Toxins

7 pages, 1871 KiB

Open AccessEditor’s ChoiceCommunication

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 29 | Viewed by 4029

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

Open AccessEditor’s ChoiceReview

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 78 | Viewed by 6988

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

Open AccessEditor’s ChoiceArticle

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 14 | Viewed by 3752

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

Open AccessEditor’s ChoiceReview

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 34 | Viewed by 7878

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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12 pages, 1465 KiB

Open AccessEditor’s ChoiceArticle

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 44 | Viewed by 4478

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, 688 KiB

Open AccessEditor’s ChoiceReview

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 47 | Viewed by 5589

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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16 pages, 26308 KiB

Open AccessEditor’s ChoiceArticle

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 32 | Viewed by 5589

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

Open AccessEditor’s ChoiceReview

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 42 | Viewed by 8156

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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20 pages, 798 KiB

Open AccessEditor’s ChoiceArticle

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 36 | Viewed by 4549

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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23 pages, 2417 KiB

Open AccessEditor’s ChoiceArticle

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 19 | Viewed by 3857

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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14 pages, 1569 KiB

Open AccessEditor’s ChoiceReview

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 77 | Viewed by 6354

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

Open AccessEditor’s ChoiceReview

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 130 | Viewed by 9408

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

Open AccessEditor’s ChoiceReview

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 62 | Viewed by 8925

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

Open AccessEditor’s ChoiceArticle

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 37 | Viewed by 4740

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

Open AccessEditor’s ChoiceReview

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 31 | Viewed by 6561

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

Open AccessEditor’s ChoiceArticle

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 30 | Viewed by 3605

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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8 pages, 506 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 14 | Viewed by 4975

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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12 pages, 3159 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 36 | Viewed by 4084

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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19 pages, 3953 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 22 | Viewed by 15156

Abstract

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

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

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

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15 pages, 1517 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 53 | Viewed by 3116

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

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 46 | Viewed by 4350

Abstract

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

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

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

18 pages, 585 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 65 | Viewed by 4911

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

Open AccessEditor’s ChoiceReview

Parathyroid Hormone: A Uremic Toxin

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

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

Cited by 36 | Viewed by 10039

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

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 57 | Viewed by 7149

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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18 pages, 1534 KiB

Open AccessEditor’s ChoiceReview

Cardiovascular Calcification in Chronic Kidney Disease—Therapeutic Opportunities

by Anika Himmelsbach, Carina Ciliox and Claudia Goettsch

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

Cited by 19 | Viewed by 7372

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, 320 KiB

Open AccessEditor’s ChoiceReview

Mycotoxin Contamination Concerns of Herbs and Medicinal Plants

by Iwona Ałtyn and Magdalena Twarużek

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

Cited by 52 | Viewed by 6907

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)

13 pages, 3818 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 44 | Viewed by 4366

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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20 pages, 2252 KiB

Open AccessEditor’s ChoiceReview

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 50 | Viewed by 5743

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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21 pages, 1417 KiB

Open AccessEditor’s ChoiceReview

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 30 | Viewed by 10297

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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17 pages, 1249 KiB

Open AccessEditor’s ChoiceArticle

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 27 | Viewed by 3313

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

Open AccessEditor’s ChoiceReview

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 34 | Viewed by 5541

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

Open AccessEditor’s ChoiceReview

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 82 | Viewed by 9293

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

Open AccessEditor’s ChoiceArticle

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 47 | Viewed by 5656

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

Open AccessEditor’s ChoiceReview

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 53 | Viewed by 5939

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

Open AccessEditor’s ChoiceArticle

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 39 | Viewed by 6230

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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16 pages, 1104 KiB

Open AccessEditor’s ChoiceArticle

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 16 | Viewed by 3083

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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24 pages, 1093 KiB

Open AccessEditor’s ChoiceReview

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 28 | Viewed by 3241

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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27 pages, 1220 KiB

Open AccessEditor’s ChoiceArticle

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

by Van Nguyen Tran, Jitka Viktorova, Katerina Augustynkova, Nikola Jelenova, Simona Dobiasova, Katerina Rehorova, Marie Fenclova, Milena Stranska-Zachariasova, Libor Vitek, Jana Hajslova and Tomas Ruml

Toxins 2020, 12(3), 148; https://doi.org/10.3390/toxins12030148 - 28 Feb 2020

Cited by 34 | Viewed by 4991

Abstract

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of [...] Read more.

