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Toxins, Volume 11, Issue 7 (July 2019)

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Cover Story (view full-size image) Corticosteroids and antimicrobial drugs are used as very effective treatments in many inflammatory [...] Read more.
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Open AccessArticle
Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients
Toxins 2019, 11(7), 431; https://doi.org/10.3390/toxins11070431 (registering DOI)
Received: 3 June 2019 / Revised: 15 July 2019 / Accepted: 18 July 2019 / Published: 23 July 2019
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Abstract
The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The [...] Read more.
The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival. Full article
(This article belongs to the Special Issue Immune Dysfunction in Uremia)
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Open AccessArticle
Mycotoxin Contamination of Edible Non-Timber Forest Products in Cameroon
Received: 8 June 2019 / Revised: 7 July 2019 / Accepted: 12 July 2019 / Published: 22 July 2019
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Abstract
The prevalence and concentrations of three major mycotoxins, total aflatoxin (AFs), fumonisin (F), and zearalenone (ZEN), were determined on seven edible non-timber forest products (ENTFP) in Cameroon. A total of 210 samples consiting of 30 samples from each ENTFP commodity was collected from [...] Read more.
The prevalence and concentrations of three major mycotoxins, total aflatoxin (AFs), fumonisin (F), and zearalenone (ZEN), were determined on seven edible non-timber forest products (ENTFP) in Cameroon. A total of 210 samples consiting of 30 samples from each ENTFP commodity was collected from farmers and local markets in three agroecological zones of Cameroon and analyzed for moisture content and mycotoxins. Mycotoxins were analyzed using commercial enzyme-linked immunosorbent assay (ELISA) kits and results were validated using the VICAM fluorometric method. The European Union regulation of mycotoxins for human consumption (N°1881/2006) was adopted as reference. The moisture content of samples varied from 5.0% to 22.6%. Aflatoxin contamination was detected in 84.3% samples and only 5.7% exceeded the legal limit (10 ppb). Similarly, 53% of samples were contaminated with fumonisin and 5% of samples exceeded the legal limit (1000 ppb). Zearalenone contamination was detected in 92% of samples and 21% of samples exceeded the legal limit (100 ppb). This is the first report on mycotoxin contamination of ENTFP in the Congo Basin forest. The findings of this study will form a basis for educating farmers and other stakeholders of ENTFP values chain on mycotoxins and mycotoxin mitigation measures to produce safe ENTFP for local and international markets. Full article
(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)
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Open AccessArticle
Aflatoxin in Chili Peppers in Nigeria: Extent of Contamination and Control Using Atoxigenic Aspergillus flavus Genotypes as Biocontrol Agents
Received: 27 June 2019 / Accepted: 17 July 2019 / Published: 22 July 2019
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Abstract
Across sub-Saharan Africa, chili peppers are fundamental ingredients of many traditional dishes. However, chili peppers may contain unsafe aflatoxin concentrations produced by Aspergillus section Flavi fungi. Aflatoxin levels were determined in chili peppers from three states in Nigeria. A total of 70 samples [...] Read more.
Across sub-Saharan Africa, chili peppers are fundamental ingredients of many traditional dishes. However, chili peppers may contain unsafe aflatoxin concentrations produced by Aspergillus section Flavi fungi. Aflatoxin levels were determined in chili peppers from three states in Nigeria. A total of 70 samples were collected from farmers’ stores and local markets. Over 25% of the samples contained unsafe aflatoxin concentrations. The chili peppers were associated with both aflatoxin producers and atoxigenic Aspergillus flavus genotypes. Efficacy of an atoxigenic biocontrol product, Aflasafe, registered in Nigeria for use on maize and groundnut, was tested for chili peppers grown in three states. Chili peppers treated with Aflasafe accumulated significantly less aflatoxins than nontreated chili peppers. The results suggest that Aflasafe is a valuable tool for the production of safe chili peppers. Use of Aflasafe in chili peppers could reduce human exposure to aflatoxins and increase chances to commercialize chili peppers in premium local and international markets. This is the first report of the efficacy of any atoxigenic biocontrol product for controlling aflatoxin in a spice crop. Full article
(This article belongs to the collection Aflatoxins)
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Open AccessArticle
Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis
Received: 29 June 2019 / Revised: 16 July 2019 / Accepted: 18 July 2019 / Published: 21 July 2019
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Abstract
Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce [...] Read more.
Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce vascular calcification. Vascular smooth muscle cell transdifferentiation, vascular calcification grade, and bone histomorphometry were examined. The presence and/or production of sclerostin was investigated in serum, aorta, and bone. Calcified human aortas were investigated to substantiate clinical relevance. Warfarin-exposed rats developed vascular calcifications in a time-dependent manner which went along with a progressive increase in serum sclerostin levels. Both osteogenic and adipogenic pathways were upregulated in calcifying vascular smooth muscle cells, as well as sclerostin mRNA and protein levels. Evidence for the local vascular action of sclerostin was found both in human and rat calcified aortas. Warfarin exposure led to a mildly decreased bone and mineralized areas. Osseous sclerostin production and bone turnover did not change significantly. This study showed local production of sclerostin in calcified vessels, which may indicate a negative feedback mechanism to prevent further calcification. Furthermore, increased levels of serum sclerostin, probably originating from excessive local production in calcified vessels, may contribute to the linkage between vascular pathology and impaired bone mineralization. Full article
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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Open AccessArticle
Pain and Lethality Induced by Insect Stings: An Exploratory and Correlational Study
Received: 3 July 2019 / Accepted: 16 July 2019 / Published: 21 July 2019
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Abstract
Pain is a natural bioassay for detecting and quantifying biological activities of venoms. The painfulness of stings delivered by ants, wasps, and bees can be easily measured in the field or lab using the stinging insect pain scale that rates the pain intensity [...] Read more.
