Toxins

37 pages, 3901 KiB

Open AccessEditor’s ChoiceReview

Detoxification of Mycotoxins through Biotransformation

by Peng Li, Ruixue Su, Ruya Yin, Daowan Lai, Mingan Wang, Yang Liu and Ligang Zhou

Toxins 2020, 12(2), 121; https://doi.org/10.3390/toxins12020121 - 14 Feb 2020

Cited by 87 | Viewed by 8832

Mycotoxins are toxic fungal secondary metabolites that pose a major threat to the safety of food and feed. Mycotoxins are usually converted into less toxic or non-toxic metabolites through biotransformation that are often made by living organisms as well as the isolated enzymes. [...] Read more.

Mycotoxins are toxic fungal secondary metabolites that pose a major threat to the safety of food and feed. Mycotoxins are usually converted into less toxic or non-toxic metabolites through biotransformation that are often made by living organisms as well as the isolated enzymes. The conversions mainly include hydroxylation, oxidation, hydrogenation, de-epoxidation, methylation, glycosylation and glucuronidation, esterification, hydrolysis, sulfation, demethylation and deamination. Biotransformations of some notorious mycotoxins such as alfatoxins, alternariol, citrinin, fomannoxin, ochratoxins, patulin, trichothecenes and zearalenone analogues are reviewed in detail. The recent development and applications of mycotoxins detoxification through biotransformation are also discussed. Full article

(This article belongs to the Section Mycotoxins)

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21 pages, 2018 KiB

Open AccessEditor’s ChoiceReview

Methicillin-Resistant Staphylococcus aureus ST80 Clone: A Systematic Review

by Assia Mairi, Abdelaziz Touati and Jean-Philippe Lavigne

Toxins 2020, 12(2), 119; https://doi.org/10.3390/toxins12020119 - 14 Feb 2020

Cited by 28 | Viewed by 4636

Abstract

This review assessed the molecular characterization of the methicillin-resistant Staphylococcus aureus (MRSA)-ST80 clone with an emphasis on its proportion of total MRSA strains isolated, PVL production, spa-typing, antibiotic resistance, and virulence. A systematic review of the literature was conducted on MRSA-ST80 clone [...] Read more.

This review assessed the molecular characterization of the methicillin-resistant Staphylococcus aureus (MRSA)-ST80 clone with an emphasis on its proportion of total MRSA strains isolated, PVL production, spa-typing, antibiotic resistance, and virulence. A systematic review of the literature was conducted on MRSA-ST80 clone published between 1 January 2000 and 31 August 2019. Citations were chosen for a review of the full text if we found evidence that MRSA-ST80 clone was reported in the study. For each isolate, the country of isolation, the sampling period, the source of isolation (the type of infection, nasal swabs, or extra-human), the total number of MRSA strains isolated, number of MRSA-ST80 strains, antibiotic resistance patterns, PVL production, virulence genes, and spa type were recorded. The data from 103 articles were abstracted into an Excel database. Analysis of the data showed that the overall proportion of MRSA-ST80 has been decreasing in many countries in recent years. The majority of MRSA-ST80 were PVL positive with spa-type t044. Only six reports of MRSA-ST80 in extra-human niches were found. This review summarizes the rise of MRSA-ST80 and the evidence that suggests that it could be in decline in many countries. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

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15 pages, 4498 KiB

Open AccessEditor’s ChoiceArticle

Mitochondria and Lysosomes Participate in Vip3Aa-Induced Spodoptera frugiperda Sf9 Cell Apoptosis

by Xiaoyue Hou, Lu Han, Baoju An, Yanli Zhang, Zhanglei Cao, Yunda Zhan, Xia Cai, Bing Yan and Jun Cai

Toxins 2020, 12(2), 116; https://doi.org/10.3390/toxins12020116 - 13 Feb 2020

Cited by 27 | Viewed by 3121

Abstract

Vip3Aa, a soluble protein produced by certain Bacillus thuringiensis strains, is capable of inducing apoptosis in Sf9 cells. However, the apoptosis mechanism triggered by Vip3Aa is unclear. In this study, we found that Vip3Aa induces mitochondrial dysfunction, as evidenced by signs of collapse [...] Read more.

Vip3Aa, a soluble protein produced by certain Bacillus thuringiensis strains, is capable of inducing apoptosis in Sf9 cells. However, the apoptosis mechanism triggered by Vip3Aa is unclear. In this study, we found that Vip3Aa induces mitochondrial dysfunction, as evidenced by signs of collapse of mitochondrial membrane potential, accumulation of reactive oxygen species, release of cytochrome c, and caspase-9 and -3 activation. Meanwhile, our results indicated that Vip3Aa reduces the ability of lysosomes in Sf9 cells to retain acridine orange. Moreover, pretreatment with Z-Phe-Tyr-CHO (a cathepsin L inhibitor) or pepstatin (a cathepsin D inhibitor) increased Sf9 cell viability, reduced cytochrome c release, and decreased caspase-9 and -3 activity. In conclusion, our findings suggested that Vip3Aa promotes Sf9 cell apoptosis by mitochondrial dysfunction, and lysosomes also play a vital role in the action of Vip3Aa. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)

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14 pages, 1851 KiB

Open AccessEditor’s ChoiceArticle

Zearalenone Removal from Corn Oil by an Enzymatic Strategy

by Xiaojiao Chang, Hujun Liu, Jing Sun, Jun Wang, Chengcheng Zhao, Wan Zhang, Jie Zhang and Changpo Sun

Toxins 2020, 12(2), 117; https://doi.org/10.3390/toxins12020117 - 13 Feb 2020

Cited by 37 | Viewed by 3862

Abstract

The estrogen-like mycotoxin zearalenone (ZEN) is one of the most widely distributed contaminants especially in maize and its commodities, such as corn oil. ZEN degrading enzymes possess the potential for counteracting the negative effect of ZEN and its associated high safety risk in [...] Read more.

The estrogen-like mycotoxin zearalenone (ZEN) is one of the most widely distributed contaminants especially in maize and its commodities, such as corn oil. ZEN degrading enzymes possess the potential for counteracting the negative effect of ZEN and its associated high safety risk in corn oil. Herein, we targeted enhancing the secretion of ZEN degrading enzyme by Pichia pastoris through constructing an expression plasmid containing three optimized expression cassettes of zlhy-6 codon and signal peptides. Further, we explored various parameters of enzymatic detoxification in neutralized oil and analyzed tocopherols and sterols losses in the corn oil. In addition, the distribution of degraded products was demonstrated as well by Agilent 6510 Quadrupole Time-of-Flight mass spectrometry. P. pastoris GSZ with the glucoamylase signal was observed with the highest ZLHY-6 secretion yield of 0.39 mg/mL. During the refining of corn oil, ZEN in the crude oil was reduced from 1257.3 to 13 µg/kg (3.69% residual) after neutralization and enzymatic detoxification. Compared with the neutralized oil, no significant difference in the total tocopherols and sterols contents was detected after enzymatic detoxification. Finally, the degraded products were found to be entirely eliminated by washing. This study presents an enzymatic strategy for efficient and safe ZEN removal with relatively low nutrient loss, which provides an important basis for further application of enzymatic ZEN elimination in the industrial process of corn oil production. Full article

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16 pages, 1569 KiB

Open AccessEditor’s ChoiceArticle

Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Multi-Residue Analysis of Mycotoxins and Pesticides in Botanical Nutraceuticals

by Alfonso Narváez, Yelko Rodríguez-Carrasco, Luigi Castaldo, Luana Izzo and Alberto Ritieni

Toxins 2020, 12(2), 114; https://doi.org/10.3390/toxins12020114 - 12 Feb 2020

Cited by 45 | Viewed by 6158

Abstract

Cannabidiol (CBD) food supplements made of Cannabis sativa L. extracts have quickly become popular products due to their health-promoting effects. However, potential contaminants, such as mycotoxins and pesticides, can be coextracted during the manufacturing process and placed into the final product. Accordingly, a [...] Read more.

Cannabidiol (CBD) food supplements made of Cannabis sativa L. extracts have quickly become popular products due to their health-promoting effects. However, potential contaminants, such as mycotoxins and pesticides, can be coextracted during the manufacturing process and placed into the final product. Accordingly, a novel methodology using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was developed to quantify 16 mycotoxins produced by major C. sativa fungi, followed by a post-target screening of 283 pesticides based on a comprehensive spectral library. The validated procedure was applied to ten CBD-based products. Up to six different Fusarium mycotoxins were found in seven samples, the most prevalent being zearalenone (60%) and enniatin B1 (30%), both found at a maximum level of 11.6 ng/g. Co-occurrence was observed in four samples, including one with enniatin B1, enniatin A and enniatin A1. On the other hand, 46 different pesticides were detected after retrospective analysis. Ethoxyquin (50%), piperonyl butoxide (40%), simazine (30%) and cyanazine (30%) were the major residues found. These results highlight the necessity of monitoring contaminants in food supplements in order to ensure a safe consumption, even more considering the increase trend in their use. Furthermore, the developed procedure is proposed as a powerful analytical tool to evaluate the potential mycotoxin profile of these particular products. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

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17 pages, 1823 KiB

Open AccessEditor’s ChoiceArticle

The Effectiveness of Durian Peel as a Multi-Mycotoxin Adsorbent

by Saowalak Adunphatcharaphon, Awanwee Petchkongkaew, Donato Greco, Vito D’Ascanio, Wonnop Visessanguan and Giuseppina Avantaggiato

Toxins 2020, 12(2), 108; https://doi.org/10.3390/toxins12020108 - 8 Feb 2020

Cited by 31 | Viewed by 6480

Abstract

Durian peel (DP) is an agricultural waste that is widely used in dyes and for organic and inorganic pollutant adsorption. In this study, durian peel was acid-treated to enhance its mycotoxin adsorption efficacy. The acid-treated durian peel (ATDP) was assessed for simultaneous adsorption [...] Read more.