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC₅₀ values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration. Full article

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

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19 pages, 388 KiB

Open AccessEditor’s ChoiceArticle

Variation of Fusarium Free, Masked, and Emerging Mycotoxin Metabolites in Maize from Agriculture Regions of South Africa

by Theodora Ijeoma Ekwomadu, Toluwase Adeseye Dada, Nancy Nleya, Ramokone Gopane, Michael Sulyok and Mulunda Mwanza

Toxins 2020, 12(3), 149; https://doi.org/10.3390/toxins12030149 - 28 Feb 2020

Cited by 34 | Viewed by 3646

Abstract

The presence of mycotoxins in cereal grain is a very important food safety issue with the occurrence of masked mycotoxins extensively investigated in recent years. This study investigated the variation of different Fusarium metabolites (including the related regulated, masked, and emerging mycotoxin) in [...] Read more.

The presence of mycotoxins in cereal grain is a very important food safety issue with the occurrence of masked mycotoxins extensively investigated in recent years. This study investigated the variation of different Fusarium metabolites (including the related regulated, masked, and emerging mycotoxin) in maize from various agriculture regions of South Africa. The relationship between the maize producing regions, the maize type, as well as the mycotoxins was established. A total of 123 maize samples was analyzed by a LC-MS/MS multi-mycotoxin method. The results revealed that all maize types exhibited a mixture of free, masked, and emerging mycotoxins contamination across the regions with an average of 5 and up to 24 out of 42 investigated Fusarium mycotoxins, including 1 to 3 masked forms at the same time. Data obtained show that fumonisin B_1, B_2, B_3, B₄, and A₁ were the most prevalent mycotoxins and had maximum contamination levels of 8908, 3383, 990, 1014, and 51.5 µg/kg, respectively. Deoxynivalenol occurred in 50% of the samples with a mean concentration of 152 µg/kg (max 1380 µg/kg). Thirty-three percent of the samples were contaminated with zearalenone at a mean concentration of 13.6 µg/kg (max 146 µg/kg). Of the masked mycotoxins, DON-3-glucoside occurred at a high incidence level of 53%. Among emerging toxins, moniliformin, fusarinolic acid, and beauvericin showed high occurrences at 98%, 98%, and 83%, and had maximum contamination levels of 1130, 3422, and 142 µg/kg, respectively. Significant differences in the contamination pattern were observed between the agricultural regions and maize types. Full article

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

28 pages, 2725 KiB

Open AccessEditor’s ChoiceReview

Aflatoxin Biosynthesis and Genetic Regulation: A Review

by Isaura Caceres, Anthony Al Khoury, Rhoda El Khoury, Sophie Lorber, Isabelle P. Oswald, André El Khoury, Ali Atoui, Olivier Puel and Jean-Denis Bailly

Toxins 2020, 12(3), 150; https://doi.org/10.3390/toxins12030150 - 28 Feb 2020

Cited by 180 | Viewed by 11794

Abstract

The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of [...] Read more.

The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway. Full article

(This article belongs to the Special Issue Production Mechanisms and Biosynthesis of Aflatoxin)

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44 pages, 2888 KiB

Open AccessEditor’s ChoiceReview

Human Biomonitoring of Mycotoxins in Blood, Plasma and Serum in Recent Years: A Review

by Beatriz Arce-López, Elena Lizarraga, Ariane Vettorazzi and Elena González-Peñas

Toxins 2020, 12(3), 147; https://doi.org/10.3390/toxins12030147 - 27 Feb 2020

Cited by 68 | Viewed by 8006

Abstract

This manuscript reviews the state-of-the-art regarding human biological monitoring (HBM) of mycotoxins in plasma, serum and blood samples. After a comprehensive and systematic literature review, with a focus on the last five years, several aspects were analyzed and summarized: (a) the biomarkers analyzed [...] Read more.

