Journal Description
Toxins
Toxins
is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to toxinology and all kinds of toxins (biotoxins) from animals, microbes and plants. Toxins is published monthly online by MDPI. The French Society on Toxinology (SFET), International Society for Mycotoxicology (ISM), Japanese Society of Mycotoxicology (JSMYCO) and European Uremic Toxins (EUTox) Work Group are affiliated with Toxins and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, CAPlus / SciFinder, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q1 (Toxicology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.4 days after submission; acceptance to publication is undertaken in 3.2 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 6 topical sections.
Impact Factor:
4.2 (2022);
5-Year Impact Factor:
4.7 (2022)
Latest Articles
Advances in the Early Warning of Shellfish Toxification by Dinophysis acuminata
Toxins 2024, 16(5), 204; https://doi.org/10.3390/toxins16050204 - 24 Apr 2024
Abstract
In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species of the dinoflagellate genus Dinophysis. Using a time series from 2014 to 2020, our study aimed
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In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species of the dinoflagellate genus Dinophysis. Using a time series from 2014 to 2020, our study aimed (i) to determine the concentration of D. acuminata in water at which shellfish toxin levels could surpass the regulatory limit (160 µg OA equiv kg−1) and (ii) to assess the predictability of toxic events for timely mitigation actions, especially concerning potential harvesting bans. The analysis considered factors such as (i) overdispersion in the data, (ii) distinct periods of presence and absence, (iii) the persistence of cells, and (iv) the temporal lag between cells in the water and toxins in shellfish. Four generalized additive models were tested, with the Tweedie (TW-GAM) model showing superior performance (>85%) and lower complexity. The results suggest existing thresholds currently employed (200 and 500 cells L−1) are well-suited for the Portuguese coast, supported by empirical evidence (54–79% accuracy). The developed algorithm allows for thresholds to be tailored on a case-by-case basis, offering flexibility for regional variations.
Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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Open AccessReview
Beyond Pain: The Effects of OnabotulinumtoxinA Therapy on Sensitization and Interictal Symptoms in Chronic Migraine
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Paolo Alonge, Filippo Brighina, Simona Maccora, Laura Pilati, Salvatore Di Marco, Davide Ventimiglia, Bruna Maggio, Ivana Cutrò, Cecilia Camarda and Angelo Torrente
Toxins 2024, 16(5), 203; https://doi.org/10.3390/toxins16050203 - 23 Apr 2024
Abstract
Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of
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Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms.
Full article
(This article belongs to the Special Issue Botulinum Toxin and Migraine: Goals and Perspectives (Volume II))
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Open AccessReview
Some Examples of Bacterial Toxins as Tools
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Gudula Schmidt
Toxins 2024, 16(5), 202; https://doi.org/10.3390/toxins16050202 - 23 Apr 2024
Abstract
Pathogenic bacteria produce diverse protein toxins to disturb the host’s defenses. This includes the opening of epithelial barriers to establish bacterial growth in deeper tissues of the host and to modulate immune cell functions. To achieve this, many toxins share the ability to
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Pathogenic bacteria produce diverse protein toxins to disturb the host’s defenses. This includes the opening of epithelial barriers to establish bacterial growth in deeper tissues of the host and to modulate immune cell functions. To achieve this, many toxins share the ability to enter mammalian cells, where they catalyze the modification of cellular proteins. The enzymatic activity is diverse and ranges from ribosyl- or glycosyl-transferase activity, the deamidation of proteins, and adenylate-cyclase activity to proteolytic cleavage. Protein toxins are highly active enzymes often with tight specificity for an intracellular protein or a protein family coupled with the intrinsic capability of entering mammalian cells. A broad understanding of their molecular mechanisms established bacterial toxins as powerful tools for cell biology. Both the enzymatic part and the pore-forming/protein transport capacity are currently used as tools engineered to study signaling pathways or to transport cargo like labeled compounds, nucleic acids, peptides, or proteins directly into the cytosol. Using several representative examples, this review is intended to provide a short overview of the state of the art in the use of bacterial toxins or parts thereof as tools.
