins 2026, 18(6), 255; https://doi.org/10.3390/toxins18060255 (registering DOI) - 5 Jun 2026

Abstract

Aconitum poisoning is a major public health concern in East Asia, and remains difficult to diagnose when the causative toxins are not covered by routine targeted assays. In a poisoning incident that occurred in 2018, 15 individuals were affected, including five fatalities, after [...] Read more.

Aconitum poisoning is a major public health concern in East Asia, and remains difficult to diagnose when the causative toxins are not covered by routine targeted assays. In a poisoning incident that occurred in 2018, 15 individuals were affected, including five fatalities, after accidentally consuming a medicinal tincture during a shared meal. The comprehensive alkaloid profile of the tincture implicated in the poisoning was achieved through the integration of targeted analysis, molecular networking, and untargeted screening based on ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry, aiming to clarify the causative agents. Targeted quantitative analysis detected nine alkaloids derived from Aconitum plants, confirming the presence of Aconitum ingredients in the medicinal tincture. However, these alkaloids were either present at low concentrations or exhibited low toxicity, and thus were not the principal causative agents of this poisoning incident. Molecular networking revealed additional hidden diester-diterpenoid alkaloids (DDAs) and monoester-diterpenoid alkaloids (MDAs) that were undetected by targeted analysis. Untargeted screening identified 58 Aconitum alkaloids, including 15 DDAs, 17 MDAs, 17 amino-diterpenoid alkaloids (ADAs), 2 C20-diterpenoid alkaloids, and seven unclassified alkaloids. The three most abundant alkaloids were structurally identified as pseudoaconitine, 8-deacetylpseudoaconitine, and 3′-methoxyacoforestinine, and were identified as the main causative agents of this poisoning. To our knowledge, this is the first detection of these alkaloids in Aconitum poisoning in China. These findings demonstrate that integrated targeted and untargeted toxicological analysis can identify undocumented toxins in poisoning events of unknown origin and clarify the chemical etiology of unusual Aconitum poisoning. Full article

(This article belongs to the Special Issue Toxic and Protective Compounds from Poisonous and Medicinal Plants: Toxicological, Mechanistic, Analytical, and Therapeutic Aspects)

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16 pages, 1359 KB

Open AccessArticle

Effects of the Temperature and Limosilactobacillus fermentum Co-Inoculation on the Expression of AFB1-Synthesis Genes and the Level of Toxin Produced by Aspergillus flavus Zt41 in Corn Silage

by Szilamér Ferenczi, Ildikó Bata-Vidács, Judit Kosztik, István Nagy, Katalin Inotai, Olívia Csernus, Natália Szeőcs, Zsuzsanna Szőke, Mónika Varga, András Szekeres and József Kukolya

Toxins 2026, 18(6), 254; https://doi.org/10.3390/toxins18060254 (registering DOI) - 4 Jun 2026

Abstract

Aflatoxin B1 (AFB1), a highly potent Group 1 human carcinogen produced by Aspergillus flavus (A. flavus), poses a significant contamination risk to corn silage, a threat that is further intensified by rising global temperatures. This study aimed to characterize the combined [...] Read more.

Aflatoxin B1 (AFB1), a highly potent Group 1 human carcinogen produced by Aspergillus flavus (A. flavus), poses a significant contamination risk to corn silage, a threat that is further intensified by rising global temperatures. This study aimed to characterize the combined effects of temperature and co-inoculation with the lactic acid bacterium Limosilactobacillus fermentum (L. fermentum) on AFB1 production and the expression of key biosynthetic genes in A. flavus colonizing corn silage. Corn silage was incubated at 20 °C, 30 °C, and 37 °C with and without L. fermentum. Using qRT-PCR and HPLC, we found that elevated temperatures, particularly 37 °C, strongly induced the expression of the aflatoxin biosynthetic cluster, including the regulatory gene aflR and structural genes such as omtA and ordA. Co-inoculation with L. fermentum consistently reduced in the final AFB1 concentration by approximately 50–60% at all three temperatures. Molecular analysis revealed that this reduction was associated with transcriptional repression at 30 °C and 37 °C. L. fermentum consistently and markedly down-regulated the expression of aflR and all structural genes. A particularly pronounced suppression was observed for the late-pathway gene ordA at 30 °C. These findings provide molecular evidence supporting the incorporation of selected L. fermentum strains into silage inoculant formulations to mitigate the AFB1 risk under high-temperature conditions. Full article

