Toxins

20 pages, 9973 KiB

Open AccessArticle

Combined (d)SPE-QuEChERS Extraction of Mycotoxins in Mixed Feed Rations and Analysis by High Performance Liquid Chromatography-High-Resolution Mass Spectrometry

by Rocio Facorro, Maria Llompart and Thierry Dagnac

Toxins 2020, 12(3), 206; https://doi.org/10.3390/toxins12030206 - 23 Mar 2020

Cited by 20 | Viewed by 4606

Abstract

The objective of this work was the development of a methodology capable of simultaneously determine 26 mycotoxins in mixed feed rations collected in 20 dairy farms. A sample preparation methodology based on a combination of (d)SPE and QuEChERS extractions was used. Liquid chromatography-high [...] Read more.

The objective of this work was the development of a methodology capable of simultaneously determine 26 mycotoxins in mixed feed rations collected in 20 dairy farms. A sample preparation methodology based on a combination of (d)SPE and QuEChERS extractions was used. Liquid chromatography-high resolution mass spectrometry was employed for both identification and quantification purposes. To this respect, a powerful workflow based on data-independent acquisition, consisting of fragmenting all precursor ions entering the mass spectrometer in narrow m/z isolation windows (SWATH), was implemented. SWATH data file then contains all the information that would be acquired in a multitude of different experimental approaches in a single all-encompassing dataset. Analytical method performance was evaluated in terms of linearity, repeatability and matrix effect. Relative recoveries were also measured, giving values above 80% for most compounds. Matrix-matched calibration was carried out and enabled reaching the low ng mL⁻¹ level for many mycotoxins. The observed matrix effect, in most cases suppressive, reached even values higher than 60%. The repeatability was also adequate, showing a relative standard deviation lower than 10%. All unified samples analyzed showed co-occurrence of two or more mycotoxins, recurrently zearalenone, fumonisin B1, and β-zearalenol, with an occurrence frequency ranging from 60% to 90%. Full article

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

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12 pages, 3159 KiB

Open AccessEditor’s ChoiceArticle

An Appetite for Destruction: Detecting Prey-Selective Binding of α-Neurotoxins in the Venom of Afro-Asian Elapids

by Richard J. Harris, Christina N. Zdenek, David Harrich, Nathaniel Frank and Bryan G. Fry

Toxins 2020, 12(3), 205; https://doi.org/10.3390/toxins12030205 - 23 Mar 2020

Cited by 38 | Viewed by 4368

Abstract

Prey-selective venoms and toxins have been documented across only a few species of snakes. The lack of research in this area has been due to the absence of suitably flexible testing platforms. In order to test more species for prey specificity of their [...] Read more.

Prey-selective venoms and toxins have been documented across only a few species of snakes. The lack of research in this area has been due to the absence of suitably flexible testing platforms. In order to test more species for prey specificity of their venom, we used an innovative taxonomically flexible, high-throughput biolayer interferometry approach to ascertain the relative binding of 29 α-neurotoxic venoms from African and Asian elapid representatives (26 Naja spp., Aspidelaps scutatus, Elapsoidea boulengeri, and four locales of Ophiophagus hannah) to the alpha-1 nicotinic acetylcholine receptor orthosteric (active) site for amphibian, lizard, snake, bird, and rodent targets. Our results detected prey-selective, intraspecific, and geographical differences of α-neurotoxic binding. The results also suggest that crude venom that shows prey selectivity is likely driven by the proportions of prey-specific α-neurotoxins with differential selectivity within the crude venom. Our results also suggest that since the α-neurotoxic prey targeting does not always account for the full dietary breadth of a species, other toxin classes with a different pathophysiological function likely play an equally important role in prey immobilisation of the crude venom depending on the prey type envenomated. The use of this innovative and taxonomically flexible diverse assay in functional venom testing can be key in attempting to understanding the evolution and ecology of α-neurotoxic snake venoms, as well as opening up biochemical and pharmacological avenues to explore other venom effects. Full article

(This article belongs to the Section Animal Venoms)

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8 pages, 506 KiB

Open AccessEditor’s ChoiceArticle

No More Tears: Mining Sequencing Data for Novel Bt Cry Toxins with CryProcessor

by Anton E. Shikov, Yury V. Malovichko, Rostislav K. Skitchenko, Anton A. Nizhnikov and Kirill S. Antonets

Toxins 2020, 12(3), 204; https://doi.org/10.3390/toxins12030204 - 23 Mar 2020

Cited by 14 | Viewed by 5295

Abstract

Bacillus thuringiensis (Bt) is a natural pathogen of insects and some other groups of invertebrates that produces three-domain Cry (3d-Cry) toxins, which are highly host-specific pesticidal proteins. These proteins represent the most commonly used bioinsecticides in the world and are used [...] Read more.

Bacillus thuringiensis (Bt) is a natural pathogen of insects and some other groups of invertebrates that produces three-domain Cry (3d-Cry) toxins, which are highly host-specific pesticidal proteins. These proteins represent the most commonly used bioinsecticides in the world and are used for commercial purposes on the market of insecticides, being convergent with the paradigm of sustainable growth and ecological development. Emerging resistance to known toxins in pests stresses the need to expand the list of known toxins to broaden the horizons of insecticidal approaches. For this purpose, we have elaborated a fast and user-friendly tool called CryProcessor, which allows productive and precise mining of 3d-Cry toxins. The only existing tool for mining Cry toxins, called a BtToxin_scanner, has significant limitations such as limited query size, lack of accuracy and an outdated database. In order to find a proper solution to these problems, we have developed a robust pipeline, capable of precise 3d-Cry toxin mining. The unique feature of the pipeline is the ability to search for Cry toxins sequences directly on assembly graphs, providing an opportunity to analyze raw sequencing data and overcoming the problem of fragmented assemblies. Moreover, CryProcessor is able to predict precisely the domain layout in arbitrary sequences, allowing the retrieval of sequences of definite domains beyond the bounds of a limited number of toxins presented in CryGetter. Our algorithm has shown efficiency in all its work modes and outperformed its analogues on large amounts of data. Here, we describe its main features and provide information on its benchmarking against existing analogues. CryProcessor is a novel, fast, convenient, open source (https://github.com/lab7arriam/cry_processor), platform-independent, and precise instrument with a console version and elaborated web interface (https://lab7.arriam.ru/tools/cry_processor). Its major merits could make it possible to carry out massive screening for novel 3d-Cry toxins and obtain sequences of specific domains for further comprehensive in silico experiments in constructing artificial toxins. Full article

(This article belongs to the Section Bacterial Toxins)

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13 pages, 2503 KiB

Open AccessArticle

Molecular Mechanism of Aflatoxin-Induced Hepatocellular Carcinoma Derived from a Bioinformatics Analysis

by Peirong Cai, Hao Zheng, Jinjin She, Nannan Feng, Hui Zou, Jianhong Gu, Yan Yuan, Xuezhong Liu, Zongping Liu and Jianchun Bian

Toxins 2020, 12(3), 203; https://doi.org/10.3390/toxins12030203 - 23 Mar 2020

Cited by 23 | Viewed by 4496

Abstract

Exposure to aflatoxin is considered to be one of the causes of hepatocellular carcinoma (HCC). With the development of bioinformation, we sought to reveal the occurrence and development of aflatoxin-induced HCC through data research. We identified differentially expressed genes (DEGs) of datasets GSE127791 [...] Read more.