Full article
(This article belongs to the Special Issue Biotoxins: Innovative Research Tools to Treat Neuropathologies and Investigate Neurophysiology—In Memory of Professor Matteo Caleo)
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Isolation and Functional Characterization of Erythrofibrase: An Alfa-Fibrinogenase Enzyme from Trimeresurus erythrurus Venom of North-East India
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Susmita Thakur, Rafika Yasmin, Anita Malhotra, Hmar Tlawmte Lalremsanga, Vishal Santra, Surajit Giri and Robin Doley
Toxins 2024, 16(4), 201; https://doi.org/10.3390/toxins16040201 - 22 Apr 2024
Abstract
Green pit viper bites induce mild toxicity with painful local swelling, blistering, cellulitis, necrosis, ecchymosis and consumptive coagulopathy. Several bite cases of green pit vipers have been reported in several south-east Asian countries including the north-eastern region of India. The present study describes
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Green pit viper bites induce mild toxicity with painful local swelling, blistering, cellulitis, necrosis, ecchymosis and consumptive coagulopathy. Several bite cases of green pit vipers have been reported in several south-east Asian countries including the north-eastern region of India. The present study describes isolation and characterization of a haemostatically active protein from Trimeresurus erythrurus venom responsible for coagulopathy. Using a two-step chromatographic method, a snake venom serine protease erythrofibrase was purified to homogeneity. SDS-PAGE of erythrofibrase showed a single band of ~30 kDa in both reducing and non-reducing conditions. The primary structure of erythrofibrase was determined by ESI LC-MS/MS, and the partial sequence obtained showed 77% sequence similarity with other snake venom thrombin-like enzymes (SVTLEs). The partial sequence obtained had the typical 12 conserved cysteine residues, as well as the active site residues (His57, Asp102 and Ser195). Functionally, erythrofibrase showed direct fibrinogenolytic activity by degrading the Aα chain of bovine fibrinogen at a slow rate, which might be responsible for causing hypofibrinogenemia and incoagulable blood for several days in envenomated patients. Moreover, the inability of Indian polyvalent antivenom (manufactured by Premium Serum Pvt. Ltd., Maharashtra, India) to neutralize the thrombin-like and plasmin-like activity of erythrofibrase can be correlated with the clinical inefficacy of antivenom therapy. This is the first study reporting an α-fibrinogenase enzyme erythrofibrase from T. erythrurus venom, which is crucial for the pathophysiological manifestations observed in envenomated victims.
Full article
(This article belongs to the Special Issue Venom Components Acting on the Hemostatic System: Structural and Mechanistic Insights)
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Open AccessArticle
The Potential of Chitosan-Based Composites for Adsorption of Diarrheic Shellfish Toxins
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Joana F. Leal, Patrícia S. M. Amado, João P. Lourenço and Maria L. S. Cristiano
Toxins 2024, 16(4), 200; https://doi.org/10.3390/toxins16040200 - 21 Apr 2024
Abstract
Okadaic acid (OA) is one of the most potent marine biotoxins, causing diarrheal shellfish poisoning (DSP). The proliferation of microalgae that produce OA and its analogues is frequent, threatening human health and socioeconomic development. Several methods have been tested to remove this biotoxin
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Okadaic acid (OA) is one of the most potent marine biotoxins, causing diarrheal shellfish poisoning (DSP). The proliferation of microalgae that produce OA and its analogues is frequent, threatening human health and socioeconomic development. Several methods have been tested to remove this biotoxin from aquatic systems, yet none has proven enough efficacy to solve the problem. In this work, we synthesized and characterized low-cost composites and tested their efficacy for OA adsorption in saltwater. For the synthesis of the composites, the following starting materials were considered: chitosan of low and medium molecular weight (CH-LW and CH-MW, respectively), activated carbon (AC), and montmorillonite (MMT). Characterization by vibrational spectroscopy (FTIR), X-ray diffraction (XRD), and microscopy revealed differences in the mode of interaction of CH-LW and CH-MW with AC and MMT, suggesting that the interaction of CH-MW with MMT has mainly occurred on the surface of the clay particles and no sufficient intercalation of CH-MW into the MMT interlayers took place. Among the composites tested (CH-LW/AC, CH-MW/AC, CH-MW/AC/MMT, and CH-MW/MMT), CH-MW/MMT was the one that revealed lower OA adsorption efficiency, given the findings evidenced by the structural characterization. On the contrary, the CH-MW/AC composite revealed the highest average percentage of OA adsorption (53 ± 11%). Although preliminary, the results obtained in this work open up good perspectives for the use of this type of composite material as an adsorbent in the removal of OA from marine environments.