(This article belongs to the Special Issue Prevention and Remediation of Mycotoxins)

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22 pages, 15863 KB

Open AccessReview

Facial Paralysis Treatment and Facial Symmetrization with Botulinum Neurotoxin: A Narrative Review with Illustrative Clinical Cases

by Monica Renga, Roberta D’Emilio, Giovanni Salti, Selene Mogavero, Marco Papagni, Federico Biglioli and Alessandro Lozza

Toxins 2026, 18(6), 253; https://doi.org/10.3390/toxins18060253 - 4 Jun 2026

Abstract

Facial paralysis leads to static and dynamic asymmetry, hyperkinesis of the non-paralyzed side, and synkinesis, with major functional and psychosocial consequences for patients. Botulinum neurotoxin serotype A (BoNT-A) injections are an effective therapeutic option since they denervate overactive muscles, thereby reducing hyperkinesis or [...] Read more.

Facial paralysis leads to static and dynamic asymmetry, hyperkinesis of the non-paralyzed side, and synkinesis, with major functional and psychosocial consequences for patients. Botulinum neurotoxin serotype A (BoNT-A) injections are an effective therapeutic option since they denervate overactive muscles, thereby reducing hyperkinesis or synkinesis and eventually improving asymmetry. This narrative review summarizes relevant literature on the use of BoNT-A for facial paralysis. It provides a summary of dosing strategies and treatment plans, discusses the use of functional scales for assessing facial paralysis and improvement after treatment, and outlines the use of electromyography (EMG) or ultrasound-guided injections to improve treatment outcomes. Finally, it discusses its potential role in the preparation for functional microsurgery. We also present the authors’ anecdotal experience, with three case reports: a woman with facial paralysis caused by Ramsay Hunt Syndrome, treated with a full-face and neck BoNT-A protocol and followed-up for 18 months with photographic documentation, to further assess the aesthetic improvement; a young woman with familiarity of facial paralysis, contralateral hyperkinesis, and synkinesis, managed with EMG-guided and landmark-guided injections; and her mother, with recurrent facial paralysis and chronic synkinesis, treated with stepwise BoNT-A sessions. All three cases demonstrated clinically meaningful improvements, as evidenced by the photographic material and functional grading scores presented. Full article

(This article belongs to the Special Issue Study on Botulinum Toxin in Facial Diseases and Aesthetics)

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21 pages, 2278 KB

Open AccessArticle

Cyclopiazonic Acid Induces Mitochondrial Oxidative Stress in SH-SY5Y Cells: Protective Effects of Extra Virgin Olive Oil Phenolics

by Carmen Martínez-Alonso, Yelko Rodríguez-Carrasco and María-José Ruiz

Toxins 2026, 18(6), 252; https://doi.org/10.3390/toxins18060252 - 2 Jun 2026

Abstract

Cyclopiazonic acid (CPA), a neurotoxin produced by Penicillium and Aspergillus genera, induces oxidative stress and neuronal damage, mechanisms implicated in neurodegenerative diseases. This study investigates the oxidative stress induced by CPA in SH-SY5Y human neuroblastoma cells, focusing on mitochondrial membrane potential, mitochondrial superoxide [...] Read more.

Cyclopiazonic acid (CPA), a neurotoxin produced by Penicillium and Aspergillus genera, induces oxidative stress and neuronal damage, mechanisms implicated in neurodegenerative diseases. This study investigates the oxidative stress induced by CPA in SH-SY5Y human neuroblastoma cells, focusing on mitochondrial membrane potential, mitochondrial superoxide levels, ROS production, lipid peroxidation and gene expression. Additionally, the cytoprotective effects of extra virgin olive oil (EVOO) extract, along with its major polyphenols oleuropein (OLE) and tyrosol (TYR), were evaluated. CPA exposure increased mitochondrial superoxide levels and lipid peroxidation, reducing mitochondrial membrane potential, although no intracellular ROS generation was observed. Gene expression analysis revealed downregulation of antioxidant defense genes (nrf2, nos2, ho1, cat, keap1, nqo1, gpx1 and gsr), with the strongest repression observed for nos2 (93%), nqo1 (83%) and ho1 (79%) at the highest CPA concentration, consistent with oxidative stress markers. EVOO extract demonstrated protective effects, enhancing cell viability across all CPA assayed concentrations (400–600 nM). Conversely, TYR and OLE exhibited variable and concentration-dependent effects, also showing protection to a lesser extent, while EVOO extract proved to be more effective due to synergistic interactions among its phenolic components. Overall, CPA induces mitochondrial oxidative damage as a key mechanism of neurotoxicity, while EVOO phenolics mitigate this toxicity. Full article