This manuscript reviews the state-of-the-art regarding human biological monitoring (HBM) of mycotoxins in plasma, serum and blood samples. After a comprehensive and systematic literature review, with a focus on the last five years, several aspects were analyzed and summarized: (a) the biomarkers analyzed and their encountered levels, (b) the analytical methodologies developed and (c) the relationship between biomarker levels and some illnesses. In the literature reviewed, aflatoxin B1-lysine (AFB1-lys) and ochratoxin A (OTA) in plasma and serum were the most widely studied mycotoxin biomarkers for HBM. Regarding analytical methodologies, a clear increase in the development of methods for the simultaneous determination of multiple mycotoxins has been observed. For this purpose, the use of liquid chromatography (LC) methodologies, especially when coupled with tandem mass spectrometry (MS/MS) or high resolution mass spectrometry (HRMS) has grown. A high percentage of the samples analyzed for OTA or aflatoxin B1 (mostly as AFB1-lys) in the reviewed papers were positive, demonstrating human exposure to mycotoxins. This review confirms the importance of mycotoxin human biomonitoring and highlights the important challenges that should be faced, such as the inclusion of other mycotoxins in HBM programs, the need to increase knowledge of mycotoxin metabolism and toxicokinetics, and the need for reference materials and new methodologies for treating samples. In addition, guidelines are required for analytical method validation, as well as equations to establish the relationship between human fluid levels and mycotoxin intake. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 2345 KiB

Open AccessEditor’s ChoiceArticle

Assessment of the Effect of Satureja montana and Origanum virens Essential Oils on Aspergillus flavus Growth and Aflatoxin Production at Different Water Activities

by Marta García-Díaz, Jessica Gil-Serna, Belén Patiño, Esther García-Cela, Naresh Magan and Ángel Medina

Toxins 2020, 12(3), 142; https://doi.org/10.3390/toxins12030142 - 25 Feb 2020

Cited by 19 | Viewed by 4365

Abstract

Aflatoxin contamination of foodstuffs poses a serious risk to food security, and it is essential to search for new control methods to prevent these toxins entering the food chain. Several essential oils are able to reduce the growth and mycotoxin biosynthesis of toxigenic [...] Read more.

Aflatoxin contamination of foodstuffs poses a serious risk to food security, and it is essential to search for new control methods to prevent these toxins entering the food chain. Several essential oils are able to reduce the growth and mycotoxin biosynthesis of toxigenic species, although their efficiency is strongly influenced by the environmental conditions. In this work, the effectiveness of Satureja montana and Origanum virens essential oils to control Aspergillus flavus growth was evaluated under three water activity levels (0.94, 0.96 and 0.98 a_w) using a Bioscreen C, a rapid in vitro spectrophotometric technique. The aflatoxin concentrations at all conditions tested were determined by HPLC-FLD. Aspergillus flavus growth was delayed by both essential oil treatments. However, only S. montana essential oil was able to significantly affect aflatoxin production, although the inhibition percentages widely differed among water activities. The most significant reduction was observed at 0.96 a_w, which is coincident with the conditions in which A. flavus reached the highest levels of aflatoxin production. On the contrary, the treatment with S. montana essential oil was not effective in significantly reducing aflatoxin production at 0.94 a_w. Therefore, it is important to study the interaction of the new control compounds with environmental factors before their application in food matrices, and in vitro ecophysiological studies are a good option since they provide accurate and rapid results. Full article

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

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10 pages, 2100 KiB

Open AccessEditor’s ChoiceArticle

Effect of Ozone and Electron Beam Irradiation on Degradation of Zearalenone and Ochratoxin A

by Kai Yang, Ke Li, Lihong Pan, Xiaohu Luo, Jiali Xing, Jing Wang, Li Wang, Ren Wang, Yuheng Zhai and Zhengxing Chen

Toxins 2020, 12(2), 138; https://doi.org/10.3390/toxins12020138 - 24 Feb 2020

Cited by 38 | Viewed by 3362

Abstract

Zearalenone (ZEN) and ochratoxin A (OTA) are key concerns of the food industry because of their toxicity and pollution scope. This study investigated the effects of ozone and electron beam irradiation (EBI) on the degradation of ZEN and OTA. Results demonstrated that 2 [...] Read more.

