Toxins

18 pages, 4204 KiB

Open AccessArticle

An Assassin’s Secret: Multifunctional Cytotoxic Compounds in the Predation Venom of the Assassin Bug Psytalla horrida (Reduviidae, Hemiptera)

by Maike Laura Fischer, Benjamin Fabian, Yannick Pauchet, Natalie Wielsch, Silke Sachse, Andreas Vilcinskas and Heiko Vogel

Toxins 2023, 15(4), 302; https://doi.org/10.3390/toxins15040302 - 20 Apr 2023

Cited by 2 | Viewed by 3141

Abstract

Predatory assassin bugs produce venomous saliva that enables them to overwhelm, kill, and pre-digest large prey animals. Venom from the posterior main gland (PMG) of the African assassin bug Psytalla horrida has strong cytotoxic effects, but the responsible compounds are yet unknown. Using [...] Read more.

Predatory assassin bugs produce venomous saliva that enables them to overwhelm, kill, and pre-digest large prey animals. Venom from the posterior main gland (PMG) of the African assassin bug Psytalla horrida has strong cytotoxic effects, but the responsible compounds are yet unknown. Using cation-exchange chromatography, we fractionated PMG extracts from P. horrida and screened the fractions for toxicity. Two venom fractions strongly affected insect cell viability, bacterial growth, erythrocyte integrity, and intracellular calcium levels in Drosophila melanogaster olfactory sensory neurons. LC-MS/MS analysis revealed that both fractions contained gelsolin, redulysins, S1 family peptidases, and proteins from the uncharacterized venom protein family 2. Synthetic peptides representing the putative lytic domain of redulysins had strong antimicrobial activity against Escherichia coli and/or Bacillus subtilis but only weak toxicity towards insect or mammalian cells, indicating a primary role in preventing the intake of microbial pathogens. In contrast, a recombinant venom protein family 2 protein significantly reduced insect cell viability but exhibited no antibacterial or hemolytic activity, suggesting that it plays a role in prey overwhelming and killing. The results of our study show that P. horrida secretes multiple cytotoxic compounds targeting different organisms to facilitate predation and antimicrobial defense. Full article

(This article belongs to the Special Issue Animal Toxins: Biodiscovery, Mechanistic Insights and Translational Potential)

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15 pages, 3169 KiB

Open AccessEditor’s ChoiceArticle

Immunomodulatory Effects of Cylindrospermopsin in Human T Cells and Monocytes

by Antonio Casas-Rodríguez, Óscar Cebadero-Dominguez, María Puerto, Ana María Cameán and Angeles Jos

Toxins 2023, 15(4), 301; https://doi.org/10.3390/toxins15040301 - 20 Apr 2023

Cited by 3 | Viewed by 2076

Abstract

Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. [...] Read more.

Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system. Full article

(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)

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13 pages, 1976 KiB

Open AccessArticle

Pyroptosis-Mediated Damage Mechanism by Deoxynivalenol in Porcine Small Intestinal Epithelial Cells

by Tae Hong Kang, Sangsu Shin, JeongWoong Park, Bo Ram Lee and Sang In Lee

Toxins 2023, 15(4), 300; https://doi.org/10.3390/toxins15040300 - 19 Apr 2023

Cited by 5 | Viewed by 2285

Abstract

Deoxynivalenol (DON) is known as a vomitoxin, which frequently contaminates feedstuffs, such as corn, wheat, and barley. Intake of DON-contaminated feed has been known to cause undesirable effects, including diarrhea, emesis, reduced feed intake, nutrient malabsorption, weight loss, and delay in growth, in [...] Read more.

Deoxynivalenol (DON) is known as a vomitoxin, which frequently contaminates feedstuffs, such as corn, wheat, and barley. Intake of DON-contaminated feed has been known to cause undesirable effects, including diarrhea, emesis, reduced feed intake, nutrient malabsorption, weight loss, and delay in growth, in livestock. However, the molecular mechanism of DON-induced damage of the intestinal epithelium requires further investigation. Treatment with DON triggered ROS in IPEC-J2 cells and increased the mRNA and protein expression levels of thioredoxin interacting protein (TXNIP). To investigate the activation of the inflammasome, we confirmed the mRNA and protein expression levels of the NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 (CASP-1). Moreover, we confirmed that caspase mediates the mature form of interleukin-18, and the cleaved form of Gasdermin D (GSDMD) was increased. Based on these results, our study suggests that DON can induce damage through oxidative stress and pyroptosis in the epithelial cells of the porcine small intestine via NLRP3 inflammasome. Full article

(This article belongs to the Special Issue Advanced Research on Mycotoxins: Detection and Removal)

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53 pages, 8232 KiB

Open AccessArticle

Natural Antioxidant By-Product Mixture Counteracts the Effects of Aflatoxin B1 and Ochratoxin A Exposure of Piglets after Weaning: A Proteomic Survey on Liver Microsomal Fraction

by Roua Gabriela Popescu, George Cătălin Marinescu, Andreea Luminița Rădulescu, Daniela Eliza Marin, Ionelia Țăranu and Anca Dinischiotu

Toxins 2023, 15(4), 299; https://doi.org/10.3390/toxins15040299 - 19 Apr 2023

Cited by 2 | Viewed by 2780

Abstract

Mycotoxins are toxic compounds produced by certain strains of fungi that can contaminate raw feed materials. Once ingested, even in small doses, they cause multiple health issues for animals and, downstream, for people consuming meat. It was proposed that inclusion of antioxidant-rich plant-derived [...] Read more.

Mycotoxins are toxic compounds produced by certain strains of fungi that can contaminate raw feed materials. Once ingested, even in small doses, they cause multiple health issues for animals and, downstream, for people consuming meat. It was proposed that inclusion of antioxidant-rich plant-derived feed might diminish the harmful effects of mycotoxins, maintaining the farm animals’ health and meat quality for human consumption. This work investigates the large scale proteomic effects on piglets’ liver of aflatoxin B1 and ochratoxin A mycotoxins and the potential compensatory effects of grapeseed and sea buckthorn meal administration as dietary byproduct antioxidants against mycotoxins’ damage. Forty cross-bred TOPIGS-40 hybrid piglets after weaning were assigned to three (n = 10) experimental groups (A, M, AM) and one control group (C) and fed with experimental diets for 30 days. After 4 weeks, liver samples were collected, and the microsomal fraction was isolated. Unbiased label-free, library-free, data-independent acquisition (DIA) mass spectrometry SWATH methods were able to relatively quantify 1878 proteins from piglets’ liver microsomes, confirming previously reported effects on metabolism of xenobiotics by cytochrome P450, TCA cycle, glutathione synthesis and use, and oxidative phosphorylation. Pathways enrichment revealed that fatty acid metabolism, steroid biosynthesis, regulation of actin cytoskeleton, regulation of gene expression by spliceosomes, membrane trafficking, peroxisome, thermogenesis, retinol, pyruvate, and amino acids metabolism pathways are also affected by the mycotoxins. Antioxidants restored expression level of proteins PRDX3, AGL, PYGL, fatty acids biosynthesis, endoplasmic reticulum, peroxisome, amino acid synthesis pathways, and, partially, OXPHOS mitochondrial subunits. However, excess of antioxidants might cause significant changes in CYP2C301, PPP4R4, COL18A1, UBASH3A, and other proteins expression levels. Future analysis of proteomics data corelated to animals growing performance and meat quality studies are necessary. Full article

(This article belongs to the Special Issue Mycotoxins in Feed, Food, Nutraceuticals, and Functional Food)

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15 pages, 2470 KiB

Open AccessArticle

Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner

by Dorsaf Bouzazi, Wael Mami, Amor Mosbah, Naziha Marrakchi, Melika Ben Ahmed and Erij Messadi

Toxins 2023, 15(4), 298; https://doi.org/10.3390/toxins15040298 - 19 Apr 2023

Cited by 3 | Viewed by 2607

Abstract

Snake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigated [...] Read more.