(This article belongs to the Special Issue Strategies for Mitigating Mycotoxin Contamination in Food and Feed)

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18 pages, 4079 KB

Open AccessArticle

Biopesticidal Properties of the Probiotic Brevibacillus laterosporus Strain B.O.D.

by M. Florencia Gil, Alessia Vinci, Manuela Casada and Luca Ruiu

Toxins 2026, 18(6), 251; https://doi.org/10.3390/toxins18060251 - 31 May 2026

Abstract

Brevibacillus laterosporus strain B.O.D. is a well-established commercial probiotic and antimicrobial microorganism that finds use in human health and in agriculture as a biofertilizer. On the other hand, while B. laterosporus is a well-known entomopathogenic species, the possible insecticidal potential of strain B.O.D. [...] Read more.

Brevibacillus laterosporus strain B.O.D. is a well-established commercial probiotic and antimicrobial microorganism that finds use in human health and in agriculture as a biofertilizer. On the other hand, while B. laterosporus is a well-known entomopathogenic species, the possible insecticidal potential of strain B.O.D. remains unexplored. To address this knowledge gap, this study combined genome sequencing and comparative analysis with other B. laterospours strains and insect bioassays. The genome of B. laterosporus B.O.D. was found to harbor a wide range of genes related to entomopathogenicity encoding putative proteases, chitinases, collagenase-like proteases, mosquitocidal proteins, bacillolysin, and spore-surface proteins. Antimicrobial compounds such as gramicidin and surfactin were also found. Sequence alignment with other well-characterized B. laterosporus strains and analysis revealed significant differences, which support the corresponding differences in insecticidal activity observed when comparing strain B.O.D. with others against a variety of lepidopteran and dipteran pest species. This study reports for the first time the genome of strain B.O.D., providing a comparative analysis and highlighting its insecticidal properties, which appear more moderate compared to previously characterized entomopathogenic strains of the same species. Everything considered, B. laterosporus strain B.O.D. appears to be remarkably versatile, underscoring wide biotechnological potential. Full article

(This article belongs to the Section Bacterial Toxins)

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18 pages, 1716 KB

Open AccessArticle

Burden of Mortality and Morbidity Caused by Snakebites Contributes to Economic Loss in a Rural Population in India

by Swapnil Kiran, Siripuram Srinivas and Karthikeyan Vasudevan

Toxins 2026, 18(6), 250; https://doi.org/10.3390/toxins18060250 - 29 May 2026

Abstract

Snakebite envenoming is a major public health concern in India that causes economic hardship for the rural populations. We estimated the per capita economic burden of snakebites in a rural population by quantifying mortality and morbidity rates. We interviewed for outcomes of snake [...] Read more.

Snakebite envenoming is a major public health concern in India that causes economic hardship for the rural populations. We estimated the per capita economic burden of snakebites in a rural population by quantifying mortality and morbidity rates. We interviewed for outcomes of snake envenomation of 541 participants from 205 villages in Jagtial, Telangana, from 2010 to 2020 using a community-based snowball sampling approach. Snakebites caused 24.21% morbidity and 12.75% mortality. The age-adjusted mortality rate and age-adjusted morbidity rate were 11.72 and 22.8 per 100,000 people, respectively. The overall annual burden of snakebites was 31.96 Disability-Adjusted Life Years (DALYs) per 100,000 people. The mean annual earning opportunity cost and the mean annual mortality cost were USD 321.27 and USD 24,016.54 per person, respectively. We highlight the need for targeted public health interventions such as monetary compensation and community support schemes to reduce the morbidity and mortality rates in rural areas. Full article

(This article belongs to the Section Animal Venoms)

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21 pages, 4489 KB

Open AccessArticle

Analgesic and Neurorestorative Effects of αO-Conotoxin GeXIVA[1,2] in Diabetic Neuropathic Pain and Postherpetic Neuralgia

by Rongyan He, Shuting Xiao, Xiaoying Liang, Qiuyu Cao, Shaoxian Wu and Sulan Luo

Toxins 2026, 18(6), 249; https://doi.org/10.3390/toxins18060249 - 29 May 2026

Abstract

Chronic neuropathic pain, particularly diabetic neuropathic pain and postherpetic neuralgia, severely impairs patients’ quality of life due to their complex mechanisms and recurrent, long-term nature, making treatment challenging. This study aimed to evaluate the analgesic efficacy of α-conotoxin GeXIVA[1,2], a selective antagonist of [...] Read more.