Durian peel (DP) is an agricultural waste that is widely used in dyes and for organic and inorganic pollutant adsorption. In this study, durian peel was acid-treated to enhance its mycotoxin adsorption efficacy. The acid-treated durian peel (ATDP) was assessed for simultaneous adsorption of aflatoxin B₁ (AFB₁), ochratoxin A (OTA), zearalenone (ZEA), deoxynivalenol (DON), and fumonisin B₁ (FB₁). The structure of the ATDP was also characterized by SEM–EDS, FT–IR, a zetasizer, and a surface-area analyzer. The results indicated that ATDP exhibited the highest mycotoxin adsorption towards AFB₁ (98.4%), ZEA (98.4%), and OTA (97.3%), followed by FB₁ (86.1%) and DON (2.0%). The pH significantly affected OTA and FB₁ adsorption, whereas AFB₁ and ZEA adsorption was not affected. Toxin adsorption by ATDP was dose-dependent and increased exponentially as the ATDP dosage increased. The maximum adsorption capacity (Q_max), determined at pH 3 and pH 7, was 40.7 and 41.6 mmol kg⁻¹ for AFB₁, 15.4 and 17.3 mmol kg⁻¹ for ZEA, 46.6 and 0.6 mmol kg⁻¹ for OTA, and 28.9 and 0.1 mmol kg⁻¹ for FB₁, respectively. Interestingly, ATDP reduced the bioaccessibility of these mycotoxins after gastrointestinal digestion using an in vitro, validated, static model. The ATDP showed a more porous structure, with a larger surface area and a surface charge modification. These structural changes following acid treatment may explain the higher efficacy of ATDP in adsorbing mycotoxins. Hence, ATDP can be considered as a promising waste material for mycotoxin biosorption. Full article

(This article belongs to the Special Issue Mycotoxin Contamination Management Tools and Efficient Strategies in Feed Industry)

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12 pages, 2568 KiB

Open AccessEditor’s ChoiceArticle

Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish

by Dandan Zhang, Wang Lin, Yinjie Liu, Honghui Guo, Lingkai Wang, Liping Yang, Li Li, Dapeng Li and Rong Tang

Toxins 2020, 12(2), 107; https://doi.org/10.3390/toxins12020107 - 7 Feb 2020

Cited by 26 | Viewed by 3935

Abstract

In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for [...] Read more.

In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for 60 days, and hepatic histopathology as well as lipid metabolic parameters were determined with mRNA levels of ERS signal molecules and downstream factors, along with genes associated with lipid metabolism in zebrafish liver. The results revealed that prolonged exposure to MC-LR remarkably altered the levels of hepatic total cholesterol and triglyceride and led to hepatic steatosis, which was also confirmed by hepatic cytoplasmic vacuolization in Hematoxylin/eosin (H&E) stain and lipid droplet accumulation in Oil Red O stain. The severity of hepatic damage and lipidation was increased in a dose-related manner. MC-LR exposure significantly upregulated transcriptional levels of ERS markers including hspa5, mapk8, and chop, indicating the occurrence of ERS in the liver of zebrafish. Concurrently, MC-LR significantly improved mRNA expression of unfolded protein response (UPR) pathway-related genes including atf6, eif2ak3, ern1, and xbp1s, suggesting that all of the three UPR branches were activated by MC-LR. MC-LR also induced significant upregulation of downstream lipid metabolism-related factors and genes including srebf1, srebf2, fatty acid synthase (fasn), acetyl-CoA carboxylase (acaca), stearoyl-CoA desaturase (scd), HMG CoA reductase (hmgcra), and HMG CoA synthase (hmgcs1), and downregulation of genes associated with lipolysis such as triglyceride hydrolase gene (atgl), hormone-sensitive enzyme gene (hsla), and carnitine palmitoyltransferase gene (cpt1aa). Our present results indicated that the cause of hepatic lipid accumulation by MC-LR was mainly by upregulating lipogenic and cholesterol genes but downregulating the expression of lipolytic genes through the induction of srebf1 and srebf2, which were involved in the activation of ERS signal pathways. Full article

(This article belongs to the Special Issue Advances in the Toxicity Mechanisms of Microcystins Revealed by Omics Approaches)

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23 pages, 1861 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Rumen Simulations Show a Reduced Disappearance of Deoxynivalenol, Nivalenol and Enniatin B at Conditions of Rumen Acidosis and Lower Microbial Activity

by Sandra Debevere, An Cools, Siegrid De Baere, Geert Haesaert, Michael Rychlik, Siska Croubels and Veerle Fievez

Toxins 2020, 12(2), 101; https://doi.org/10.3390/toxins12020101 - 5 Feb 2020

Cited by 32 | Viewed by 3830

Abstract

Ruminants are generally considered to be less susceptible to the effects of mycotoxins than monogastric animals as the rumen microbiota are capable of detoxifying some of these toxins. Despite this potential degradation, mycotoxin-associated subclinical health problems are seen in dairy cows. In this [...] Read more.

Ruminants are generally considered to be less susceptible to the effects of mycotoxins than monogastric animals as the rumen microbiota are capable of detoxifying some of these toxins. Despite this potential degradation, mycotoxin-associated subclinical health problems are seen in dairy cows. In this research, the disappearance of several mycotoxins was determined in an in vitro rumen model and the effect of realistic concentrations of those mycotoxins on fermentation was assessed by volatile fatty acid production. In addition, two hypotheses were tested: (1) a lower rumen pH leads to a decreased degradation of mycotoxins and (2) rumen fluid of lactating cows degrade mycotoxins better than rumen fluid of non-lactating cows. Maize silage was spiked with a mixture of deoxynivalenol (DON), nivalenol (NIV), enniatin B (ENN B), mycophenolic acid (MPA), roquefortine C (ROQ-C) and zearalenone (ZEN). Fresh rumen fluid of two lactating cows (L) and two non-lactating cows (N) was added to a buffer of normal pH (6.8) and low pH (5.8), leading to four combinations (L6.8, L5.8, N6.8, N5.8), which were added to the spiked maize substrate. In this study, mycotoxins had no effect on volatile fatty acid production. However, not all mycotoxins fully disappeared during incubation. ENN B and ROQ-C disappeared only partially, whereas MPA showed almost no disappearance. The disappearance of DON, NIV, and ENN B was hampered when pH was low, especially when the inoculum of non-lactating cows was used. For ZEN, a limited transformation of ZEN to α-ZEL and β-ZEL was observed, but only at pH 6.8. In conclusion, based on the type of mycotoxin and the ruminal conditions, mycotoxins can stay intact in the rumen. Full article

(This article belongs to the Special Issue Mycotoxins in Feed: Harm to Animals)

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8 pages, 299 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin M₁ Determination in Infant Formulae Distributed in Monterrey, Mexico

by Patricia A. Quevedo-Garza, Genaro G. Amador-Espejo, Rogelio Salas-García, Esteban G. Ramos-Peña and Antonio-José Trujillo

Toxins 2020, 12(2), 100; https://doi.org/10.3390/toxins12020100 - 4 Feb 2020

Cited by 21 | Viewed by 2640

Abstract

The occurrence of aflatoxin M₁ (AFM₁) in infant formulae commercialized in the metropolitan area of Monterrey (Nuevo León, Mexico) was determined by using immunoaffinity column clean-up followed by HPLC determination with fluorimetric detection. For this, 55 infant formula powders were [...] Read more.

The occurrence of aflatoxin M₁ (AFM₁) in infant formulae commercialized in the metropolitan area of Monterrey (Nuevo León, Mexico) was determined by using immunoaffinity column clean-up followed by HPLC determination with fluorimetric detection. For this, 55 infant formula powders were classified in two groups, starter (49 samples) and follow-on (6 samples) formulae. Eleven of the evaluated samples (20%) presented values above the permissible limit set by the European Union for infant formulae (25 ng/L), ranging from 40 to 450 ng/L. The estimated daily intake (EDI) for AFM₁ was determined employing the average body weight (bw) of the groups of age in the ranges of 0–6 and 6–12 months, and 1–2 years. The results evidenced high intake values, ranging from 1.56 to 14 ng/kg bw/day, depending on the group. Finally, with the EDI value, the carcinogenic risk index was determined, presenting a high risk for all the evaluated groups. Based on these results, it is a necessary extra effort by the regulatory agencies to reduce the AFM₁ presence in infant formulae consumed in Mexico. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

15 pages, 3046 KiB

Open AccessEditor’s ChoiceArticle

Domain Shuffling between Vip3Aa and Vip3Ca: Chimera Stability and Insecticidal Activity against European, American, African, and Asian Pests

by Joaquín Gomis-Cebolla, Rafael Ferreira dos Santos, Yueqin Wang, Javier Caballero, Primitivo Caballero, Kanglai He, Juan Luis Jurat-Fuentes and Juan Ferré

Toxins 2020, 12(2), 99; https://doi.org/10.3390/toxins12020099 - 4 Feb 2020

Cited by 14 | Viewed by 3419

Abstract

The bacterium Bacillus thuringiensis produces insecticidal Vip3 proteins during the vegetative growth phase with activity against several lepidopteran pests. To date, three different Vip3 protein families have been identified based on sequence identity: Vip3A, Vip3B, and Vip3C. In this study, we report the [...] Read more.

The bacterium Bacillus thuringiensis produces insecticidal Vip3 proteins during the vegetative growth phase with activity against several lepidopteran pests. To date, three different Vip3 protein families have been identified based on sequence identity: Vip3A, Vip3B, and Vip3C. In this study, we report the construction of chimeras by exchanging domains between Vip3Aa and Vip3Ca, two proteins with marked specificity differences against lepidopteran pests. We found that some domain combinations made proteins insoluble or prone to degradation by trypsin as most abundant insect gut protease. The soluble and trypsin-stable chimeras, along with the parental proteins Vip3Aa and Vip3Ca, were tested against lepidopteran pests from different continents: Spodoptera exigua, Spodoptera littoralis, Spodoptera frugiperda, Helicoverpa armigera, Mamestra brassicae, Anticarsia gemmatalis, and Ostrinia furnacalis. The exchange of the Nt domain (188 N-terminal amino acids) had little effect on the stability and toxicity (equal or slightly lower) of the resulting chimeric protein against all insects except for S. frugiperda, for which the chimera with the Nt domain from Vip3Aa and the rest of the protein from Vip3Ca showed a significant increase in toxicity compared to the parental Vip3Ca. Chimeras with the C-terminal domain from Vip3Aa (from amino acid 510 of Vip3Aa to the Ct) with the central domain of Vip3Ca (amino acids 189–509 based on the Vip3Aa sequence) made proteins that could not be solubilized. Finally, the chimera including the Ct domain of Vip3Ca and the Nt and central domain from Vip3Aa was unstable. Importantly, an insect species tolerant to Vip3Aa but susceptible to Vip3Ca, such as Ostrinia furnacalis, was also susceptible to chimeras maintaining the Ct domain from Vip3Ca, in agreement with the hypothesis that the Ct region of the protein is the one conferring specificity to Vip3 proteins. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)

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32 pages, 2688 KiB

Open AccessEditor’s ChoiceArticle

Cultivation Area Affects the Presence of Fungal Communities and Secondary Metabolites in Italian Durum Wheat Grains

by Giovanni Beccari, Antonio Prodi, Maria Teresa Senatore, Virgilio Balmas, Francesco Tini, Andrea Onofri, Luca Pedini, Michael Sulyok, Luca Brocca and Lorenzo Covarelli

Toxins 2020, 12(2), 97; https://doi.org/10.3390/toxins12020097 - 3 Feb 2020

Cited by 23 | Viewed by 4403

Abstract

In this study, durum wheat kernels harvested in three climatically different Italian cultivation areas (Emilia Romagna, Umbria and Sardinia) in 2015, were analyzed with a combination of different isolation methods to determine their fungal communities, with a focus on Fusarium head blight (FHB) [...] Read more.