Snake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigated the effect of L2 on macrophage polarization in lipopolysaccharide (LPS)-activated RAW264.7 cells in vitro and explored the associated underlying mechanisms. TNF-α, IL-6 and IL-10 levels were assessed using an ELISA assay, and M2 macrophage polarization was determined by flow cytometry. L2 was used at non-cytotoxic concentrations determined by a preliminary MTT cell viability assay, and compared to B-type natriuretic peptide (BNP). In LPS-activated cells, both peptides reduced TNF-α and IL-6 release compared to controls. However, only L2 increased IL-10 release in a sustained manner and promoted downstream M2 macrophage polarization. Pretreatment of LPS-activated RAW264.7 cells with the selective NP receptor (NPR) antagonist isatin abolished both IL-10 and M2-like macrophage potentiation provided by L2. In addition, cell pretreatment with the IL-10 inhibitor suppressed L2-induced M2 macrophage polarization. We conclude that L2 exerts an anti-inflammatory response to LPS by regulating the release of inflammatory cytokines via stimulating of NP receptors and promoting M2 macrophage polarization through activation of IL-10 signaling. Full article

(This article belongs to the Special Issue Potential Therapeutic Applications of Animal Venoms and Toxins)

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14 pages, 2739 KiB

Open AccessArticle

Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells

by Tipaporn Kumkoon, Chalongrat Noree and Panadda Boonserm

Toxins 2023, 15(4), 297; https://doi.org/10.3390/toxins15040297 - 18 Apr 2023

Viewed by 2597

Abstract

Breast cancer is one of the most common cancers in women worldwide. Conventional cancer chemotherapy always has adverse side effects on the patient’s healthy tissues. Consequently, combining pore-forming toxins with cell-targeting peptides (CTPs) is a promising anticancer strategy for selectively destroying cancer cells. [...] Read more.

Breast cancer is one of the most common cancers in women worldwide. Conventional cancer chemotherapy always has adverse side effects on the patient’s healthy tissues. Consequently, combining pore-forming toxins with cell-targeting peptides (CTPs) is a promising anticancer strategy for selectively destroying cancer cells. Here, we aim to improve the target specificity of the BinB toxin produced from Lysinibacillus sphaericus (Ls) by fusing a luteinizing hormone-releasing hormone (LHRH) peptide to its pore-forming domain (BinB_C) to target MCF-7 breast cancer cells as opposed to human fibroblast cells (Hs68). The results showed that LHRH-BinB_C inhibited MCF-7 cell proliferation in a dose-dependent manner while leaving Hs68 cells unaffected. BinB_C, at any concentration tested, did not affect the proliferation of MCF-7 or Hs68 cells. In addition, the LHRH-BinB_C toxin caused the efflux of the cytoplasmic enzyme lactate dehydrogenase (LDH), demonstrating the efficacy of the LHRH peptide in directing the BinB_C toxin to damage the plasma membranes of MCF-7 cancer cells. LHRH-BinB_C also caused MCF-7 cell apoptosis by activating caspase-8. In addition, LHRH-BinB_C was predominantly observed on the cell surface of MCF-7 and Hs68 cells, without colocalization with mitochondria. Overall, our findings suggest that LHRH-BinB_C could be investigated further as a potential cancer therapeutic agent. Full article

(This article belongs to the Special Issue New Frontiers in Pore-Forming Toxins and Related Proteins: Molecular Mechanisms, Functions and Applications)

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14 pages, 1259 KiB

Open AccessArticle

Long-Term Muscular Atrophy and Weakness Following Cessation of Botulinum Toxin Type A Injections in the Flexor Digitorum Muscle of Musicians with Focal Hand Dystonia

by Christos I. Ioannou, Franziska L. Hodde-Chriske and Eckart Altenmüller

Toxins 2023, 15(4), 296; https://doi.org/10.3390/toxins15040296 - 18 Apr 2023

Cited by 4 | Viewed by 5040

Abstract

The present study assessed muscular atrophy and weakness of the flexor digitorum superficialis (FDS) and profundus (FDP) muscle as possible long-term side effects of botulinum toxin (BoNT) injections in hand dystonia patients after the termination of their treatment. For the assessment of both [...] Read more.

The present study assessed muscular atrophy and weakness of the flexor digitorum superficialis (FDS) and profundus (FDP) muscle as possible long-term side effects of botulinum toxin (BoNT) injections in hand dystonia patients after the termination of their treatment. For the assessment of both parameters, a group of 12 musicians diagnosed with focal hand dystonia was compared with a group of 12 healthy matched musicians. The minimum and maximum times since the last injection across patients were 0.5 to 3.5 years, respectively. The thickness and strength of the FDS and FDP were assessed via ultrasonography and a strength measurement device. Group differences were estimated through the calculation of the symmetry index between the dominant and non-dominant hand. The results revealed that compared to the control group, thickness and flexion strength of the injected FDS and FDP were decreased by 10.6% ± 5.3% (95% CI) and 12.5% ± 6.4% (95% CI), respectively, in the patient group. The amount of weakness and atrophy was predicted significantly by the total amount of BoNT injected throughout the entire treatment period. In contrast, the time after the last injection did not predict the amount of strength and muscle mass recovery after the cessation of the treatment. The current study revealed that even up to 3.5 years after the termination of BoNT injections, long-term side effects such as weakness and atrophy can still be observed. We suggest that the total BoNT dose should remain as small as possible to reduce long-lasting side effects to the minimum. Although side effects differ significantly among patients, a potential full recovery of atrophy and weakness after the cessation of BoNT treatment might be observed after periods longer than 3.5 years. Full article

(This article belongs to the Special Issue Application of Botulinum Toxins in Non-spastic and Neurodegenerative Disorders)

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18 pages, 1292 KiB

Open AccessFeature PaperArticle

Biomonitoring of 19 Mycotoxins in Plasma from Food-Producing Animals (Cattle, Poultry, Pigs, and Sheep)

by Borja Muñoz-Solano and Elena González-Peñas

Toxins 2023, 15(4), 295; https://doi.org/10.3390/toxins15040295 - 18 Apr 2023

Cited by 2 | Viewed by 1807

Abstract

Mycotoxins are of great concern in relation to food safety. When animals are exposed to them, health problems, economic losses in farms and related industries, and the carryover of these compounds to animal-derived foods can occur. Therefore, control of animal exposure is of [...] Read more.