Zearalenone (ZEN) and ochratoxin A (OTA) are key concerns of the food industry because of their toxicity and pollution scope. This study investigated the effects of ozone and electron beam irradiation (EBI) on the degradation of ZEN and OTA. Results demonstrated that 2 mL of 50 μg/mL ZEN was completely degraded after 10 s of treatment by 2.0 mg/L ozone. The degradation rate of 1 μg/mL ZEN by 16 kGy EBI was 92.76%. Methanol was superior to acetonitrile in terms of degrading ZEN when the irradiation dose was higher than 6 kGy. The degradation rate of 2 mL of 5 μg/mL OTA by 50 mg/L ozone at 180 s was 34%, and that of 1 μg/mL OTA by 16 kGy EBI exceeded 90%. Moreover, OTA degraded more rapidly in acetonitrile. Ozone performed better in the degradation of ZEN, whereas EBI was better for OTA. The conclusions provide theoretical and practical bases for the degradation of different fungal toxins. Full article

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

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12 pages, 2528 KiB

Open AccessEditor’s ChoiceArticle

A Lateral Flow Strip Based on a Truncated Aptamer-Complementary Strand for Detection of Type-B Aflatoxins in Nuts and Dried Figs

by Zhilei Zhao, He Wang, Wenlei Zhai, Xiaoyuan Feng, Xia Fan, Ailiang Chen and Meng Wang

Toxins 2020, 12(2), 136; https://doi.org/10.3390/toxins12020136 - 22 Feb 2020

Cited by 43 | Viewed by 4400

Abstract

Type-B aflatoxins (AFB₁ and AFB₂) frequently contaminate food, especially nuts and fried figs, and seriously threaten human health; hence, it is necessary for the newly rapid and sensitive detection methods to prevent the consumption of potentially contaminated food. Here, a [...] Read more.

Type-B aflatoxins (AFB₁ and AFB₂) frequently contaminate food, especially nuts and fried figs, and seriously threaten human health; hence, it is necessary for the newly rapid and sensitive detection methods to prevent the consumption of potentially contaminated food. Here, a lateral flow aptasensor for the detection of type-B aflatoxins was developed. It is based on the use of fluorescent dye Cy5 as a label for the aptamer, and on the competition between type-B aflatoxins and the complementary DNA of the aptamer. This is the first time that the complementary strand of the aptamer has been used as the test line (T-line) to detect type-B aflatoxins. In addition, the truncated aptamer was used to improve the affinity with type-B aflatoxins in our study. Therefore, the lengths of aptamer and cDNA probe were optimized as key parameters for higher sensitivity. In addition, binding buffer and organic solvent were investigated. The results showed that the best pair for achieving improved sensitivity and accuracy in detecting AFB₁ was formed by a shorter aptamer (32 bases) coupled with the probe complementary to the AFB₁ binding region of the aptamer. Under the optimal experimental conditions, the test strip showed an excellent linear relationship in the range from 0.2 to 20 ng/mL with a limit of detection of 0.16 ng/mL. This aptamer-based strip was successfully applied to the determination of type-B aflatoxins in spiked and commercial peanuts, almonds, and dried figs, and the recoveries of the spiked samples were from 93.3%−112.0%. The aptamer-complementary strand-based lateral flow test strip is a potential alternative tool for the rapid and sensitive detection of type-B aflatoxins in nuts and dried figs. It is of help for monitoring aflatoxins to avoid the consumption of unsafe food. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 2344 KiB

Open AccessEditor’s ChoiceArticle

Toxicity Characterisation of Gambierdiscus Species from the Canary Islands

by Araceli E. Rossignoli, Angels Tudó, Isabel Bravo, Patricio A. Díaz, Jorge Diogène and Pilar Riobó

Toxins 2020, 12(2), 134; https://doi.org/10.3390/toxins12020134 - 21 Feb 2020

Cited by 31 | Viewed by 4607

Abstract

In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae [...] Read more.