Exposure to aflatoxin is considered to be one of the causes of hepatocellular carcinoma (HCC). With the development of bioinformation, we sought to reveal the occurrence and development of aflatoxin-induced HCC through data research. We identified differentially expressed genes (DEGs) of datasets GSE127791 (Aflatoxin-treated pluripotent stem cell derived human hepatocytes vs. controls) and GSE64041 (liver carcinoma with unknown cause vs. non-cancerous tissue) by GEO2R to find the common DEGs. Gene ontology (GO) and KEGG path enrichment analysis were used to annotate the function of DEGs. Hub genes were screened from identified DEGs by protein-protein interaction (PPI) network analysis. The prognostic value of hub genes in cancer databases were evaluated. We obtained 132 common DEGs and 11 hub genes. According to cluster analysis and protein co-expression networks, we screened out the key genes, histidine-rich glycoprotein (HRG) and phosphoenolpyruvate carboxykinase 2 (PCK2). Oncomine database and survival curve analysis showed that the decline in HRG and PCK2 expression in the development of HCC indicated poor prognosis. We speculated that the decreased expression of HRG and PCK2 after aflatoxin exposure to hepatocyte may be related to aflatoxin induced hepatocyte injury and carcinogenesis. In addition, the decreased expression of HRG and PCK2 in the occurrence and development of HCC suggests a poor prognosis of HCC. Full article

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10 pages, 3349 KiB

Open AccessArticle

Anatomical Considerations When Treating Compensatory Hypertrophy of the Upper Part of the Masseter after Long-Term Botulinum Neurotoxin Type A Injections

by Kyu-Lim Lee, Hyun Jin Cho, Hyungkyu Bae, Hyun Jin Park, Min Sun Park and Hee-Jin Kim

Toxins 2020, 12(3), 202; https://doi.org/10.3390/toxins12030202 - 22 Mar 2020

Cited by 7 | Viewed by 5318

Abstract

The masseter is the most targeted muscle when treating hypertrophy to produce a smooth face shape. Compensatory hypertrophy is a well known clinical sequela that occurs in botulinum neurotoxin (BoNT) treatments and is limited to the lower part of the masseter. Based on [...] Read more.

The masseter is the most targeted muscle when treating hypertrophy to produce a smooth face shape. Compensatory hypertrophy is a well known clinical sequela that occurs in botulinum neurotoxin (BoNT) treatments and is limited to the lower part of the masseter. Based on the masseteric hypertrophy procedure, which targets a confined area, we predicted the possibility of compensatory hypertrophy occurring in the upper part of the masseter. If the patient complains about an unexpected result, additional injections must be performed, but the involved anatomical structures have not been revealed yet. The aim of this study was to identify the morphological patterns of the masseter. Deep tendons were observed in most specimens of the upper part of the masseter and mostly appeared in a continuous pattern (69.7%). The superficial and deep tendons could be classified into a simply connected form and forms surrounding part of the muscle. In 45.5% of cases there were tendon capsules that completely enclosed the muscle, which can interfere with how the injected toxin spreads. Interdigitation patterns in which the tendons could be identified independently between the muscles were present in 9.1% of cases. The present findings provide anatomical knowledge for use when injecting BoNT into the masseter. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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19 pages, 3953 KiB

Open AccessEditor’s ChoiceArticle

Fangs for the Memories? A Survey of Pain in Snakebite Patients Does Not Support a Strong Role for Defense in the Evolution of Snake Venom Composition

by Harry Ward-Smith, Kevin Arbuckle, Arno Naude and Wolfgang Wüster

Toxins 2020, 12(3), 201; https://doi.org/10.3390/toxins12030201 - 22 Mar 2020

Cited by 23 | Viewed by 16386

Abstract

Animals use venoms for multiple purposes, most prominently for prey acquisition and self-defense. In snakes, venom composition often evolves as a result of selection for optimization for local diet. However, whether selection for a defensive function has also played a role in driving [...] Read more.

Animals use venoms for multiple purposes, most prominently for prey acquisition and self-defense. In snakes, venom composition often evolves as a result of selection for optimization for local diet. However, whether selection for a defensive function has also played a role in driving the evolution of venom composition has remained largely unstudied. Here, we use an online survey of snakebite victims to test a key prediction of a defensive function, that envenoming should result in the rapid onset of severe pain. From the analysis of 584 snakebite reports, involving 192 species of venomous snake, we find that the vast majority of bites do not result in severe early pain. Phylogenetic comparative analysis shows that where early pain after a bite evolves, it is often lost rapidly. Our results, therefore, do not support the hypothesis that natural selection for antipredator defense played an important role in the origin of venom or front-fanged delivery systems in general, although there may be intriguing exceptions to this rule. Full article

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

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15 pages, 1517 KiB

Open AccessEditor’s ChoiceArticle

Natural Occurrence of Deoxynivalenol and Its Acetylated Derivatives in Chinese Maize and Wheat Collected in 2017

by Pianpian Yan, Zhezhe Liu, Shiqiao Liu, Liyun Yao, Yan Liu, Yongning Wu and Zhiyong Gong

Toxins 2020, 12(3), 200; https://doi.org/10.3390/toxins12030200 - 22 Mar 2020

Cited by 58 | Viewed by 3454

Abstract

Deoxynivalenol (DON), along with 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl-deoxynivalenol (15-ADON), occur in grains and cereal products and is often hazardous to humans and livestock. In this study, 579 wheat samples and 606 maize samples intended for consumption were collected from China in 2017 and [...] Read more.

Deoxynivalenol (DON), along with 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl-deoxynivalenol (15-ADON), occur in grains and cereal products and is often hazardous to humans and livestock. In this study, 579 wheat samples and 606 maize samples intended for consumption were collected from China in 2017 and analyzed to determine the co-occurrence of type-B trichothecenes (DON, 3-ADON, and 15-ADON). All the wheat samples tested positive for DON, while 99.83% of the maize samples were DON-positive with mean DON concentrations of 165.87 and 175.30 μg/kg, respectively. Per the Chinese standard limits for DON, 3.63% of wheat and 2.97% of the maize samples were above the maximum limit of 1000 μg/kg. The DON derivatives (3-ADON and 15-ADON) were less frequently found and were present at lower levels than DON in wheat. 3-ADON and 15-ADON had incidences of 13.53% and 76.40%, respectively, in maize. By analyzing the distribution ratio of DON and its derivatives in wheat and maize, DON (95.51%) was the predominant toxin detected in wheat samples, followed by 3.97% for the combination of DON + 3-ADON, while DON + 3-ADON + 15-ADON and DON + 15-ADON were only found in 0.17% and 0.35% of wheat samples, respectively. Additionally, a large amount of the maize samples were contaminated with DON + 15-ADON (64.19%) and DON (22.11%). The samples with a combination of DON + 3-ADON and DON + 3-ADON + 15-ADON accounted for 1.32% and 12.21%, respectively. Only one maize sample did not contain all three mycotoxins. Our study shows the necessity of raising awareness of the co-occurrence of mycotoxin contamination in grains from China to protect consumers from the risk of exposure to DON and its derivatives. Full article