Mycotoxins are of great concern in relation to food safety. When animals are exposed to them, health problems, economic losses in farms and related industries, and the carryover of these compounds to animal-derived foods can occur. Therefore, control of animal exposure is of great importance. This control may be carried out by analyzing raw material and/or feed or through the analysis of biomarkers of exposure in biological matrixes. This second approach has been chosen in the present study. Firstly, a methodology capable of analyzing mycotoxins and some derivatives (AFB1, OTA, ZEA, DON, 3- and 15-ADON, DOM-1, T-2, HT-2, AFM1, STER, NEO, DAS, FUS-X, AFB2, AFG1, AFG2, OTB, and NIV) by LC-MS/MS in human plasma, has been revalidated to be applied in animal plasma. Secondly, this methodology was used in 80 plasma samples obtained from animals dedicated to food production: cattle, pigs, poultry, and sheep (20 samples of each), with and without being treated with a mixture of β-glucuronidase-arylsulfatase to determine possible glucuronide and sulfate conjugates. Without enzymatic treatment, no mycotoxin was detected in any of the samples. Only one sample from poultry presented levels of DON and 3- and 15-ADON. With enzymatic treatment, only DON (1 sample) and STER were detected. The prevalence of STER was 100% of the samples, without significant differences among the four species; however, the prevalence and levels of this mycotoxin in the previously analyzed feed were low. This could be explained by the contamination of the farm environment. Animal biomonitoring can be a useful tool to assess animal exposure to mycotoxins. However, for these studies to be carried out and to be useful, knowledge must be increased on appropriate biomarkers for each mycotoxin in different animal species. In addition, adequate and validated analytical methods are needed, as well as knowledge of the relationships between the levels found in biological matrices and mycotoxin intake and toxicity. Full article

(This article belongs to the Special Issue Biomonitoring Study of Mycotoxins)

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22 pages, 3174 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Application of an Extracellular Matrix-Mimicking Fluorescent Polymer for the Detection of Proteolytic Venom Toxins

by Eric Wachtel, Matyas A. Bittenbinder, Bas van de Velde, Julien Slagboom, Axel de Monts de Savasse, Luis L. Alonso, Nicholas R. Casewell, Freek J. Vonk and Jeroen Kool

Toxins 2023, 15(4), 294; https://doi.org/10.3390/toxins15040294 - 18 Apr 2023

Cited by 1 | Viewed by 2299

Abstract

The cytotoxicity caused by snake venoms is a serious medical problem that greatly contributes to the morbidity observed in snakebite patients. The cytotoxic components found in snake venoms belong to a variety of toxin classes and may cause cytotoxic effects by targeting a [...] Read more.

The cytotoxicity caused by snake venoms is a serious medical problem that greatly contributes to the morbidity observed in snakebite patients. The cytotoxic components found in snake venoms belong to a variety of toxin classes and may cause cytotoxic effects by targeting a range of molecular structures, including cellular membranes, the extracellular matrix (ECM) and the cytoskeleton. Here, we present a high-throughput assay (384-well plate) that monitors ECM degradation by snake venom toxins via the application of fluorescent versions of model ECM substrates, specifically gelatin and collagen type I. Both crude venoms and fractionated toxins of a selection of medically relevant viperid and elapid species, separated via size-exclusion chromatography, were studied using the self-quenching, fluorescently labelled ECM–polymer substrates. The viperid venoms showed significantly higher proteolytic degradation when compared to elapid venoms, although the venoms with higher snake venom metalloproteinase content did not necessarily exhibit stronger substrate degradation than those with a lower one. Gelatin was generally more readily cleaved than collagen type I. In the viperid venoms, which were subjected to fractionation by SEC, two (B. jararaca and C. rhodostoma, respectively) or three (E. ocellatus) active proteases were identified. Therefore, the assay allows the study of proteolytic activity towards the ECM in vitro for crude and fractionated venoms. Full article

(This article belongs to the Special Issue Animal Venoms: Proteomics, Biochemical Activities and Application)

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16 pages, 2212 KiB

Open AccessArticle

Microcystins Exposure Associated with Blood Lipid Profiles and Dyslipidemia: A Cross-Sectional Study in Hunan Province, China

by Shuidong Feng, Mengyue Cao, Peng Tang, Shuxiang Deng, Limou Chen, Yan Tang, Lemei Zhu, Xiang Chen, Zhijun Huang, Minxue Shen and Fei Yang

Toxins 2023, 15(4), 293; https://doi.org/10.3390/toxins15040293 - 18 Apr 2023

Cited by 1 | Viewed by 1992

Abstract

Increasing evidence from experimental research suggests that exposure to microcystins (MCs) may induce lipid metabolism disorder. However, population-based epidemiological studies of the association between MCs exposure and the risk of dyslipidemia are lacking. Therefore, we conducted a population-based cross-sectional study involving 720 participants [...] Read more.

Increasing evidence from experimental research suggests that exposure to microcystins (MCs) may induce lipid metabolism disorder. However, population-based epidemiological studies of the association between MCs exposure and the risk of dyslipidemia are lacking. Therefore, we conducted a population-based cross-sectional study involving 720 participants in Hunan Province, China, and evaluated the effects of MCs on blood lipids. After adjusting the lipid related metals, we used binary logistic regression and multiple linear regression models to examine the associations among serum MCs concentration, the risk of dyslipidemia and blood lipids (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)). Moreover, the additive model was used to explore the interaction effects on dyslipidemia between MCs and metals. Compared to the lowest quartile of MCs exposure, the risk of dyslipidemia [odds ratios (OR) = 2.27, 95% confidence interval (CI): 1.46, 3.53] and hyperTG (OR = 3.01, 95% CI: 1.79, 5.05) in the highest quartile was significantly increased, and showed dose–response relationships. MCs were positively associated with TG level (percent change, 9.43%; 95% CI: 3.53%, 15.67%) and negatively associated with HDL-C level (percent change, −3.53%; 95% CI: −5.70%, −2.10%). In addition, an additive antagonistic effect of MCs and Zn on dyslipidemia was also reported [relative excess risk due to interaction (RERI) = −1.81 (95% CI: −3.56, −0.05)], and the attributable proportion of the reduced risk of dyslipidemia due to the antagonism of these two exposures was 83% (95% CI: −1.66, −0.005). Our study first indicated that MCs exposure is an independent risk factor for dyslipidemia in a dose–response manner. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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18 pages, 7902 KiB

Open AccessArticle

SakA Regulates Morphological Development, Ochratoxin A Biosynthesis and Pathogenicity of Aspergillus westerdijkiae and the Response to Different Environmental Stresses

by Peidong Si, Gang Wang, Wenqing Wu, Sarfaraz Hussain, Ling Guo, Wei Wu, Qingli Yang and Fuguo Xing

Toxins 2023, 15(4), 292; https://doi.org/10.3390/toxins15040292 - 17 Apr 2023

Cited by 3 | Viewed by 1847

Abstract

Ochratoxin A (OTA), as a common mycotoxin, has seriously harmful effects on agricultural products, livestock and humans. There are reports on the regulation of SakA in the MAPK pathway, which regulates the production of mycotoxins. However, the role of SakA in the regulation [...] Read more.