In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae, G. carolinianus and G. caribaeus, have been detected in macrophytes from this area and are known to produce the ciguatoxins (CTXs) that cause CFP. A characterization of the toxicity of these species is the first step in identifying locations in the Canary Islands at risk of CFP. Therefore, in this study the toxicity of 63 strains of these five Gambierdiscus species were analysed using the erythrocyte lysis assay to evaluate their maitotoxin (MTX) content. In addition, 20 of the strains were also analysed in a neuroblastoma Neuro-2a (N2a) cytotoxicity assay to determine their CTX-like toxicity. The results allowed the different species to be grouped according to their ratios of CTX-like and MTX-like toxicity. MTX-like toxicity was especially high in G. excentricus and G. australes but much lower in the other species and lowest in G. silvae. CTX-like toxicity was highest in G. excentricus, which produced the toxin in amounts ranging between 128.2 ± 25.68 and 510.6 ± 134.2 fg CTX1B equivalents (eq) cell⁻¹ (mean ± SD). In the other species, CTX concentrations were as follows: G. carolinianus (100.84 ± 18.05 fg CTX1B eq cell⁻¹), G. australes (31.1 ± 0.56 to 107.16 ± 21.88 fg CTX1B eq cell⁻¹), G. silvae (12.19 ± 0.62 to 76.79 ± 4.97 fg CTX1B eq cell⁻¹) and G. caribaeus (<LOD to 90.37 ± 15.89 fg CTX1B eq cell⁻¹). Unlike the similar CTX-like toxicity of G. australes and G. silvae strains from different locations, G. excentricus and G. caribaeus differed considerably according to the origin of the strain. These differences emphasise the importance of species identification to assess the regional risk of CFP. Full article

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

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12 pages, 942 KiB

Open AccessEditor’s ChoiceArticle

Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms

by José María Gutiérrez, Matthew R. Lewin, David. J. Williams and Bruno Lomonte

Toxins 2020, 12(2), 131; https://doi.org/10.3390/toxins12020131 - 20 Feb 2020

Cited by 61 | Viewed by 6195

Abstract

The phospholipase A₂ (PLA₂) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA₂ activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay [...] Read more.

The phospholipase A₂ (PLA₂) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA₂ activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay lethality of potent neurotoxic snake venoms was tested in a mouse model. The venoms of Notechis scutatus, Crotalus durissus terrificus, Bungarus multicinctus, and Oxyuranus scutellatus, all of which have potent presynaptically acting neurotoxic PLA₂s of variable quaternary structure, were used to evaluate simple dosing regimens. A supralethal dose of each venom was injected subcutaneously in mice, followed by the bolus intravenous (LY315920) or oral (LY333013) administration of the inhibitors, immediately and at various time intervals after envenoming. Control mice receiving venom alone died within 3 h of envenoming. Mice injected with O. scutellatus venom and treated with LY315920 or LY333013 survived the 24 h observation period, whereas those receiving C. d. terrificus and B. multicinctus venoms survived at 3 h or 6 h with a single dose of either form of Varespladib, but not at 24 h. In contrast, mice receiving N. scutatus venom and then the inhibitors died within 3 h, similarly to the control animals injected with venom alone. LY315920 was able to reverse the severe paralytic manifestations in mice injected with venoms of O. scutellatus, B. multicinctus, and C. d. terrificus. Overall, results suggest that the two forms of Varespladib are effective in abrogating, or delaying, neurotoxic manifestations induced by some venoms whose neurotoxicity is mainly dependent on presynaptically acting PLA₂s. LY315920 is able to reverse paralytic manifestations in severely envenomed mice, but further work is needed to understand the significance of species-specific differences in animal models as they compare to clinical syndromes in human and for potential use in veterinary medicine. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 2502 KiB

Open AccessEditor’s ChoiceArticle

Phytotoxic Metabolites Isolated from Neufusicoccum batangarum, the Causal Agent of the Scabby Canker of Cactus Pear (Opuntia ficus-indica L.)

by Marco Masi, Francesco Aloi, Paola Nocera, Santa Olga Cacciola, Giuseppe Surico and Antonio Evidente

Toxins 2020, 12(2), 126; https://doi.org/10.3390/toxins12020126 - 18 Feb 2020

Cited by 20 | Viewed by 3637

Abstract

Six phytotoxins were obtained from the culture filtrates of the ascomycete Neofusicoccum batangarum, the causal agent of the scabby canker of cactus pear (Opuntia ficus-indica L.) in minor Sicily islands. The phytotoxins were identified as (−)-(R)-mellein (1); [...] Read more.