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(This article belongs to the Section Marine and Freshwater Toxins)
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Open AccessArticle
First Synthesis of Ergotamine-13CD3 and Ergotaminine-13CD3 from Unlabeled Ergotamine
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Sven-Oliver Herter, Hajo Haase and Matthias Koch
Toxins 2024, 16(4), 199; https://doi.org/10.3390/toxins16040199 - 20 Apr 2024
Abstract
Ergot alkaloids (EAs) formed by Claviceps fungi are one of the most common food contaminants worldwide, affecting cereals such as rye, wheat, and barley. To accurately determine the level of contamination and to monitor EAs maximum levels set by the European Union, the
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Ergot alkaloids (EAs) formed by Claviceps fungi are one of the most common food contaminants worldwide, affecting cereals such as rye, wheat, and barley. To accurately determine the level of contamination and to monitor EAs maximum levels set by the European Union, the six most common EAs (so-called priority EAs) and their corresponding epimers are quantified using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The quantification of EAs in complex food matrices without appropriate internal standards is challenging but currently carried out in the standard method EN 17425:2021 due to their commercial unavailability. To address the need for isotopically labeled EAs, we focus on two semi-synthetic approaches for the synthesis of these reference standards. Therefore, we investigate the feasibility of the N6-demethylation of native ergotamine to yield norergotamine, which can subsequently be remethylated with an isotopically labeled methylating reagent, such as iodomethane (13CD3-I), to yield isotopically labeled ergotamine and its C8-epimer ergotaminine. Testing the isotopically labeled ergotamine/-inine against native ergotamine/-inine with HPLC coupled to high-resolution HR-MS/MS proved the structure of ergotamine-13CD3 and ergotaminine-13CD3. Thus, for the first time, we can describe their synthesis from unlabeled, native ergotamine. Furthermore, this approach is promising as a universal way to synthesize other isotopically labeled EAs.
Full article
(This article belongs to the Special Issue Detection, Control and Contamination of Mycotoxins (Volume II))
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Analytical Methods for Anatoxin-a Determination: A Review
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Cristina Plata-Calzado, Ana I. Prieto, Ana M. Cameán and Angeles Jos
Toxins 2024, 16(4), 198; https://doi.org/10.3390/toxins16040198 - 19 Apr 2024
Abstract
Anatoxin-a (ATX-a) is a potent neurotoxin produced by several species of cyanobacteria whose exposure can have direct consequences, including neurological disorders and death. The increasing prevalence of harmful cyanobacterial blooms makes the detection and reliable assessment of ATX-a levels essential to prevent the
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Anatoxin-a (ATX-a) is a potent neurotoxin produced by several species of cyanobacteria whose exposure can have direct consequences, including neurological disorders and death. The increasing prevalence of harmful cyanobacterial blooms makes the detection and reliable assessment of ATX-a levels essential to prevent the risk associated with public health. Therefore, the aim of this review is to compile the analytical methods developed to date for the detection and quantification of ATX-a levels alone and in mixtures with other cyanotoxins and their suitability. A classification of the analytical methods available is fundamental to make an appropriate choice according to the type of sample, the equipment available, and the required sensitivity and specificity for each specific purpose. The most widely used detection technique for the quantification of this toxin is liquid chromatography–tandem mass spectrometry (LC-MS/MS). The analytical methods reviewed herein focus mainly on water and cyanobacterial samples, so the need for validated analytical methods in more complex matrices (vegetables and fish) for the determination of ATX-a to assess dietary exposure to this toxin is evidenced. There is currently a trend towards the validation of multitoxin methods as opposed to single-ATX-a determination methods, which corresponds to the real situation of cyanotoxins’ confluence in nature.
Full article
(This article belongs to the Special Issue Toxic Cyano Blooms around the World and Related Molecules)
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Effectiveness of Extracorporeal Shock Wave Therapy after Botulinum Toxin Injection for Post-Stroke Upper Extremity Spasticity: A Randomized Controlled Study
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Junhee Lee and Seung Nam Yang
Toxins 2024, 16(4), 197; https://doi.org/10.3390/toxins16040197 - 19 Apr 2024
Abstract
Post-stroke spasticity is a common complication that limits the functional performance of patients. Botulinum toxin (BTx) is an effective treatment for spasticity. Numerous researchers have applied extracorporeal shock wave therapy (ESWT) to address post-stroke spasticity, yielding positive clinical outcomes. We aimed to clarify
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Post-stroke spasticity is a common complication that limits the functional performance of patients. Botulinum toxin (BTx) is an effective treatment for spasticity. Numerous researchers have applied extracorporeal shock wave therapy (ESWT) to address post-stroke spasticity, yielding positive clinical outcomes. We aimed to clarify the add-on effects of ESWT on BTx therapy for spasticity in patients with post-stroke. Sixteen eligible patients with upper extremity spasticity after stroke were recruited for this study. They were randomized to either a BTx with focused ESWT treatment group or a BTx alone group. Spasticity, measured using the modified Ashworth score (MAS) and modified Tardieu scale (MTS), showed statistically significant improvements in the elbow and wrist flexor muscles in both BTx + ESWT group and BTx alone groups. However, no significant differences were observed between the two groups with time flow. The BTx + ESWT group showed significantly decreased MAS of the finger flexors at follow-up and increased R1 (MTS) of the finger flexors at 3 weeks after treatment, which was not observed in the BTx alone group. This is the first study to identify the add-on effect of ESWT on BTx injections to improve post-stroke upper limb spasticity.
