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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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35 pages, 1913 KiB  
Review
Extracting and Analyzing Pyrrolizidine Alkaloids in Medicinal Plants: A Review
by Thomas Kopp, Mona Abdel-Tawab and Boris Mizaikoff
Toxins 2020, 12(5), 320; https://doi.org/10.3390/toxins12050320 - 13 May 2020
Cited by 53 | Viewed by 9388
Abstract
Pyrrolizidine alkaloids (PAs) are distributed in plant families of Asteraceae, Boraginaceae, and Fabaceae and serve in the chemical defense mechanism against herbivores. However, they became a matter of concern due to their toxicity associated with the high risk of intake within herbal [...] Read more.
Pyrrolizidine alkaloids (PAs) are distributed in plant families of Asteraceae, Boraginaceae, and Fabaceae and serve in the chemical defense mechanism against herbivores. However, they became a matter of concern due to their toxicity associated with the high risk of intake within herbal preparations, e.g., phytopharmaceutical formulations, medicinal teas, or other plant-derived drug products. In 1992, the German Federal Ministry of Health established the first limits of PA content for fourteen medicinal plants. Because of the toxic effects of PAs, the Federal Institute of Risk Assessment (BfR) established more stringent limits in 2011, whereby a daily intake <0.007 µg/kg body weight was recommended and valid until 2018. A threefold higher limit was then advised by BfR. To address consumer safety, there is the need for more efficient extraction procedures along with robust, selective, and sensitive analytical methods to address these concerns. With the increased prevalence of, e.g., phytopharmaceutical formulations, this timely review comprehensively focuses on the most relevant extraction and analysis strategies for each of those fourteen plant genera. While a variety of extraction procedures has been reported, differences in PA content of up to 1110 ppm (0.11% (w/w)) were obtained dependent on the nature of the solvent and the applied extraction technique. It is evident that the efficient extraction of PAs requires further improvements or at least standardization of the extraction conditions. Comparing the various analytical techniques applied regarding selectivity and sensitivity, LC-MS methods appear most suited. This review shows that both standardized extraction and sensitive determination of PAs is required for achieving appropriate safety levels concerning public health in future. Full article
(This article belongs to the Collection Toxicity of Natural Alkaloids)
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19 pages, 1937 KiB  
Article
Efficacy of Mycotoxin Detoxifiers on Health and Growth of Newly-Weaned Pigs under Chronic Dietary Challenge of Deoxynivalenol
by Debora Muratori Holanda and Sung Woo Kim
Toxins 2020, 12(5), 311; https://doi.org/10.3390/toxins12050311 - 9 May 2020
Cited by 43 | Viewed by 4957
Abstract
The efficacy of yeast-based mycotoxin detoxifiers on health and growth performance of newly-weaned pigs (27-d-old) fed diets naturally contaminated with deoxynivalenol was investigated. Sixty pigs were individually assigned to five treatments for 34 d: NC (negative control, 1.2 mg/kg of deoxynivalenol); PC (positive [...] Read more.
The efficacy of yeast-based mycotoxin detoxifiers on health and growth performance of newly-weaned pigs (27-d-old) fed diets naturally contaminated with deoxynivalenol was investigated. Sixty pigs were individually assigned to five treatments for 34 d: NC (negative control, 1.2 mg/kg of deoxynivalenol); PC (positive control, 3.2 mg/kg of deoxynivalenol); CYC (PC + clay/yeast culture-based product, 0.2%); CYE (PC + clay/yeast cell wall/plant extracts/antioxidants-based product, 0.2%); and CYB (PC + clay/inactivated yeast/botanicals/antioxidants-based product, 0.2%). Blood and jejunal mucosa were sampled, and data were analyzed using Proc Mixed of SAS with pre-planned contrasts. Deoxynivalenol reduced the average daily gain (ADG) in phase 3. Pigs fed CYC had greater overall ADG, average daily feed intake during phase 3, and gain to feed ratio during phase 2 than PC. At d 14, deoxynivalenol reduced blood urea nitrogen/creatinine and tended to reduce blood urea nitrogen. Pigs fed CYB tended to have greater aspartate aminotransferase than PC. At d 34, pigs fed CYC and CYB tended to have lower serum creatine phosphokinase than PC. Pigs fed CYE had lower blood urea nitrogen/creatinine than PC. In jejunal mucosa, deoxynivalenol tended to increase malondialdehydes and decrease glutathione. Pigs fed CYE and CYB had lower malondialdehydes, pigs fed CYB had greater glutathione and tended to have lower immunoglobulin A than PC. Pigs fed CYC and CYE tended to have lower interleukin 8 than PC. In summary, deoxynivalenol challenge (1.2 vs. 3.2 mg/kg) mildly compromised growth performance and increased the oxidative stress of pigs. Mycotoxin detoxifiers could partially overcome deoxynivalenol toxicity enhancing liver health, whereas CYE and CYB reduced oxidative stress, and CYC and CYB reduced immune activation. In conclusion, yeast-based detoxifiers with functional components as clay/inactivated yeast/botanicals/antioxidants had increased detoxifying properties in newly-weaned pigs challenged with deoxynivalenol, potentially by enhancing adsorbability, immune function, gut health, and reducing oxidative stress. Full article
(This article belongs to the Special Issue Impact of Naturally Contaminated Mycotoxins in Feedstuffs and Feeds on Animal Growth and Health)
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27 pages, 1728 KiB  
Article
The First Proteomic Study of Nostoc sp. PCC 7120 Exposed to Cyanotoxin BMAA under Nitrogen Starvation
by Olga A. Koksharova, Ivan O. Butenko, Olga V. Pobeguts, Nina A. Safronova and Vadim M. Govorun
Toxins 2020, 12(5), 310; https://doi.org/10.3390/toxins12050310 - 9 May 2020
Cited by 16 | Viewed by 5090
Abstract
The oldest prokaryotic photoautotrophic organisms, cyanobacteria, produce many different metabolites. Among them is the water-soluble neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (BMAA), whose biological functions in cyanobacterial metabolism are of fundamental scientific and practical interest. An early BMAA inhibitory effect on nitrogen fixation and [...] Read more.
The oldest prokaryotic photoautotrophic organisms, cyanobacteria, produce many different metabolites. Among them is the water-soluble neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (BMAA), whose biological functions in cyanobacterial metabolism are of fundamental scientific and practical interest. An early BMAA inhibitory effect on nitrogen fixation and heterocyst differentiation was shown in strains of diazotrophic cyanobacteria Nostoc sp. PCC 7120, Nostoc punctiforme PCC 73102 (ATCC 29133), and Nostoc sp. strain 8963 under conditions of nitrogen starvation. Herein, we present a comprehensive proteomic study of Nostoc (also called Anabaena) sp. PCC 7120 in the heterocyst formation stage affecting by BMAA treatment under nitrogen starvation conditions. BMAA disturbs proteins involved in nitrogen and carbon metabolic pathways, which are tightly co-regulated in cyanobacteria cells. The presented evidence shows that exogenous BMAA affects a key nitrogen regulatory protein, PII (GlnB), and some of its protein partners, as well as glutamyl-tRNA synthetase gltX and other proteins that are involved in protein synthesis, heterocyst differentiation, and nitrogen metabolism. By taking into account the important regulatory role of PII, it becomes clear that BMAA has a severe negative impact on the carbon and nitrogen metabolism of starving Nostoc sp. PCC 7120 cells. BMAA disturbs carbon fixation and the carbon dioxide concentrating mechanism, photosynthesis, and amino acid metabolism. Stress response proteins and DNA repair enzymes are upregulated in the presence of BMAA, clearly indicating severe intracellular stress. This is the first proteomic study of the effects of BMAA on diazotrophic starving cyanobacteria cells, allowing a deeper insight into the regulation of the intracellular metabolism of cyanobacteria by this non-protein amino acid. Full article
(This article belongs to the Special Issue Biological Role of Cyanotoxins: Experimental and In-Field Evidence)
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17 pages, 2683 KiB  
Article
Repurposing Cancer Drugs Batimastat and Marimastat to Inhibit the Activity of a Group I Metalloprotease from the Venom of the Western Diamondback Rattlesnake, Crotalus atrox
by Harry J. Layfield, Harry F. Williams, Divyashree Ravishankar, Amita Mehmi, Medha Sonavane, Anika Salim, Rajendran Vaiyapuri, Karthik Lakshminarayanan, Thomas M. Vallance, Andrew B. Bicknell, Steven A. Trim, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2020, 12(5), 309; https://doi.org/10.3390/toxins12050309 - 9 May 2020
Cited by 28 | Viewed by 7035
Abstract
Snakebite envenomation causes over 140,000 deaths every year, predominantly in developing countries. As a result, it is one of the most lethal neglected tropical diseases. It is associated with incredibly complex pathophysiology due to the vast number of unique toxins/proteins present in the [...] Read more.