Chronic neuropathic pain, particularly diabetic neuropathic pain and postherpetic neuralgia, severely impairs patients’ quality of life due to their complex mechanisms and recurrent, long-term nature, making treatment challenging. This study aimed to evaluate the analgesic efficacy of α-conotoxin GeXIVA[1,2], a selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR), in rat models of diabetic neuropathic pain and postherpetic neuralgia and investigate its associated physiological and pathological effects. GeXIVA[1,2] was administered continuously for three weeks, with mechanical hypersensitivity assessed through pain sensitivity tests, and behavioral assessments conducted to examine motor coordination and gait. Additionally, neural tissue structure and inflammation were analyzed. The results demonstrated that GeXIVA[1,2] significantly alleviated mechanical hypersensitivity in both diabetic neuropathic pain and postherpetic neuralgia models, with greater efficacy than gabapentin and no signs of tolerance. Behavioral tests indicated no significant effects on motor coordination or gait. Further analysis revealed that GeXIVA[1,2] reduced pro-inflammatory cytokine levels, decreased immune cell infiltration, and promoted repair of damaged nerve fibers. Overall, these findings suggest that GeXIVA[1,2] exerts analgesic effects through anti-inflammatory and neuroprotective mechanisms, providing a potential new therapeutic strategy for diabetic neuropathic pain and postherpetic neuralgia. Full article

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

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17 pages, 2552 KB

Open AccessReview

Botulinumtoxin Type-A (BoNTA) in the Management of Refractory Trigeminal Neuralgia: An Expert-Opinion, Practice-Oriented Narrative Review on Behalf of the GRASP Study Group

by Andreas A. Argyriou, Emmanouil V. Dermitzakis, Dimitrios Rikos, Georgia Xiromerisiou, Panagiotis Soldatos, Maria Chondrogianni, Eleni Mavraki and Michail Vikelis

Toxins 2026, 18(6), 248; https://doi.org/10.3390/toxins18060248 - 29 May 2026

Abstract

Trigeminal neuralgia (TN) ranks among the most excruciating neuropathic pain syndromes, characterized clinically by multiple daily episodes of unilateral, paroxysmal, electric shock-like facial pain. The daily activities and quality of life of affected patients are profoundly diminished. First-line pharmacological agents, such as carbamazepine [...] Read more.

Trigeminal neuralgia (TN) ranks among the most excruciating neuropathic pain syndromes, characterized clinically by multiple daily episodes of unilateral, paroxysmal, electric shock-like facial pain. The daily activities and quality of life of affected patients are profoundly diminished. First-line pharmacological agents, such as carbamazepine and oxcarbazepine, provide initial relief for many patients. However, a significant proportion eventually develops refractory symptoms or experience intolerable adverse effects, leading to the discontinuation of traditional oral medications. For these patients with complex clinical phenotypes who fail to respond or are intolerant to these therapies, alternative pharmacological strategies are required before considering invasive surgical procedures. Over the past two decades, botulinumtoxin type-A (BoNTA) has become an effective and safe, minimally invasive therapeutic option for refractory TN. This review provides a practical framework for BoNTA use in the clinical setting of refractory TN. To connect the pathophysiological background with clinical patient care, we summarize the current understanding of TN pathophysiology, the proposed mechanisms by which BoNTA exerts its antinociceptive effects and the evolving clinical evidence supporting its efficacy and safety. We also critically examine dosing protocols, injection techniques, long-term outcomes and the integration of BoNTA into the management algorithm of refractory TN. Full article

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

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14 pages, 13099 KB

Open AccessArticle

Identification and Analysis of the Mpp5Ab1-Interacting Protein in the Midgut of the Colaphellus bowringi Baly

by Yaning Huang, Qiao Li, Jiaqi Wang, Yulei Wang, Daolong Liao, Xiaodong Sun and Haitao Li

Toxins 2026, 18(6), 247; https://doi.org/10.3390/toxins18060247 - 29 May 2026

Abstract

To elucidate the mode of action of Mpp5Ab1 against Colaphellus bowringi Baly larvae, this study aimed to identify midgut proteins interacting with the toxin. A validated bait plasmid, pBT3-SUC-mpp5Ab1, was used to screen a larval midgut cDNA library via the split-ubiquitin yeast two-hybrid [...] Read more.