Full article
(This article belongs to the Special Issue Application of Botulinum Toxins in Diseases Treatment)
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Microcystin Contamination in Irrigation Water and Health Risk
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Mohammed Haida, Fatima El Khalloufi, Richard Mugani, Yasser Essadki, Alexandre Campos, Vitor Vasconcelos and Brahim Oudra
Toxins 2024, 16(4), 196; https://doi.org/10.3390/toxins16040196 - 19 Apr 2024
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Microcystins (MCs), natural hepatotoxic compounds produced by cyanobacteria, pose significant risks to water quality, ecosystem stability, and the well-being of animals, plants, and humans when present in elevated concentrations. The escalating contamination of irrigation water with MCs presents a growing threat to terrestrial
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Microcystins (MCs), natural hepatotoxic compounds produced by cyanobacteria, pose significant risks to water quality, ecosystem stability, and the well-being of animals, plants, and humans when present in elevated concentrations. The escalating contamination of irrigation water with MCs presents a growing threat to terrestrial plants. The customary practice of irrigating crops from local water sources, including lakes and ponds hosting cyanobacterial blooms, serves as a primary conduit for transferring these toxins. Due to their high chemical stability and low molecular weight, MCs have the potential to accumulate in various parts of plants, thereby increasing health hazards for consumers of agricultural products, which serve as the foundation of the Earth’s food chain. MCs can bioaccumulate, migrate, potentially biodegrade, and pose health hazards to humans within terrestrial food systems. This study highlights that MCs from irrigation water reservoirs can bioaccumulate and come into contact with plants, transferring into the food chain. Additionally, it investigates the natural mechanisms that organisms employ for conjugation and the microbial processes involved in MC degradation. To gain a comprehensive understanding of the role of MCs in the terrestrial food chain and to elucidate the specific health risks associated with consuming crops irrigated with water contaminated with these toxins, further research is necessary.
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Open AccessArticle
Overexpressing the cpr1953 Orphan Histidine Kinase Gene in the Absence of cpr1954 Orphan Histidine Kinase Gene Expression, or Vice Versa, Is Sufficient to Obtain Significant Sporulation and Strong Production of Clostridium perfringens Enterotoxin or Spo0A by Clostridium perfringens Type F Strain SM101
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Iman Mehdizadeh Gohari, Jessica L. Gonzales, Francisco A. Uzal and Bruce A. McClane
Toxins 2024, 16(4), 195; https://doi.org/10.3390/toxins16040195 - 18 Apr 2024
Abstract
The CPR1953 and CPR1954 orphan histidine kinases profoundly affect sporulation initiation and Clostridium perfringens enterotoxin (CPE) production by C. perfringens type F strain SM101, whether cultured in vitro (modified Duncan–Strong sporulation medium (MDS)) or ex vivo (mouse small intestinal contents (MIC)). To help
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The CPR1953 and CPR1954 orphan histidine kinases profoundly affect sporulation initiation and Clostridium perfringens enterotoxin (CPE) production by C. perfringens type F strain SM101, whether cultured in vitro (modified Duncan–Strong sporulation medium (MDS)) or ex vivo (mouse small intestinal contents (MIC)). To help distinguish whether CPR1953 and CPR1954 act independently or in a stepwise manner to initiate sporulation and CPE production, cpr1953 and cpr1954 null mutants of SM101 were transformed with plasmids carrying the cpr1954 or cpr1953 genes, respectively, causing overexpression of cpr1954 in the absence of cpr1953 expression and vice versa. RT-PCR confirmed that, compared to SM101, the cpr1953 mutant transformed with a plasmid encoding cpr1954 expressed cpr1954 at higher levels while the cpr1954 mutant transformed with a plasmid encoding cpr1953 expressed higher levels of cpr1953. Both overexpressing strains showed near wild-type levels of sporulation, CPE toxin production, and Spo0A production in MDS or MIC. These findings suggest that CPR1953 and CPR1954 do not function together in a step-wise manner, e.g., as a novel phosphorelay. Instead, it appears that, at natural expression levels, the independent kinase activities of both CPR1953 and CPR1954 are necessary for obtaining sufficient Spo0A production and phosphorylation to initiate sporulation and CPE production.