Snakebite envenomation causes over 140,000 deaths every year, predominantly in developing countries. As a result, it is one of the most lethal neglected tropical diseases. It is associated with incredibly complex pathophysiology due to the vast number of unique toxins/proteins present in the venoms of diverse snake species found worldwide. Here, we report the purification and functional characteristics of a Group I (PI) metalloprotease (CAMP-2) from the venom of the western diamondback rattlesnake, Crotalus atrox. Its sensitivity to matrix metalloprotease inhibitors (batimastat and marimastat) was established using specific in vitro experiments and in silico molecular docking analysis. CAMP-2 shows high sequence homology to atroxase from the venom of Crotalus atrox and exhibits collagenolytic, fibrinogenolytic and mild haemolytic activities. It exerts a mild inhibitory effect on agonist-induced platelet aggregation in the absence of plasma proteins. Its collagenolytic activity is completely inhibited by batimastat and marimastat. Zinc chloride also inhibits the collagenolytic activity of CAMP-2 by around 75% at 50 μM, while it is partially potentiated by calcium chloride. Molecular docking studies have demonstrated that batimastat and marimastat are able to bind strongly to the active site residues of CAMP-2. This study demonstrates the impact of matrix metalloprotease inhibitors in the modulation of a purified, Group I metalloprotease activities in comparison to the whole venom. By improving our understanding of snake venom metalloproteases and their sensitivity to small molecule inhibitors, we can begin to develop novel and improved treatment strategies for snakebites. Full article
(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)
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20 pages, 5835 KiB  
Article
Use of Mass Spectrometry to Determine the Diversity of Toxins Produced by Gambierdiscus and Fukuyoa Species from Balearic Islands and Crete (Mediterranean Sea) and the Canary Islands (Northeast Atlantic)
by Pablo Estevez, Manoëlla Sibat, José Manuel Leão-Martins, Angels Tudó, Maria Rambla-Alegre, Katerina Aligizaki, Jorge Diogène, Ana Gago-Martinez and Philipp Hess
Toxins 2020, 12(5), 305; https://doi.org/10.3390/toxins12050305 - 7 May 2020
Cited by 33 | Viewed by 4765
Abstract
Over the last decade, knowledge has significantly increased on the taxonomic identity and distribution of dinoflagellates of the genera Gambierdiscus and Fukuyoa. Additionally, a number of hitherto unknown bioactive metabolites have been described, while the role of these compounds in ciguatera poisoning [...] Read more.
Over the last decade, knowledge has significantly increased on the taxonomic identity and distribution of dinoflagellates of the genera Gambierdiscus and Fukuyoa. Additionally, a number of hitherto unknown bioactive metabolites have been described, while the role of these compounds in ciguatera poisoning (CP) remains to be clarified. Ciguatoxins and maitotoxins are very toxic compounds produced by these dinoflagellates and have been described since the 1980s. Ciguatoxins are generally described as the main contributors to this food intoxication. Recent reports of CP in temperate waters of the Canary Islands (Spain) and the Madeira archipelago (Portugal) triggered the need for isolation and cultivation of dinoflagellates from these areas, and their taxonomic and toxicological characterization. Maitotoxins, and specifically maitotoxin-4, has been described as one of the most toxic compounds produced by these dinoflagellates (e.g., G. excentricus) in the Canary Islands. Thus, characterization of toxin profiles of Gambierdiscus species from adjacent regions appears critical. The combination of liquid chromatography coupled to either low- or high-resolution mass spectrometry allowed for characterization of several strains of Gambierdiscus and Fukuyoa from the Mediterranean Sea and the Canary Islands. Maitotoxin-3, two analogues tentatively identified as gambieric acid C and D, a putative gambierone analogue and a putative gambieroxide were detected in all G. australes strains from Menorca and Mallorca (Balearic Islands, Spain) while only maitotoxin-3 was present in an F. paulensis strain of the same region. An unidentified Gambierdiscus species (Gambierdiscus sp.2) from Crete (Greece) showed a different toxin profile, detecting both maitotoxin-3 and gambierone, while the availability of a G. excentricus strain from the Canary Islands (Spain) confirmed the presence of maitotoxin-4 in this species. Overall, this study shows that toxin profiles not only appear to be species-specific but probably also specific to larger geographic regions. Full article
(This article belongs to the Special Issue Ciguatoxins)
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22 pages, 1703 KiB  
Review
The Cytocidal Spectrum of Bacillus thuringiensis Toxins: From Insects to Human Cancer Cells
by Gretel Mendoza-Almanza, Edgar L. Esparza-Ibarra, Jorge L. Ayala-Luján, Marisa Mercado-Reyes, Susana Godina-González, Marisa Hernández-Barrales and Jorge Olmos-Soto
Toxins 2020, 12(5), 301; https://doi.org/10.3390/toxins12050301 - 6 May 2020
Cited by 40 | Viewed by 9101
Abstract
Bacillus thuringiensis (Bt) is a ubiquitous bacterium in soils, insect cadavers, phylloplane, water, and stored grain, that produces several proteins, each one toxic to different biological targets such as insects, nematodes, mites, protozoa, and mammalian cells. Most Bt toxins identify their particular target [...] Read more.
Bacillus thuringiensis (Bt) is a ubiquitous bacterium in soils, insect cadavers, phylloplane, water, and stored grain, that produces several proteins, each one toxic to different biological targets such as insects, nematodes, mites, protozoa, and mammalian cells. Most Bt toxins identify their particular target through the recognition of specific cell membrane receptors. Cry proteins are the best-known toxins from Bt and a great amount of research has been published. Cry are cytotoxic to insect larvae that affect important crops recognizing specific cell membrane receptors such as cadherin, aminopeptidase-N, and alkaline phosphatase. Furthermore, some Cry toxins such as Cry4A, Cry4B, and Cry11A act synergistically with Cyt toxins against dipteran larvae vectors of human disease. Research developed with Cry proteins revealed that these toxins also could kill human cancer cells through the interaction with specific receptors. Parasporins are a small group of patented toxins that may or may not have insecticidal activity. These proteins could kill a wide variety of mammalian cancer cells by recognizing specific membrane receptors, just like Cry toxins do. Surface layer proteins (SLP), unlike the other proteins produced by Bt, are also produced by most bacteria and archaebacteria. It was recently demonstrated that SLP produced by Bt could interact with membrane receptors of insect and human cancer cells to kill them. Cyt toxins have a structure that is mostly unrelated to Cry toxins; thereby, other mechanisms of action have been reported to them. These toxins affect mainly mosquitoes that are vectors of human diseases like Anopheles spp (malaria), Aedes spp (dengue, zika, and chikungunya), and Culex spp (Nile fever and Rift Valley fever), respectively. In addition to the Cry, Cyt, and parasporins toxins produced during spore formation as inclusion bodies, Bt strains also produce Vip (Vegetative insecticidal toxins) and Sip (Secreted insecticidal proteins) toxins with insecticidal activity during their vegetative growth phase. Full article
(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)
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16 pages, 1434 KiB  
Review
Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells
by Maxime Espi, Laetitia Koppe, Denis Fouque and Olivier Thaunat
Toxins 2020, 12(5), 300; https://doi.org/10.3390/toxins12050300 - 6 May 2020
Cited by 93 | Viewed by 19251
Abstract
Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade [...] Read more.
Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes. Full article
(This article belongs to the Special Issue Immune Dysfunction in Uremia)
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18 pages, 665 KiB  
Review
The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease
by Pieter Evenepoel, Sander Dejongh, Kristin Verbeke and Bjorn Meijers
Toxins 2020, 12(5), 285; https://doi.org/10.3390/toxins12050285 - 29 Apr 2020
Cited by 25 | Viewed by 4802
Abstract
Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as [...] Read more.
Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the ‘calcification paradox’ or the bone–vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone–vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone–vascular axis may open avenues for novel therapeutics, including nutriceuticals. Full article
(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))
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34 pages, 1973 KiB  
Article
Revisiting the Neuroblastoma Cell-Based Assay (CBA-N2a) for the Improved Detection of Marine Toxins Active on Voltage Gated Sodium Channels (VGSCs)
by Jérôme Viallon, Mireille Chinain and Hélène Taiana Darius
Toxins 2020, 12(5), 281; https://doi.org/10.3390/toxins12050281 - 27 Apr 2020
Cited by 40 | Viewed by 5943
Abstract
The neuroblastoma cell-based assay (CBA-N2a) is widely used for the detection of marine biotoxins in seafood products, yet a consensus protocol is still lacking. In this study, six key parameters of CBA-N2a were revisited: cell seeding densities, cell layer viability after 26 h [...] Read more.