To elucidate the mode of action of Mpp5Ab1 against Colaphellus bowringi Baly larvae, this study aimed to identify midgut proteins interacting with the toxin. A validated bait plasmid, pBT3-SUC-mpp5Ab1, was used to screen a larval midgut cDNA library via the split-ubiquitin yeast two-hybrid system. A total of 33 positive clones representing five distinct proteins were obtained, among which bioinformatic analyses prioritized three candidates: Cb-RP-L23e, Cb-CTSL, and Cb-TsetseEP. Subsequent bimolecular fluorescence complementation (BiFC) assays in Sf9 cells specifically confirmed interactions between Mpp5Ab1 and both Cb-CTSL and Cb-TsetseEP, whereas no fluorescence signal was observed for Cb-RP-L23e. Molecular docking further supported stable interactions between Mpp5Ab1 and the validated candidate proteins through hydrogen bonds, salt bridges, and hydrophobic interactions. These findings suggest that Cb-CTSL and Cb-TsetseEP may function as candidate interacting proteins associated with the activity of Mpp5Ab1 in the larval midgut of C. bowringi. Overall, this study provides new insight into the molecular interactions of Mpp5Ab1 and establishes a foundation for future functional studies on its insecticidal mechanism and receptor validation. Full article

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11 pages, 266 KB

Open AccessArticle

Serum Acrolein and Peripheral Arterial Stiffness in Non-Dialysis Chronic Kidney Disease: A Cross-Sectional Study

by Ho-Hsiang Chang, Yu-Li Lin, Chi-Chong Tang, Chiu-Huang Kuo, Chih-Hsien Wang and Bang-Gee Hsu

Toxins 2026, 18(6), 246; https://doi.org/10.3390/toxins18060246 - 29 May 2026

Abstract

Background: Arterial stiffness is a major predictor of cardiovascular-related mortality in chronic kidney disease (CKD). While acrolein—an endogenous reactive aldehyde that accumulates with declining renal function—may be linked to vascular injury, its association with high peripheral arterial stiffness (HPAS) remains unclear. Methods: This [...] Read more.

Background: Arterial stiffness is a major predictor of cardiovascular-related mortality in chronic kidney disease (CKD). While acrolein—an endogenous reactive aldehyde that accumulates with declining renal function—may be linked to vascular injury, its association with high peripheral arterial stiffness (HPAS) remains unclear. Methods: This cross-sectional study used the cardio-ankle vascular index (CAVI) to examine the association between serum acrolein levels and HPAS (CAVI ≥ 9.0) in 204 adults with non-dialysis CKD stages 3–5. Results: HPAS was identified in 90 patients (44.1%) and was associated with a higher prevalence of diabetes (p = 0.047), older age (p = 0.023), higher spot urine protein–creatinine ratio (UPCR, p = 0.046), higher serum fasting glucose (p = 0.041), higher interleukin-6 (p = 0.025), and higher acrolein (p = 0.008). In multivariable logistic regression analysis, serum acrolein (odds ratio, 1.015; 95% confidence interval, 1.002–1.028; p = 0.025), age (p = 0.010), and UPCR (p = 0.046) remained independently associated with HPAS. Log-transformed acrolein was positively correlated with bilateral CAVI (all p < 0.001) and log-transformed UPCR (p < 0.001) but negatively correlated with the estimated glomerular filtration rate (p = 0.001). Conclusions: Elevated serum acrolein is independently associated with HPAS in non-dialysis CKD stages 3–5. Full article

(This article belongs to the Special Issue Uremic Toxins and Chronic Kidney Disease)

17 pages, 2110 KB

Open AccessArticle

Intradermal and Subcutaneous Botulinum Toxin Type A Injections Do Not Differ in the Induction of Neutralizing Antibody Formation

by Stefanie Honndorf, Jessica Moser and Klaus Fink

Toxins 2026, 18(6), 245; https://doi.org/10.3390/toxins18060245 - 27 May 2026

Abstract

The neurotoxin botulinum toxin type A (BoNT/A), produced by the bacteria Clostridium botulinum, is commonly injected intramuscularly (IM) for the management of chronic muscle hyperactivity, such as post-stroke spasticity. New indications such as peripheral neuropathic pain require alternative routes of BoNT/A administration, [...] Read more.