In this study, durum wheat kernels harvested in three climatically different Italian cultivation areas (Emilia Romagna, Umbria and Sardinia) in 2015, were analyzed with a combination of different isolation methods to determine their fungal communities, with a focus on Fusarium head blight (FHB) complex composition, and to detect fungal secondary metabolites in the grains. The genus Alternaria was the main component of durum wheat mycobiota in all investigated regions, with the Central Italian cultivation area showing the highest incidence of this fungal genus and of its secondary metabolites. Fusarium was the second most prevalent genus of the fungal community in all cultivation environments, even if regional differences in species composition were detected. In particular, Northern areas showed the highest Fusarium incidence, followed by Central and then Southern cultivation areas. Focusing on the FHB complex, a predominance of Fusarium poae, in particular in Northern and Central cultivation areas, was found. Fusarium graminearum, in the analyzed year, was mainly detected in Emilia Romagna. Because of the highest Fusarium incidence, durum wheat harvested in the Northern cultivation area showed the highest presence of Fusarium secondary metabolites. These results show that durum wheat cultivated in Northern Italy may be subject to a higher FHB infection risk and to Fusarium mycotoxins accumulation. Full article

(This article belongs to the Section Mycotoxins)

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19 pages, 2918 KiB

Open AccessEditor’s ChoiceArticle

Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components

by Michelle Teixeira de Almeida, Luciana Aparecida Freitas-de-Sousa, Monica Colombini, Sarah N. C. Gimenes, Eduardo S. Kitano, Eliana L. Faquim-Mauro, Solange M. T. Serrano and Ana Maria Moura-da-Silva

Toxins 2020, 12(2), 96; https://doi.org/10.3390/toxins12020096 - 2 Feb 2020

Cited by 24 | Viewed by 3006

Abstract

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products [...] Read more.

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 μg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 10⁶ with ATXL and 5 × 10⁶ with BATXH. TNF-α was identified in the supernatant of BATXH—or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC–MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4–5 × 10⁶) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways. Full article

(This article belongs to the Section Animal Venoms)

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11 pages, 1898 KiB

Open AccessEditor’s ChoiceArticle

A Liquid Chromatographic Method for Rapid and Sensitive Analysis of Aflatoxins in Laboratory Fungal Cultures

by Ahmad F. Alshannaq and Jae-Hyuk Yu

Toxins 2020, 12(2), 93; https://doi.org/10.3390/toxins12020093 - 30 Jan 2020

Cited by 15 | Viewed by 5058

Abstract

Culture methods supplemented with high-performance liquid chromatography (HPLC) technique provide a rapid and simple tool for detecting levels of aflatoxins (AFs) produced by fungi. This study presents a robust method for simultaneous quantification of aflatoxin (AF) B1, B2, G1, and G2 levels in [...] Read more.

Culture methods supplemented with high-performance liquid chromatography (HPLC) technique provide a rapid and simple tool for detecting levels of aflatoxins (AFs) produced by fungi. This study presents a robust method for simultaneous quantification of aflatoxin (AF) B1, B2, G1, and G2 levels in several fungal cultivation states: submerged shake culture, liquid slant culture, and solid-state culture. The recovery of the method was evaluated by spiking a mixture of AFs at several concentrations to the test medium. The applicability of the method was evaluated by using aflatoxigenic and non-aflatoxigenic Aspergilli. A HPLC coupled with the diode array (DAD) and fluorescence (FLD) detectors was used to determine the presence and amounts of AFs. Both detectors showed high sensitivity in detecting spiked AFs or AFs produced in situ by toxigenic fungi. Our methods showed 76%–88% recovery from medium spiked with 2.5, 10, 50, 100, and 500 ng/mL AFs. The limit of quantification (LOQ) for AFs were 2.5 to 5.0 ng/mL with DAD and 0.025 to 2.5 ng/mL with FLD. In this work, we described in detail a protocol, which can be considered the foremost and only verified method, to extract, detect, and quantify AFs employing both aflatoxigenic and non-toxigenic Aspergilli. Full article

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

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13 pages, 2854 KiB

Open AccessEditor’s ChoiceArticle

T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes

by Huadong Yin, Shunshun Han, Yuqi Chen, Yan Wang, Diyan Li and Qing Zhu

Toxins 2020, 12(2), 90; https://doi.org/10.3390/toxins12020090 - 29 Jan 2020

Cited by 47 | Viewed by 3808

Abstract

T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven [...] Read more.

T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven that T-2 toxin caused hepatotoxicity in chicken, but the regulatory mechanism is unclear. In the present study, we assessed the toxicological effect of T-2 toxin on apoptosis and autophagy in hepatocytes. The total of 120 1-day-old healthy broilers were allocated randomly into four groups and reared for 21 day with complete feed containing 0 mg/kg, 0.5 mg/kg, 1 mg/kg or 2 mg/kg T-2 toxin, respectively. The results showed that the apoptosis rate and pathological changes degree hepatocytes were aggravated with the increase of T-2 toxin. At the molecular mechanism level, T-2 toxin induced mitochondria-mediated apoptosis by producing reactive oxygen species, promoting cytochrome c translocation between the mitochondria and cytoplasm, and thus promoting apoptosomes formation. Meanwhile, the expression of the autophagy-related protein, ATG5, ATG7 and Beclin-1, and the LC3-II/LC3-I ratio were increased, while p62 was downregulated, suggesting T-2 toxin caused autophagy in hepatocytes. Further experiments demonstrated that the PI3K/AKT/mTOR signal may be participated in autophagy induced by T-2 toxin in chicken hepatocytes. These data suggest a possible underlying molecular mechanism for T-2 toxin that induces apoptosis and autophagy in chicken hepatocytes Full article

(This article belongs to the Special Issue Toxicological Effects of Mycotoxins on Target Cells)

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10 pages, 884 KiB

Open AccessEditor’s ChoiceArticle

Acute Oral Toxicity of Pinnatoxin G in Mice

by Silvio Sosa, Marco Pelin, Federica Cavion, Fabienne Hervé, Philipp Hess and Aurelia Tubaro

Toxins 2020, 12(2), 87; https://doi.org/10.3390/toxins12020087 - 28 Jan 2020

Cited by 25 | Viewed by 3676

Abstract

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, [...] Read more.

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg⁻¹). At the dose of 220 µg kg⁻¹ and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg⁻¹, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD₅₀ for PnTx-G equal to 208 μg kg⁻¹ (95% confidence limits: 155–281 µg kg⁻¹) and to estimate a provisional NOEL of 120 µg kg⁻¹. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

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22 pages, 1204 KiB

Open AccessEditor’s ChoiceArticle

Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population

by Dina Raafat, Daniel M. Mrochen, Fawaz Al’Sholui, Elisa Heuser, René Ryll, Kathleen R. Pritchett-Corning, Jens Jacob, Bernd Walther, Franz-Rainer Matuschka, Dania Richter, Uta Westerhüs, Jiri Pikula, Jens van den Brandt, Werner Nicklas, Stefan Monecke, Birgit Strommenger, Sarah van Alen, Karsten Becker, Rainer G. Ulrich and Silva Holtfreter

Toxins 2020, 12(2), 80; https://doi.org/10.3390/toxins12020080 - 24 Jan 2020

Cited by 16 | Viewed by 5242

Abstract

Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and [...] Read more.

Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4%) than laboratory rats (12.3%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

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15 pages, 6311 KiB

Open AccessEditor’s ChoiceArticle

Bioprospecting Sponge-Associated Marine Cyanobacteria to Produce Bioactive Compounds

by Despoina Konstantinou, Eleni Mavrogonatou, Sevasti-Kiriaki Zervou, Panagiotis Giannogonas and Spyros Gkelis

Toxins 2020, 12(2), 73; https://doi.org/10.3390/toxins12020073 - 23 Jan 2020

Cited by 20 | Viewed by 6577

Abstract

Marine cyanobacteria are considered a prolific source of bioactive natural products with a range of biotechnological and pharmacological applications. However, data on the production of natural compounds from sponge-associated cyanobacteria are scarce. This study aimed to assess the potential of sponge-associated cyanobacteria strains [...] Read more.

Marine cyanobacteria are considered a prolific source of bioactive natural products with a range of biotechnological and pharmacological applications. However, data on the production of natural compounds from sponge-associated cyanobacteria are scarce. This study aimed to assess the potential of sponge-associated cyanobacteria strains representing different taxonomic groups for the production of bioactive compounds and the biological activity of their extracts. Phylogenetic analysis of sponge-associated cyanobacteria and screening for the presence of genes encoding non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) were performed. Methanol extracts of the sponge-associated strains were analyzed for cyanotoxin production and tested for antioxidant activity and cytotoxic activity against several human cancer cell lines and pathogenic bacteria. PKS were detected in all sponge-associated strains examined, indicating the metabolic potential of the isolates. PKS genes were more ubiquitous than NRPS genes. Cyanotoxins (i.e., cylindrospermopsin, anatoxin-a, nodularin, and microcystins) were not detected in any of the sponge-associated cyanobacterial strains. Strains belonging to Leptothoe, Pseudanabaena, and Synechococcus were found to have activity mainly against Staphylococcus aureus. In addition, sponge-associated Leptothoe strains (TAU-MAC 0915, 1015, 1115, and 1215) were found to be highly cytotoxic and in most cases more effective against human cancer cell lines than against normal cells. Extracts with the most promising bioactivity deserve further investigation in order to isolate and identify the bioactive molecule(s). Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Conference on Toxic Cyanobacteria)

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15 pages, 1359 KiB

Open AccessEditor’s ChoiceArticle

Isolation and Characterization of [D-Leu¹]microcystin-LY from Microcystis aeruginosa CPCC-464

by Patricia LeBlanc, Nadine Merkley, Krista Thomas, Nancy I. Lewis, Khalida Békri, Susan LeBlanc Renaud, Frances R. Pick, Pearse McCarron, Christopher O. Miles and Michael A. Quilliam

Toxins 2020, 12(2), 77; https://doi.org/10.3390/toxins12020077 - 23 Jan 2020

Cited by 12 | Viewed by 3346

Abstract

[D-Leu¹]MC-LY (1) ([M + H]⁺ m/z 1044.5673, Δ 2.0 ppm), a new microcystin, was isolated from Microcystis aeruginosa strain CPCC-464. The compound was characterized by ¹H and ¹³C NMR spectroscopy, liquid chromatography–high resolution tandem [...] Read more.