Ochratoxin A (OTA), as a common mycotoxin, has seriously harmful effects on agricultural products, livestock and humans. There are reports on the regulation of SakA in the MAPK pathway, which regulates the production of mycotoxins. However, the role of SakA in the regulation of Aspergillus westerdijkiae and OTA production is not clear. In this study, a SakA deletion mutant (ΔAwSakA) was constructed. The effects of different concentrations of D-sorbitol, NaCl, Congo red and H₂O₂ on the mycelia growth, conidia production and biosynthesis of OTA were investigated in A. westerdijkiae WT and ΔAwSakA. The results showed that 100 g/L NaCl and 3.6 M D-sorbitol significantly inhibited mycelium growth and that a concentration of 0.1% Congo red was sufficient to inhibit the mycelium growth. A reduction in mycelium development was observed in ΔAwSakA, especially in high concentrations of osmotic stress. A lack of AwSakA dramatically reduced OTA production by downregulating the expression of the biosynthetic genes otaA, otaY, otaB and otaD. However, otaC and the transcription factor otaR1 were slightly upregulated by 80 g/L NaCl and 2.4 M D-sorbitol, whereas they were downregulated by 0.1% Congo red and 2 mM H₂O₂. Furthermore, ΔAwSakA showed degenerative infection ability toward pears and grapes. These results suggest that AwSakA is involved in the regulation of fungal growth, OTA biosynthesis and the pathogenicity of A. westerdijkiae and could be influenced by specific environmental stresses. Full article

(This article belongs to the Special Issue Advances in Rapid Detection and Reduction of Aflatoxins)

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17 pages, 1210 KiB

Open AccessArticle

Mycotoxins in Rice Correlate with Other Contaminants? A Pilot Study of the Portuguese Scenario and Human Risk Assessment

by Liliana J. G. Silva, André M. P. T. Pereira, Sofia Duarte, Inês Pedro, Catarina Perdigão, Alexandra Silva, Celeste M. Lino, Anabela Almeida and Angelina Pena

Toxins 2023, 15(4), 291; https://doi.org/10.3390/toxins15040291 - 17 Apr 2023

Cited by 4 | Viewed by 2281

Abstract

Rice is the second most important cereal crop and is vital for the diet of billions of people. However, its consumption can increase human exposure to chemical contaminants, namely mycotoxins and metalloids. Our goal was to evaluate the occurrence and human exposure of [...] Read more.

Rice is the second most important cereal crop and is vital for the diet of billions of people. However, its consumption can increase human exposure to chemical contaminants, namely mycotoxins and metalloids. Our goal was to evaluate the occurrence and human exposure of aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), and inorganic arsenic (InAs) in 36 rice samples produced and commercialized in Portugal and evaluate their correlation. The analysis of mycotoxins involved ELISA, with limits of detection (LODs) of 0.8, 1 and 1.75 μg kg⁻¹ for OTA, AFB1, and ZEN, respectively. InAs analysis was carried out by inductively coupled plasma mass spectrometry (ICP-MS; LOD = 3.3 μg kg⁻¹). No sample showed contamination by OTA. AFB1 was present in 2 (4.8%) samples (1.96 and 2.20 μg kg⁻¹), doubling the European maximum permitted level (MPL). Concerning ZEN, 88.89% of the rice samples presented levels above the LOD up to 14.25 µg kg⁻¹ (average of 2.75 µg kg⁻¹). Regarding InAs, every sample presented concentration values above the LOD up to 100.0 µg kg⁻¹ (average of 35.3 µg kg⁻¹), although none surpassed the MPL (200 µg kg⁻¹). No correlation was observed between mycotoxins and InAs contamination. As for human exposure, only AFB1 surpassed the provisional maximum tolerable daily intake. Children were recognized as the most susceptible group. Full article

(This article belongs to the Special Issue Mycotoxins: Risk Assessment, Biomonitoring and Toxicology)

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11 pages, 556 KiB

Open AccessArticle

The Effect of Experimental Protocol on the Toxicity of Saxitoxin in Mice

by Sarah C. Finch, Michael J. Boundy, Nicola G. Webb and D. Tim Harwood

Toxins 2023, 15(4), 290; https://doi.org/10.3390/toxins15040290 - 17 Apr 2023

Cited by 7 | Viewed by 2251

Abstract

Regulatory limits for toxins in shellfish are required to ensure the health of consumers. However, these limits also impact the profitability of shellfish industries making it critical that they are fit for purpose. Since human toxicity data is rarely available, the setting of [...] Read more.

Regulatory limits for toxins in shellfish are required to ensure the health of consumers. However, these limits also impact the profitability of shellfish industries making it critical that they are fit for purpose. Since human toxicity data is rarely available, the setting of regulatory limits is dependent on animal data which can then be extrapolated for use in the assessment of human risk. The dependence on animal data to keep humans safe means that it is critical that the toxicity data used is robust and of high quality. Worldwide, the protocols used in toxicity testing are varied, making it hard to compare results and adding confusion over which results better reflect the true toxicity. In this study, we look at the effect of mouse gender, i.p. dose volume, mouse body weight and feeding protocols (both acute and sub-acute) on the toxicity of saxitoxin. This allowed the effect of different variables used in toxicity testing to be understood and showed that the feeding protocol used in both acute and sub-acute studies greatly influenced the toxicity of saxitoxin in mice. Therefore, the adoption of a standard protocol for the testing of shellfish toxins is recommended. Full article

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

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24 pages, 1599 KiB

Open AccessReview

Cyanobacterial Harmful Algal Bloom Toxin Microcystin and Increased Vibrio Occurrence as Climate-Change-Induced Biological Co-Stressors: Exposure and Disease Outcomes via Their Interaction with Gut–Liver–Brain Axis

by Saurabh Chatterjee and Madhura More

Toxins 2023, 15(4), 289; https://doi.org/10.3390/toxins15040289 - 17 Apr 2023

Cited by 17 | Viewed by 5656

Abstract

The effects of global warming are not limited to rising global temperatures and have set in motion a complex chain of events contributing to climate change. A consequence of global warming and the resultant climate change is the rise in cyanobacterial harmful algal [...] Read more.

The effects of global warming are not limited to rising global temperatures and have set in motion a complex chain of events contributing to climate change. A consequence of global warming and the resultant climate change is the rise in cyanobacterial harmful algal blooms (cyano-HABs) across the world, which pose a threat to public health, aquatic biodiversity, and the livelihood of communities that depend on these water systems, such as farmers and fishers. An increase in cyano-HABs and their intensity is associated with an increase in the leakage of cyanotoxins. Microcystins (MCs) are hepatotoxins produced by some cyanobacterial species, and their organ toxicology has been extensively studied. Recent mouse studies suggest that MCs can induce gut resistome changes. Opportunistic pathogens such as Vibrios are abundantly found in the same habitat as phytoplankton, such as cyanobacteria. Further, MCs can complicate human disorders such as heat stress, cardiovascular diseases, type II diabetes, and non-alcoholic fatty liver disease. Firstly, this review describes how climate change mediates the rise in cyanobacterial harmful algal blooms in freshwater, causing increased levels of MCs. In the later sections, we aim to untangle the ways in which MCs can impact various public health concerns, either solely or in combination with other factors resulting from climate change. In conclusion, this review helps researchers understand the multiple challenges brought forth by a changing climate and the complex relationships between microcystin, Vibrios, and various environmental factors and their effect on human health and disease. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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12 pages, 308 KiB

Open AccessReview

Treating Neurogenic Lower Urinary Tract Dysfunction in Chronic Spinal Cord Injury Patients—When Intravesical Botox Injection or Urethral Botox Injection Are Indicated

by Po-Cheng Chen, Kau-Han Lee, Wei-Chia Lee, Ting-Chun Yeh, Yuh-Chen Kuo, Bing-Juin Chiang, Chun-Hou Liao, En Meng, Yao-Lin Kao, Yung-Chin Lee and Hann-Chorng Kuo

Toxins 2023, 15(4), 288; https://doi.org/10.3390/toxins15040288 - 17 Apr 2023

Cited by 4 | Viewed by 2129

Abstract

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further [...] Read more.

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient’s QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment. Full article

(This article belongs to the Special Issue Application of Botulinum Neurotoxin in Lower Urinary Tract Dysfunctions: Where Are We Now?)