The neuroblastoma cell-based assay (CBA-N2a) is widely used for the detection of marine biotoxins in seafood products, yet a consensus protocol is still lacking. In this study, six key parameters of CBA-N2a were revisited: cell seeding densities, cell layer viability after 26 h growth, MTT incubation time, Ouabain and Veratridine treatment and solvent and matrix effects. A step-by-step protocol was defined identifying five viability controls for the validation of CBA-N2a results. Specific detection of two voltage gated sodium channel activators, pacific ciguatoxin (P-CTX3C) and brevetoxin (PbTx3) and two inhibitors, saxitoxin (STX) and decarbamoylsaxitoxin (dc-STX) was achieved, with EC50 values of 1.7 ± 0.35 pg/mL, 5.8 ± 0.9 ng/mL, 3 ± 0.5 ng/mL and 15.8 ± 3 ng/mL, respectively. When applied to the detection of ciguatoxin (CTX)-like toxicity in fish samples, limit of detection (LOD) and limit of quantification (LOQ) values were 0.031 ± 0.008 and 0.064 ± 0.016 ng P-CTX3C eq/g of flesh, respectively. Intra and inter-assays comparisons of viability controls, LOD, LOQ and toxicity in fish samples gave coefficients of variation (CVs) ranging from 3% to 29%. This improved test adaptable to either high throughput screening or composite toxicity estimation is a useful starting point for a standardization of the CBA-N2a in the field of marine toxin detection. 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, 634 KiB  
Article
Molecular Identification and Mycotoxin Production by Alternaria Species Occurring on Durum Wheat, Showing Black Point Symptoms
by Mario Masiello, Stefania Somma, Antonia Susca, Veronica Ghionna, Antonio Francesco Logrieco, Matteo Franzoni, Stefano Ravaglia, Giuseppe Meca and Antonio Moretti
Toxins 2020, 12(4), 275; https://doi.org/10.3390/toxins12040275 - 23 Apr 2020
Cited by 38 | Viewed by 5406
Abstract
Black point is a fungal disease of wheat, mainly associated with mycotoxigenic Alternaria species. Affected wheat kernels are characterized by dark brown discolouration of the embryo region and reduction of grain quality. Potential risk is the possible accumulation of Alternaria mycotoxins, alternariol (AOH), [...] Read more.
Black point is a fungal disease of wheat, mainly associated with mycotoxigenic Alternaria species. Affected wheat kernels are characterized by dark brown discolouration of the embryo region and reduction of grain quality. Potential risk is the possible accumulation of Alternaria mycotoxins, alternariol (AOH), alternariol-monomethyl ether (AME), tenuazonic acid (TA), and altenuene (ALT), provided by haemato-toxic, genotoxic, and mutagenic activities. One hundred and twenty durum wheat samples belonging to 30 different genotypes grown in Bologna and Modena areas, in Italy, showing black point symptoms, were analyzed for Alternaria species and their mycotoxin contamination. Alternariol was selected as an indicator of the capability of the Alternaria species to produce mycotoxin in vivo in field conditions. The data showed that Alternaria species occurred in 118 out of 120 wheat kernels samples, with the incidence of infected kernels ranging between 1% and 26%. Moreover, AOH was detected by using a HPLC with a diode array detector (LC-DAD) in 98 out of 120 samples with values ranging between 24 and 262 µg Kg−1. Ninety-two Alternaria representative strains, previously identified morphologically, were identified at species/section level using gene sequencing, and therefore were analyzed for their mycotoxin profiles. Eighty-four strains, phylogenetically grouped in the Alternaria section, produced AOH, AME, and TA with values up to 8064, 14,341, and 3683 µg g−1, respectively, analyzed by using a LC-DAD. On the other hand, eight Alternaria strains, included in Infectoriae Section, showed a very low or no capability to produce mycotoxins. Full article
(This article belongs to the Special Issue Mycotoxins in Food: Origin and Management of Risk)
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12 pages, 3411 KiB  
Article
Oligomer Formation and Insecticidal Activity of Bacillus thuringiensis Vip3Aa Toxin
by Ensi Shao, Aishan Zhang, Yaqi Yan, Yaomin Wang, Xinyi Jia, Li Sha, Xiong Guan, Ping Wang and Zhipeng Huang
Toxins 2020, 12(4), 274; https://doi.org/10.3390/toxins12040274 - 23 Apr 2020
Cited by 11 | Viewed by 3774
Abstract
Bacillus thuringiensis (Bt) Vip3A proteins are important insecticidal proteins used for control of lepidopteran insects. However, the mode of action of Vip3A toxin is still unclear. In this study, the amino acid residue S164 in Vip3Aa was identified to be critical for the [...] Read more.
Bacillus thuringiensis (Bt) Vip3A proteins are important insecticidal proteins used for control of lepidopteran insects. However, the mode of action of Vip3A toxin is still unclear. In this study, the amino acid residue S164 in Vip3Aa was identified to be critical for the toxicity in Spodoptera litura. Results from substitution mutations of the S164 indicate that the insecticidal activity of Vip3Aa correlated with the formation of a >240 kDa complex of the toxin upon proteolytic activation. The >240 kDa complex was found to be composed of the 19 kDa and the 65 kDa fragments of Vip3Aa. Substitution of the S164 in Vip3Aa protein with Ala or Pro resulted in loss of the >240 kDa complex and loss of toxicity in Spodoptera litura. In contrast, substitution of S164 with Thr did not affect the >240 kDa complex formation, and the toxicity of the mutant was only reduced by 35%. Therefore, the results from this study indicated that formation of the >240 kDa complex correlates with the toxicity of Vip3Aa in insects and the residue S164 is important for the formation of the complex. Full article
(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)
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12 pages, 980 KiB  
Article
Critical Comparison of Analytical Performances of Two Immunoassay Methods for Rapid Detection of Aflatoxin M1 in Milk
by Ivan Pecorelli, Natascia Guarducci, Cristoph von Holst, Rita Bibi, Michelangelo Pascale, Biancamaria Ciasca, Antonio F. Logrieco and Veronica M. T. Lattanzio
Toxins 2020, 12(4), 270; https://doi.org/10.3390/toxins12040270 - 22 Apr 2020
Cited by 15 | Viewed by 4172
Abstract
Aflatoxin B1 (AFB1) is a secondary metabolite produced by some Aspergillus spp. fungi affecting many crops and feed materials. Aflatoxin M1 (AFM1), the 4-hydroxylated metabolite of AFB1, is the main AFB1-related compound present [...] Read more.
Aflatoxin B1 (AFB1) is a secondary metabolite produced by some Aspergillus spp. fungi affecting many crops and feed materials. Aflatoxin M1 (AFM1), the 4-hydroxylated metabolite of AFB1, is the main AFB1-related compound present in milk, and it is categorized by the International Agency for Research on Cancer (IARC) as a “group 1 human carcinogen”. The aim of this work was to evaluate and compare the analytical performances of two commercial immunoassays widely applied for the detection of AFM1 in milk, namely strip test immunoassay and enzyme linked immunosorbent assay (ELISA). Assay validation included samples at AFM1 levels of 25, 50, 75 ng/kg and blank samples (AFM1 < 0.5 ng/kg). With respect to a screening target concentration (STC) of 50 ng/kg the two assays showed cut-off values of 37.7 ng/kg and 47.5 ng/kg for strip test and ELISA, respectively, a false suspect rate for blanks <0.1% (for both assays) and a false negative rate for samples containing AFM1 at levels higher than STC, of 0.4% (for both assays). The intermediate precision (RSDip) was <32% for the strip test and <15% for the ELISA. Method verification through long-term intra-laboratory quality control (QC) measurements confirmed the results from the validation study. Furthermore, a satisfactory correlation of the results obtained with both immunoassays and the AOAC Official Method 2000.08 was obtained for the analysis of cow milk samples naturally contaminated with AFM1 at levels within “not detected” (< 0.5 ng/kg) and 50 ng/kg. Finally, the extension of the scope of the strip test method to goat and sheep milk was evaluated by applying the experimental design foreseen in the EU regulation. 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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11 pages, 931 KiB  
Review
Treatment of Blepharospasm and Oromandibular Dystonia with Botulinum Toxins
by Travis J.W. Hassell and David Charles
Toxins 2020, 12(4), 269; https://doi.org/10.3390/toxins12040269 - 22 Apr 2020
Cited by 41 | Viewed by 12289
Abstract
Blepharospasm and oromandibular dystonia are focal dystonias characterized by involuntary and often patterned, repetitive muscle contractions. There is a long history of medical and surgical therapies, with the current first-line therapy, botulinum neurotoxin (BoNT), becoming standard of care in 1989. This comprehensive review [...] Read more.