(This article belongs to the Special Issue Occurrence, Prevention and Control of Mycotoxins and Mycotoxigenic Fungi on Nuts and Dried Fruits)

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18 pages, 4708 KiB

Open AccessArticle

ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

by Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kamila Domińska, Kinga Anna Urbanek and Agnieszka Wanda Piastowska-Ciesielska

Toxins 2020, 12(3), 199; https://doi.org/10.3390/toxins12030199 - 22 Mar 2020

Cited by 15 | Viewed by 3624

Abstract

Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) is commonly expressed in prostate cancer (PCa) cells and is associated with increased proliferation, metastases and androgen independence. Zearalenone (ZEA) is one of the most common mycotoxins contaminating food, which might mimic estrogens and bind [...] Read more.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) is commonly expressed in prostate cancer (PCa) cells and is associated with increased proliferation, metastases and androgen independence. Zearalenone (ZEA) is one of the most common mycotoxins contaminating food, which might mimic estrogens and bind to estrogen receptors (ERs). The ratio of androgens to estrogens in men decreases physiologically with age, and is believed to participate in prostate carcinogenesis. In this study, we evaluated the role of NFκB and ERβ in the induction of oxidative stress in human PCa cells by ZEA. As observed, ZEA at a dose of 30 µM induces oxidative stress in PCa cells associated with DNA damage and G2/M cell cycle arrest. We also observed that the inhibition of ERβ and NFΚB via specific inhibitors (PHTPP and BAY 117082) significantly increased ZEA-induced oxidative stress, although the mechanism seems to be different for androgen-dependent and androgen-independent cells. Based on our findings, it is possible that the activation of ERβ and NFΚB in PCa might protect cancer cells from ZEA-induced oxidative stress. We therefore shed new light on the mechanism of ZEA toxicity in human cells. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 3704 KiB

Open AccessArticle

Bee Venom Phospholipase A2 Induces Regulatory T Cell Populations by Suppressing Apoptotic Signaling Pathway

by Hyunjung Baek, Seon-Young Park, Su Jeong Ku, Kihyun Ryu, Younsub Kim, Hyunsu Bae and Ye-Seul Lee

Toxins 2020, 12(3), 198; https://doi.org/10.3390/toxins12030198 - 22 Mar 2020

Cited by 21 | Viewed by 4931

Abstract

Bee venom phospholipase A2 is a lipolytic enzyme in bee venom that catalyzes hydrolysis of the sn-2 ester bond of membrane phospholipids to produce free fatty acid and lysophospholipids. Current evidence suggests that bee venom phospholipase A2 (bvPLA2) induces regulatory T cell expansion [...] Read more.

Bee venom phospholipase A2 is a lipolytic enzyme in bee venom that catalyzes hydrolysis of the sn-2 ester bond of membrane phospholipids to produce free fatty acid and lysophospholipids. Current evidence suggests that bee venom phospholipase A2 (bvPLA2) induces regulatory T cell expansion and attenuates several immune system-related diseases, including Alzheimer’s disease. The induction of Treg cells is directly mediated by binding to mannose receptors on dendritic cells. This interaction induces the PGE2-EP2 signaling pathway, which promotes Treg induction in CD4⁺ T cells. In this study, we investigated the effects of bvPLA2 treatment on the apoptotic signaling pathway in Treg populations. Flow cytometry was performed to identify early apoptotic cells. As a result, early apoptotic cells were dramatically decreased in bvPLA2-treated splenocytes, whereas rapamycin-treated cells showed levels of apoptotic cells similar to those of PBS-treated cells. Furthermore, bvPLA2 treatment increased expression of anti-apoptotic molecules including CTLA-4 and PD-1. The survival rate increased in bvPLA2-treated Tregs. Our findings indicate that bvPLA2-mediated modulation of apoptotic signaling is strongly associated with the Treg induction, which exhibits protective effects against various immune-related diseases. To our knowledge, this study is the first to demonstrate that bvPLA2 is the major bee venom (BV) compound capable of inducing Treg expansion through altering apoptotic signal. Full article

(This article belongs to the Special Issue Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics)

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29 pages, 4221 KiB

Open AccessArticle

αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish

by Matthew J. Rybin, Henrik O’Brien, Iris Bea L. Ramiro, Layla Azam, J. Michael McIntosh, Baldomero M. Olivera, Helena Safavi-Hemami and Doju Yoshikami

Toxins 2020, 12(3), 197; https://doi.org/10.3390/toxins12030197 - 21 Mar 2020

Cited by 10 | Viewed by 3845

Abstract

We report the discovery and functional characterization of αM-Conotoxin MIIIJ, a peptide from the venom of the fish-hunting cone snail Conus magus. Injections of αM-MIIIJ induced paralysis in goldfish (Carassius auratus) but not mice. Intracellular recording from skeletal muscles of [...] Read more.

We report the discovery and functional characterization of αM-Conotoxin MIIIJ, a peptide from the venom of the fish-hunting cone snail Conus magus. Injections of αM-MIIIJ induced paralysis in goldfish (Carassius auratus) but not mice. Intracellular recording from skeletal muscles of fish (C. auratus) and frog (Xenopus laevis) revealed that αM-MIIIJ inhibited postsynaptic nicotinic acetylcholine receptors (nAChRs) with an IC₅₀ of ~0.1 μM. With comparable potency, αM-MIIIJ reversibly blocked ACh-gated currents (I_ACh) of voltage-clamped X. laevis oocytes exogenously expressing nAChRs cloned from zebrafish (Danio rerio) muscle. αM-MIIIJ also protected against slowly-reversible block of I_ACh by α-bungarotoxin (α-BgTX, a snake neurotoxin) and α-conotoxin EI (α-EI, from Conus ermineus another fish hunter) that competitively block nAChRs at the ACh binding site. Furthermore, assessment by fluorescence microscopy showed that αM-MIIIJ inhibited the binding of fluorescently-tagged α-BgTX at neuromuscular junctions of X. laevis, C. auratus, and D. rerio. (Note, we observed that αM-MIIIJ can block adult mouse and human muscle nAChRs exogenously expressed in X. laevis oocytes, but with IC₅₀s ~100-times higher than those of zebrafish nAChRs.) Taken together, these results indicate that αM-MIIIJ inhibits muscle nAChRs and furthermore apparently does so by interfering with the binding of ACh to its receptor. Comparative alignments with homologous sequences identified in other fish hunters revealed that αM-MIIIJ defines a new class of muscle nAChR inhibitors from cone snails. Full article

(This article belongs to the Section Animal Venoms)

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24 pages, 3315 KiB

Open AccessArticle

Physiological and Metabolic Responses of Marine Mussels Exposed to Toxic Cyanobacteria Microcystis aeruginosa and Chrysosporum ovalisporum

by Flavio Oliveira, Leticia Diez-Quijada, Maria V. Turkina, João Morais, Aldo Barreiro Felpeto, Joana Azevedo, Angeles Jos, Ana M. Camean, Vitor Vasconcelos, José Carlos Martins and Alexandre Campos

Toxins 2020, 12(3), 196; https://doi.org/10.3390/toxins12030196 - 20 Mar 2020

Cited by 8 | Viewed by 4524

Abstract

Toxic cyanobacterial blooms are a major contaminant in inland aquatic ecosystems. Furthermore, toxic blooms are carried downstream by rivers and waterways to estuarine and coastal ecosystems. Concerning marine and estuarine animal species, very little is known about how these species are affected by [...] Read more.