13 pages, 2198 KiB

Open AccessArticle

The Influence of the Toxic Dinoflagellate Alexandrium minutum, Grown under Different N:P Ratios, on the Marine Copepod Acartia tonsa

by Epaminondas D. Christou, Ioanna Varkitzi, Isabel Maneiro, Soultana Zervoudaki and Kalliopi Pagou

Toxins 2023, 15(4), 287; https://doi.org/10.3390/toxins15040287 - 16 Apr 2023

Viewed by 2379

Abstract

HABs pose a threat to coastal ecosystems, the economic sector and human health, and are expanding globally. However, their influence on copepods, a major connector between primary producers and upper trophic levels, remains essentially unknown. Microalgal toxins can eventually control copepod survival and [...] Read more.

HABs pose a threat to coastal ecosystems, the economic sector and human health, and are expanding globally. However, their influence on copepods, a major connector between primary producers and upper trophic levels, remains essentially unknown. Microalgal toxins can eventually control copepod survival and reproduction by deterring grazing and hence reducing food availability. We present several 24-h experiments in which the globally distributed marine copepod, Acartia tonsa, was exposed to different concentrations of the toxic dinoflagellate, Alexandrium minutum, grown under three N:P ratios (4:1, 16:1 and 80:1), with the simultaneous presence of non-toxic food (the dinoflagellate Prorocentrum micans). The different N:P ratios did not affect the toxicity of A. minutum, probably due to the low toxicity of the tested strain. Production of eggs and pellets as well as ingested carbon appeared to be affected by food toxicity. Toxicity levels in A. minutum also had an effect on hatching success and on the toxin excreted in pellets. Overall, A. minutum toxicity affected the reproduction, toxin excretion and, to an extent, the feeding behavior of A. tonsa. This work indicates that even short-term exposure to toxic A. minutum can impact the vital functions of A. tonsa and might ultimately pose serious threats to copepod recruitment and survival. Still, further investigation is required for identifying and understanding, in particular, the long-term effects of harmful microalgae on marine copepods. Full article

(This article belongs to the Special Issue Advances in Microalgae Toxins: Production, Detection, and Application)

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16 pages, 2402 KiB

Open AccessArticle

Two-Step Epimerization of Deoxynivalenol by Quinone-Dependent Dehydrogenase and Candida parapsilosis ACCC 20221

by Yuqian Tang, Dingna Xiao and Chendi Liu

Toxins 2023, 15(4), 286; https://doi.org/10.3390/toxins15040286 - 16 Apr 2023

Cited by 1 | Viewed by 1904

Abstract

Deoxynivalenol (DON), one of the main mycotoxins with enteric toxicity, genetic toxicity, and immunotoxicity, and is widely found in corn, barley, wheat, and rye. In order to achieve effective detoxification of DON, the least toxic 3-epi-DON (1/357th of the toxicity of DON) was [...] Read more.

Deoxynivalenol (DON), one of the main mycotoxins with enteric toxicity, genetic toxicity, and immunotoxicity, and is widely found in corn, barley, wheat, and rye. In order to achieve effective detoxification of DON, the least toxic 3-epi-DON (1/357th of the toxicity of DON) was chosen as the target for degradation. Quinone-dependent dehydrogenase (QDDH) reported from Devosia train D6-9 detoxifies DON by converting C3-OH to a ketone group with toxicity of less than 1/10 that of DON. In this study, the recombinant plasmid pPIC9K-QDDH was constructed and successfully expressed in Pichia pastoris GS115. Within 12 h, recombinant QDDH converted 78.46% of the 20 μg/mL DON to 3-keto-DON. Candida parapsilosis ACCC 20221 was screened for its activity in reducing 86.59% of 3-keto-DON within 48 h; its main products were identified as 3-epi-DON and DON. In addition, a two-step method was performed for epimerizing DON: 12 h catalysis by recombinant QDDH and 6 h transformation of the C. parapsilosis ACCC 20221 cell catalyst. The production rates of 3-keto-DON and 3-epi-DON were 51.59% and 32.57%, respectively, after manipulation. Through this study, effective detoxification of 84.16% of DON was achieved, with the products being mainly 3-keto-DON and 3-epi-DON. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 338 KiB

Open AccessArticle

Mycotoxins Exposure of Lactating Women and Its Relationship with Dietary and Pre/Post-Harvest Practices in Rural Ethiopia

by Addisalem Mesfin, Carl Lachat, Seifu Hagos Gebreyesus, Meselech Roro, Kokeb Tesfamariam, Tefera Belachew, Marthe De Boevre and Sarah De Saeger

Toxins 2023, 15(4), 285; https://doi.org/10.3390/toxins15040285 - 16 Apr 2023

Cited by 4 | Viewed by 2062

Abstract

Mycotoxins can be transferred to breast milk during lactation. Hence, the presence of multiple mycotoxins (aflatoxins B1, B2, G1, G2, and M1, alpha and beta zearalanol, deoxynivalenol, fumonisins B1, B2, B3, and hydrolyzed B1, nivalenol, ochratoxin A, ochratoxin alpha, and zearalenone) in breast [...] Read more.

Mycotoxins can be transferred to breast milk during lactation. Hence, the presence of multiple mycotoxins (aflatoxins B1, B2, G1, G2, and M1, alpha and beta zearalanol, deoxynivalenol, fumonisins B1, B2, B3, and hydrolyzed B1, nivalenol, ochratoxin A, ochratoxin alpha, and zearalenone) in breast milk samples was assessed in our study. Furthermore, the relationship between total fumonisins and pre/post-harvest and the women’s dietary practices was examined. Liquid chromatography coupled with tandem mass spectrometry was used to analyze the 16 mycotoxins. An adjusted censored regression model was fitted to identify predictors of mycotoxins, i.e., total fumonisins. We detected only fumonisin B2 (15% of the samples) and fumonisin B3 (9% of the samples) while fumonisin B1 and nivalenol were detected only in a single breast milk sample. No association between total fumonisins and pre/post-harvest and dietary practices was found (p < 0.05). The overall exposure to mycotoxins was low in the studied women, although fumonisins contamination was not negligible. Moreover, the recorded total fumonisins was not associated with any of the pre/post-harvest and dietary practices. Therefore, to better identify predictors of fumonisin contamination in breast milk, longitudinal studies with food samples in addition to breast milk samples and with larger sample sizes are needed for the future. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd African Society of Mycotoxicology Joint MYTOX-SOUTH Conference)

12 pages, 1938 KiB

Open AccessEditor’s ChoiceArticle

Quantitative and Qualitative Pain Evaluation in Response to OnabotulinumtoxinA for Chronic Migraine: An Observational Real-Life Study

by Claudia Altamura, Nicoletta Brunelli, Giovanna Viticchi, Sergio Salvemini, Gianluca Cecchi, Marilena Marcosano, Luisa Fofi, Mauro Silvestrini and Fabrizio Vernieri

Toxins 2023, 15(4), 284; https://doi.org/10.3390/toxins15040284 - 15 Apr 2023

Cited by 6 | Viewed by 1966

Abstract

(1) Background: Randomized controlled trials and real-life studies demonstrated the efficacy of OnabotulinumtoxinA (OBT-A) for CM prevention. However, no studies specifically addressed its effect on pain’s quantitative intensity and qualitative characteristics. (2) Methods: This is an ambispective study: a post-hoc retrospective analysis of [...] Read more.