Blepharospasm and oromandibular dystonia are focal dystonias characterized by involuntary and often patterned, repetitive muscle contractions. There is a long history of medical and surgical therapies, with the current first-line therapy, botulinum neurotoxin (BoNT), becoming standard of care in 1989. This comprehensive review utilized MEDLINE and PubMed and provides an overview of the history of these focal dystonias, BoNT, and the use of toxin to treat them. We present the levels of clinical evidence for each toxin for both, focal dystonias and offer guidance for muscle and site selection as well as dosing. Full article
(This article belongs to the Special Issue Treatment of Dystonia with Botulinum Toxins)
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7 pages, 1871 KiB  
Communication
Liquid Chromatography Coupled to High-Resolution Mass Spectrometry for the Confirmation of Caribbean Ciguatoxin-1 as the Main Toxin Responsible for Ciguatera Poisoning Caused by Fish from European Atlantic Coasts
by Pablo Estevez, Manoella Sibat, José Manuel Leão-Martins, Pedro Reis Costa, Ana Gago-Martínez and Philipp Hess
Toxins 2020, 12(4), 267; https://doi.org/10.3390/toxins12040267 - 21 Apr 2020
Cited by 32 | Viewed by 4875
Abstract
Ciguatera poisoning (CP) is a common seafood intoxication mainly caused by the consumption of fish contaminated by ciguatoxins. Recent studies showed that Caribbean ciguatoxin-1 (C-CTX1) is the main toxin causing CP through fish caught in the Northeast Atlantic, e.g., Canary Islands (Spain) and [...] Read more.
Ciguatera poisoning (CP) is a common seafood intoxication mainly caused by the consumption of fish contaminated by ciguatoxins. Recent studies showed that Caribbean ciguatoxin-1 (C-CTX1) is the main toxin causing CP through fish caught in the Northeast Atlantic, e.g., Canary Islands (Spain) and Madeira (Portugal). The use of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) combined with neuroblastoma cell assay (N2a) allowed the initial confirmation of the presence of C-CTX1 in contaminated fish samples from the abovementioned areas, nevertheless the lack of commercially available reference materials for these particular ciguatoxin (CTX) analogues has been a major limitation to progress research. The EuroCigua project allowed the preparation of C-CTX1 laboratory reference material (LRM) from fish species (Seriola fasciata) from the Madeira archipelago (Portugal). This reference material was used to implement a liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) for the detection of C-CTX1, acquisition of full-scan as well as collision-induced mass spectra of this particular analogue. Fragmentation pathways were proposed based on fragments obtained. The optimized LC-HRMS method was then applied to confirm C-CTX1 in fish (Bodianus scrofa) caught in the Selvagens Islands (Portugal). Full article
(This article belongs to the Special Issue Ciguatoxins)
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21 pages, 1008 KiB  
Review
A Mini Review on Microcystins and Bacterial Degradation
by Isaac Yaw Massey and Fei Yang
Toxins 2020, 12(4), 268; https://doi.org/10.3390/toxins12040268 - 21 Apr 2020
Cited by 108 | Viewed by 8333
Abstract
Microcystins (MCs) classified as hepatotoxic and carcinogenic are the most commonly reported cyanobacterial toxins found in the environment. Microcystis sp. possessing a series of MC synthesis genes (mcyA-mcyJ) are well documented for their excessive abundance, numerous bloom occurrences and MC producing capacity. About [...] Read more.
Microcystins (MCs) classified as hepatotoxic and carcinogenic are the most commonly reported cyanobacterial toxins found in the environment. Microcystis sp. possessing a series of MC synthesis genes (mcyA-mcyJ) are well documented for their excessive abundance, numerous bloom occurrences and MC producing capacity. About 246 variants of MC which exert severe animal and human health hazards through the inhibition of protein phosphatases (PP1 and PP2A) have been characterized. To minimize and prevent MC health consequences, the World Health Organization proposed 1 µg/L MC guidelines for safe drinking water quality. Further the utilization of bacteria that represent a promising biological treatment approach to degrade and remove MC from water bodies without harming the environment has gained global attention. Thus the present review described toxic effects and bacterial degradation of MCs. Full article
(This article belongs to the Special Issue Cyanobacterial Toxins: Their Occurrence, Detection and Removal)
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17 pages, 4120 KiB  
Article
The Importance of Allelopathic Picocyanobacterium Synechococcus sp. on the Abundance, Biomass Formation, and Structure of Phytoplankton Assemblages in Three Freshwater Lakes
by Iwona Bubak, Sylwia Śliwińska-Wilczewska, Paulina Głowacka, Agnieszka Szczerba and Katarzyna Możdżeń
Toxins 2020, 12(4), 259; https://doi.org/10.3390/toxins12040259 - 16 Apr 2020
Cited by 16 | Viewed by 4324
Abstract
The contribution of picocyanobacteria to summer phytoplankton blooms, accompanied by an ecological crisis, is a new phenomenon in Europe. This issue requires careful investigation. We studied allelopathic activity of freshwater picocyanobacterium Synechococcus sp. on phytoplankton assemblages from three freshwater lakes. In this study, [...] Read more.
The contribution of picocyanobacteria to summer phytoplankton blooms, accompanied by an ecological crisis, is a new phenomenon in Europe. This issue requires careful investigation. We studied allelopathic activity of freshwater picocyanobacterium Synechococcus sp. on phytoplankton assemblages from three freshwater lakes. In this study, the allelopathic activity of the Synechococcus sp. on the total abundance, biomass, as well as structure of the phytoplankton assemblages were investigated. Our results indicated that addition of exudates obtained from Synechococcus sp. affected the number of cells and biomass of the phytoplankton communities; the degree of inhibition or stimulation was different for each species, causing a change in the phytoplankton abundance and dominance during the experiment. We observed that some group of organisms (especially cyanobacteria from the genus Aphanothece, Limnothrix, Microcystis, and Synechococcus) showed tolerance for allelopathic compounds produced and released by Synechococcus sp. It is also worth noting that in some samples, Bacillariophyceae (e.g., Amphora pediculus, Navicula pygmaea, and Nitzschia paleacea) were completely eliminated in the experimental treatments, while present in the controls. This work demonstrated that the allelopathic activity exhibited by the Synechococcus sp. is probably one of the major competitive strategies affecting some of the coexisting phytoplankton species in freshwater ecosystems. To our best knowledge this is the first report of the allelopathic activity of Synechococcus sp. in the freshwater reservoirs, and one of the few published works showing allelopathic properties of freshwater picocyanobacteria on coexisting phytoplankton species. 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, 4671 KiB  
Review
Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs
by Clara Pérez-Peinado, Sira Defaus and David Andreu
Toxins 2020, 12(4), 255; https://doi.org/10.3390/toxins12040255 - 15 Apr 2020
Cited by 42 | Viewed by 9262
Abstract
For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of [...] Read more.
For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads. Full article
(This article belongs to the Special Issue Identification and Functional Characterization of Novel Venom Components)
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16 pages, 688 KiB  
Review
Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease
by Griet Glorieux, Tessa Gryp and Alessandra Perna
Toxins 2020, 12(4), 245; https://doi.org/10.3390/toxins12040245 - 11 Apr 2020
Cited by 63 | Viewed by 6571
Abstract
Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects [...] Read more.
Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H2S affect the intestinal barrier structure and function while in the circulation the related uremic toxins stimulate cells of the immune system. Both conditions contribute to the pro-inflammatory status of patients with chronic kidney disease (CKD). Generation and/or absorption of these toxin precursors could be targeted to decrease plasma levels of their respective uremic toxins and to reduce micro-inflammation in CKD. Full article
(This article belongs to the Special Issue Immune Dysfunction in Uremia)
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12 pages, 1465 KiB  
Article
CRISPR-Mediated Knockout of the ABCC2 Gene in Ostrinia furnacalis Confers High-Level Resistance to the Bacillus thuringiensis Cry1Fa Toxin
by Xingliang Wang, Yanjun Xu, Jianlei Huang, Wenzhong Jin, Yihua Yang and Yidong Wu
Toxins 2020, 12(4), 246; https://doi.org/10.3390/toxins12040246 - 11 Apr 2020
Cited by 55 | Viewed by 5341
Abstract
The adoption of transgenic crops expressing Bacillus thuringiensis (Bt) insecticidal crystalline (Cry) proteins has reduced insecticide application, increased yields, and contributed to food safety worldwide. However, the efficacy of transgenic Bt crops is put at risk by the adaptive resistance evolution of target [...] Read more.