The neurotoxin botulinum toxin type A (BoNT/A), produced by the bacteria Clostridium botulinum, is commonly injected intramuscularly (IM) for the management of chronic muscle hyperactivity, such as post-stroke spasticity. New indications such as peripheral neuropathic pain require alternative routes of BoNT/A administration, such as subcutaneous (SC) or intradermal (ID). While IM BoNT/A injections may elicit anti-drug-antibodies (ADAs), their occurrence following SC or ID administration is unknown. Therefore, we investigated whether repeated SC or ID injections of 150 kDa BoNT/A can elicit ADAs in a dose-dependent manner, and whether these differ depending upon the route of administration. Mice were injected 5 times ID or SC with 150 kDa BoNT/A or, for higher doses, inactive mutant BoNT/A (DRBoNT/A) or inactivated toxoid (IA-BoNT/A). Total ADAs were analyzed by an immunoassay and the subgroup of neutralizing ADAs by an in vivo digit abduction score (DAS) assay following a challenge of 0.6 U BoNT/A IM. DRBoNT/A and IA-BoNT/A injections elicit ADAs (22.7 U/mL vs. 460.5 U/mL for ID; 4.7 U/mL vs. 339.4 U/mL for SC), while therapeutic doses of 150 kDa BoNT/A do not. Whereas mice with repeated 150 kDa BoNT/A injections at therapeutic dose show an unrestricted DAS of 3.7 (ID) or 3.4 (SC), mice injected repeatedly with 1.8 µg/kg DRBoNT/A or 500 µg/kg IA-BoNT/A show only a minimal DAS of ≤0.7, indicating a high titer of neutralizing ADAs. No differences were observed between administration routes. Accordingly, repeated ID or SC injections of pure 150 kDa BoNT/A at therapeutic doses fail to induce ADA formation in mice. On the other hand, DRBoNT/A ID injections induce higher ADA concentrations than SC, but generate similar amounts of neutralizing ADAs. IA-BoNT/A injections induce ADAs and neutralizing ADAs similarly after ID and SC injections. ADA development at intermediate BoNT/A doses can be higher after ID injection, but does not lead to differences in neutralizing ADAs. Our data demonstrate that the antibody response to botulinum toxin depends predominantly on the protein load, and less on the administration route. Full article

(This article belongs to the Special Issue The Neutralization Mechanism and Immunological Studies of Botulinum Neurotoxin)

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28 pages, 4961 KB

Open AccessReview

Mechanisms of Aflatoxin Detoxification: Adsorption and Inhibition Strategies

by Yilin Tang, Lu Ding, Shujuan Sun, Mengmeng Mi, Minqi Shao, Yan Zhao, Mingxia Zhu, Yun Wang, Muhammad Zahoor Khan, Changfa Wang and Mengmeng Li

Toxins 2026, 18(6), 244; https://doi.org/10.3390/toxins18060244 - 25 May 2026

Abstract

Aflatoxins (AFs), toxic secondary metabolites produced by Aspergillus species, represent a major threat to food safety and public health due to their pronounced hepatotoxic, carcinogenic, and mutagenic effects. With increasing global contamination risks driven by climate change and agricultural practices, the development of [...] Read more.