(1) Background: Randomized controlled trials and real-life studies demonstrated the efficacy of OnabotulinumtoxinA (OBT-A) for CM prevention. However, no studies specifically addressed its effect on pain’s quantitative intensity and qualitative characteristics. (2) Methods: This is an ambispective study: a post-hoc retrospective analysis of real-life prospectively collected data from two Italian headache centers on CM patients treated with OBT-A over one year (i.e., Cy1-4). The primary endpoint was the changes in pain intensity (Numeric Rating Scale, NRS; the Present Pain Intensity (PPI) scale, the 6-point Behavioral Rating Scale (BRS-6)) and quality scale (the short-form McGill Pain Questionnaire (SF-MPQ)) scores. We also assessed the relationship between changes in intensity and quality of pain and disability scale (MIDAS; HIT-6) scores, monthly headache days (MHDs), and monthly acute medication intake (MAMI) (3) Results: We retrieved 152 cases (51.5 years SD 11.3, 80.3% females). From baseline to Cy-4, MHDs, MAMI, NRS, PPI, and BRS-6 scores decreased (consistently p < 0.001). Only the throbbing (p = 0.004), splitting (p = 0.018), and sickening (p = 0.017) qualities of pain collected in the SF-MPQ were reduced. Score variations in MIDAS related to those in PPI scales (p = 0.035), in the BRS-6 (p = 0.001), and in the NRS (p = 0.003). Similarly, HIT-6 score changes related to PPI score modifications (p = 0.027), in BRS-6 (p = 0.001) and NRS (p = 0.006). Conversely, MAMI variation was not associated with qualitative or quantitative pain score modifications except BRS-6 (p = 0.018). (4) Conclusions: Our study shows that OBT-A alleviates migraine by reducing its impact on multiple aspects, such as frequency, disability, and pain intensity. The beneficial effect on pain intensity seems specific to pain characteristics related to C-fiber transmission and is associated with a reduction in migraine-related disability. Full article

(This article belongs to the Special Issue Botulinum Toxin and Migraine: Goals and Perspectives)

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13 pages, 3808 KiB

Open AccessArticle

Protective Effects of Epigallocatechin-3-gallate (EGCG) against the Jellyfish Nemopilema nomurai Envenoming

by Jie Li, Qianqian Wang, Shuaijun Zou, Juxingsi Song, Peipei Zhang, Fan Wang, Yichao Huang, Qian He and Liming Zhang

Toxins 2023, 15(4), 283; https://doi.org/10.3390/toxins15040283 - 14 Apr 2023

Cited by 4 | Viewed by 1640

Abstract

Jellyfish stings are the most common marine animal injuries worldwide, with approximately 150 million envenomation cases annually, and the victims may suffer from severe pain, itching, swelling, inflammation, arrhythmias, cardiac failure, or even death. Consequently, identification of effective first aid reagents for jellyfish [...] Read more.

Jellyfish stings are the most common marine animal injuries worldwide, with approximately 150 million envenomation cases annually, and the victims may suffer from severe pain, itching, swelling, inflammation, arrhythmias, cardiac failure, or even death. Consequently, identification of effective first aid reagents for jellyfish envenoming is urgently needed. Here, we found that the polyphenol epigallocatechin-3-gallate (EGCG) markedly antagonized the hemolytic toxicity, proteolytic activity, and cardiomyocyte toxicity of the jellyfish Nemopilema nomurai venom in vitro and could prevent and treat systemic envenoming caused by N. nomurai venom in vivo. Moreover, EGCG is a natural plant active ingredient and widely used as a food additive without toxic side effects. Hence, we suppose that EGCG might be an effective antagonist against systemic envenoming induced by jellyfish venom. Full article

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14 pages, 18643 KiB

Open AccessArticle

Pathophysiological and Clinical Significance of Crotalus durissus cascavella Venom-Induced Pulmonary Impairment in a Murine Model

by Ricardo G. Figueiredo, Marcos Lázaro da Silva Guerreiro, Elen Azevedo, Mateus Souza de Moura, Soraya Castro Trindade, José de Bessa, Jr. and Ilka Biondi

Toxins 2023, 15(4), 282; https://doi.org/10.3390/toxins15040282 - 14 Apr 2023

Viewed by 2036

Abstract

Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 [...] Read more.

Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes. Full article

(This article belongs to the Special Issue Animal Toxins: Biodiscovery, Mechanistic Insights and Translational Potential)

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22 pages, 948 KiB

Open AccessReview

Comparative Aspects of Ricin Toxicity by Inhalation

by Alexander Stoll, Daniel P. Shenton, A. Christopher Green and Jane L. Holley

Toxins 2023, 15(4), 281; https://doi.org/10.3390/toxins15040281 - 13 Apr 2023

Cited by 3 | Viewed by 2559

Abstract

The pathogenesis of ricin toxicity following inhalation has been investigated in many animal models, including the non-human primate (predominantly the rhesus macaque), pig, rabbit and rodent. The toxicity and associated pathology described in animal models are broadly similar, but variation appears to exist. [...] Read more.

The pathogenesis of ricin toxicity following inhalation has been investigated in many animal models, including the non-human primate (predominantly the rhesus macaque), pig, rabbit and rodent. The toxicity and associated pathology described in animal models are broadly similar, but variation appears to exist. This paper reviews the published literature and some of our own unpublished data and describes some of the possible reasons for this variation. Methodological variation is evident, including method of exposure, breathing parameters during exposure, aerosol characteristics, sampling protocols, ricin cultivar, purity and challenge dose and study duration. The model species and strain used represent other significant sources of variation, including differences in macro- and microscopic anatomy, cell biology and function, and immunology. Chronic pathology of ricin toxicity by inhalation, associated with sublethal challenge or lethal challenge and treatment with medical countermeasures, has received less attention in the literature. Fibrosis may follow acute lung injury in survivors. There are advantages and disadvantages to the different models of pulmonary fibrosis. To understand their potential clinical significance, these factors need to be considered when choosing a model for chronic ricin toxicity by inhalation, including species and strain susceptibility to fibrosis, time it takes for fibrosis to develop, the nature of the fibrosis (e.g., self-limiting, progressive, persistent or resolving) and ensuring that the analysis truly represents fibrosis. Understanding the variables and comparative aspects of acute and chronic ricin toxicity by inhalation is important to enable meaningful comparison of results from different studies, and for the investigation of medical countermeasures. Full article

(This article belongs to the Special Issue Advances in Ricin Antitoxins: From Intoxication to Diagnosis and Treatment)

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10 pages, 1963 KiB

Open AccessArticle

Trends in Botulinum Toxin Use among Patients with Multiple Sclerosis: A Population-Based Study

by Djamel Bensmail, Pierre Karam, Anne Forestier, Jean-Yves Loze and Jonathan Lévy

Toxins 2023, 15(4), 280; https://doi.org/10.3390/toxins15040280 - 12 Apr 2023

Cited by 7 | Viewed by 2276

Abstract

There are limited real-world data on the use of botulinum toxin type A (BoNT-A) in patients with multiple sclerosis (MS). Accordingly, this nationwide, population-based, retrospective cohort study aimed to describe BoNT-A treatment trends in patients with MS between 2014 and 2020 in France. [...] Read more.