Toxic cyanobacterial blooms are a major contaminant in inland aquatic ecosystems. Furthermore, toxic blooms are carried downstream by rivers and waterways to estuarine and coastal ecosystems. Concerning marine and estuarine animal species, very little is known about how these species are affected by the exposure to freshwater cyanobacteria and cyanotoxins. So far, most of the knowledge has been gathered from freshwater bivalve molluscs. This work aimed to infer the sensitivity of the marine mussel Mytilus galloprovincialis to single as well as mixed toxic cyanobacterial cultures and the underlying molecular responses mediated by toxic cyanobacteria. For this purpose, a mussel exposure experiment was outlined with two toxic cyanobacteria species, Microcystis aeruginosa and Chrysosporum ovalisporum at 1 × 10⁵ cells/mL, resembling a natural cyanobacteria bloom. The estimated amount of toxins produced by M. aeruginosa and C. ovalisporum were respectively 0.023 pg/cell of microcystin-LR (MC-LR) and 7.854 pg/cell of cylindrospermopsin (CYN). After 15 days of exposure to single and mixed cyanobacteria, a depuration phase followed, during which mussels were fed only non-toxic microalga Parachlorella kessleri. The results showed that the marine mussel is able to filter toxic cyanobacteria at a rate equal or higher than the non-toxic microalga P. kessleri. Filtration rates observed after 15 days of feeding toxic microalgae were 1773.04 mL/ind.h (for M. aeruginosa), 2151.83 mL/ind.h (for C. ovalisporum), 1673.29 mL/ind.h (for the mixture of the 2 cyanobacteria) and 2539.25 mL/ind.h (for the non-toxic P. kessleri). Filtering toxic microalgae in combination resulted in the accumulation of 14.17 ng/g dw MC-LR and 92.08 ng/g dw CYN. Other physiological and biochemical endpoints (dry weight, byssus production, total protein and glycogen) measured in this work did not change significantly in the groups exposed to toxic cyanobacteria with regard to control group, suggesting that mussels were not affected with the toxic microalgae. Nevertheless, proteomics revealed changes in metabolism of mussels related to diet, specially evident in those fed on combined cyanobacteria. Changes in metabolic pathways related with protein folding and stabilization, cytoskeleton structure, and gene transcription/translation were observed after exposure and feeding toxic cyanobacteria. These changes occur in vital metabolic processes and may contribute to protect mussels from toxic effects of the toxins MC-LR and CYN. Full article

(This article belongs to the Special Issue Proteomics and the Study of Marine Toxins: Implications for Life Sciences)

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17 pages, 390 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease

by Hyemin Gu, Sang Mi Han and Kwan-Kyu Park

Toxins 2020, 12(3), 195; https://doi.org/10.3390/toxins12030195 - 19 Mar 2020

Cited by 52 | Viewed by 4765

Abstract

Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%–3% dry weight of bee [...] Read more.

Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%–3% dry weight of bee venom and is a peptide neurotoxin that contains 18 amino acid residues that are tightly crosslinked by two disulfide bonds. It is well known for its pharmacological functions, which irreversibly block Ca2+-activated K+ (SK) channels. Apamin regulates gene expression in various signal transduction pathways involved in cell development. The aim of this study was to review the current understanding of apamin in the treatment of apoptosis, fibrosis, and central nervous system diseases, which are the pathological processes of various diseases. Apamin’s potential therapeutic and pharmacological applications are also discussed. Full article

(This article belongs to the Special Issue Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics)

18 pages, 585 KiB

Open AccessEditor’s ChoiceArticle

Multi-Mycotoxin Occurrence and Exposure Assessment Approach in Foodstuffs from Algeria

by Choukri Khelifa Mahdjoubi, Natalia Arroyo-Manzanares, Nisserine Hamini-Kadar, Ana M. García-Campaña, Kihel Mebrouk and Laura Gámiz-Gracia

Toxins 2020, 12(3), 194; https://doi.org/10.3390/toxins12030194 - 19 Mar 2020

Cited by 71 | Viewed by 5319

Abstract

A survey on 120 cereal samples (barley, maize, rice and wheat) from Algerian markets has been carried out to evaluate the presence of 15 mycotoxins (ochratoxin A, deoxynivalenol, fumonisin B1 and B2, T-2 and HT-2 toxins, zearalenone, fusarenon X, citrinin, sterigmatocystin, enniatins A, [...] Read more.

A survey on 120 cereal samples (barley, maize, rice and wheat) from Algerian markets has been carried out to evaluate the presence of 15 mycotoxins (ochratoxin A, deoxynivalenol, fumonisin B1 and B2, T-2 and HT-2 toxins, zearalenone, fusarenon X, citrinin, sterigmatocystin, enniatins A, A1, B and B1, and beauvericin). With this purpose, a QuEChERS-based extraction and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) were used. Analytical results showed that 78 cereal samples (65%) were contaminated with at least one toxin, while 50% were contaminated with three to nine mycotoxins. T-2 toxin, citrinin, beauvericin and deoxynivalenol were the most commonly found mycotoxins (frequency of 50%, 41.6%, 40.8% and 33.3%, respectively). Fumonisins (B1 + B2), enniatins B and B1, deoxynivalenol and zearalenone registered high concentrations (289–48878 µg/kg, 1.2–5288 µg/kg, 15–4569 µg/kg, 48–2055 µg/kg and 10.4–579 µg/kg, respectively). Furthermore, concentrations higher than those allowed by the European Union (EU) were observed in 21, 8 and 1 samples for fumonisins, zearalenone and deoxinivalenol, respectively. As a conclusion, the high levels of fumonisins (B1 + B2) in maize and deoxynivalenol, zearalenone and HT-2 + T-2 toxins in wheat, represent a health risk for the average adult consumer in Algeria. These results pointed out the necessity of a consistent control and the definition of maximum allowed levels for mycotoxins in Algerian foodstuffs. Full article

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

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19 pages, 5086 KiB

Open AccessArticle

Development of a Sensitive and Reliable UHPLC-MS/MS Method for the Determination of Multiple Urinary Biomarkers of Mycotoxin Exposure

by Zhezhe Liu, Xiaoxue Zhao, Libiao Wu, Shuang Zhou, Zhiyong Gong, Yunfeng Zhao and Yongning Wu

Toxins 2020, 12(3), 193; https://doi.org/10.3390/toxins12030193 - 18 Mar 2020

Cited by 17 | Viewed by 3696

Abstract

A variety of mycotoxins from different sources frequently contaminate farm products, presenting a potential toxicological concern for animals and human. Mycotoxin exposure has been the focus of attention for governments around the world. To date, biomarkers are used to monitor mycotoxin exposure and [...] Read more.