Aflatoxins (AFs), toxic secondary metabolites produced by Aspergillus species, represent a major threat to food safety and public health due to their pronounced hepatotoxic, carcinogenic, and mutagenic effects. With increasing global contamination risks driven by climate change and agricultural practices, the development of effective detoxification strategies has become a critical priority. This review provides a comprehensive and mechanistic overview of current aflatoxin (AF) decontamination approaches, focusing on two principal pathways: adsorption and inhibition strategies. Adsorption mechanisms involve the physicochemical sequestration of aflatoxins by inorganic materials, biological adsorbents, and engineered nanocomposites, thereby reducing toxin bioavailability. In contrast, inhibition strategies target fungal growth, toxin biosynthesis pathways, or promote enzymatic and microbial degradation of aflatoxins, offering more specific and potentially sustainable control. We critically analyze the underlying mechanisms, advantages, and limitations of each approach, including issues related to specificity, environmental stability, safety, and interactions with food matrices. Particular emphasis is placed on the toxicological implications of detoxification processes, including the reduction in aflatoxin-induced health risks and the safety of degradation products. Finally, this review highlights the importance of integrating adsorption and inhibition strategies to achieve synergistic decontamination and detoxification effects. Future perspectives on multifunctional materials, biological control systems, and intelligent monitoring technologies are discussed to advance the development of efficient, safe, and sustainable aflatoxin mitigation strategies. Full article

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

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8 pages, 3098 KB

Open AccessCase Report

Pattern Changes and Recurrent Remissions in Cervical Dystonia: Insights from a Long-Term Treated Case

by Simone Aloisio, Massimiliano Passaretti, Luca Angelini, Martina De Riggi, Francesca Santachiara, Anna Sofia Grandolfo, Daniele Birreci and Matteo Bologna

Toxins 2026, 18(6), 243; https://doi.org/10.3390/toxins18060243 - 25 May 2026

Abstract

Cervical dystonia (CD) is increasingly recognized as a disorder with a dynamic clinical course rather than a fixed phenomenological profile. This report describes the long-term observation of a man with isolated CD followed for nearly 12 years from symptom onset. The course was [...] Read more.

Cervical dystonia (CD) is increasingly recognized as a disorder with a dynamic clinical course rather than a fixed phenomenological profile. This report describes the long-term observation of a man with isolated CD followed for nearly 12 years from symptom onset. The course was characterized by multiple pattern changes, including a clear shift from left- to right-sided torticollis in 2019, followed by alternating and mixed dystonic patterns. Three remission phases were documented during follow-up: two prolonged periods in 2017–2018 and 2020–2021, and a further phase from March to November 2022. Over time, treatment requirements decreased from higher initial doses (500–700 U abobotulinumtoxinA and up to 130 U onabotulinumtoxinA) to lower maintenance doses of 30–50 U incobotulinumtoxinA/onabotulinumtoxinA, with longer injection intervals and no obvious documented need for dose adjustment to maintain clinical responsiveness. This case highlights the coexistence of pattern changes and recurrent remissions within a single continuously followed patient over an unusually long period. Although a treatment-related mechanism remains speculative and alternative explanations cannot be excluded, the observation underscores the value of prolonged follow-up and individualized treatment strategies in CD. Full article

(This article belongs to the Section Bacterial Toxins)

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36 pages, 2651 KB

Open AccessReview

Sex-Dependent Determinants of Uremic Toxicity in Chronic Kidney Disease

by Oriana Nobus, Aurélie Carlier, Silvia M. Mihăilă and Vanessa Dubois

Toxins 2026, 18(6), 242; https://doi.org/10.3390/toxins18060242 - 25 May 2026

Abstract

Chronic kidney disease (CKD) is characterized by the progressive accumulation of uremic toxins (UTs), which contribute to systemic complications, increased cardiovascular risk, and disease progression. Epidemiological and experimental evidence demonstrate pronounced sex differences in CKD progression and outcomes, yet the mechanisms underlying sex-specific [...] Read more.

Chronic kidney disease (CKD) is characterized by the progressive accumulation of uremic toxins (UTs), which contribute to systemic complications, increased cardiovascular risk, and disease progression. Epidemiological and experimental evidence demonstrate pronounced sex differences in CKD progression and outcomes, yet the mechanisms underlying sex-specific uremic toxicity remain unclear. This review synthesizes current knowledge on sex differences in the origin, metabolism, transport, and biological effects of UTs, with a focus on sex-dependent regulatory mechanisms along the gut–liver–kidney axis. Sex hormones influence key determinants of toxin handling, including gut microbiota composition, hepatic enzyme activity, plasma protein binding, membrane transporter expression, and intracellular signaling pathways. Together, these factors regulate systemic toxin exposure and tissue susceptibility to injury. CKD also disrupts endocrine homeostasis, creating bidirectional interactions between hormonal regulation and toxin accumulation. Experimental and limited clinical evidence suggest that sex may influence circulating toxin profiles and susceptibility to toxin-associated complications. Collectively, sex is an important modulator of uremic toxicity, with sex hormones mediating at least part of the sex differences. A sex-informed framework may improve fundamental understanding through mechanistic studies and future clinical research may help clarify its relevance for biomarker development and support the development of personalized therapeutic strategies for 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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72 pages, 7729 KB