[D-Leu¹]MC-LY (1) ([M + H]⁺ m/z 1044.5673, Δ 2.0 ppm), a new microcystin, was isolated from Microcystis aeruginosa strain CPCC-464. The compound was characterized by ¹H and ¹³C NMR spectroscopy, liquid chromatography–high resolution tandem mass spectrometry (LC–HRMS/MS) and UV spectroscopy. A calibration reference material was produced after quantitation by ¹H NMR spectroscopy and LC with chemiluminescence nitrogen detection. The potency of 1 in a protein phosphatase 2A inhibition assay was essentially the same as for MC-LR (2). Related microcystins, [D-Leu¹]MC-LR (3) ([M + H]⁺ m/z 1037.6041, Δ 1.0 ppm), [D-Leu¹]MC-M(O)R (6) ([M + H]⁺ m/z 1071.5565, Δ 2.0 ppm) and [D-Leu¹]MC-MR (7) ([M + H]⁺ m/z 1055.5617, Δ 2.2 ppm), were also identified in culture extracts, along with traces of [D-Leu¹]MC-M(O₂)R (8) ([M + H]⁺ m/z 1087.5510, Δ 1.6 ppm), by a combination of chemical derivatization and LC–HRMS/MS experiments. The relative abundances of 1, 3, 6, 7 and 8 in a freshly extracted culture in the positive ionization mode LC–HRMS were ca. 84, 100, 3.0, 11 and 0.05, respectively. These and other results indicate that [D-Leu¹]-containing MCs may be more common in cyanobacterial blooms than is generally appreciated but are easily overlooked with standard targeted LC–MS/MS screening methods. Full article

(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)

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12 pages, 1331 KiB

Open AccessEditor’s ChoiceArticle

Diet Breadth Mediates the Prey Specificity of Venom Potency in Snakes

by Keith Lyons, Michel M. Dugon and Kevin Healy

Toxins 2020, 12(2), 74; https://doi.org/10.3390/toxins12020074 - 23 Jan 2020

Cited by 40 | Viewed by 6616

Abstract

Venoms are best known for their ability to incapacitate prey. In predatory groups, venom potency is predicted to reflect ecological and evolutionary drivers relating to diet. While venoms have been found to have prey-specific potencies, the role of diet breadth on venom potencies [...] Read more.

Venoms are best known for their ability to incapacitate prey. In predatory groups, venom potency is predicted to reflect ecological and evolutionary drivers relating to diet. While venoms have been found to have prey-specific potencies, the role of diet breadth on venom potencies has yet to be tested at large macroecological scales. Here, using a comparative analysis of 100 snake species, we show that the evolution of prey-specific venom potencies is contingent on the breadth of a species’ diet. We find that while snake venom is more potent when tested on species closely related to natural prey items, we only find this prey-specific pattern in species with taxonomically narrow diets. While we find that the taxonomic diversity of a snakes’ diet mediates the prey specificity of its venom, the species richness of its diet was not found to affect these prey-specific potency patterns. This indicates that the physiological diversity of a species’ diet is an important driver of the evolution of generalist venom potencies. These findings suggest that the venoms of species with taxonomically diverse diets may be better suited to incapacitating novel prey species and hence play an important role for species within changing environments. Full article

(This article belongs to the Special Issue Evolutionary Ecology of Venom)

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22 pages, 6180 KiB

Open AccessEditor’s ChoiceArticle

Ostreopsis cf. ovata (Dinophyceae) Molecular Phylogeny, Morphology, and Detection of Ovatoxins in Strains and Field Samples from Brazil

by Silvia M. Nascimento, Raquel A. F. Neves, Gabriela A. L. De’Carli, Geovanna T. Borsato, Rodrigo A. F. da Silva, Guilherme A. Melo, Agatha M. de Morais, Thais C. Cockell, Santiago Fraga, Adriana D. Menezes-Salgueiro, Luiz L. Mafra, Philipp Hess and Fabiano Salgueiro

Toxins 2020, 12(2), 70; https://doi.org/10.3390/toxins12020070 - 22 Jan 2020

Cited by 19 | Viewed by 3348

Abstract

Recurrent blooms of Ostreopsis cf. ovata have been reported in Brazil and the Mediterranean Sea with associated ecological, and in the latter case, health impacts. Molecular data based on the D1–D3 and D8–D10 regions of the LSU rDNA and ITS loci, and the [...] Read more.

Recurrent blooms of Ostreopsis cf. ovata have been reported in Brazil and the Mediterranean Sea with associated ecological, and in the latter case, health impacts. Molecular data based on the D1–D3 and D8–D10 regions of the LSU rDNA and ITS loci, and the morphology of O. cf. ovata isolates and field populations from locations along the Brazilian tropical and subtropical coastal regions and three oceanic islands are presented. Additional ITS sequences from three single cells from the tropical coast are provided. Toxin profiles and quantities of PLTX and their analogues; OVTXs; contained in cells from two clonal cultures and two field blooms from Rio de Janeiro were investigated. Morphology was examined using both light and epifluorescence microscopy. Morphometric analysis of different strains and field populations from diverse locations were compared. Molecular analysis showed that six of the seven sequences grouped at the large “Atlantic/Mediterranean/Pacific” sub-clade, while one sequence branched in a sister clade with sequences from Madeira Island and Greece. The toxin profile of strains and bloom field samples from Rio de Janeiro were dominated by OVTX-a and -b, with total cell quotas (31.3 and 39.3 pg cell⁻¹) in the range of that previously reported for strains of O. cf. ovata. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

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26 pages, 1819 KiB

Open AccessEditor’s ChoiceReview

Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways

by Philip E. Bickler

Toxins 2020, 12(2), 68; https://doi.org/10.3390/toxins12020068 - 22 Jan 2020

Cited by 52 | Viewed by 14948

Abstract

The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, [...] Read more.

The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, inflammation, coagulopathy, cell/organ injury, and disruption of homeostatic mechanisms of normal physiology. In this review, we describe how snakebite is not only a condition mediated directly by venom, but by the amplification of signals dysregulating inflammation, coagulation, neurotransmission, and cell survival. Although venom proteins are diverse, the majority of important pathologic events following envenoming follow from a small group of enzyme-like activities and the actions of small toxic peptides. This review focuses on two of the most important enzymatic activities: snake venom phospholipases (svPLA₂) and snake venom metalloproteases (svMP). These two enzyme classes are adept at enabling venom to recruit homologous endogenous signaling systems with sufficient magnitude and duration to produce and amplify cell injury beyond what would be expected from the direct impact of a whole venom dose. This magnification produces many of the most acutely important consequences of envenoming as well as chronic sequelae. Snake venom PLA₂s and MPs enzymes recruit prey analogs of similar activity. The transduction mechanisms that recruit endogenous responses include arachidonic acid, intracellular calcium, cytokines, bioactive peptides, and possibly dimerization of venom and prey protein homologs. Despite years of investigation, the precise mechanism of svPLA₂-induced neuromuscular paralysis remains incomplete. Based on recent studies, paralysis results from a self-amplifying cycle of endogenous PLA₂ activation, arachidonic acid, increases in intracellular Ca²⁺ and nicotinic receptor deactivation. When prolonged, synaptic suppression supports the degeneration of the synapse. Interaction between endothelium-damaging MPs, sPLA₂s and hyaluronidases enhance venom spread, accentuating venom-induced neurotoxicity, inflammation, coagulopathy and tissue injury. Improving snakebite treatment requires new tools to understand direct and indirect effects of envenoming. Homologous PLA₂ and MP activities in both venoms and prey/snakebite victim provide molecular targets for non-antibody, small molecule agents for dissecting mechanisms of venom toxicity. Importantly, these tools enable the separation of venom-specific and prey-specific pathological responses to venom. Full article

(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)

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22 pages, 3218 KiB

Open AccessEditor’s ChoiceReview

Bacterial Genotoxin-Induced DNA Damage and Modulation of the Host Immune Microenvironment

by Océane C.B. Martin and Teresa Frisan

Toxins 2020, 12(2), 63; https://doi.org/10.3390/toxins12020063 - 21 Jan 2020

Cited by 37 | Viewed by 5081

Abstract

Bacterial genotoxins (BTGX) induce DNA damage, which results in senescence or apoptosis of the target cells if not properly repaired. Three BTGXs have been identified: the cytolethal distending toxin (CDT) family produced by several Gram-negative bacteria, the typhoid toxin produced by several Salmonella [...] Read more.

Bacterial genotoxins (BTGX) induce DNA damage, which results in senescence or apoptosis of the target cells if not properly repaired. Three BTGXs have been identified: the cytolethal distending toxin (CDT) family produced by several Gram-negative bacteria, the typhoid toxin produced by several Salmonella enterica serovars, and colibactin, a peptide-polyketide, produced mainly by the phylogenetic group B2 Escherichia coli. The cellular responses induced by BTGXs resemble those of well-characterized carcinogenic agents, and several lines of evidence indicate that bacteria carrying genotoxin genes can contribute to tumor development under specific circumstances. Given their unusual mode of action, it is still enigmatic why these effectors have been acquired by microbes and what is their role in the context of the biology of the producing bacterium, since it is unlikely that their primary purpose is to induce/promote cancer in the mammalian host. In this review, we will discuss the possibility that the DNA damage induced by BTGX modulates the host immune response, acting as immunomodulator, leading to the establishment of a suitable niche for the producing bacterium. We will further highlight open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins. Full article

(This article belongs to the Special Issue Current Knowledge on Bacterial Genotoxins and Their Effects on Host Cells)

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15 pages, 1366 KiB

Open AccessEditor’s ChoiceReview

Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities

by Andreas Aufschnaiter, Verena Kohler, Shaden Khalifa, Aida Abd El-Wahed, Ming Du, Hesham El-Seedi and Sabrina Büttner

Toxins 2020, 12(2), 66; https://doi.org/10.3390/toxins12020066 - 21 Jan 2020

Cited by 48 | Viewed by 9040

Abstract

Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent [...] Read more.

Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent years, multifactorial diseases such as cancer, rheumatoid arthritis and neurodegenerative diseases remain major healthcare issues at present. Although pure bee venom, apitoxin, is mostly described to mediate anti-inflammatory, anti-arthritic and neuroprotective effects, its primary component melittin may represent an anticancer therapeutic. In this review, we approach the possibilities and limitations of apitoxin and its components in the treatment of these multifactorial diseases. We further discuss the observed unspecific cytotoxicity of melittin that strongly restricts its therapeutic use and review interesting possibilities of a beneficial use by selectively targeting melittin to cancer cells. Full article

(This article belongs to the Section Animal Venoms)

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46 pages, 2076 KiB

Open AccessEditor’s ChoiceReview

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

by Adrien Joseph, Aurélie Cointe, Patricia Mariani Kurkdjian, Cédric Rafat and Alexandre Hertig

Toxins 2020, 12(2), 67; https://doi.org/10.3390/toxins12020067 - 21 Jan 2020

Cited by 125 | Viewed by 12774

Abstract

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their [...] Read more.