A variety of mycotoxins from different sources frequently contaminate farm products, presenting a potential toxicological concern for animals and human. Mycotoxin exposure has been the focus of attention for governments around the world. To date, biomarkers are used to monitor mycotoxin exposure and promote new understanding of their role in chronic diseases. The goal of this research was to develop and validate a sensitive UHPLC-MS/MS method using isotopically-labeled internal standards suitable for accurate determination of 18 mycotoxin biomarkers, including fumonisins, ochratoxins, Alternaria and emerging Fusarium mycotoxins (fumonisin B₁, B₂, and B₃, hydrolyzed fumonisin B₁ and B₂, ochratoxin A, B, and alpha, alternariol, alternariol monomethyl ether, altenuene, tentoxin, tenuazonic acid, beauvericin, enniatin A, A₁, B, and B₁) in human urine. After enzymatic digestion with β-glucuronidase, human urine samples were cleaned up using HLB solid phase extraction cartridges prior to instrument analysis. The multi-mycotoxin and analyte-specific method was validated in-house, providing satisfactory results. The method provided good linearity in the tested concentration range (from LOQ up to 25–500 ng/mL for different analytes), with R² from 0.997 to 0.999. The limits of quantitation varied from 0.0002 to 0.5 ng/mL for all analytes in urine. The recoveries for spiked samples were between 74.0% and 133%, with intra-day precision of 0.5%–8.7% and inter-day precision of 2.4%–13.4%. This method was applied to 60 urine samples collected from healthy volunteers in Beijing, and 10 biomarkers were found. At least one biomarker was found in all but one of the samples. The high sensitivity and accuracy of this method make it practical for human biomonitoring and mycotoxin exposure assessment. Full article

(This article belongs to the Section Mycotoxins)

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18 pages, 3268 KiB

Open AccessArticle

Salt Shock Responses of Microcystis Revealed through Physiological, Transcript, and Metabolomic Analyses

by Maxime Georges des Aulnois, Damien Réveillon, Elise Robert, Amandine Caruana, Enora Briand, Arthur Guljamow, Elke Dittmann, Zouher Amzil and Myriam Bormans

Toxins 2020, 12(3), 192; https://doi.org/10.3390/toxins12030192 - 18 Mar 2020

Cited by 15 | Viewed by 4168

Abstract

The transfer of Microcystis aeruginosa from freshwater to estuaries has been described worldwide and salinity is reported as the main factor controlling the expansion of M. aeruginosa to coastal environments. Analyzing the expression levels of targeted genes and employing both targeted and non-targeted [...] Read more.

The transfer of Microcystis aeruginosa from freshwater to estuaries has been described worldwide and salinity is reported as the main factor controlling the expansion of M. aeruginosa to coastal environments. Analyzing the expression levels of targeted genes and employing both targeted and non-targeted metabolomic approaches, this study investigated the effect of a sudden salt increase on the physiological and metabolic responses of two toxic M. aeruginosa strains separately isolated from fresh and brackish waters, respectively, PCC 7820 and 7806. Supported by differences in gene expressions and metabolic profiles, salt tolerance was found to be strain specific. An increase in salinity decreased the growth of M. aeruginosa with a lesser impact on the brackish strain. The production of intracellular microcystin variants in response to salt stress correlated well to the growth rate for both strains. Furthermore, the release of microcystins into the surrounding medium only occurred at the highest salinity treatment when cell lysis occurred. This study suggests that the physiological responses of M. aeruginosa involve the accumulation of common metabolites but that the intraspecific salt tolerance is based on the accumulation of specific metabolites. While one of these was determined to be sucrose, many others remain to be identified. Taken together, these results provide evidence that M. aeruginosa is relatively salt tolerant in the mesohaline zone and microcystin (MC) release only occurs when the capacity of the cells to deal with salt increase is exceeded. Full article

(This article belongs to the Special Issue Environmental Drivers of Algal and Cyanobacterial Toxin Dynamics)

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14 pages, 1027 KiB

Open AccessArticle

Red-Crowned Crane (Grus japonensis) Reproduction Was Improved by Inhibiting Mycotoxins with Montmorillonite in Feed

by Dawei Liu, Chao Gu, Changhu Lu, Qinghua Wu, Kamil Kuca and Wenda Wu

Toxins 2020, 12(3), 191; https://doi.org/10.3390/toxins12030191 - 18 Mar 2020

Cited by 2 | Viewed by 55799

Abstract

The red-crowned crane (Grus japonensis) is a vulnerable bird species. Mycotoxins are toxic substances produced by filamentous fungi and are considered as naturally unavoidable contaminants in animal feed. Our recent survey indicated that feeds designed for captive red-crowned cranes were contaminated [...] Read more.

The red-crowned crane (Grus japonensis) is a vulnerable bird species. Mycotoxins are toxic substances produced by filamentous fungi and are considered as naturally unavoidable contaminants in animal feed. Our recent survey indicated that feeds designed for captive red-crowned cranes were contaminated with mycotoxins. This study was conducted to investigate the protective effects of the mycotoxin binder montmorillonite on the reproductive behavior, sex hormone levels, and egg quality of red-crowned cranes. Twelve pairs of G. japonensis were divided into four groups, and each group was fed one of the following: a selected diet (with extra low levels of mycotoxins), a regular diet, a selected diet with 0.5% montmorillonite added, or a regular diet with 0.5% montmorillonite added. Consumption of the regular diet decreased courtship and mating behaviors, testosterone concentration, egg weight, and shell thickness. However, feed supplementation with montmorillonite increased the courtship, mating behaviors and testosterone concentration during the pre-breeding period, as well as egg weight and shell thickness. These findings suggest that the addition of dietary montmorillonite is effective for controlling mycotoxins in the feed, resulting in improvements in reproductive behaviors, testosterone concentrations, and some egg quality parameters of the red-crowned crane. Full article

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

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15 pages, 2292 KiB

Open AccessArticle

Minimal Concentrations of Deoxynivalenol Reduce Cytokine Production in Individual Lymphocyte Populations in Pigs

by Karolina Hlavová, Hana Štěpánová, Kamil Šťastný, Lenka Levá, Nikola Hodkovicová, Monika Vícenová, Ján Matiašovic and Martin Faldyna

Toxins 2020, 12(3), 190; https://doi.org/10.3390/toxins12030190 - 18 Mar 2020

Cited by 9 | Viewed by 3163

Abstract

Deoxynivalenol (DON) is a mycotoxin frequently found in cereals, and pigs are one of the most sensitive farm species to DON. The aim of this study was to determine the effects of DON in very low doses on peripheral blood mononuclear cells (PBMC) [...] Read more.