The adoption of transgenic crops expressing Bacillus thuringiensis (Bt) insecticidal crystalline (Cry) proteins has reduced insecticide application, increased yields, and contributed to food safety worldwide. However, the efficacy of transgenic Bt crops is put at risk by the adaptive resistance evolution of target pests. Previous studies indicate that resistance to Bacillus thuringiensis Cry1A and Cry1F toxins was genetically linked with mutations of ATP-binding cassette (ABC) transporter subfamily C gene ABCC2 in at least seven lepidopteran insects. Several strains selected in the laboratory of the Asian corn borer, Ostrinia furnacalis, a destructive pest of corn in Asian Western Pacific countries, developed high levels of resistance to Cry1A and Cry1F toxins. The causality between the O. furnacalis ABCC2 (OfABCC2) gene and resistance to Cry1A and Cry1F toxins remains unknown. Here, we successfully generated a homozygous strain (OfC2-KO) of O. furnacalis with an 8-bp deletion mutation of ABCC2 by the CRISPR/Cas9 approach. The 8-bp deletion mutation results in a frame shift in the open reading frame of transcripts, which produced a predicted protein truncated in the TM4-TM5 loop region. The knockout strain OfC2-KO showed much more than a 300-fold resistance to Cry1Fa, and low levels of resistance to Cry1Ab and Cry1Ac (<10-fold), but no significant effects on the toxicities of Cry1Aa and two chemical insecticides (abamectin and chlorantraniliprole), compared to the background NJ-S strain. Furthermore, we found that the Cry1Fa resistance was autosomal, recessive, and significantly linked with the 8-bp deletion mutation of OfABCC2 in the OfC2-KO strain. In conclusion, in vivo functional investigation demonstrates the causality of the OfABCC2 truncating mutation with high-level resistance to the Cry1Fa toxin in O. furnacalis. Our results suggest that the OfABCC2 protein might be a functional receptor for Cry1Fa and reinforces the association of this gene to the mode of action of the Cry1Fa toxin. Full article
(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)
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16 pages, 26308 KiB  
Article
Phylogenomic Analysis of Secondary Metabolism in the Toxic Cyanobacterial Genera Anabaena, Dolichospermum and Aphanizomenon
by Julia Österholm, Rafael V. Popin, David P. Fewer and Kaarina Sivonen
Toxins 2020, 12(4), 248; https://doi.org/10.3390/toxins12040248 - 11 Apr 2020
Cited by 44 | Viewed by 6626
Abstract
Cyanobacteria produce an array of toxins that pose serious health risks to humans and animals. The closely related diazotrophic genera, Anabaena, Dolichospermum and Aphanizomenon, frequently form poisonous blooms in lakes and brackish waters around the world. These genera form a complex [...] Read more.
Cyanobacteria produce an array of toxins that pose serious health risks to humans and animals. The closely related diazotrophic genera, Anabaena, Dolichospermum and Aphanizomenon, frequently form poisonous blooms in lakes and brackish waters around the world. These genera form a complex now termed the Anabaena, Dolichospermum and Aphanizomenon (ADA) clade and produce a greater array of toxins than any other cyanobacteria group. However, taxonomic confusion masks the distribution of toxin biosynthetic pathways in cyanobacteria. Here we obtained 11 new draft genomes to improve the understanding of toxin production in these genera. Comparison of secondary metabolite pathways in all available 31 genomes for these three genera suggests that the ability to produce microcystin, anatoxin-a, and saxitoxin is associated with specific subgroups. Each toxin gene cluster was concentrated or even limited to a certain subgroup within the ADA clade. Our results indicate that members of the ADA clade encode a variety of secondary metabolites following the phylogenetic clustering of constituent species. The newly sequenced members of the ADA clade show that phylogenetic separation of planktonic Dolichospermum and benthic Anabaena is not complete. This underscores the importance of taxonomic revision of Anabaena, Dolichospermum and Aphanizomenon genera to reflect current phylogenomic understanding. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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23 pages, 1344 KiB  
Review
Talkin’ Toxins: From Coley’s to Modern Cancer Immunotherapy
by Robert D. Carlson, John C. Flickinger, Jr. and Adam E. Snook
Toxins 2020, 12(4), 241; https://doi.org/10.3390/toxins12040241 - 9 Apr 2020
Cited by 63 | Viewed by 10327
Abstract
The ability of the immune system to precisely target and eliminate aberrant or infected cells has long been studied in the field of infectious diseases. Attempts to define and exploit these potent immunological processes in the fight against cancer has been a longstanding [...] Read more.
The ability of the immune system to precisely target and eliminate aberrant or infected cells has long been studied in the field of infectious diseases. Attempts to define and exploit these potent immunological processes in the fight against cancer has been a longstanding effort dating back over 100 years to when Dr. William Coley purposefully infected cancer patients with a cocktail of heat-killed bacteria to stimulate anti-cancer immune processes. Although the field of cancer immunotherapy has been dotted with skepticism at times, the success of immune checkpoint inhibitors and recent FDA approvals of autologous cell therapies have pivoted immunotherapy to center stage as one of the most promising strategies to treat cancer. This review aims to summarize historic milestones throughout the field of cancer immunotherapy as well as highlight current and promising immunotherapies in development. Full article
(This article belongs to the Special Issue Toxins and Cancer Therapy)
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23 pages, 2417 KiB  
Article
Cylindrospermopsin- and Deoxycylindrospermopsin-Producing Raphidiopsis raciborskii and Microcystin-Producing Microcystis spp. in Meiktila Lake, Myanmar
by Andreas Ballot, Thida Swe, Marit Mjelde, Leonardo Cerasino, Vladyslava Hostyeva and Christopher O. Miles
Toxins 2020, 12(4), 232; https://doi.org/10.3390/toxins12040232 - 7 Apr 2020
Cited by 22 | Viewed by 4491
Abstract
Meiktila Lake is a shallow reservoir located close to Meiktila city in central Myanmar. Its water is used for irrigation, domestic purposes and drinking water. No detailed study of the presence of cyanobacteria and their potential toxin production has been conducted so far. [...] Read more.
Meiktila Lake is a shallow reservoir located close to Meiktila city in central Myanmar. Its water is used for irrigation, domestic purposes and drinking water. No detailed study of the presence of cyanobacteria and their potential toxin production has been conducted so far. To ascertain the cyanobacterial composition and presence of cyanobacterial toxins in Meiktila Lake, water samples were collected in March and November 2017 and investigated for physico-chemical and biological parameters. Phytoplankton composition and biomass determination revealed that most of the samples were dominated by the cyanobacterium Raphidiopsis raciborskii. In a polyphasic approach, seven isolated cyanobacterial strains were classified morphologically and phylogenetically as R. raciborskii, and Microcystis spp. and tested for microcystins (MCs), cylindrospermopsins (CYNs), saxitoxins and anatoxins by enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–mass spectrometry (LC–MS). ELISA and LC–MS analyses confirmed CYNs in three of the five Raphidiopsis strains between 1.8 and 9.8 μg mg−1 fresh weight. Both Microcystis strains produced MCs, one strain 52 congeners and the other strain 20 congeners, including 22 previously unreported variants. Due to the presence of CYN- and MC-producing cyanobacteria, harmful effects on humans, domestic and wild animals cannot be excluded in Meiktila Lake. Full article
(This article belongs to the Special Issue Cyanotoxins in Bloom: Ever-Increasing Occurrence and Global Distribution of Freshwater Cyanotoxins from Planktic and Benthic Cyanobacteria)
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20 pages, 798 KiB  
Article
Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome
by Maaike K. van Gelder, Igor R. Middel, Robin W. M. Vernooij, Michiel L. Bots, Marianne C. Verhaar, Rosalinde Masereeuw, Muriel P. Grooteman, Menso J. Nubé, M. A. van den Dorpel, Peter J. Blankestijn, Maarten B. Rookmaaker and Karin G.F. Gerritsen
Toxins 2020, 12(4), 234; https://doi.org/10.3390/toxins12040234 - 7 Apr 2020
Cited by 43 | Viewed by 5457
Abstract
Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients [...] Read more.
Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (−15.3 to 34.6) in patients treated with HDF and increased by 11.9% (−15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints. Full article
(This article belongs to the Section Uremic Toxins)
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14 pages, 1569 KiB  
Review
Indoxyl Sulfate, a Uremic Endotheliotoxin
by Guillaume Lano, Stéphane Burtey and Marion Sallée
Toxins 2020, 12(4), 229; https://doi.org/10.3390/toxins12040229 - 5 Apr 2020
Cited by 96 | Viewed by 7497
Abstract
Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)—derived from tryptophan metabolism—accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial [...] Read more.
Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)—derived from tryptophan metabolism—accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial dysfunction implicated in cardiovascular morbidity and mortality during CKD. In this review, we describe clinical and experimental evidence for IS endothelial toxicity and focus on the various molecular pathways implicated. In patients with CKD, plasma concentrations of IS correlate with cardiovascular events and mortality, with vascular calcification and atherosclerotic markers. Moreover, IS induces a prothrombotic state and impaired neovascularization. IS reduction by AST-120 reverse these abnormalities. In vitro, IS induces endothelial aryl hydrocarbon receptor (AhR) activation and proinflammatory transcription factors as NF-κB or AP-1. IS has a prooxidant effect with reduction of nitric oxide (NO) bioavailability. Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients. Full article
(This article belongs to the Special Issue Uremic Toxin-Mediated Mechanisms in Cardiovascular and Renal Disease)
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21 pages, 848 KiB  
Review
Inflammation and Premature Ageing in Chronic Kidney Disease
by Thomas Ebert, Sven-Christian Pawelzik, Anna Witasp, Samsul Arefin, Sam Hobson, Karolina Kublickiene, Paul G. Shiels, Magnus Bäck and Peter Stenvinkel
Toxins 2020, 12(4), 227; https://doi.org/10.3390/toxins12040227 - 4 Apr 2020
Cited by 167 | Viewed by 11744
Abstract
Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment [...] Read more.
Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them. Full article
(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))
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25 pages, 345 KiB  
Review
A Review of the Impact of Mycotoxins on Dairy Cattle Health: Challenges for Food Safety and Dairy Production in Sub-Saharan Africa
by David Chebutia Kemboi, Gunther Antonissen, Phillis E. Ochieng, Siska Croubels, Sheila Okoth, Erastus K. Kangethe, Johannes Faas, Johanna F. Lindahl and James K. Gathumbi
Toxins 2020, 12(4), 222; https://doi.org/10.3390/toxins12040222 - 2 Apr 2020
Cited by 80 | Viewed by 10418
Abstract
Mycotoxins are secondary metabolites of fungi that contaminate food and feed and have a significant negative impact on human and animal health and productivity. The tropical condition in Sub-Saharan Africa (SSA) together with poor storage of feed promotes fungal growth and subsequent mycotoxin [...] Read more.
Mycotoxins are secondary metabolites of fungi that contaminate food and feed and have a significant negative impact on human and animal health and productivity. The tropical condition in Sub-Saharan Africa (SSA) together with poor storage of feed promotes fungal growth and subsequent mycotoxin production. Aflatoxins (AF) produced by Aspergillus species, fumonisins (FUM), zearalenone (ZEN), T-2 toxin (T-2), and deoxynivalenol (DON) produced by Fusarium species, and ochratoxin A (OTA) produced by Penicillium and Aspergillus species are well-known mycotoxins of agricultural importance. Consumption of feed contaminated with these toxins may cause mycotoxicoses in animals, characterized by a range of clinical signs depending on the toxin, and losses in the animal industry. In SSA, contamination of dairy feed with mycotoxins has been frequently reported, which poses a serious constraint to animal health and productivity, and is also a hazard to human health since some mycotoxins and their metabolites are excreted in milk, especially aflatoxin M1. This review describes the major mycotoxins, their occurrence, and impact in dairy cattle diets in SSA highlighting the problems related to animal health, productivity, and food safety and the up-to-date post-harvest mitigation strategies for the prevention and reduction of contamination of dairy feed. Full article
(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)
13 pages, 1606 KiB  
Article
Effects of Nutrient Limitation on the Synthesis of N-Rich Phytoplankton Toxins: A Meta-Analysis
by Karen Brandenburg, Laura Siebers, Joost Keuskamp, Thomas G. Jephcott and Dedmer B. Van de Waal
Toxins 2020, 12(4), 221; https://doi.org/10.3390/toxins12040221 - 1 Apr 2020
Cited by 47 | Viewed by 5888
Abstract
Eutrophication has played a major role in the worldwide increase of harmful algal blooms (HABs). Higher input of key nutrients, such as nitrogen (N) and phosphorus (P), can stimulate the growth of harmful algal species in freshwater, estuarine, and coastal marine ecosystems. Some [...] Read more.
Eutrophication has played a major role in the worldwide increase of harmful algal blooms (HABs). Higher input of key nutrients, such as nitrogen (N) and phosphorus (P), can stimulate the growth of harmful algal species in freshwater, estuarine, and coastal marine ecosystems. Some HAB-forming taxa, particularly several cyanobacteria and dinoflagellate species, are harmful through the production of N-rich toxins that have detrimental effects on the environment and human health. Here, we test how changes in nutrient availability affect N-rich toxin synthesis in cyanobacteria and dinoflagellates using a meta-analysis approach. Overall, N-rich toxin content showed an increase with P limitation, while it tended to decrease with N limitation, but we also observed substantial variation in responses both within and across genera and toxin groups. For instance, in response to N limitation, microcystin content varied from a 297% decrease up to a 273% increase, and paralytic shellfish poisoning (PSP) toxin content varied from a 204% decrease to an 82% increase. Cylindrospermopsin, produced by N2-fixing cyanobacteria, showed no clear direction in response to nutrient limitation, and cellular contents of this compound may thus vary independently of nutrient fluctuations. Our results confirm earlier reported stoichiometric regulation of N-rich phytoplankton toxins, showing increased toxin content with an increase in cellular N:P ratios, and vice versa. Thus, changes in N-rich toxin content largely follow the changes in relative cellular N content. Consequently, although nutrient limitation may limit bloom biomass and thereby bloom toxicity, our results warn that P limitation can cause accumulation of cellular toxins and thus lead to unexpected increases in bloom toxicity. Full article
(This article belongs to the Special Issue Environmental Drivers of Algal and Cyanobacterial Toxin Dynamics)
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19 pages, 1356 KiB  
Review
Bacterial Factors Targeting the Nucleus: The Growing Family of Nucleomodulins
by Hélène Bierne and Renaud Pourpre
Toxins 2020, 12(4), 220; https://doi.org/10.3390/toxins12040220 - 31 Mar 2020
Cited by 39 | Viewed by 8060
Abstract
Pathogenic bacteria secrete a variety of proteins that manipulate host cell function by targeting components of the plasma membrane, cytosol, or organelles. In the last decade, several studies identified bacterial factors acting within the nucleus on gene expression or other nuclear processes, which [...] Read more.
Pathogenic bacteria secrete a variety of proteins that manipulate host cell function by targeting components of the plasma membrane, cytosol, or organelles. In the last decade, several studies identified bacterial factors acting within the nucleus on gene expression or other nuclear processes, which has led to the emergence of a new family of effectors called “nucleomodulins”. In human and animal pathogens, Listeria monocytogenes for Gram-positive bacteria and Anaplasma phagocytophilum, Ehrlichia chaffeensis, Chlamydia trachomatis, Legionella pneumophila, Shigella flexneri, and Escherichia coli for Gram-negative bacteria, have led to pioneering discoveries. In this review, we present these paradigms and detail various mechanisms and core elements (e.g., DNA, histones, epigenetic regulators, transcription or splicing factors, signaling proteins) targeted by nucleomodulins. We particularly focus on nucleomodulins interacting with epifactors, such as LntA of Listeria and ankyrin repeat- or tandem repeat-containing effectors of Rickettsiales, and nucleomodulins from various bacterial species acting as post-translational modification enzymes. The study of bacterial nucleomodulins not only generates important knowledge about the control of host responses by microbes but also creates new tools to decipher the dynamic regulations that occur in the nucleus. This research also has potential applications in the field of biotechnology. Finally, this raises questions about the epigenetic effects of infectious diseases. Full article
(This article belongs to the Special Issue Toxins and Virulence Factors of Listeria monocytogenes)
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16 pages, 2963 KiB  
Article
Individual and Combined Effect of Zearalenone Derivates and Beauvericin Mycotoxins on SH-SY5Y Cells
by Fojan Agahi, Guillermina Font, Cristina Juan and Ana Juan-García
Toxins 2020, 12(4), 212; https://doi.org/10.3390/toxins12040212 - 27 Mar 2020
Cited by 34 | Viewed by 4284
Abstract
Beauvericin (BEA) and zearalenone derivatives, α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL), are produced by several Fusarium species. Considering the impact of various mycotoxins on human’s health, this study determined and evaluated the cytotoxic effect of individual, binary, and tertiary mycotoxin treatments consisting of α-ZEL, [...] Read more.