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

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12 pages, 913 KiB

Open AccessEditor’s ChoiceReview

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

by Britt Opdebeeck, Patrick C. D’Haese and Anja Verhulst

Toxins 2020, 12(1), 58; https://doi.org/10.3390/toxins12010058 - 19 Jan 2020

Cited by 38 | Viewed by 5442

Abstract

The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired [...] Read more.

The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired coronary perfusion in the elderly and patients with chronic kidney disease (CKD) and diabetes. Recently, we reported that both IS and PCS trigger moderate to severe calcification in the aorta and peripheral vessels of CKD rats. This review describes the molecular and cellular mechanisms by which these uremic toxins induce arterial media calcification. A complex interplay between inflammation, coagulation, and lipid metabolism pathways, influenced by epigenetic factors, is crucial in IS/PCS-induced arterial media calcification. High levels of glucose are linked to these events, suggesting that a good balance between glucose and lipid levels might be important. On the cellular level, effects on endothelial cells, which act as the primary sensors of circulating pathological triggers, might be as important as those on vascular smooth muscle cells. Endothelial dysfunction, provoked by IS and PCS triggered oxidative stress, may be considered a key event in the onset and development of arterial media calcification. In this review a number of important outstanding questions such as the role of miRNA’s, phenotypic switching of both endothelial and vascular smooth muscle cells and new types of programmed cell death in arterial media calcification related to protein-bound uremic toxins are put forward and discussed. Full article

(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))

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10 pages, 817 KiB

Open AccessEditor’s ChoiceArticle

Patulin Mycotoxin in Mango and Orange Fruits, Juices, Pulps, and Jams Marketed in Pakistan

by Shabbir Hussain, Muhammad Rafique Asi, Mazhar Iqbal, Nisha Khalid, Syed Wajih-ul-Hassan and Agustín Ariño

Toxins 2020, 12(1), 52; https://doi.org/10.3390/toxins12010052 - 16 Jan 2020

Cited by 33 | Viewed by 5159

Abstract

The objective of the study was to explore the incidence of patulin (PAT) mycotoxin in mango and orange fruits and derived products marketed in Pakistan. A total of 274 samples, including 70 mango fruits, 63 mango-based products (juices, pulp, and jam), 77 orange [...] Read more.

The objective of the study was to explore the incidence of patulin (PAT) mycotoxin in mango and orange fruits and derived products marketed in Pakistan. A total of 274 samples, including 70 mango fruits, 63 mango-based products (juices, pulp, and jam), 77 orange fruits, and 64 orange-based products, were collected. PAT was determined by reverse-phase high-performance liquid chromatography (HPLC) with UV-Vis detector (276 nm). Linear detector response was observed (R² > 0.99), the limit of detection (LOD) was 5 µg/kg and recovery percentage was 97.4%. The incidence of PAT in mango samples was 61.7%, and the concentration ranged from <LOD to 6415 µg/kg with a mean of 110.9 µg/kg. Our results showed the high susceptibility of mango fruits to patulin, and it was observed that decayed mango fruits were most contaminated with PAT. Among the mango samples, PAT concentration was higher in fruits than in processed products such as mango juice, pulp, and jam. Toxin incidence in orange samples was 52.5% with concentrations from <LOD to 61 µg/kg and a mean of 6.3 µg/kg. As much as 29 samples of mango (21.8%) contained PAT concentration above the regulatory limit (50 µg/kg), whereas there was only one exceeding orange sample (0.7%). Our results show that PAT seems to be a problem in fruits, juices, and derived solid products, especially from mango, and needs surveillance on regular basis. Full article

(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)

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16 pages, 6888 KiB

Open AccessEditor’s ChoiceArticle

Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics

by Chunfang Xie, Julien Slagboom, Laura-Oana Albulescu, Ben Bruyneel, Kristina B. M. Still, Freek J. Vonk, Govert W. Somsen, Nicholas R. Casewell and Jeroen Kool

Toxins 2020, 12(1), 53; https://doi.org/10.3390/toxins12010053 - 16 Jan 2020

Cited by 19 | Viewed by 5877

Abstract

Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused [...] Read more.

Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused by the multitude of injected toxins. In this study, the coagulopathic toxicities of venoms from the medically relevant snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus and Echis ocellatus were assessed. The venoms were separated by liquid chromatography (LC) followed by nanofractionation and parallel mass spectrometry (MS). A recently developed high-throughput coagulation assay was employed to assess both the pro- and anticoagulant activity of separated venom toxins. The neutralization capacity of antivenoms on separated venom components was assessed and the coagulopathic venom peptides and enzymes that were either neutralized or remained active in the presence of antivenom were identified by correlating bioassay results with the MS data and with off-line generated proteomics data. The results showed that most snake venoms analyzed contained both procoagulants and anticoagulants. Most anticoagulants were identified as phospholipases A₂s (PLA₂s) and most procoagulants correlated with snake venom metalloproteinases (SVMPs) and serine proteases (SVSPs). This information can be used to better understand antivenom neutralization and can aid in the development of next-generation antivenom treatments. Full article

(This article belongs to the Special Issue Medically Relevant Snake Toxins, Current Antivenoms and the Development of Next-Generation Antivenoms)

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21 pages, 1728 KiB

Open AccessEditor’s ChoiceReview

Ciguatera Fish Poisoning: The Risk from an Aotearoa/New Zealand Perspective

by Lesley L. Rhodes, Kirsty F. Smith, J. Sam Murray, Tomohiro Nishimura and Sarah C. Finch

Toxins 2020, 12(1), 50; https://doi.org/10.3390/toxins12010050 - 15 Jan 2020

Cited by 27 | Viewed by 4296

Abstract

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s [...] Read more.

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s northern subtropical coastline heighten the risk of Gambierdiscus proliferating in New Zealand. If this occurs, the risk of ciguatera fish poisoning due to consumption of locally caught fish will increase. Research, including the development and testing of sampling methods, molecular assays, and chemical and toxicity tests, will continue. Reliable monitoring strategies are important to manage and mitigate the risk posed by this emerging threat. The research approaches that have been made, many of which will continue, are summarised in this review. Full article

(This article belongs to the Special Issue Dinoflagellate Toxins)

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12 pages, 1198 KiB

Open AccessEditor’s ChoiceArticle

Dispersive Solid-Phase Extraction using Magnetic Carbon Nanotube Composite for the Determination of Emergent Mycotoxins in Urine Samples

by Natalia Arroyo-Manzanares, Rosa Peñalver-Soler, Natalia Campillo and Pilar Viñas

Toxins 2020, 12(1), 51; https://doi.org/10.3390/toxins12010051 - 15 Jan 2020

Cited by 15 | Viewed by 3341

Abstract

Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and [...] Read more.

Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and B1, and beauvericin) is investigated for the first time. Different magnetic nanoparticles were tested and a magnetic multiwalled carbon nanotube (Fe₃O₄@MWCNT) composite was selected for the extraction and preconcentration of the five target mycotoxins in human urine samples before their analysis by ultrahigh performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). The nanocomposite was characterized by energy dispersive X-ray spectrometry, scanning electron microscopy, Fourier transform infrared spectrophotometry, and X-ray diffraction. Several parameters affecting the adsorption and desorption of DMSPE steps were optimized and the method was fully validated. Due to a matrix effect, matrix-matched calibration curves were necessary to carry out quantification. In this way, limits of quantification of between 0.04 and 0.1 μg/L, relative standard deviation values lower than 12% and recoveries between 89.3% and 98.9% were obtained. Finally, a study of the reuse of the Fe₃O₄@MWCNT composite was carried out, confirming that it can be reused at least four times. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

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13 pages, 742 KiB

Open AccessEditor’s ChoiceArticle

Degradation of Aflatoxin B₁ by a Sustainable Enzymatic Extract from Spent Mushroom Substrate of Pleurotus eryngii

by Maria Teresa Branà, Lucrezia Sergio, Miriam Haidukowski, Antonio F. Logrieco and Claudio Altomare

Toxins 2020, 12(1), 49; https://doi.org/10.3390/toxins12010049 - 14 Jan 2020

Cited by 34 | Viewed by 4887

Abstract

Ligninolytic enzymes from white-rot fungi, such as laccase (Lac) and Mn-peroxidase (MnP), are able to degrade aflatoxin B₁ (AFB1), the most harmful among the known mycotoxins. The high cost of purification of these enzymes has limited their implementation into practical technologies. Every [...] Read more.

Ligninolytic enzymes from white-rot fungi, such as laccase (Lac) and Mn-peroxidase (MnP), are able to degrade aflatoxin B₁ (AFB1), the most harmful among the known mycotoxins. The high cost of purification of these enzymes has limited their implementation into practical technologies. Every year, tons of spent mushroom substrate (SMS) are produced as a by-product of edible mushroom cultivation, such as Pleurotus spp., and disposed at a cost for farmers. SMS may still bea source of ligninolytic enzymes useful for AFB1 degradation. The in vitro AFB1-degradative activity of an SMS crude extract (SMSE) was investigated. Results show that: (1) in SMSE, high Lac activity (4 U g⁻¹ dry matter) and low MnP activity (0.4 U g⁻¹ dry matter) were present; (2) after 1 d of incubation at 25 °C, the SMSE was able to degrade more than 50% of AFB1, whereas after 3 and 7 d of incubation, the percentage of degradation reached the values of 75% and 90%, respectively; (3) with increasing pH values, the degradation percentage increased, reaching 90% after 3 d at pH 8. Based on these results, SMS proved to be a suitable source of AFB1 degrading enzymes and the use of SMSE to detoxify AFB1 contaminated commodities appears conceivable. Full article

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16 pages, 6490 KiB

Open AccessEditor’s ChoiceArticle

T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line

by Junhua Yang, Wenbo Guo, Jianhua Wang, Xianli Yang, Zhiqi Zhang and Zhihui Zhao

Toxins 2020, 12(1), 43; https://doi.org/10.3390/toxins12010043 - 10 Jan 2020

Cited by 39 | Viewed by 4589

Abstract

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission [...] Read more.

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis. Full article

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19 pages, 2734 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Evaluation of the Efficiency of Yeast Cell Wall Extract to Adsorb Ochratoxin A and Mitigate Accumulation of the Toxin in Broiler Chickens

by Suvi Vartiainen, Alexandros Yiannikouris, Juha Apajalahti and Colm A. Moran

Toxins 2020, 12(1), 37; https://doi.org/10.3390/toxins12010037 - 7 Jan 2020

Cited by 19 | Viewed by 3998

Abstract

Ochratoxin A (OTA) is a common mycotoxin contaminant in animal feed. When absorbed from the gastrointestinal tract, OTA has a propensity for pathological effects on animal health and deposition in animal tissues. In this study, the potential of yeast cell wall extracts (YCWE) [...] Read more.