Deoxynivalenol (DON) is a mycotoxin frequently found in cereals, and pigs are one of the most sensitive farm species to DON. The aim of this study was to determine the effects of DON in very low doses on peripheral blood mononuclear cells (PBMC) and on particular lymphocyte subpopulations. The cells were exposed to 1, 10 and 100 ng/mL of DON and lymphocyte viability, proliferation, and cytokine (Interleukin (IL)-1β, IL-2, IL-8, IL-17, Interferon (IFN) γ and tumor necrosis factor (TNF) α production were studied. Cells exposed to DON for 5 days in concentrations of 1 and 10 ng/mL showed higher viability compared to control cells. After 18 h of DON (100 ng/mL) exposure, a significantly lower proliferation after mitogen stimulation was observed. In contrast, an increase of spontaneous proliferation induced by DON (100 ng/mL) was detected. After DON exposure, the expression of cytokine genes decreased, with the exception of IL-1β and IL-8, which increased after 18 h exposure to 100 ng/mL of DON. Among lymphocyte subpopulations, helper T-cells and γδ T-cells exhibiting lower production of IL-17, IFNγ and TNFα were most affected by DON exposure (10 ng/mL). These findings show that subclinical doses of DON lead to changes in immune response. Full article

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

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16 pages, 1517 KiB

Open AccessEditor’s ChoiceReview

Parathyroid Hormone: A Uremic Toxin

by Eduardo J. Duque, Rosilene M. Elias and Rosa M. A. Moysés

Toxins 2020, 12(3), 189; https://doi.org/10.3390/toxins12030189 - 17 Mar 2020

Cited by 42 | Viewed by 10841

Abstract

Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]₂D₃). PTH promotes calcium release from the bone and enhances [...] Read more.

Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]₂D₃). PTH promotes calcium release from the bone and enhances tubular calcium resorption through direct action on these sites. Hallmarks of secondary hyperparathyroidism associated with chronic kidney disease (CKD) include increase in serum fibroblast growth factor 23 (FGF-23), reduction in renal 1,25[OH]₂D₃ production with a decline in its serum levels, decrease in intestinal calcium absorption, and, at later stages, hyperphosphatemia and high levels of PTH. In this paper, we aim to critically discuss severe CKD-related hyperparathyroidism, in which PTH, through calcium-dependent and -independent mechanisms, leads to harmful effects and manifestations of the uremic syndrome, such as bone loss, skin and soft tissue calcification, cardiomyopathy, immunodeficiency, impairment of erythropoiesis, increase of energy expenditure, and muscle weakness. Full article

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

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14 pages, 2225 KiB

Open AccessArticle

The Influence of the Different Disposition Characteristics of Snake Toxins on the Pharmacokinetics of Snake Venom

by Suchaya Sanhajariya, Geoffrey K. Isbister and Stephen B. Duffull

Toxins 2020, 12(3), 188; https://doi.org/10.3390/toxins12030188 - 16 Mar 2020

Cited by 10 | Viewed by 3864

Abstract

Snake venom is comprised of a combination of different proteins and peptides with a wide range of molecular weights and different disposition processes inherent to each compound. This causes venom to have a complex exposure profile. Our study investigates 1) how each molecular [...] Read more.

Snake venom is comprised of a combination of different proteins and peptides with a wide range of molecular weights and different disposition processes inherent to each compound. This causes venom to have a complex exposure profile. Our study investigates 1) how each molecular weight fraction (toxin) of venom contributes to the overall time course of the snake venom, and 2) the ability to determine toxin profiles based on the profile of the overall venom only. We undertook an in silico simulation and modelling study. Sixteen variations of venom, comprising of two to nine toxins with different molecular weights were investigated. The pharmacokinetic parameters (i.e., clearance,

C L

, and volume of distribution,

V

) of each toxin were generated based on a log-linear relationship with molecular weight. The concentration–time data of each toxin were simulated for 100 virtual patients using MATLAB and the total concentration–time data of each toxin were modelled using NONMEM. We found that the data of sixteen mixtures were best described by either two- or three-compartment models, despite the venom being made up of more than three different toxins. This suggests that it is generally not possible to determine individual toxin profiles based on measurements of total venom concentrations only. Full article

(This article belongs to the Section Animal Venoms)

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16 pages, 10131 KiB

Open AccessArticle

Biological Activities and Proteomic Profile of the Venom of Vipera ursinii ssp., a very Rare Karst Viper from Croatia

by Maja Lang Balija, Adrijana Leonardi, Marija Brgles, Dora Sviben, Tihana Kurtović, Beata Halassy and Igor Križaj

Toxins 2020, 12(3), 187; https://doi.org/10.3390/toxins12030187 - 16 Mar 2020

Cited by 13 | Viewed by 5058

Abstract

The karst viper (Vipera ursinii ssp.) favours high-mountain dry grasslands in southern and south-eastern Croatia. It is medically less important than other Vipera species, because of its remote habitat and the very small amount of venom that it injects by its relatively [...] Read more.

The karst viper (Vipera ursinii ssp.) favours high-mountain dry grasslands in southern and south-eastern Croatia. It is medically less important than other Vipera species, because of its remote habitat and the very small amount of venom that it injects by its relatively short fangs. The scientific literature on Vipera ursinii deals mostly with the morphology, ecology and distribution range of this snake, due to the species’ conservation issues, while the toxinological aspects of its venom have not so far been investigated. Here we report on the composition and biological activity of the Vipera ursinii ssp. venom. Using a proteomics approach, we have identified 25 proteins in the venom that belong to seven protein families: snake venom metalloproteinase, serine protease, secreted phospholipase A₂, cysteine-rich secretory protein, snake C-type lectin-like protein, serine protease inhibitor and nerve growth factor. The Vipera ursinii ssp. venom was found to be distinctively insecticidal. Its lethal toxicity towards crickets was more than five times greater than that of Vipera ammodytes ammodytes venom, while the opposite held in mice. Interestingly, the mode of dying after injecting a mouse with Vipera ursinii ssp. venom may suggest the presence of a neurotoxic component. Neurotoxic effects of European vipers have so far been ascribed exclusively to ammodytoxins and ammodytoxin-like basic secreted phospholipases A₂. Structural and immunological analyses of the Vipera ursinii ssp. venom, however, confirmed that ammodytoxin-like proteins are not present in this venom. Full article

(This article belongs to the Section Animal Venoms)

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9 pages, 677 KiB

Open AccessReview

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A

by Chung-Cheng Wang, Yung-Hong Jiang and Hann-Chorng Kuo

Toxins 2020, 12(3), 186; https://doi.org/10.3390/toxins12030186 - 16 Mar 2020

Cited by 16 | Viewed by 4085

Abstract

Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation [...] Read more.

Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely “botulinum toxin A” (BoNT-A) and “overactive bladder”, with or without the additional keywords “detrusor overactivity”, “diabetes mellitus”, “inflammation”, and “urodynamic study”. We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy. Full article

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

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17 pages, 682 KiB

Open AccessEditor’s ChoiceReview

Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

by Juan Rafael Muñoz-Castañeda, Cristian Rodelo-Haad, Maria Victoria Pendon-Ruiz de Mier, Alejandro Martin-Malo, Rafael Santamaria and Mariano Rodriguez

Toxins 2020, 12(3), 185; https://doi.org/10.3390/toxins12030185 - 16 Mar 2020

Cited by 61 | Viewed by 7692

Abstract

Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney [...] Read more.

Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney disease (CKD). This effect of FGF23 requires the presence of Klotho in the renal tubules. However, Klotho expression is reduced as soon as renal function is starting to fail to generate a state of FGF23 resistance. Changes in these proteins directly affect to other mineral metabolism parameters; they may affect renal function and can produce damage in other organs such as bone, heart, or vessels. Some of the mechanisms responsible for the changes in FGF23 and Klotho levels are related to modifications in the Wnt signaling. This review examines the link between FGF23/Klotho and Wnt/β-catenin in different organs: kidney, heart, and bone. Activation of the canonical Wnt signaling produces changes in FGF23 and Klotho and vice versa; therefore, this pathway emerges as a potential therapeutic target that may help to prevent CKD-associated complications. Full article

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

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13 pages, 3670 KiB

Open AccessArticle

Isolation and Characterization of a Deoxynivalenol-Degrading Bacterium Bacillus licheniformis YB9 with the Capability of Modulating Intestinal Microbial Flora of Mice

by Shiwei Wang, Qiuqiu Hou, Qianqian Guo, Jian Zhang, Yanmei Sun, Hong Wei and Lixin Shen

Toxins 2020, 12(3), 184; https://doi.org/10.3390/toxins12030184 - 15 Mar 2020

Cited by 41 | Viewed by 4105

Abstract

Deoxynivalenol (DON) is one of the most prevalent food- and feed-associated mycotoxins. It frequently contaminates agricultural commodities and poses serious threats to human and animal health and leads to tremendous economic losses globally. Much attention has been paid to using microorganisms to detoxify [...] Read more.

Deoxynivalenol (DON) is one of the most prevalent food- and feed-associated mycotoxins. It frequently contaminates agricultural commodities and poses serious threats to human and animal health and leads to tremendous economic losses globally. Much attention has been paid to using microorganisms to detoxify DON. In this study, a Bacillus licheniformis strain named YB9 with a strong ability to detoxify DON was isolated and characterized from a moldy soil sample. YB9 could degrade more than 82.67% of 1 mg/L DON within 48 h at 37 °C and showed strong survival and DON degradation rate at simulated gastric fluid. The effects of YB9 on mice with DON intragastrical administration were further investigated by biochemical and histopathological examination and the gut microbiota was analyzed by 16S rRNA Illumina sequencing technology. The results showed that DON increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine (Cr), decreased those of immunoglobulin G (IgG) and IgM in serum, and resulted in severe pathological damage of the liver, kidney, and spleen. By contrast, YB9 supplementation obviously inhibited or attenuated the damages caused by DON in mice. In addition, YB9 addition repaired the DON-induced dysbiosis of intestinal flora, characterized by recovering the balance of Firmicutes and Bacteroidetes to the normal level and decreasing the abundance of the potentially harmful bacterium Turicibacter and the excessive Lactobacillus caused by DON. Taken together, DON-degrading strain YB9 might be used as potential probiotic additive for improving food and feed safety and modulating the intestinal microbial flora of humans and animals. Full article

(This article belongs to the Collection Strategies to Minimising Mycotoxin Contamination in Foods and Feeds)

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16 pages, 2390 KiB

Open AccessArticle

Effects of Microcystin-LR on Metabolic Functions and Structure Succession of Sediment Bacterial Community under Anaerobic Conditions

by Qin Ding, Kaiyan Liu, Zhiquan Song, Rongli Sun, Juan Zhang, Lihong Yin and Yuepu Pu

Toxins 2020, 12(3), 183; https://doi.org/10.3390/toxins12030183 - 15 Mar 2020

Cited by 17 | Viewed by 3665

Abstract

Microcystins (MCs), which are produced by harmful cyanobacteria blooms, pose a serious threat to environmental health. However, the effect of MCs on the bacterial community under anaerobic conditions is still unclear. This study examined the dynamic changes of MC-degrading capacity, metabolic activity, and [...] Read more.

Microcystins (MCs), which are produced by harmful cyanobacteria blooms, pose a serious threat to environmental health. However, the effect of MCs on the bacterial community under anaerobic conditions is still unclear. This study examined the dynamic changes of MC-degrading capacity, metabolic activity, and structure of the bacterial community in lake sediment repeatedly treated with 1 mg/L microcystin-LR (MC-LR) under anaerobic conditions. The results showed that the MC-degrading capacity of the bacterial community was increased nearly three-fold with increased treatment frequency. However, the metabolic profile behaved in exactly opposite trend, in which the overall carbon metabolic activity was inhibited by repeated toxin addition. Microbial diversity was suppressed by the first addition of MC-LR and then gradually recovered. The 16S amplicon sequencing showed that the dominant genera were changed from Exiguobacterium and Acinetobacter to Prosthecobacter, Dechloromonas, and Agrobacterium. Furthermore, the increase in the relative abundance of Dechloromonas, Pseudomonas, Hydrogenophaga, and Agrobacterium was positively correlated with the MC-LR treatment times. This indicates that they might be responsible for MC degradation under anaerobic conditions. Our findings reveal the relationship between MC-LR and the sediment bacterial community under anaerobic conditions and indicate that anaerobic biodegradation is an effective and promising method to remediate MCs pollution. Full article

(This article belongs to the Special Issue Cyanobacterial Toxins: Their Occurrence, Detection and Removal)

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13 pages, 320 KiB

Open AccessEditor’s ChoiceReview

Mycotoxin Contamination Concerns of Herbs and Medicinal Plants

by Iwona Ałtyn and Magdalena Twarużek

Toxins 2020, 12(3), 182; https://doi.org/10.3390/toxins12030182 - 14 Mar 2020

Cited by 60 | Viewed by 7568

Abstract

Plants and medicinal herbs that are available on the market do not always meet quality and safety standards. One particular concern is the risk of contamination with mycotoxins. Aflatoxins and ochratoxin A are the most frequently described mycotoxins in herbal products and have [...] Read more.

Plants and medicinal herbs that are available on the market do not always meet quality and safety standards. One particular concern is the risk of contamination with mycotoxins. Aflatoxins and ochratoxin A are the most frequently described mycotoxins in herbal products and have repeatedly been reported to occur at concentrations which exceed regulatory levels set by the European Union (EU). Possible solutions include enforcing existing limits, and for the new materials, establishing tighter limits and mandate the growth of medicinal plants in EU member countries under more strict conditions. Full article

(This article belongs to the Section Mycotoxins)

18 pages, 1534 KiB

Open AccessEditor’s ChoiceReview

Cardiovascular Calcification in Chronic Kidney Disease—Therapeutic Opportunities

by Anika Himmelsbach, Carina Ciliox and Claudia Goettsch

Toxins 2020, 12(3), 181; https://doi.org/10.3390/toxins12030181 - 14 Mar 2020

Cited by 21 | Viewed by 7838

Abstract

Patients with chronic kidney disease (CKD) are highly susceptible to cardiovascular (CV) complications, thus suffering from clinical manifestations such as heart failure and stroke. CV calcification greatly contributes to the increased CV risk in CKD patients. However, no clinically viable therapies towards treatment [...] Read more.