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(This article belongs to the Special Issue Toxins: 15th Anniversary)
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Open AccessArticle
Sortase-Modified Cholera Toxoids Show Specific Golgi Localization
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Darren C. Machin, Daniel J. Williamson, Peter Fisher, Victoria J. Miller, Zoe L. P. Arnott, Charlotte M. E. Stevenson, Gemma C. Wildsmith, James F. Ross, Christopher W. Wasson, Andrew Macdonald, Benjamin I. Andrews, Daniel Ungar, W. Bruce Turnbull and Michael E. Webb
Toxins 2024, 16(4), 194; https://doi.org/10.3390/toxins16040194 - 16 Apr 2024
Abstract
Cholera toxoid is an established tool for use in cellular tracing in neuroscience and cell biology. We use a sortase labeling approach to generate site-specific N-terminally modified variants of both the A2-B5 heterohexamer and B5 pentamer forms of the toxoid. Both
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Cholera toxoid is an established tool for use in cellular tracing in neuroscience and cell biology. We use a sortase labeling approach to generate site-specific N-terminally modified variants of both the A2-B5 heterohexamer and B5 pentamer forms of the toxoid. Both forms of the toxoid are endocytosed by GM1-positive mammalian cells, and while the heterohexameric toxoid was principally localized in the ER, the B5 pentamer showed an unexpectedly specific localization in the medial/trans-Golgi. This study suggests a future role for specifically labeled cholera toxoids in live-cell imaging beyond their current applications in neuronal tracing and labeling of lipid rafts in fixed cells.
Full article
(This article belongs to the Special Issue Cholera Toxin)
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Open AccessArticle
Toxicity of Cry- and Vip3Aa-Class Proteins and Their Interactions against Spodoptera frugiperda (Lepidoptera: Noctuidae)
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Xiaobei Liu, Shen Liu, Shuxiong Bai, Kanglai He, Yongjun Zhang, Hui Dong, Tiantao Zhang and Zhenying Wang
Toxins 2024, 16(4), 193; https://doi.org/10.3390/toxins16040193 - 16 Apr 2024
Abstract
The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is one of the most important insect pests affecting corn crops worldwide. Although planting transgenic corn expressing Bacillus thuringiensis (Bt) toxins has been approved as being effective against FAW, its populations’ resistance to Bt crops
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The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is one of the most important insect pests affecting corn crops worldwide. Although planting transgenic corn expressing Bacillus thuringiensis (Bt) toxins has been approved as being effective against FAW, its populations’ resistance to Bt crops has emerged in different locations around the world. Therefore, it is important to understand the interaction between different Bt proteins, thereby delaying the development of resistance. In this study, we performed diet-overlay bioassays to evaluate the toxicity of Cry1Ab, Cry1Ac, Cry1B, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, Vip3Aa11, Vip3Aa19, and Vip3Aa20, as well as the interaction between Cry1Ab-, Cry1F-, Cry2Ab-, and Vip3Aa-class proteins against FAW. According to our results, the LC50 values of Bt proteins varied from 12.62 ng/cm2 to >9000 ng/cm2 (protein/diet), among which the Vip3Aa class had the best insecticidal effect. The combination of Cry1Ab and Vip3Aa11 exhibited additive effects at a 5:1 ratio. Cry1F and Vip3Aa11 combinations exhibited additive effects at 1:1, 1:2, and 5:1 ratios. The combination of Cry1F and Vip3Aa19 showed an antagonistic effect when the ratio was 1:1 and an additive effect when the ratio was 1:2, 2:1, 1:5, and 5:1. Additionally, the combinations of Cry1F and Vip3Aa20 showed antagonistic effects at 1:2 and 5:1 ratios and additive effects at 1:1 and 2:1 ratios. In addition to the above combinations, which had additive or antagonistic effects, other combinations exhibited synergistic effects, with variations in synergistic factors (SFs). These results can be applied to the establishment of new pyramided transgenic crops with suitable candidates, providing a basis for FAW control and resistance management strategies.