Six phytotoxins were obtained from the culture filtrates of the ascomycete Neofusicoccum batangarum, the causal agent of the scabby canker of cactus pear (Opuntia ficus-indica L.) in minor Sicily islands. The phytotoxins were identified as (−)-(R)-mellein (1); (±)-botryoisocoumarin A (2); (−)-(3R,4R)- and (−)-(3R,4S)-4-hydroxymellein (3 and 4); (−)-terpestacin (5); and (+)-3,4-dihydro-4,5,8-trihydroxy-3-methylisocoumarin, which we named (+)-neoisocoumarin (6). This identification was done by comparing their spectral and optical data with those already reported in literature. The absolute configuration (3R,4S) to (+)-neoisocoumarin (6) was determined using the advanced Mosher method. All six metabolites were shown to have phytotoxicity on the host (cactus pear) and non-host (tomato) plants, and the most active compounds were (±)-botryoisocoumarin A (2), (−)-terpestacin (5), and (+)-neoisocoumarin (6). Full article

(This article belongs to the Special Issue Microbial and Plant Phytotoxins)

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11 pages, 295 KiB

Open AccessEditor’s ChoiceReview

Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders

by Yu-Hua Lin, Bing-Juin Chiang and Chun-Hou Liao

Toxins 2020, 12(2), 129; https://doi.org/10.3390/toxins12020129 - 18 Feb 2020

Cited by 22 | Viewed by 3559

Abstract

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from [...] Read more.

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment. Full article

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

17 pages, 2678 KiB

Open AccessEditor’s ChoiceReview

Comparing the Efficacy of OnabotulinumtoxinA, Sacral Neuromodulation, and Peripheral Tibial Nerve Stimulation as Third Line Treatment for the Management of Overactive Bladder Symptoms in Adults: Systematic Review and Network Meta-Analysis

by Chi-Wen Lo, Mei-Yi Wu, Stephen Shei-Dei Yang, Fu-Shan Jaw and Shang-Jen Chang

Toxins 2020, 12(2), 128; https://doi.org/10.3390/toxins12020128 - 18 Feb 2020

Cited by 27 | Viewed by 5153

Abstract

The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to [...] Read more.

The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to compare the efficacy of these three modalities for managing adult OAB syndrome. We performed systematic literature searches of several databases from January 1995 to September 2019 with language restricted to English. All randomized control trials that compared any dose of OnabotulinumtoxinA, SNM, and PTNS with each other or a placebo for the management of adult OAB were included in the study. Overall, 17 randomized control trials, with a follow up of 3–6 months in the predominance of trials (range 1.5–24 months), were included for analysis. For each trial outcome, the results were reported as an average number of episodes of the outcome at baseline. Compared with the placebo, all three treatments were more efficacious for the selected outcome parameters. OnabotulinumtoxinA resulted in a higher number of complications, including urinary tract infection and urine retention. Compared with OnabotulinumtoxinA and PTNS, SNM resulted in the greatest reduction in urinary incontinence episodes and voiding frequency. However, comparison of their long-term efficacy was lacking. Further studies on the long-term effectiveness of the three treatment options, with standardized questionnaires and parameters are warranted. Full article

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

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10 pages, 2260 KiB

Open AccessEditor’s ChoiceArticle

Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine

by Candace S. Bever, Kenneth D. Swanson, Elizabeth I. Hamelin, Michael Filigenzi, Robert H. Poppenga, Jennifer Kaae, Luisa W. Cheng and Larry H. Stanker

Toxins 2020, 12(2), 123; https://doi.org/10.3390/toxins12020123 - 15 Feb 2020

Cited by 23 | Viewed by 10463

Abstract

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the [...] Read more.

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of α-amanitin (α-AMA) or γ-AMA, and 100 ng/mL of β-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography–mass spectrometry (LC-MS) methods. 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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