Open AccessReview

A New Frontier in Food Safety: Cold Plasma Strategies for Effective Control of Fungi and Mycotoxins

by Eva María Mateo, Fernando Mateo, Andrea Tarazona, María Ángeles García-Esparza, José Miguel Soria and Misericordia Jiménez

Toxins 2026, 18(6), 241; https://doi.org/10.3390/toxins18060241 - 23 May 2026

Abstract

Mycotoxins are compounds produced by the secondary metabolism of certain fungi. These compounds contaminate foods worldwide and pose a severe threat to the health of humans and animals. They also cause huge economic losses. A plethora of methodologies, encompassing agricultural, biological, chemical, and [...] Read more.

Mycotoxins are compounds produced by the secondary metabolism of certain fungi. These compounds contaminate foods worldwide and pose a severe threat to the health of humans and animals. They also cause huge economic losses. A plethora of methodologies, encompassing agricultural, biological, chemical, and physical approaches, have been devised to curtail the presence of mycotoxins in food commodities. Among the physical processes, cold plasma (CP) has emerged as a useful technique for controlling the presence of toxigenic fungi in foods and for degrading the mycotoxins occurring in them without significantly affecting the quality and organoleptic properties of the treated commodities. The present review endeavors to demonstrate the efficacy of CP as a method of eradicating or reducing both the toxigenic mycobiota and the mycotoxins present in the most contaminated foods, including nuts, dried fruits, and cereal grains. The mechanisms of toxin degradation proposed by the different researchers are also examined and compared. Furthermore, the impact of the CP effect on the quality, sensorial characteristics, and toxicological properties of the treated food is thoroughly examined. Full article

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

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19 pages, 11651 KB

Open AccessArticle

Antimicrobial Activity of Micrurus Venoms and Bioactive Films Functionalized with Purified L-Amino Acid Oxidase

by Vitelbina Núñez Rangel, Paola Rey-Suárez, Daniel Buitrago-Chinchilla, Laura Reyes-Méndez, Leidy Gómez-Sampedro, Alejandro Carmona-Jiménez, Mateo Rivillas-Ochoa and Adriana Muñoz-Bravo

Toxins 2026, 18(6), 240; https://doi.org/10.3390/toxins18060240 - 22 May 2026

Abstract

Phytopathogenic bacteria and fungi significantly reduce fruit and vegetable yields, resulting in substantial economic losses. Conventional management relies on synthetic agrochemicals; however, their intensive use poses risks to human health, environmental integrity, and biodiversity. Snake venoms have evolved under selective pressure, developing specialized [...] Read more.

Phytopathogenic bacteria and fungi significantly reduce fruit and vegetable yields, resulting in substantial economic losses. Conventional management relies on synthetic agrochemicals; however, their intensive use poses risks to human health, environmental integrity, and biodiversity. Snake venoms have evolved under selective pressure, developing specialized components with potent antimicrobial properties as part of a defense mechanism against prey-borne microorganisms. This study evaluated the inhibitory potential of Micrurus venoms against pathogens of agricultural interest and developed bioactive gelatin-based films incorporated with purified L-amino acid oxidases (LAAOs) as a novel biocontrol strategy. Venoms from M. ancoralis, M. mipartitus, and M. dumerilii exhibited significant growth inhibition against Xanthomonas and Fusarium strains. The primary active component was identified as LAAO through biological activity and mass spectrometry. Biofilms were formulated by incorporating M. ancoralis venom and its purified LAAO into a gelatin matrix. Physicochemical and microbiological characterization, alongside in situ assays on strawberries, demonstrated that the functionalized biofilms retained potent antimicrobial activity. Furthermore, LAAO incorporation did not significantly alter the physicochemical properties of the fruit but effectively extended shelf life by reducing weight loss and maintaining sensory appearance. These findings highlight the biotechnological potential of elapid venom components in the development of alternatives for phytopathogen control and active food packaging. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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