There are limited real-world data on the use of botulinum toxin type A (BoNT-A) in patients with multiple sclerosis (MS). Accordingly, this nationwide, population-based, retrospective cohort study aimed to describe BoNT-A treatment trends in patients with MS between 2014 and 2020 in France. This study extracted data from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d’Information, PMSI) covering the entire French population. Among 105,206 patients coded with MS, we identified those who received ≥1 BoNT-A injection, administered within striated muscle for MS-related spasticity and/or within the detrusor smooth muscle for neurogenic detrusor overactivity (NDO). A total of 8427 patients (8.0%) received BoNT-A injections for spasticity, 52.9% of whom received ≥3 BoNT-A injections with 61.9% of the repeated injections administered every 3 to 6 months. A total of 2912 patients (2.8%) received BoNT-A injections for NDO, with a mean of 4.7 injections per patient. Most repeated BoNT-A injections within the detrusor smooth muscle (60.0%) were administered every 5 to 8 months. There were 585 patients (0.6%) who received both BoNT-A injections within striated muscle and the detrusor smooth muscle. Overall, our study highlights a broad range of BoNT-A treatment practices between 2014 and 2020 in patients with MS. Full article

(This article belongs to the Special Issue Botulinum Neurotoxins: From Toxin to Medicine)

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12 pages, 1622 KiB

Open AccessArticle

Tetrodotoxin and the Geographic Distribution of the Blue-Lined Octopus Hapalochlaena fasciata on the Korean Coast

by Ji-Hoe Kim, Dong-Wook Kim, Sung-Rae Cho, Ka-Jeong Lee and Jong-Soo Mok

Toxins 2023, 15(4), 279; https://doi.org/10.3390/toxins15040279 - 11 Apr 2023

Cited by 2 | Viewed by 2642

Abstract

The genus Hapalochlaena, including the blue-lined octopus Hapalochlaena fasciata (H. fasciata), is highly toxic. Venomous, blue-lined octopuses were recently found in Korea, but their toxicity, toxin composition, and distribution remain largely unknown. Here we estimated the geographic distribution of the organisms along the [...] Read more.

The genus Hapalochlaena, including the blue-lined octopus Hapalochlaena fasciata (H. fasciata), is highly toxic. Venomous, blue-lined octopuses were recently found in Korea, but their toxicity, toxin composition, and distribution remain largely unknown. Here we estimated the geographic distribution of the organisms along the Korean coast and clarified their toxicity. Tetrodotoxin (TTX) was present in all three specimens of H. fasciata examined, although the toxicity varied largely between individuals. The mean TTX concentration in the whole body of the three specimens was 6.5 ± 2.2 μg/g (range 3.3–8.5 μg/g). Among the body parts examined, the salivary glands exhibited the highest concentration (22.4 ± 9.7 μg/g). From 2012 to 2021, 26 individuals were obtained nearly every month from different regions of the Korean coast. A non-fatal case of a blue-lined octopus bite was reported along the Korean coast in June 2015. This is the first report on the widespread distribution of blue-lined octopuses on the Korean coast and TTX detection. The widespread distribution of the TTX-bearing H. fasciata along the Korean coast within the temperate zone indicates that the species may soon become a serious health issue in Korea. The toxicity of this species is also a potentially significant human health risk. Full article

(This article belongs to the Special Issue Advances in Marine Toxins: Characterization, Analysis and Surveillance)

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13 pages, 1303 KiB

Open AccessArticle

Botulinum Toxin and Percutaneous Needle Electrolysis for the Treatment of Chronic Masticatory Myalgia

by Luis-Miguel Gonzalez-Perez, Ramon Vera-Martin, Enrique Montes-Latorre, Eusebio Torres-Carranza and Pedro Infante-Cossio

Toxins 2023, 15(4), 278; https://doi.org/10.3390/toxins15040278 - 10 Apr 2023

Cited by 4 | Viewed by 2527

Abstract

Botulinum toxin type A (BTA) is applied in muscle hyperactivity disorders and injected into affected muscles, producing deep and persistent muscle relaxation. Several multidisciplinary groups investigated the treatment of temporomandibular disorders for several years, and there is currently some data on the beneficial [...] Read more.

Botulinum toxin type A (BTA) is applied in muscle hyperactivity disorders and injected into affected muscles, producing deep and persistent muscle relaxation. Several multidisciplinary groups investigated the treatment of temporomandibular disorders for several years, and there is currently some data on the beneficial effects of BTA in specific cases of chronic masticatory myalgia. Percutaneous needle electrolysis (PNE), which applies a low-intensity galvanic current to promote tissue regeneration, has been shown to be effective in reducing pain and improving masticatory function. The purpose of this study was to investigate the efficacy and safety of BTA and to assess whether its application in patients with localized masticatory myalgia can significantly reduce pain and improve function compared to a group treated with PNE. Fifty-two patients with long-term refractory masticatory myalgia were randomly assigned to two groups. The BTA group (n = 26) received a bilateral botulinum toxin injection and the PNE group (n = 26) received percutaneous electrolysis. The dose of BTA injected was 100 units distributed among the main primary masticatory muscles, and PNE was administered at 0.5 mA/3 s/3 consecutive times in a single session. Patient assessments were performed prior to treatment and one, two, and three months after treatment. The results revealed good therapeutic response in both groups. In the long term, both BTA and PNE showed high efficacy and safety in reducing pain and improving muscle function for the treatment of chronic masticatory myalgia. This improvement was sustained over a three-month period in both groups. Therefore, the use of BTA and PNE could be considered a valid and safe therapeutic alternative among the available options to treat refractory and localized masticatory myalgia when a better therapeutic response is expected as it demonstrated high efficacy. Full article

(This article belongs to the Special Issue Botulinum Toxin: From Poison to Possible Treatment for Spasticity and Movement Disorder)

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14 pages, 1718 KiB

Open AccessArticle

Optimization and Validation of Dispersive Liquid–Liquid Microextraction for Simultaneous Determination of Aflatoxins B1, B2, G1, and G2 in Senna Leaves and Pods Using HPLC-FLD with Pre-Column Derivatization

by Thanapoom Maneeboon, Chananya Chuaysrinule and Warapa Mahakarnchanakul

Toxins 2023, 15(4), 277; https://doi.org/10.3390/toxins15040277 - 7 Apr 2023

Cited by 4 | Viewed by 2263

Abstract

Dispersive liquid–liquid microextraction (DLLME) was optimized for the simultaneous extraction of aflatoxins (AFB1, AFB2, AFG1, and AFG2) from powdered senna leaves and pods. Detection was performed using high-performance liquid chromatography with fluorescence detection (HPLC-FLD) and pre-column derivatization. The parameters affecting the DLLME extraction [...] Read more.