Full article
Open AccessReview
Antifungal Activity of Ribosome-Inactivating Proteins
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Rosario Iglesias, Lucía Citores, Claudia C. Gay and José M. Ferreras
Toxins 2024, 16(4), 192; https://doi.org/10.3390/toxins16040192 - 15 Apr 2024
Abstract
The control of crop diseases caused by fungi remains a major problem and there is a need to find effective fungicides that are environmentally friendly. Plants are an excellent source for this purpose because they have developed defense mechanisms to cope with fungal
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The control of crop diseases caused by fungi remains a major problem and there is a need to find effective fungicides that are environmentally friendly. Plants are an excellent source for this purpose because they have developed defense mechanisms to cope with fungal infections. Among the plant proteins that play a role in defense are ribosome-inactivating proteins (RIPs), enzymes obtained mainly from angiosperms that, in addition to inactivating ribosomes, have been studied as antiviral, fungicidal, and insecticidal proteins. In this review, we summarize and discuss the potential use of RIPs (and other proteins with similar activity) as antifungal agents, with special emphasis on RIP/fungus specificity, possible mechanisms of antifungal action, and the use of RIP genes to obtain fungus-resistant transgenic plants. It also highlights the fact that these proteins also have antiviral and insecticidal activity, which makes them very versatile tools for crop protection.
Full article
(This article belongs to the Special Issue Biological Activities of Ribosome Inactivating Proteins II)
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Open AccessSystematic Review
Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape
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Ilya Demchenko, Alyssa Swiderski, Helen Liu, Hyejung Jung, Wendy Lou and Venkat Bhat
Toxins 2024, 16(4), 191; https://doi.org/10.3390/toxins16040191 - 15 Apr 2024
Abstract
Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders
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Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.
Full article
(This article belongs to the Special Issue Uses of Botulinum Toxin Injection in Medicine)
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Open AccessReview
Cyanobacteria and Macroinvertebrate Relationships in Freshwater Benthic Communities beyond Cytotoxicity
by
Nicolás Ubero-Pascal and Marina Aboal
Toxins 2024, 16(4), 190; https://doi.org/10.3390/toxins16040190 - 15 Apr 2024
Abstract
Cyanobacteria are harmful algae that are monitored worldwide to prevent the effects of the toxins that they can produce. Most research efforts have focused on direct or indirect effects on human populations, with a view to gain easy accurate detection and quantification methods,
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Cyanobacteria are harmful algae that are monitored worldwide to prevent the effects of the toxins that they can produce. Most research efforts have focused on direct or indirect effects on human populations, with a view to gain easy accurate detection and quantification methods, mainly in planktic communities, but with increasing interest shown in benthos. However, cyanobacteria have played a fundamental role from the very beginning in both the development of our planet’s biodiversity and the construction of new habitats. These organisms have colonized almost every possible planktic or benthic environment on earth, including the most extreme ones, and display a vast number of adaptations. All this explains why they are the most important or the only phototrophs in some habitats. The negative effects of cyanotoxins on macroinvertebrates have been demonstrated, but usually under conditions that are far from natural, and on forms of exposure, toxin concentration, or composition. The cohabitation of cyanobacteria with most invertebrate groups is long-standing and has probably contributed to the development of detoxification means, which would explain the survival of some species inside cyanobacteria colonies. This review focuses on benthic cyanobacteria, their capacity to produce several types of toxins, and their relationships with benthic macroinvertebrates beyond toxicity.
Full article
(This article belongs to the Special Issue Editorial Board Members' Collection Series: Contribution of Information Technologies in Marine and Freshwater Toxins Research and Regulatory Practice)
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Open AccessCommunication
First Detection of Algal Caribbean Ciguatoxin in Amberjack Causing Ciguatera Poisoning in the Canary Islands (Spain)
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Pablo Estevez, Juan Oses-Prieto, David Castro, Alejandro Penin, Alma Burlingame and Ana Gago-Martinez
Toxins 2024, 16(4), 189; https://doi.org/10.3390/toxins16040189 - 13 Apr 2024
Abstract
Ciguatera Poisoning (CP) is an illness associated with the consumption of fish contaminated with potent natural toxins found in the marine environment, commonly known as ciguatoxins (CTXs). The risk characterization of CP has become a worldwide concern due to the widespread expansion of
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Ciguatera Poisoning (CP) is an illness associated with the consumption of fish contaminated with potent natural toxins found in the marine environment, commonly known as ciguatoxins (CTXs). The risk characterization of CP has become a worldwide concern due to the widespread expansion of these natural toxins. The identification of CTXs is hindered by the lack of commercially available reference materials. This limitation impedes progress in developing analytical tools and conducting toxicological studies essential for establishing regulatory levels for control. This study focuses on characterizing the CTX profile of an amberjack responsible for a recent CP case in the Canary Islands (Spain), located on the east Atlantic coast. The exceptional sensitivity offered by Capillary Liquid Chromatography coupled with High-Resolution Mass Spectrometry (cLC-HRMS) enabled the detection, for the first time in fish contaminated in the Canary Islands, of traces of an algal ciguatoxin recently identified in G. silvae and G. caribeaus from the Caribbean Sea. This algal toxin was structurally characterized by cLC-HRMS being initially identified as C-CTX5. The total toxin concentration of CTXs was eight times higher than the guidance level proposed by the Food and Drug Administration (0.1 ng C-CTX1/g fish tissue), with C-CTX1 and 17-hydroxy-C-CTX1 as major CTXs.