Patients with chronic kidney disease (CKD) are highly susceptible to cardiovascular (CV) complications, thus suffering from clinical manifestations such as heart failure and stroke. CV calcification greatly contributes to the increased CV risk in CKD patients. However, no clinically viable therapies towards treatment and prevention of CV calcification or early biomarkers have been approved to date, which is largely attributed to the asymptomatic progression of calcification and the dearth of high-resolution imaging techniques to detect early calcification prior to the ‘point of no return’. Clearly, new intervention and management strategies are essential to reduce CV risk factors in CKD patients. In experimental rodent models, novel promising therapeutic interventions demonstrate decreased CKD-induced calcification and prevent CV complications. Potential diagnostic markers such as the serum T50 assay, which demonstrates an association of serum calcification propensity with all-cause mortality and CV death in CKD patients, have been developed. This review provides an overview of the latest observations and evaluates the potential of these new interventions in relation to CV calcification in CKD patients. To this end, potential therapeutics have been analyzed, and their properties compared via experimental rodent models, human clinical trials, and meta-analyses. Full article

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

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13 pages, 3818 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Induces Inflammation in IPEC-J2 Cells by Activating P38 Mapk And Erk1/2

by Hua Zhang, Xiwen Deng, Chuang Zhou, Wenda Wu and Haibin Zhang

Toxins 2020, 12(3), 180; https://doi.org/10.3390/toxins12030180 - 13 Mar 2020

Cited by 50 | Viewed by 4725

Abstract

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 [...] Read more.

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2. Full article

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

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16 pages, 2667 KiB

Open AccessArticle

Toxins of Okadaic Acid-Group Increase Malignant Properties in Cells of Colon Cancer

by Danae Jiménez-Cárcamo, Carlos García and Héctor R. Contreras

Toxins 2020, 12(3), 179; https://doi.org/10.3390/toxins12030179 - 13 Mar 2020

Cited by 20 | Viewed by 3913

Abstract

Diarrhetic shellfish poisoning (DSP) is a syndrome caused by the intake of shellfish contaminated with a group of lipophilic and thermostable toxins, which consists of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and dinophysistoxin-2 (DTX-2). These toxins are potent protein Ser/Thr phosphatase inhibitors, mainly type [...] Read more.

Diarrhetic shellfish poisoning (DSP) is a syndrome caused by the intake of shellfish contaminated with a group of lipophilic and thermostable toxins, which consists of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and dinophysistoxin-2 (DTX-2). These toxins are potent protein Ser/Thr phosphatase inhibitors, mainly type 1 protein phosphatase (PP1) and type 2A protein phosphatase (PP2A). Different effects have been reported at the cellular, molecular and genetic levels. In this study, changes in cell survival and cell mobility induced by OA, DTX-1 and DTX-2 were determined in epithelial cell lines of the colon and colon cancer. The cell viability results showed that tumoral cell lines were more resistant to toxins than the nontumoral cell line. The results of the functional assays for testing cell migration, evaluation of cell death and the expression of proteins associated with cell adhesion showed a dual effect of toxins since in the nontumoral cell line, a greater induction of cell death, presumably by anoikis, was detected. In the tumoral cell lines, there was an induction of a more aggressive phenotype characterized by increased resistance to toxins, increased migration and increased FAK activation. In tumoral cell lines of colon cancer, OA, DTX-1/DTX-2 induce a more aggressive phenotype. Full article

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

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20 pages, 3028 KiB

Open AccessArticle

Analysis of Covalently Bound Microcystins in Sediments and Clam Tissue in the Sacramento–San Joaquin River Delta, California, USA

by Melissa Bolotaolo, Tomofumi Kurobe, Birgit Puschner, Bruce G Hammock, Matt J. Hengel, Sarah Lesmeister and Swee J. Teh

Toxins 2020, 12(3), 178; https://doi.org/10.3390/toxins12030178 - 13 Mar 2020

Cited by 9 | Viewed by 4626

Abstract

Harmful cyanobacterial blooms compromise human and environmental health, mainly due to the cyanotoxins they often produce. Microcystins (MCs) are the most commonly measured group of cyanotoxins and are hepatotoxic, neurotoxic, and cytotoxic. Due to MCs ability to covalently bind to proteins, quantification in [...] Read more.

Harmful cyanobacterial blooms compromise human and environmental health, mainly due to the cyanotoxins they often produce. Microcystins (MCs) are the most commonly measured group of cyanotoxins and are hepatotoxic, neurotoxic, and cytotoxic. Due to MCs ability to covalently bind to proteins, quantification in complex matrices is difficult. To analyze bound and unbound MCs, analytical methods were optimized for analysis in sediment and clam tissues. A clean up step was incorporated to remove lipids, improving percent yield. This method was then applied to sediment and clam samples collected from the Sacramento–San Joaquin River Delta (Delta) in the spring and fall of 2017. Water samples were also tested for intracellular and extracellular MCs. These analyses were used to quantify the partitioning of MCs among sediment, clams, and water, and to examine whether MCs persist during non-summer months. Toxin analysis revealed that multiple sediment samples collected in the Delta were positive for MCs, with a majority of the positive samples from sites in the San Joaquin River, even while water samples from the same location were below detection limit. These data highlight the importance of analyzing MCs in complex matrices to accurately evaluate environmental risk. Full article

(This article belongs to the Special Issue Cyanobacterial Toxins: Identification and Structural Characterisation to Better Understand Their Distribution and Diversity)

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16 pages, 1200 KiB

Open AccessArticle

Discovery of the Gene Encoding a Novel Small Serum Protein (SSP) of Protobothrops flavoviridis and the Evolution of SSPs

by Kento Inamaru, Ami Takeuchi, Marie Maeda, Hiroki Shibata, Yasuyuki Fukumaki, Naoko Oda-Ueda, Shosaku Hattori, Motonori Ohno and Takahito Chijiwa

Toxins 2020, 12(3), 177; https://doi.org/10.3390/toxins12030177 - 12 Mar 2020

Cited by 1 | Viewed by 2590

Abstract

Small serum proteins (SSPs) are low-molecular-weight proteins in snake serum with affinities for various venom proteins. Five SSPs, PfSSP-1 through PfSSP-5, have been reported in Protobothrops flavoviridis (“habu”, Pf) serum so far. Recently, we reported that the five genes encoding [...] Read more.

Small serum proteins (SSPs) are low-molecular-weight proteins in snake serum with affinities for various venom proteins. Five SSPs, PfSSP-1 through PfSSP-5, have been reported in Protobothrops flavoviridis (“habu”, Pf) serum so far. Recently, we reported that the five genes encoding these PfSSPs are arranged in tandem on a single chromosome. However, the physiological functions and evolutionary origins of the five SSPs remain poorly understood. In a detailed analysis of the habu draft genome, we found a gene encoding a novel SSP, SSP-6. Structural analysis of the genes encoding SSPs and their genomic arrangement revealed the following: (1) SSP-6 forms a third SSP subgroup; (2) SSP-5 and SSP-6 were present in all snake genomes before the divergence of non-venomous and venomous snakes, while SSP-4 was acquired only by venomous snakes; (3) the composition of paralogous SSP genes in snake genomes seems to reflect snake habitat differences; and (4) the evolutionary emergence of SSP genes is probably related to the physiological functions of SSPs, with an initial snake repertoire of SSP-6 and SSP-5. SSP-4 and its derivative, SSP-3, as well as SSP-1 and SSP-2, appear to be venom-related and were acquired later. Full article

(This article belongs to the Special Issue Identification and Functional Characterization of Novel Venom Components)

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