Dispersive liquid–liquid microextraction (DLLME) was optimized for the simultaneous extraction of aflatoxins (AFB1, AFB2, AFG1, and AFG2) from powdered senna leaves and pods. Detection was performed using high-performance liquid chromatography with fluorescence detection (HPLC-FLD) and pre-column derivatization. The parameters affecting the DLLME extraction efficiency were evaluated. Chloroform (200 µL) was used as an extraction solvent, 500 µL of distilled water was used as a dispersive solvent, and the extraction was performed at pH 5.6 with no salt added. The optimized method was validated using leaves and pods according to the European Commission guidelines. The linear range for all aflatoxins was 2–50 µg/kg, with values for regression coefficients of determination exceeding 0.995. The recoveries of spiked senna leaves and pods were in the ranges of 91.77–108.71% and 83.50–102.73%, respectively. The RSD values for intra-day and inter-day precisions were in the ranges of 2.30–7.93% and 3.13–10.59%, respectively. The limits of detection and quantification varied in the ranges of 0.70–1.27 µg/kg and 2.13–3.84 µg/kg, respectively. The validated method was successfully applied for the quantification of aflatoxins in 60 real samples of dried senna leaves and pods. Full article

(This article belongs to the Special Issue Rapid Detection of Mycotoxin Contamination 2.0)

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12 pages, 329 KiB

Open AccessEditor’s ChoiceArticle

Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients with Chronic Kidney Disease

by Carolla El Chamieh, Islam Amine Larabi, Solène M. Laville, Christian Jacquelinet, Christian Combe, Denis Fouque, Maurice Laville, Luc Frimat, Roberto Pecoits-Filho, Céline Lange, Bénédicte Stengel, Natalia Alencar De Pinho, Jean-Claude Alvarez, Ziad A. Massy and Sophie Liabeuf

Toxins 2023, 15(4), 276; https://doi.org/10.3390/toxins15040276 - 7 Apr 2023

Cited by 2 | Viewed by 2800

Abstract

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney’s tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription [...] Read more.

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney’s tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m²), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Our results indicate that PPI prescription is independently associated with serum UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies. Full article

(This article belongs to the Section Uremic Toxins)

11 pages, 2989 KiB

Open AccessCommunication

Processing Properties and Potency of Bacillus thuringiensis Cry Toxins in the Rice Leaffolder Cnaphalocrocis medinalis (Guenée)

by Yajun Yang, Zhihong Wu, Xiaochan He, Hongxing Xu and Zhongxian Lu

Toxins 2023, 15(4), 275; https://doi.org/10.3390/toxins15040275 - 6 Apr 2023

Viewed by 1758

Abstract

Different Cry toxins derived from Bacillus thuringiensis (Bt) possess different insecticidal spectra, whereas insects show variations in their susceptibilities to different Cry toxins. Degradation of Cry toxins by insect midgut extracts was involved in the action of toxins. In this study, we explored [...] Read more.

Different Cry toxins derived from Bacillus thuringiensis (Bt) possess different insecticidal spectra, whereas insects show variations in their susceptibilities to different Cry toxins. Degradation of Cry toxins by insect midgut extracts was involved in the action of toxins. In this study, we explored the processing patterns of different Cry toxins in Cnaphalocrocis medinalis (Lepidoptera: Crambidae) midgut extracts and evaluated the impact of Cry toxins degradation on their potency against C. medinalis to better understand the function of midgut extracts in the action of different Cry toxins. The results indicated that Cry1Ac, Cry1Aa, and Cry1C toxins could be degraded by C. medinalis midgut extracts, and degradation of Cry toxins by midgut extracts differed among time or concentration effects. Bioassays demonstrated that the toxicity of Cry1Ac, Cry1Aa, and Cry1C toxins decreased after digestion by midgut extracts of C. medinalis. Our findings in this study suggested that midgut extracts play an important role in the action of Cry toxins against C. medinalis, and the degradation of Cry toxins by C. medinalis midgut extracts could reduce their toxicities to C. medinalis. They will provide insights into the action of Cry toxins and the application of Cry toxins in C. medinalis management in paddy fields. Full article

(This article belongs to the Special Issue Bacillus thuringiensis: A Broader View of Its Biocidal Activity)

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10 pages, 844 KiB

Open AccessFeature PaperArticle

Botulinum Toxin Type A for the Treatment of Auriculotemporal Neuralgia—A Case Series

by Yan Tereshko, Enrico Belgrado, Christian Lettieri, Gian Luigi Gigli and Mariarosaria Valente

Toxins 2023, 15(4), 274; https://doi.org/10.3390/toxins15040274 - 6 Apr 2023

Cited by 5 | Viewed by 2728

Abstract

Auriculotemporal neuralgia is a rare pain disorder in which anesthetic nerve blockade is usually effective but not always resolutive. Botulinum toxin type A has proven to be effective in treating neuropathic pain, and patients with auriculotemporal neuralgia could also benefit from this treatment. [...] Read more.

Auriculotemporal neuralgia is a rare pain disorder in which anesthetic nerve blockade is usually effective but not always resolutive. Botulinum toxin type A has proven to be effective in treating neuropathic pain, and patients with auriculotemporal neuralgia could also benefit from this treatment. We described nine patients with auriculotemporal neuralgia treated with botulinum toxin type A in the territory of auriculotemporal nerve innervation. We compared the basal NRS and Penn facial pain scale scores with those obtained 1 month after BoNT/A injections. Both Penn facial pain scale (96.67 ± 24.61 vs. 45.11 ± 36.70, p 0.004; mean reduction 52.57 ± 36.50) and NRS scores (8.11 ± 1.27 vs. 4.22 ± 2.95, p 0.009; mean reduction 3.89 ± 2.52) improved significantly at one month after treatment. The mean duration of the effect of BoNT/A on pain was 95.00 ± 53.03 days and no adverse effects were reported. Full article

(This article belongs to the Collection Botulinum Toxins on Human Pain)

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Open AccessArticle

Analysis of the Effect of Plutella xylostella Polycalin and ABCC2 Transporter on Cry1Ac Susceptibility by CRISPR/Cas9-Mediated Knockout

by Lei Xiong, Zhaoxia Liu, Jingge Li, Shuyuan Yao, Zeyun Li, Xuanhao Chen, Lingling Shen, Zhen Zhang, Yongbin Li, Qing Hou, Yuhang Zhang, Minsheng You, Zhiguang Yuchi and Shijun You

Toxins 2023, 15(4), 273; https://doi.org/10.3390/toxins15040273 - 6 Apr 2023

Cited by 1 | Viewed by 2241

Abstract

Many insects, including the Plutella xylostella (L.), have developed varying degrees of resistance to many insecticides, including Bacillus thuringiensis (Bt) toxins, the bioinsecticides derived from Bt. The polycalin protein is one of the potential receptors for Bt toxins, and previous [...] Read more.

Many insects, including the Plutella xylostella (L.), have developed varying degrees of resistance to many insecticides, including Bacillus thuringiensis (Bt) toxins, the bioinsecticides derived from Bt. The polycalin protein is one of the potential receptors for Bt toxins, and previous studies have confirmed that the Cry1Ac toxin can bind to the polycalin protein of P. xylostella, but whether polycalin is associated with the resistance of Bt toxins remains controversial. In this study, we compared the midgut of larvae from Cry1Ac-susceptible and -resistant strains, and found that the expression of the Pxpolycalin gene was largely reduced in the midgut of the resistant strains. Moreover, the spatial and temporal expression patterns of Pxpolycalin showed that it was mainly expressed in the larval stage and midgut tissue. However, genetic linkage experiments showed that the Pxpolycalin gene and its transcript level were not linked to Cry1Ac resistance, whereas both the PxABCC2 gene and its transcript levels were linked to Cry1Ac resistance. The larvae fed on a diet containing the Cry1Ac toxin showed no significant change in the expression of the Pxpolycalin gene in a short term. Furthermore, the knockout of polycalin and ATP-binding cassette transporter subfamily C2 (ABCC2) genes separately by CRISPR/Cas9 technology resulted in resistance to decreased susceptibility to Cry1Ac toxin. Our results provide new insights into the potential role of polycalin and ABCC2 proteins in Cry1Ac resistance and the mechanism underlying the resistance of insects to Bt toxins. Full article

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Toxins, Volume 15, Issue 4 (April 2023) – 69 articles

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