Beauvericin (BEA) and zearalenone derivatives, α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL), are produced by several Fusarium species. Considering the impact of various mycotoxins on human’s health, this study determined and evaluated the cytotoxic effect of individual, binary, and tertiary mycotoxin treatments consisting of α-ZEL, β-ZEL, and BEA at different concentrations over 24, 48, and 72 h on SH-SY5Y neuronal cells, by using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide). Subsequently, the isobologram method was applied to elucidate if the mixtures produced synergism, antagonism, or additive effects. Ultimately, we determined the amount of mycotoxin recovered from the media after treatment using liquid chromatography coupled with electrospray ionization–quadrupole time-of-flight mass spectrometry (LC–ESI–qTOF-MS). The IC50 values detected at all assayed times ranged from 95 to 0.2 μM for the individual treatments. The result indicated that β-ZEL was the most cytotoxic mycotoxin when tested individually. The major effect detected for all combinations assayed was synergism. Among the combinations assayed, α-ZEL + β-ZEL + BEA and α-ZEL + BEA presented the highest cytotoxic potential with respect to the IC value. In individual treatment, α-ZEL was the most recovered mycotoxin; while, this was observed for BEA in binary combination α-ZEL + BEA. Full article
(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)
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12 pages, 3159 KiB  
Article
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 42 | Viewed by 4773
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  
Article
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 16 | Viewed by 5673
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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19 pages, 3953 KiB  
Article
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 25 | Viewed by 17346
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  
Article
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 65 | Viewed by 3906
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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17 pages, 390 KiB  
Review
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 55 | Viewed by 5421
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  
Article
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 80 | Viewed by 5919
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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16 pages, 1517 KiB  
Review
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 50 | Viewed by 11945
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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17 pages, 682 KiB  
Review
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 66 | Viewed by 8593
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, 320 KiB  
Review
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 74 | Viewed by 8468
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  
Review
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 24 | Viewed by 8586
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  
Article
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 51 | Viewed by 5208
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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21 pages, 1417 KiB  
Review
Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus?
by Goran Abdurrahman, Frieder Schmiedeke, Claus Bachert, Barbara M. Bröker and Silva Holtfreter
Toxins 2020, 12(3), 176; https://doi.org/10.3390/toxins12030176 - 12 Mar 2020
Cited by 38 | Viewed by 11987
Abstract
Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive [...] Read more.
Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive cytokine release. To date, 26 different SAgs have been described in the species S. aureus; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls). SAgs can cause staphylococcal food poisoning and toxic shock syndrome and contribute to the clinical symptoms of staphylococcal infection. In addition, there is growing evidence that SAgs are involved in allergic diseases. This review provides an overview on recent epidemiological data on the involvement of S. aureus SAgs and anti-SAg-IgE in allergy, demonstrating that being sensitized to SEs—in contrast to inhalant allergens—is associated with a severe disease course in patients with chronic airway inflammation. The mechanisms by which SAgs trigger or amplify allergic immune responses, however, are not yet fully understood. Here, we discuss known and hypothetical pathways by which SAgs can drive an atopic disease. Full article
(This article belongs to the Special Issue Immunotherapies and Vaccines against Diseases Caused by Staphylococcal Toxins)
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20 pages, 2252 KiB  
Review
Cysteine-Rich Secretory Proteins (CRISPs) from Venomous Snakes: An Overview of the Functional Diversity in a Large and Underappreciated Superfamily
by Takashi Tadokoro, Cassandra M. Modahl, Katsumi Maenaka and Narumi Aoki-Shioi
Toxins 2020, 12(3), 175; https://doi.org/10.3390/toxins12030175 - 12 Mar 2020
Cited by 66 | Viewed by 6936
Abstract
The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins) is widely distributed, but for toxinologists, snake venom CRISPs are the most familiar members. Although CRISPs are found in the majority of venoms, very few of these [...] Read more.
The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins) is widely distributed, but for toxinologists, snake venom CRISPs are the most familiar members. Although CRISPs are found in the majority of venoms, very few of these proteins have been functionally characterized, but those that have been exhibit diverse activities. Snake venom CRISPs (svCRISPs) inhibit ion channels and the growth of new blood vessels (angiogenesis). They also increase vascular permeability and promote inflammatory responses (leukocyte and neutrophil infiltration). Interestingly, CRISPs in lamprey buccal gland secretions also manifest some of these activities, suggesting an evolutionarily conserved function. As we strive to better understand the functions that CRISPs serve in venoms, it is worth considering the broad range of CRISP physiological activities throughout the animal kingdom. In this review, we summarize those activities, known crystal structures and sequence alignments, and we discuss predicted functional sites. CRISPs may not be lethal or major components of venoms, but given their almost ubiquitous occurrence in venoms and the accelerated evolution of svCRISP genes, these venom proteins are likely to have functions worth investigating. Full article
(This article belongs to the Special Issue Identification and Functional Characterization of Novel Venom Components)
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17 pages, 1249 KiB  
Article
Efficacy of Divinylbenzenic Resin in Removing Indoxyl Sulfate and P-cresol Sulfate in Hemodialysis Patients: Results from an In Vitro Study and an In Vivo Pilot Trial (xuanro4-Nature 3.2)
by Maria Teresa Rocchetti, Carmela Cosola, Ighli di Bari, Stefania Magnani, Vanessa Galleggiante, Letizia Scandiffio, Giuseppe Dalfino, Giuseppe Stefano Netti, Mauro Atti, Roberto Corciulo and Loreto Gesualdo
Toxins 2020, 12(3), 170; https://doi.org/10.3390/toxins12030170 - 10 Mar 2020
Cited by 30 | Viewed by 4016
Abstract
High serum levels of microbiota-derived uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and cardiovascular complications. IS and PCS cannot be efficiently removed by conventional hemodialysis (HD), due to their high binding affinity for [...] Read more.
High serum levels of microbiota-derived uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and cardiovascular complications. IS and PCS cannot be efficiently removed by conventional hemodialysis (HD), due to their high binding affinity for albumin. This study evaluates the efficacy of a divinylbenzene-polyvinylpyrrolidone (DVB-PVP) cartridge and a synbiotic to reduce uremic toxins in HD patients. First, the in vitro efficacy of DVB-PVP in adsorbing IS and PCS was evaluated. Second, a randomized, placebo-controlled pilot study in HD patients was carried out to establish whether the administration of a synbiotic, either individually and in association with DVB-PVP-HD, could reduce the production of uremic toxins. In vitro data showed that DVB-PVP resin removed a mean of 56% PCS and around 54% IS, after 6 h of perfusion. While, in the in vivo study, the DVB-PVP cartridge showed its adsorbing efficacy only for IS plasma levels. The combination of synbiotic treatment with DVB-PVP HD decreased IS and PCS both at pre- and post-dialysis levels. In conclusion, this study provides the first line of evidence on the synergistic action of gut microbiota modulation and an innovative absorption-based approach in HD patients, aimed at reducing plasma levels of IS and PCS. Full article
(This article belongs to the Section Uremic Toxins)
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28 pages, 3877 KiB  
Review
Forty Years of the Description of Brown Spider Venom Phospholipases-D
by Luiza Helena Gremski, Hanna Câmara da Justa, Thaís Pereira da Silva, Nayanne Louise Costacurta Polli, Bruno César Antunes, João Carlos Minozzo, Ana Carolina Martins Wille, Andrea Senff-Ribeiro, Raghuvir Krishnaswamy Arni and Silvio Sanches Veiga
Toxins 2020, 12(3), 164; https://doi.org/10.3390/toxins12030164 - 6 Mar 2020
Cited by 44 | Viewed by 6840
Abstract
Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in [...] Read more.
Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and loxoscelism. Present and future aspects of loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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16 pages, 354 KiB  
Review
Cardiac Remodeling in Chronic Kidney Disease
by Nadine Kaesler, Anne Babler, Jürgen Floege and Rafael Kramann
Toxins 2020, 12(3), 161; https://doi.org/10.3390/toxins12030161 - 5 Mar 2020
Cited by 100 | Viewed by 10844
Abstract
Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As kidney function declines, numerous metabolic pathways are disturbed. Kidney and heart functions are highly connected by organ crosstalk. Among others, [...] Read more.
Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As kidney function declines, numerous metabolic pathways are disturbed. Kidney and heart functions are highly connected by organ crosstalk. Among others, altered volume and pressure status, ischemia, accelerated atherosclerosis and arteriosclerosis, disturbed mineral metabolism, renal anemia, activation of the renin-angiotensin system, uremic toxins, oxidative stress and upregulation of cytokines stress the sensitive interplay between different cardiac cell types. The fatal consequences are left-ventricular hypertrophy, fibrosis and capillary rarefaction, which lead to systolic and/or diastolic left-ventricular failure. Furthermore, fibrosis triggers electric instability and sudden cardiac death. This review focuses on established and potential pathophysiological cardiorenal crosstalk mechanisms that drive uremia-induced senescence and disease progression, including potential known targets and animal models that might help us to better understand the disease and to identify novel therapeutics. Full article
(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))
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11 pages, 2338 KiB  
Article
Biological Control of Aflatoxin in Maize Grown in Serbia
by Zagorka Savić, Tatjana Dudaš, Marta Loc, Mila Grahovac, Dragana Budakov, Igor Jajić, Saša Krstović, Tijana Barošević, Rudolf Krska, Michael Sulyok, Vera Stojšin, Mladen Petreš, Aleksandra Stankov, Jelena Vukotić and Ferenc Bagi
Toxins 2020, 12(3), 162; https://doi.org/10.3390/toxins12030162 - 5 Mar 2020
Cited by 52 | Viewed by 6382
Abstract
Aspergillus flavus is the main producer of aflatoxin B1, one of the most toxic contaminants of food and feed. With global warming, climate conditions have become favourable for aflatoxin contamination of agricultural products in several European countries, including Serbia. The infection of maize [...] Read more.
Aspergillus flavus is the main producer of aflatoxin B1, one of the most toxic contaminants of food and feed. With global warming, climate conditions have become favourable for aflatoxin contamination of agricultural products in several European countries, including Serbia. The infection of maize with A. flavus, and aflatoxin synthesis can be controlled and reduced by application of a biocontrol product based on non-toxigenic strains of A. flavus. Biological control relies on competition between atoxigenic and toxigenic strains. This is the most commonly used biological control mechanism of aflatoxin contamination in maize in countries where aflatoxins pose a significant threat. Mytoolbox Af01, a native atoxigenic A. flavus strain, was obtained from maize grown in Serbia and used to produce a biocontrol product that was applied in irrigated and non-irrigated Serbian fields during 2016 and 2017. The application of this biocontrol product reduced aflatoxin levels in maize kernels (51–83%). The biocontrol treatment had a highly significant effect of reducing total aflatoxin contamination by 73%. This study showed that aflatoxin contamination control in Serbian maize can be achieved through biological control methods using atoxigenic A. flavus strains. Full article
(This article belongs to the Special Issue Biocontrol Agents and Natural Compounds against Mycotoxinogenic Fungi)
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25 pages, 420 KiB  
Review
Occurrence of Mycotoxins in Fish Feed and Its Effects: A Review
by Mariana Oliveira and Vitor Vasconcelos
Toxins 2020, 12(3), 160; https://doi.org/10.3390/toxins12030160 - 4 Mar 2020
Cited by 69 | Viewed by 7412
Abstract
Plant-based ingredients have been successfully replacing fishmeal in finished fish feeds. However, using crops in feeds results in an increased risk of contamination by fungi and mycotoxins and a higher incidence of mycotoxicosis in fish. This might decrease aquaculture’s productivity as mycotoxicosis generally [...] Read more.
Plant-based ingredients have been successfully replacing fishmeal in finished fish feeds. However, using crops in feeds results in an increased risk of contamination by fungi and mycotoxins and a higher incidence of mycotoxicosis in fish. This might decrease aquaculture’s productivity as mycotoxicosis generally result in decreased body weight, growth impairment and higher rates of disease and mortality in fish. Additionally, some mycotoxins might accumulate in the fish musculature. As such, fish consumption might become another way for mycotoxins to enter the human food chain, threatening food security and public health as mycotoxins are important genotoxins, carcinogens and immunosuppressors to humans. In this work we aim to provide a review on the most important mycotoxins found in crops and in finished fish feed, i.e., aflatoxins, fumonisins, ochratoxins, trichothecenes and zearalenone. We present their effects on the health of fish and humans and their regulations in the European Union. Although work has been performed in mycotoxin research ever since the 1960s, a lot of information is still lacking regarding its effects. However, it is noticed that in order to use crops in aquafeed production, efforts should be made in order to monitor its contamination by mycotoxinogenic fungi and mycotoxins. Full article
15 pages, 1003 KiB  
Article
Occurrence and Risk Assessment of Pyrrolizidine Alkaloids in Spices and Culinary Herbs from Various Geographical Origins
by Florian Kaltner, Michael Rychlik, Manfred Gareis and Christoph Gottschalk
Toxins 2020, 12(3), 155; https://doi.org/10.3390/toxins12030155 - 1 Mar 2020
Cited by 45 | Viewed by 7204
Abstract
Pyrrolizidine alkaloids (PA) and their N-oxides (PANO) are a group of toxic secondary plant metabolites occurring predominantly as contaminants in (herbal) teas, honeys and food supplements, as well as in spices and culinary herbs. Depending on the botanical origin of the contaminating [...] Read more.
Pyrrolizidine alkaloids (PA) and their N-oxides (PANO) are a group of toxic secondary plant metabolites occurring predominantly as contaminants in (herbal) teas, honeys and food supplements, as well as in spices and culinary herbs. Depending on the botanical origin of the contaminating plant, the pattern of PA/PANO can strongly vary within a sample. The current study aimed to broaden the existing data on the occurrence of PA/PANO in spices and culinary herbs. For this, 305 authentic samples covering 15 different matrices mainly harvested in 2016 or 2017 and originating from 36 countries were investigated for the presence of 44 PA/PANO. Fifty-eight percent of the samples contained at least one PA/PANO. The average sum content over all samples was 323 µg/kg (median of 0.9 µg/kg, 95% percentile of 665 µg/kg). The highest amount of 24.6 mg/kg was detected in an oregano sample. Additionally, conspicuous analyte patterns were discovered in samples from similar cultivation regions, indicating related botanical sources of PA/PANO contaminations. Particularly, oregano and cumin from Turkey often contained high amounts of PA/PANO. The results were used to assess the acute and chronic health risks related to PA/PANO intake via spices and culinary herbs, indicating a potential health risk in particular for adults and children with high consumption or when considering worst-case contamination scenarios of a sum content of 5500 µg/kg. Full article
(This article belongs to the Section Plant Toxins)
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24 pages, 1093 KiB  
Review
Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?
by Domagoj Kifer, Daniela Jakšić and Maja Šegvić Klarić
Toxins 2020, 12(3), 153; https://doi.org/10.3390/toxins12030153 - 29 Feb 2020
Cited by 34 | Viewed by 3965
Abstract
In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several [...] Read more.
In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several described mathematical models, the arithmetic definition of additivity and factorial analysis of variance were the most commonly used in mycotoxicology. These models are incorrectly based on the assumption that mycotoxin dose-effect curves are linear. More appropriate mathematical models for assessing mycotoxin interactions include Bliss independence, Loewe’s additivity law, combination index, and isobologram analysis, Chou-Talalays median-effect approach, response surface, code for the identification of synergism numerically efficient (CISNE) and MixLow method. However, it seems that neither model is ideal. This review discusses the advantages and disadvantages of these mathematical models. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxins on Target Cells)
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16 pages, 1104 KiB  
Article
Cyanotoxins Occurrence in Portugal: A New Report on Their Recent Multiplication
by Cristiana Moreira, Cidália Gomes, Vitor Vasconcelos and Agostinho Antunes
Toxins 2020, 12(3), 154; https://doi.org/10.3390/toxins12030154 - 29 Feb 2020
Cited by 20 | Viewed by 3638
Abstract
Historical reports show that in Portugal, cyanotoxins reports were mainly in the Center (cylindrospermopsins) and South (cylindrospermopsins, saxitoxins) regions of the country apart from the well distributed microcystins. Therefore, in our study, seven freshwater ecosystems located in the North and Center Regions of [...] Read more.
Historical reports show that in Portugal, cyanotoxins reports were mainly in the Center (cylindrospermopsins) and South (cylindrospermopsins, saxitoxins) regions of the country apart from the well distributed microcystins. Therefore, in our study, seven freshwater ecosystems located in the North and Center Regions of Portugal were screened between April and September of 2017 for the main cyanotoxins (microcystins, cylindrospermopsins, anatoxin-a, and saxitoxins) by a two methods approach that combined the application of molecular (PCR) and immunological (ELISA) assays. Results from our survey reveal that both methods revealed the presence of all main cyanotoxins. ELISA results showed that 48% of the samples were above (1.6–18.8 μg/L) the guideline value established for microcystins (1 μg/L), while in the remaining cyanotoxins, 33% of the samples were above (1.1–6.8 μg/L) the guideline value established for anatoxin–a (1 μg/L). Further, for saxitoxins, only one sample gave a value above (4.3 μg/L) the guideline (3 μg/L) and this corresponded to a North Region ecosystem. In the cytotoxin cylindrospermopsins, none of the samples were above the guideline established value (1 μg/L). This study will improve the risk assessment strategy in Portugal, as well as advance water quality and water management. Full article
(This article belongs to the Special Issue Selected Papers from the 6th Iberian and 2nd Ibero-American Cyanotoxin Congress CIC2019)
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