Ochratoxin A (OTA) is a common mycotoxin contaminant in animal feed. When absorbed from the gastrointestinal tract, OTA has a propensity for pathological effects on animal health and deposition in animal tissues. In this study, the potential of yeast cell wall extracts (YCWE) to adsorb OTA was evaluated using an in vitro method in which consecutive animal digestion events were simulated. Low pH markedly increased OTA binding to YCWE, which was reversed with a pH increased to 6.5. Overall, in vitro analysis revealed that 30% of OTA was adsorbed to YCWE. Additional computational molecular modelling revealed that change in pH alters the OTA charge and modulates the interaction with the YCWE β-d-glucans. The effectiveness of YCWE was tested in a 14-day broiler chicken trial. Birds were subjected to five dietary treatments; with and without OTA, and OTA combined with YCWE at three dosages. At the end of the trial, liver OTA deposition was evaluated. Data showed a decrease of up to 30% in OTA deposits in the liver of broilers fed both OTA and YCWE. In the case of OTA, a tight correlation between the mitigation efficacy of YCWE between in vitro and in vivo model could be observed. Full article

(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)

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26 pages, 1038 KiB

Open AccessEditor’s ChoiceReview

Natural Sources and Bioactivities of 2,4-Di-Tert-Butylphenol and Its Analogs

by Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su and Shiyou Li

Toxins 2020, 12(1), 35; https://doi.org/10.3390/toxins12010035 - 6 Jan 2020

Cited by 156 | Viewed by 10881

Abstract

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and [...] Read more.

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, eight families), and animals (five species, five families). 2,4-DTBP is often a major component of violate or essential oils and it exhibits potent toxicity against almost all testing organisms, including the producers; however, it is not clear why organisms produce autotoxic 2,4-DTBP and its analogs. The accumulating evidence indicates that the endocidal regulation seems to be the primary function of the phenols in the producing organisms. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

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14 pages, 820 KiB

Open AccessEditor’s ChoiceReview

Botulinum Neurotoxins and Cancer—A Review of the Literature

by Shivam O. Mittal and Bahman Jabbari

Toxins 2020, 12(1), 32; https://doi.org/10.3390/toxins12010032 - 5 Jan 2020

Cited by 26 | Viewed by 6198

Abstract

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the [...] Read more.

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed. Full article

(This article belongs to the Special Issue Toxins and Cancer Therapy)

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14 pages, 1783 KiB

Open AccessEditor’s ChoiceArticle

Occurrence and Characterization of Fungi and Mycotoxins in Contaminated Medicinal Herbs

by Ling Chen, Weipeng Guo, Yuqing Zheng, Jinzhen Zhou, Tingting Liu, Wei Chen, Daqing Liang, Meiping Zhao, Yudan Zhu, Qingping Wu and Jumei Zhang

Toxins 2020, 12(1), 30; https://doi.org/10.3390/toxins12010030 - 3 Jan 2020

Cited by 40 | Viewed by 8814

Abstract

Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In [...] Read more.

Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In total, 70.8% of herbs were slightly contaminated with aflatoxins (<5 μg kg⁻¹). Codonopsis radix samples contained ochratoxin A (OTA) (360–515 μg kg⁻¹), and Scutellariae radix samples contained OTA (49–231 μg kg⁻¹) and citrinin (15–53 μg kg⁻¹). Forty samples (83.3%) contained fungal contamination. Sixty-nine strains were characterized via morphological and molecular identification. The predominant mycoflora comprised four genera, Aspergillus spp. (26.1%), Penicillium spp. (24.6%), Rhizopus spp. (14.5%), and Trichoderma spp. (11.6%). Aflatoxins, OTA, and citrinin were detected in 37 cultures by high-performance liquid chromatography-tandem mass spectrometry. Approximately 21.6% of Aspergillus and Penicillium isolates produced mycotoxins. One Penicillium polonicum strain isolated from Scutellariae radix synthesized citrinin. Multiplex PCR analysis showed that three Aspergillus flavus strains harbored aflatoxin biosynthesis genes. One Aspergillus flavus strain isolated from Amomi fructus produced AFB₁ and AFB₂. To the best of our knowledge, the citrinin production by Aspergillus chevalieri and Penicillium sacculum was first reported in this study, which poses a potential risk of mycotoxin contamination in medicinal herbs. Full article

(This article belongs to the Section Mycotoxins)

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21 pages, 1574 KiB

Open AccessEditor’s ChoiceReview

Control of Aflatoxigenic Molds by Antagonistic Microorganisms: Inhibitory Behaviors, Bioactive Compounds, Related Mechanisms, and Influencing Factors

by Xianfeng Ren, Qi Zhang, Wen Zhang, Jin Mao and Peiwu Li

Toxins 2020, 12(1), 24; https://doi.org/10.3390/toxins12010024 - 1 Jan 2020

Cited by 55 | Viewed by 5900

Abstract

Aflatoxin contamination has been causing great concern worldwide due to the major economic impact on crop production and their toxicological effects to human and animals. Contamination can occur in the field, during transportation, and also in storage. Post-harvest contamination usually derives from the [...] Read more.

Aflatoxin contamination has been causing great concern worldwide due to the major economic impact on crop production and their toxicological effects to human and animals. Contamination can occur in the field, during transportation, and also in storage. Post-harvest contamination usually derives from the pre-harvest infection of aflatoxigenic molds, especially aflatoxin-producing Aspergilli such as Aspergillus flavus and A. parasiticus. Many strategies preventing aflatoxigenic molds from entering food and feed chains have been reported, among which biological control is becoming one of the most praised strategies. The objective of this article is to review the biocontrol strategy for inhibiting the growth of and aflatoxin production by aflatoxigenic fungi. This review focuses on comparing inhibitory behaviors of different antagonistic microorganisms including various bacteria, fungi and yeasts. We also reviewed the bioactive compounds produced by microorganisms and the mechanisms leading to inhibition. The key factors influencing antifungal activities of antagonists are also discussed in this review. Full article

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16 pages, 2816 KiB

Open AccessEditor’s ChoiceArticle

Phytotoxic Responses of Soybean (Glycine max L.) to Botryodiplodin, a Toxin Produced by the Charcoal Rot Disease Fungus, Macrophomina phaseolina

by Hamed K. Abbas, Nacer Bellaloui, Alemah M. Butler, Justin L. Nelson, Mohamed Abou-Karam and W. Thomas Shier

Toxins 2020, 12(1), 25; https://doi.org/10.3390/toxins12010025 - 1 Jan 2020

Cited by 25 | Viewed by 4202

Abstract

Toxins have been proposed to facilitate fungal root infection by creating regions of readily-penetrated necrotic tissue when applied externally to intact roots. Isolates of the charcoal rot disease fungus, Macrophomina phaseolina, from soybean plants in Mississippi produced a phytotoxic toxin, (−)-botryodiplodin, but [...] Read more.

Toxins have been proposed to facilitate fungal root infection by creating regions of readily-penetrated necrotic tissue when applied externally to intact roots. Isolates of the charcoal rot disease fungus, Macrophomina phaseolina, from soybean plants in Mississippi produced a phytotoxic toxin, (−)-botryodiplodin, but no detectable phaseolinone, a toxin previously proposed to play a role in the root infection mechanism. This study was undertaken to determine if (−)-botryodiplodin induces toxic responses of the types that could facilitate root infection. (±)-Botryodiplodin prepared by chemical synthesis caused phytotoxic effects identical to those observed with (−)-botryodiplodin preparations from M. phaseolina culture filtrates, consistent with fungus-induced phytotoxicity being due to (−)-botryodiplodin, not phaseolinone or other unknown impurities. Soybean leaf disc cultures of Saline cultivar were more susceptible to (±)-botryodiplodin phytotoxicity than were cultures of two charcoal rot-resistant genotypes, DS97-84-1 and DT97-4290. (±)-Botryodiplodin caused similar phytotoxicity in actively growing duckweed (Lemna pausicostata) plantlet cultures, but at much lower concentrations. In soybean seedlings growing in hydroponic culture, (±)-botryodiplodin added to culture medium inhibited lateral and tap root growth, and caused loss of root caps and normal root tip cellular structure. Thus, botryodiplodin applied externally to undisturbed soybean roots induced phytotoxic responses of types expected to facilitate fungal root infection. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

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20 pages, 595 KiB

Open AccessEditor’s ChoiceArticle

Suppressing Cyanobacteria with Hydrogen Peroxide Is More Effective at High Light Intensities

by Tim Piel, Giovanni Sandrini, Emily White, Tianshuo Xu, J. Merijn Schuurmans, Jef Huisman and Petra M. Visser

Toxins 2020, 12(1), 18; https://doi.org/10.3390/toxins12010018 - 31 Dec 2019

Cited by 36 | Viewed by 5683

Abstract

Hydrogen peroxide (H₂O₂) can be used as an emergency method to selectively suppress cyanobacterial blooms in lakes and drinking water reservoirs. However, it is largely unknown how environmental parameters alter the effectiveness of H₂O₂ treatments. In [...] Read more.

Hydrogen peroxide (H₂O₂) can be used as an emergency method to selectively suppress cyanobacterial blooms in lakes and drinking water reservoirs. However, it is largely unknown how environmental parameters alter the effectiveness of H₂O₂ treatments. In this study, the toxic cyanobacterial strain Microcystis aeruginosa PCC 7806 was treated with a range of H₂O₂ concentrations (0 to 10 mg/L), while being exposed to different light intensities and light colors. H₂O₂ treatments caused a stronger decline of the photosynthetic yield in high light than in low light or in the dark, and also a stronger decline in orange than in blue light. Our results are consistent with the hypothesis that H₂O₂ causes major damage at photosystem II (PSII) and interferes with PSII repair, which makes cells more sensitive to photoinhibition. Furthermore, H₂O₂ treatments caused a decrease in cell size and an increase in extracellular microcystin concentrations, indicative of leakage from disrupted cells. Our findings imply that even low H₂O₂ concentrations of 1–2 mg/L can be highly effective, if cyanobacteria are exposed to high light intensities. We therefore recommend performing lake treatments during sunny days, when a low H₂O₂ dosage is sufficient to suppress cyanobacteria, and may help to minimize impacts on non-target organisms. Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Conference on Toxic Cyanobacteria)

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23 pages, 4732 KiB

Open AccessEditor’s ChoiceReview

Two-Dimensional Layered Nanomaterial-Based Electrochemical Biosensors for Detecting Microbial Toxins

by Zhuheng Li, Xiaotong Li, Minghong Jian, Girma Selale Geleta and Zhenxin Wang

Toxins 2020, 12(1), 20; https://doi.org/10.3390/toxins12010020 - 31 Dec 2019

Cited by 26 | Viewed by 5292

Abstract

Toxin detection is an important issue in numerous fields, such as agriculture/food safety, environmental monitoring, and homeland security. During the past two decades, nanotechnology has been extensively used to develop various biosensors for achieving fast, sensitive, selective and on-site analysis of toxins. In [...] Read more.