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(This article belongs to the Special Issue Advances in Marine Toxins: Characterization, Analysis and Surveillance)
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Effect of Seaweed-Derived Fucoidans from Undaria pinnatifida and Fucus vesiculosus on Coagulant, Proteolytic, and Phospholipase A2 Activities of Snake Bothrops jararaca, B. jararacussu, and B. neuwiedi Venom
by
Camila Castro-Pinheiro, Luiz Carlos Simas Pereira Junior, Eladio Flores Sanchez, Ana Cláudia Rodrigues da Silva, Corinna A. Dwan, Samuel S. Karpiniec, Alan Trevor Critchley and Andre Lopes Fuly
Toxins 2024, 16(4), 188; https://doi.org/10.3390/toxins16040188 - 12 Apr 2024
Abstract
Background: Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to block local tissue damage, leading to an increase in the severity of envenomation; thus, seeking alternative treatments is crucial. Methods:
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Background: Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to block local tissue damage, leading to an increase in the severity of envenomation; thus, seeking alternative treatments is crucial. Methods: This study analyzed the potential of two fucoidan sulfated polysaccharides extracted from brown seaweeds Fucus vesiculosus (FVF) and Undaria pinnatifida (UPF) against the fibrinogen or plasma coagulation, proteolytic, and phospholipase A2 (PLA2) activities of Bothrops jararaca, B. jararacussu, and B. neuwiedi venom. The toxicity of FVF and UPF was assessed by the hemocompatibility test. Results: FVF and UPF did not lyse human red blood cells. FVF and UPF inhibited the proteolytic activity of Bothrops jararaca, B. jararacussu, and B. neuwiedi venom by approximately 25%, 50%, and 75%, respectively, while all venoms led to a 20% inhibition of PLA2 activity. UPF and FVF delayed plasma coagulation caused by the venoms of B. jararaca and B. neuwiedi but did not affect the activity of B. jararacussu venom. FVF and UPF blocked the coagulation of fibrinogen induced by all these Bothropic venoms. Conclusion: FVF and UPF may be of importance as adjuvants for SBE caused by species of Bothrops, which are the most medically relevant snakebite incidents in South America, especially Brazil.
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(This article belongs to the Special Issue Snake Venom: Toxicology and Associated Countermeasures)
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Molecular Aspects Involved in the Mechanisms of Bothrops jararaca Venom-Induced Hyperalgesia: Participation of NK1 Receptor and Glial Cells
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Ariela de Oliveira Pedro Bom, Monique Dias-Soares, Raíssa Cristina Darroz Corrêa, Camila Lima Neves, Natalia Gabriele Hosch, Gabriela Gomes de Lucena, Camilla Garcia Oliveira, Rosana Lima Pagano, Marucia Chacur and Renata Giorgi
Toxins 2024, 16(4), 187; https://doi.org/10.3390/toxins16040187 - 10 Apr 2024
Abstract
Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and
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Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and central nervous systems in this phenomenon remain unclear. To clarify this, we induced hyperalgesia in rats using Bjv and collected tissues from dorsal root ganglia (DRGs) and spinal cord (SC) at 2 and 4 h post-induction. Samples were labeled for Iba-1 (macrophage and microglia), GFAP (satellite cells and astrocytes), EGR1 (neurons), and NK1 receptors. Additionally, we investigated the impact of minocycline, an inhibitor of microglia, and GR82334 antagonist on Bjv-induced hyperalgesia. Our findings reveal an increase in Iba1 in DRG at 2 h and EGR1 at 4 h. In the SC, markers for microglia, astrocytes, neurons, and NK1 receptors exhibited increased expression after 2 h, with EGR1 continuing to rise at 4 h. Minocycline and GR82334 inhibited venom-induced hyperalgesia, highlighting the crucial roles of microglia and NK1 receptors in this phenomenon. Our results suggest that the hyperalgesic effects of Bjv involve the participation of microglial and astrocytic cells, in addition to the activation of NK1 receptors.