Toxin detection is an important issue in numerous fields, such as agriculture/food safety, environmental monitoring, and homeland security. During the past two decades, nanotechnology has been extensively used to develop various biosensors for achieving fast, sensitive, selective and on-site analysis of toxins. In particular, the two dimensional layered (2D) nanomaterials (such as graphene and transition metal dichalcogenides (TMDs)) and their nanocomposites have been employed as label and/or biosensing transducers to construct electrochemical biosensors for cost-effective detection of toxins with high sensitivity and specificity. This is because the 2D nanomaterials have good electrical conductivity and a large surface area with plenty of active groups for conjugating 2D nanomaterials with the antibodies and/or aptamers of the targeted toxins. Herein, we summarize recent developments in the application of 2D nanomaterial-based electrochemical biosensors for detecting toxins with a particular focus on microbial toxins including bacterial toxins, fungal toxins and algal toxins. The integration of 2D nanomaterials with some existing antibody/aptamer technologies into electrochemical biosensors has led to an unprecedented impact on improving the assaying performance of microbial toxins, and has shown great promise in public health and environmental protection. Full article

(This article belongs to the Special Issue Improved Analytical Technologies for the Detection of Natural Toxins and Their Metabolites in Food)

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16 pages, 1177 KiB

Open AccessEditor’s ChoiceArticle

Potential Application of Lactic Acid Bacteria to Reduce Aflatoxin B₁ and Fumonisin B₁ Occurrence on Corn Kernels and Corn Ears

by Tiago de Melo Nazareth, Carlos Luz, Raquel Torrijos, Juan Manuel Quiles, Fernando Bittencourt Luciano, Jordi Mañes and Giuseppe Meca

Toxins 2020, 12(1), 21; https://doi.org/10.3390/toxins12010021 - 31 Dec 2019

Cited by 56 | Viewed by 4737

Abstract

Fungal spoilage is an important issue for the food industry, leading to food sensory defects, food waste, economic losses and public health concern through the production of mycotoxins. Concomitantly, the search for safer natural products has gained importance since consumers began to look [...] Read more.

Fungal spoilage is an important issue for the food industry, leading to food sensory defects, food waste, economic losses and public health concern through the production of mycotoxins. Concomitantly, the search for safer natural products has gained importance since consumers began to look for less processed and chemically treated foods. In this context, the aim of this study was to evaluate the antifungal and antimycotoxigenic effect of seven strains of Lactobacillus plantarum. Lactic acid bacteria (LAB) were grown on Man Rogosa Sharpe (MRS) broth at 37 °C in anaerobic conditions. After that, the cell-free supernatant (CFS) were recovered to determine its antifungal activity by halo diffusion agar test. In addition, minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) was determined for each L. plantarum CFS by 96-well microplates method. Additionally, CFS was used as a natural biocontrol agent on corn kernels and corn ears contaminated with Aspergillus flavus and Fusarium verticillioides, respectively. The L. plantarum CECT 749 CFS showed the highest antifungal effect against all essayed strains. Moreover, the employment of this CFS in food reduced the mycotoxin production at a percentage ranging from 73.7 to 99.7%. These results suggest that the L. plantarum CECT 749 CFS could be promising for the biocontrol of corn. Full article

(This article belongs to the Special Issue Aflatoxins: Food Sources, Occurrence and Toxicological Effects)

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15 pages, 3082 KiB

Open AccessEditor’s ChoiceArticle

Inflammasome Activation Induced by a Snake Venom Lys49-Phospholipase A₂ Homologue

by Charles Nunes Boeno, Mauro Valentino Paloschi, Jéssica Amaral Lopes, Weverson Luciano Pires, Sulamita da Silva Setúbal, Jaína Rodrigues Evangelista, Andreimar Martins Soares and Juliana Pavan Zuliani

Toxins 2020, 12(1), 22; https://doi.org/10.3390/toxins12010022 - 31 Dec 2019

Cited by 22 | Viewed by 4103

Abstract

Background: Snake venom phospholipases A₂ (PLA₂s) have hemolytic, anticoagulant, myotoxic, oedematogenic, bactericidal, and inflammatory actions. BthTX-I, a Lys49-PLA₂ isolated from Bothrops jararacussu venom, is an example of Lys49-PLA₂ that presents such actions. NLRP3 is a cytosolic receptor from [...] Read more.

Background: Snake venom phospholipases A₂ (PLA₂s) have hemolytic, anticoagulant, myotoxic, oedematogenic, bactericidal, and inflammatory actions. BthTX-I, a Lys49-PLA₂ isolated from Bothrops jararacussu venom, is an example of Lys49-PLA₂ that presents such actions. NLRP3 is a cytosolic receptor from the NLR family responsible for inflammasome activation via caspase-1 activation and IL-1β liberation. The study of NLRs that recognize tissue damage and activate the inflammasome is relevant in envenomation. Methods: Male mice (18–20 g) received an intramuscular injection of BthTX-I or sterile saline. The serum was collected for creatine-kinase (CK), lactate dehydrogenase (LDH), and interleukin-1β (IL-1β) assays, and muscle was removed for inflammasome activation immunoblotting and qRT-PCR expression for nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin-containing domain 3 receptor (NLRP3) inflammasome components. Results: BthTX-I-induced inflammation and myonecrosis, shown by intravital microscope, and LDH and CK release, respectively. Mouse treatment with A438079, a P2X7 receptor antagonist, did not modify these effects. BthTX-I induced inflammasome activation in muscle, but P2X7R participation in this effect was not observed. Conclusion: Together, the results showed for the first time that BthTX-I in gastrocnemius muscle induces inflammation and consequently, inflammasome activation via NLRP3 with caspase-1 activation and IL-1β liberation. Full article

(This article belongs to the Section Animal Venoms)

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24 pages, 846 KiB

Open AccessEditor’s ChoiceReview

Public Health Risk Associated with Botulism as Foodborne Zoonoses

by Christine Rasetti-Escargueil, Emmanuel Lemichez and Michel R. Popoff

Toxins 2020, 12(1), 17; https://doi.org/10.3390/toxins12010017 - 30 Dec 2019

Cited by 51 | Viewed by 12062

Abstract

Botulism is a rare but severe neurological disease in man and animals that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum and atypical strains from other Clostridium and non-Clostridium species. BoNTs are divided into more than seven toxinotypes based on [...] Read more.

Botulism is a rare but severe neurological disease in man and animals that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum and atypical strains from other Clostridium and non-Clostridium species. BoNTs are divided into more than seven toxinotypes based on neutralization with specific corresponding antisera, and each toxinotype is subdivided into subtypes according to amino acid sequence variations. Animal species show variable sensitivity to the different BoNT toxinotypes. Thereby, naturally acquired animal botulism is mainly due to BoNT/C, D and the mosaic variants CD and DC, BoNT/CD being more prevalent in birds and BoNT/DC in cattle, whereas human botulism is more frequently in the types A, B and E, and to a lower extent, F. Botulism is not a contagious disease, since there is no direct transmission from diseased animals or man to a healthy subject. Botulism occurs via the environment, notably from food contaminated with C. botulinum spores and preserved in conditions favorable for C. botulinum growth and toxin production. The high prevalence of botulism types C, D and variants DC and CD in farmed and wild birds, and to a lower extent in cattle, raises the risk of transmission to human beings. However, human botulism is much rarer than animal botulism, and botulism types C and D are exceptional in humans. Only 15 cases or suspected cases of botulism type C and one outbreak of botulism type D have been reported in humans to date. In contrast, animal healthy carriers of C. botulinum group II, such as C. botulinum type E in fish of the northern hemisphere, and C. botulinum B4 in pigs, represent a more prevalent risk of botulism transmission to human subjects. Less common botulism types in animals but at risk of transmission to humans, can sporadically be observed, such as botulism type E in farmed chickens in France (1998–2002), botulism type B in cattle in The Netherlands (1977–1979), botulism types A and B in horses, or botulism type A in dairy cows (Egypt, 1976). In most cases, human and animal botulisms have distinct origins, and cross transmissions between animals and human beings are rather rare, accidental events. But, due to the severity of this disease, human and animal botulism requires a careful surveillance. Full article

(This article belongs to the Special Issue New Challenges in Foodborne Botulism Outbreaks)

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17 pages, 5501 KiB

Open AccessEditor’s ChoiceArticle

Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria

by Tania Keiko Shishido, Rafael Vicentini Popin, Jouni Jokela, Matti Wahlsten, Marli Fatima Fiore, David P. Fewer, Lars Herfindal and Kaarina Sivonen

Toxins 2020, 12(1), 12; https://doi.org/10.3390/toxins12010012 - 24 Dec 2019

Cited by 27 | Viewed by 6556

Abstract

Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. [...] Read more.

Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. We tested 62 cyanobacterial strains isolated from various Brazilian biomes for antileukemic and antimicrobial activities. Extracts from 39 strains induced selective apoptosis in acute myeloid leukemia (AML) cancer cell lines. Five of these extracts also exhibited antifungal and antibacterial activities. Chemical and dereplication analyses revealed the production of nine known natural products. Natural products possibly responsible for the observed bioactivities and five unknown, chemically related chlorinated compounds present only in Brazilian cyanobacteria were illustrated in a molecular network. Our results provide new information on the vast biosynthetic potential of cyanobacteria isolated from Brazilian environments. Full article

(This article belongs to the Special Issue Biosynthesis, Accumulation, and Bioactivity of Secondary Metabolites in Cyanobacteria)

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9 pages, 408 KiB

Open AccessEditor’s ChoiceArticle

Serum P-Cresyl Sulfate Is a Predictor of Central Arterial Stiffness in Patients on Maintenance Hemodialysis

by Yu-Hsien Lai, Chih-Hsien Wang, Chiu-Huang Kuo, Yu-Li Lin, Jen-Pi Tsai and Bang-Gee Hsu

Toxins 2020, 12(1), 10; https://doi.org/10.3390/toxins12010010 - 21 Dec 2019

Cited by 17 | Viewed by 2534

Abstract

Arterial stiffness (AS) has an important impact on the outcomes of patients on hemodialysis (HD), and p-cresyl sulfate (PC) can mediate the process of vascular damage. We aimed to investigate the relationship between carotid–femoral pulse wave velocity (cfPWV) and the level of [...] Read more.

Arterial stiffness (AS) has an important impact on the outcomes of patients on hemodialysis (HD), and p-cresyl sulfate (PC) can mediate the process of vascular damage. We aimed to investigate the relationship between carotid–femoral pulse wave velocity (cfPWV) and the level of PCs in HD patients. Serum PCs were quantified using liquid chromatography mass spectrometry. Patients who were on standard HD for more than 3 months were enrolled and categorized according to the cfPWV into the high AS (>10 m/s) and control (≤10 m/s) groups. Forty-nine (41.5%) patients belonged to the high AS group and had a higher incidence of diabetes mellitus (DM) and increased systolic blood pressure, serum C-reactive protein, and PC levels but had lower creatinine, compared with those in the control group. In HD patients, the risk for developing high AS increased in the presence of DM (OR 4.147, 95% confidence interval (CI) 1.497–11.491) and high PCs (OR 1.067, 95% CI 1.002–1.136). Having DM (r = 0.446) and high PC level (r = 0.174) were positively associated with cfPWV. The most optimal cutoff value of PC for predicting AS was 18.99 mg/L (area under the curve 0.661, 95% CI 0.568–0.746). We concluded that DM and PCs were promising predictors of high AS in patients on maintenance HD. Full article

(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))

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15 pages, 662 KiB

Open AccessEditor’s ChoiceReview

A Review on the Study of Cyanotoxins in Paleolimnological Research: Current Knowledge and Future Needs

by Eliana Henao, Piotr Rzymski and Matthew N. Waters

Toxins 2020, 12(1), 6; https://doi.org/10.3390/toxins12010006 - 20 Dec 2019

Cited by 21 | Viewed by 4435

Abstract

Cyanobacterial metabolites are increasingly studied, in regards to their biosynthesis, ecological role, toxicity, and potential biomedical applications. However, the history of cyanotoxins prior to the last few decades is virtually unknown. Only a few paleolimnological studies have been undertaken to date, and these [...] Read more.

Cyanobacterial metabolites are increasingly studied, in regards to their biosynthesis, ecological role, toxicity, and potential biomedical applications. However, the history of cyanotoxins prior to the last few decades is virtually unknown. Only a few paleolimnological studies have been undertaken to date, and these have focused exclusively on microcystins and cylindrospermopsins, both successfully identified in lake sediments up to 200 and 4700 years old, respectively. In this paper, we review direct extraction, quantification, and application of cyanotoxins in sediment cores, and put forward future research prospects in this field. Cyanobacterial toxin research is also compared to other paleo-cyanobacteria tools, such as sedimentary pigments, akinetes, and ancient DNA isolation, to identify the role of each tool in reproducing the history of cyanobacteria. Such investigations may also be beneficial for further elucidation of the biological role of cyanotoxins, particularly if coupled with analyses of other abiotic and biotic sedimentary features. In addition, we identify current limitations as well as future directions for applications in the field of paleolimnological studies on cyanotoxins. Full article

(This article belongs to the Special Issue Biological Role of Cyanotoxins: Experimental and In-Field Evidence)

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26 pages, 3207 KiB

Open AccessEditor’s ChoiceReview

Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications

by Xabier Guruceaga, Uxue Perez-Cuesta, Ana Abad-Diaz de Cerio, Oskar Gonzalez, Rosa M. Alonso, Fernando Luis Hernando, Andoni Ramirez-Garcia and Aitor Rementeria

Toxins 2020, 12(1), 7; https://doi.org/10.3390/toxins12010007 - 20 Dec 2019

Cited by 49 | Viewed by 9834

Abstract

Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses [...] Read more.

Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses through the production of secondary metabolites, including several mycotoxins (gliotoxin, fumagillin, pseurotin A, etc.) also seem to play an important role in causing these infections. Since the discovery of the A. fumigatus fumagillin in 1949, many studies have focused on this toxin and in this review we gather all the information currently available. First of all, the structural characteristics of this mycotoxin and the different methods developed for its determination are given in detail. Then, the biosynthetic gene cluster and the metabolic pathway involved in its production and regulation are explained. The activity of fumagillin on its target, the methionine aminopeptidase type 2 (MetAP2) enzyme, and the effects of blocking this enzyme in the host are also described. Finally, the applications that this toxin and its derivatives have in different fields, such as the treatment of cancer and its microsporicidal activity in the treatment of honeybee hive infections with Nosema spp., are reviewed. Therefore, this work offers a complete review of all the information currently related to the fumagillin mycotoxin secreted by A. fumigatus, important because of its role in the fungal infection process but also because it has many other applications, notably in beekeeping, the treatment of infectious diseases, and in oncology. Full article

(This article belongs to the Special Issue Mycotoxin Biosynthesis and Genetic Transformation Systems in Fungi)

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14 pages, 6161 KiB

Open AccessEditor’s ChoiceArticle

The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA

by Yongfeng Fan, Jason R. Barash, Fraser Conrad, Jianlong Lou, Christina Tam, Luisa W. Cheng, Stephen S. Arnon and James D. Marks

Toxins 2020, 12(1), 9; https://doi.org/10.3390/toxins12010009 - 20 Dec 2019

Cited by 14 | Viewed by 3248

Abstract

Background: Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the [...] Read more.

Background: Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the C-terminus to BoNT/A and neutralization studies. The purpose of this study was to define the immunologic identity of the novel BoNT. Methods: monoclonal antibodies (mAbs) to the novel BoNT/H N-terminus were generated by antibody repertoire cloning and yeast display after immunization with BoNT/H LC-H_N or BoNT/F LC-H_N. Results: 21 unique BoNT/H LC-H_N mAbs were obtained; 15 from the BoNT/H LC-H_N immunized library (K_D 0.78 nM to 182 nM) and six from the BoNT/F-immunized libraries (K_D 20.5 nM to 1490 nM). A total of 15 of 21 mAbs also bound catalytically inactive BoNT/H holotoxin. The mAbs bound nine non-overlapping epitopes on the BoNT/H LC-H_N. None of the mAbs showed binding to BoNT serotypes A-G, nor any of the seven subtypes of BoNT/F, except for one mAb that weakly bound BoNT/F5. Conclusions: The results, combined with the chimeric structure and neutralization by anti-A, but not anti-F antitoxin indicate that immunologically the novel BoNT is BoNT/HA. This determination has significant implications for existing countermeasures and potential vulnerabilities. Full article

(This article belongs to the Section Bacterial Toxins)

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23 pages, 1793 KiB

Open AccessEditor’s ChoiceArticle

Intraspecific Variability in the Toxin Production and Toxin Profiles of In Vitro Cultures of Gambierdiscus polynesiensis (Dinophyceae) from French Polynesia

by Sébastien Longo, Manoella Sibat, Jérôme Viallon, Hélène Taiana Darius, Philipp Hess and Mireille Chinain

Toxins 2019, 11(12), 735; https://doi.org/10.3390/toxins11120735 - 17 Dec 2019

Cited by 42 | Viewed by 4508

Abstract

Ciguatera poisoning (CP) is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates in the genera Gambierdiscus and Fukuyoa. The toxin production and toxin profiles were explored in four clones of G. polynesiensis originating from [...] Read more.

Ciguatera poisoning (CP) is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates in the genera Gambierdiscus and Fukuyoa. The toxin production and toxin profiles were explored in four clones of G. polynesiensis originating from different islands in French Polynesia with contrasted CP risk: RIK7 (Mangareva, Gambier), NHA4 (Nuku Hiva, Marquesas), RAI-1 (Raivavae, Australes), and RG92 (Rangiroa, Tuamotu). Productions of CTXs, maitotoxins (MTXs), and gambierone group analogs were examined at exponential and stationary growth phases using the neuroblastoma cell-based assay and liquid chromatography–tandem mass spectrometry. While none of the strains was found to produce known MTX compounds, all strains showed high overall P-CTX production ranging from 1.1 ± 0.1 to 4.6 ± 0.7 pg cell⁻¹. In total, nine P-CTX analogs were detected, depending on strain and growth phase. The production of gambierone, as well as 44-methylgamberione, was also confirmed in G. polynesiensis. This study highlighted: (i) intraspecific variations in toxin production and profiles between clones from distinct geographic origins and (ii) the noticeable increase in toxin production of both CTXs, in particular CTX4A/B, and gambierone group analogs from the exponential to the stationary phase. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

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13 pages, 8640 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Induces Inflammatory Injury in IPEC-J2 Cells via NF-κB Signaling Pathway

by Xichun Wang, Yafei Zhang, Jie Zhao, Li Cao, Lei Zhu, Yingying Huang, Xiaofang Chen, Sajid Ur Rahman, Shibin Feng, Yu Li and Jinjie Wu

Toxins 2019, 11(12), 733; https://doi.org/10.3390/toxins11120733 - 16 Dec 2019

Cited by 29 | Viewed by 3759

Abstract

The aim of this study was to investigate the effects of deoxynivalenol (DON) exposure on the inflammatory injury nuclear factor kappa-B (NF-κB) pathway in intestinal epithelial cells (IPEC-J2 cells) of pig. The different concentrations of DON (0, 125, 250, 500, 1000, 2000 ng/mL) [...] Read more.

The aim of this study was to investigate the effects of deoxynivalenol (DON) exposure on the inflammatory injury nuclear factor kappa-B (NF-κB) pathway in intestinal epithelial cells (IPEC-J2 cells) of pig. The different concentrations of DON (0, 125, 250, 500, 1000, 2000 ng/mL) were added to the culture solution for treatment. The NF-κB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) was used as a reference. The results showed that when the DON concentration increased, the cell density decreased and seemed damaged. With the increase of DON concentration in the culture medium, the action of diamine oxidase (DAO) in the culture supernatant also increased. The activities of IL-6, TNF-α, and NO in the cells were increased with the increasing DON concentration. The relative mRNA expression of IL-1β and IL-6 were increased in the cells. The mRNA relative expression of NF-κB p65, IKKα, and IKKβ were upregulated with the increasing of DON concentration, while the relative expression of IκB-α mRNA was downregulated. At the same time, the expression of NF-κB p65 protein increased gradually in the cytoplasm and nucleus with a higher concentration of DON. These results showed that DON could change the morphology of IPEC-J2 cells, destroy its submicroscopic structure, and enhance the permeability of cell membrane, as well as upregulate the transcription of some inflammatory factors and change the expression of NF-κB-related gene or protein in cells. Full article

(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)

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17 pages, 341 KiB

Open AccessEditor’s ChoiceReview

The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction

by Yao-Lin Kao, Kuan-Hsun Huang, Hann-Chorng Kuo and Yin-Chien Ou

Toxins 2019, 11(12), 728; https://doi.org/10.3390/toxins11120728 - 13 Dec 2019

Cited by 19 | Viewed by 3650

Abstract

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor [...] Read more.

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler’s syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed. Full article

(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)

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