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(This article belongs to the Section Animal Venoms)
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Tetrodotoxins in Tissues and Cells of Different Body Regions of Ribbon Worms Kulikovia alborostrata and K. manchenkoi from Spokoynaya Bay, Sea of Japan
by
Anna E. Vlasenko, Alexandra O. Pereverzeva, Peter V. Velansky and Timur Yu. Magarlamov
Toxins 2024, 16(4), 186; https://doi.org/10.3390/toxins16040186 - 10 Apr 2024
Abstract
Nemerteans, or ribbon worms, possess tetrodotoxin and its analogues (TTXs), neurotoxins of bacterial origin, which they presumably use for capturing prey and self-defense. Most TTXs-containing nemertean species have low levels of these toxins and, therefore, have usually been neglected in studies of TTXs
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Nemerteans, or ribbon worms, possess tetrodotoxin and its analogues (TTXs), neurotoxins of bacterial origin, which they presumably use for capturing prey and self-defense. Most TTXs-containing nemertean species have low levels of these toxins and, therefore, have usually been neglected in studies of TTXs functions and accumulation. In the present study, Kulikovia alborostrata and K. manchenkoi, two closely related species, were analyzed for TTXs distribution in the body using the HPLC–MS/MS and fluorescence microscopy methods. The abundance of TTXs-positive cells was determined in the proboscis, integument, and digestive system epithelium. As a result, six TTXs-positive cell types were identified in each species; however, only four were common. Moreover, the proportions of the toxins in different body parts were estimated. According to the HPLC–MS/MS analysis, the TTXs concentrations in K. alborostrata varied from 0.91 ng/g in the proboscis to 5.52 ng/g in the precerebral region; in K. manchenkoi, the concentrations ranged from 7.47 ng/g in the proboscis to 72.32 ng/g in the posterior body region. The differences observed between the two nemerteans in the distribution of the TTXs were consistent with the differences in the localization of TTXs-positive cells. In addition, TTXs-positive glandular cell types were found in the intestine and characterized for the first time. TTXs in the new cell types were assumed to play a unique physiological role for nemerteans.
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(This article belongs to the Special Issue Advances in Marine Toxins: Characterization, Analysis and Surveillance)
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Edodin: A New Type of Toxin from Shiitake Mushroom (Lentinula edodes) That Inactivates Mammalian Ribosomes
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Lucía Citores, Sara Ragucci, Claudia C. Gay, Rosita Russo, Angela Chambery, Antimo Di Maro, Rosario Iglesias and José M. Ferreras
Toxins 2024, 16(4), 185; https://doi.org/10.3390/toxins16040185 - 10 Apr 2024
Abstract
Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that irreversibly inhibit protein synthesis and consequently cause cell death. Recently, an RIP called ledodin has been found in shiitake; it is cytotoxic, strongly inhibits protein synthesis, and shows rRNA N-glycosylase
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Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that irreversibly inhibit protein synthesis and consequently cause cell death. Recently, an RIP called ledodin has been found in shiitake; it is cytotoxic, strongly inhibits protein synthesis, and shows rRNA N-glycosylase activity. In this work, we isolated and characterized a 50 kDa cytotoxic protein from shiitake that we named edodin. Edodin inhibits protein synthesis in a mammalian cell-free system, but not in insect-, yeast-, and bacteria-derived systems. It exhibits rRNA N-glycosylase and DNA-nicking activities, which relate it to plant RIPs. It was also shown to be toxic to HeLa and COLO 320 cells. Its structure is not related to other RIPs found in plants, bacteria, or fungi, but, instead, it presents the characteristic structure of the fold type I of pyridoxal phosphate-dependent enzymes. Homologous sequences have been found in other fungi of the class Agaricomycetes; thus, edodin could be a new type of toxin present in many fungi, some of them edible, which makes them of great interest in health, both for their involvement in food safety and for their potential biomedical and biotechnological applications.
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(This article belongs to the Special Issue Biological Activities of Ribosome Inactivating Proteins II)
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