Pain is a natural bioassay for detecting and quantifying biological activities of venoms. The painfulness of stings delivered by ants, wasps, and bees can be easily measured in the field or lab using the stinging insect pain scale that rates the pain intensity from 1 to 4, with 1 being minor pain, and 4 being extreme, debilitating, excruciating pain. The painfulness of stings of 96 species of stinging insects and the lethalities of the venoms of 90 species was determined and utilized for pinpointing future directions for investigating venoms having pharmaceutically active principles that could benefit humanity. The findings suggest several under- or unexplored insect venoms worthy of future investigations, including: those that have exceedingly painful venoms, yet with extremely low lethality—tarantula hawk wasps (Pepsis) and velvet ants (Mutillidae); those that have extremely lethal venoms, yet induce very little pain—the ants, Daceton and Tetraponera; and those that have venomous stings and are both painful and lethal—the ants Pogonomyrmex, Paraponera, Myrmecia, Neoponera, and the social wasps Synoeca, Agelaia, and Brachygastra. Taken together, and separately, sting pain and venom lethality point to promising directions for mining of pharmaceutically active components derived from insect venoms. Full article
(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)
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Open AccessArticle
Comparative Analysis of Listeria monocytogenes Plasmids and Expression Levels of Plasmid-Encoded Genes during Growth under Salt and Acid Stress Conditions
Received: 11 June 2019 / Revised: 12 July 2019 / Accepted: 15 July 2019 / Published: 20 July 2019
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Abstract
Listeria monocytogenes strains are known to harbour plasmids that confer resistance to sanitizers, heavy metals, and antibiotics; however, very little research has been conducted into how plasmids may influence L. monocytogenes’ ability to tolerate food-related stresses. To investigate this, a library ( [...] Read more.
Listeria monocytogenes strains are known to harbour plasmids that confer resistance to sanitizers, heavy metals, and antibiotics; however, very little research has been conducted into how plasmids may influence L. monocytogenes’ ability to tolerate food-related stresses. To investigate this, a library (n = 93) of L. monocytogenes plasmid sequences were compared. Plasmid sequences were divided into two groups (G1 and G2) based on a repA phylogeny. Twenty-six unique plasmid types were observed, with 13 belonging to each of the two repA-based groups. G1 plasmids were significantly (p < 0.05) smaller than G2 plasmids but contained a larger diversity of genes. The most prevalent G1 plasmid (57,083 bp) was observed in 26 strains from both Switzerland and Canada and a variety of serotypes. Quantitative PCR (qPCR) revealed a >2-fold induction of plasmid-contained genes encoding an NADH peroxidase, cadmium ATPase, multicopper oxidase, and a ClpL chaperone protein during growth under salt (6% NaCl) and acid conditions (pH 5) and ProW, an osmolyte transporter, under salt stress conditions. No differences in salt and acid tolerance were observed between plasmid-cured and wildtype strains. This work highlights the abundance of specific plasmid types among food-related L. monocytogenes strains, the unique characteristics of G1 and G2 plasmids, and the possible contributions of plasmids to L. monocytogenes tolerance to food-related stresses. Full article
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Open AccessArticle
The Dual α-Amidation System in Scorpion Venom Glands
Received: 4 June 2019 / Revised: 18 July 2019 / Accepted: 18 July 2019 / Published: 20 July 2019
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Abstract
Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion proproteins suggests that a conserved [...] Read more.
Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion proproteins suggests that a conserved enzymatic α-amidation system must be responsible for this modification of scorpion peptides. A transcriptomic approach was employed to identify sequences putatively encoding enzymes of the α-amidation pathway. A dual enzymatic α-amidation system was found, consisting of the membrane-anchored, bifunctional, peptidylglycine α-amidating monooxygenase (PAM) and its paralogs, soluble monofunctional peptidylglycine α-hydroxylating monooxygenase (PHMm) and peptidyl-α-hydroxyglycine α-amidating lyase (PALm). Independent genes encode these three enzymes. Amino acid residues responsible for ion coordination and enzymatic activity are conserved in these sequences, suggesting that the enzymes are functional. Potential endoproteolytic recognition sites for proprotein convertases in the PAM sequence indicate that PAM-derived soluble isoforms may also be expressed. Sequences potentially encoding proprotein convertases (PC1 and PC2), carboxypeptidase E (CPE), and other enzymes of the α-amidation pathway, were also found, confirming the presence of this pathway in scorpions. Full article
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Open AccessArticle
Virulence Characteristics and Antimicrobial Resistance Profiles of Shiga Toxin-Producing Escherichia coli Isolates from Humans in South Africa: 2006–2013
Received: 9 June 2019 / Revised: 1 July 2019 / Accepted: 3 July 2019 / Published: 19 July 2019
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Abstract
Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC O26:H11 (24%) was the most frequent serotype associated with human disease, followed by O111:H8 (16%), O157:H7 (13%) and O117:H7 (13%). The majority of isolates were positive for key virulence-associated genes including stx1 (84%), eaeA (61%), ehxA (68.4%) and espP (55%), but lacked stx2 (29%), katP (42%), etpD (16%), saa (16%) and subA (3%). stx2 positive isolates carried stx2c (26%) and/or stx2d (26%) subtypes. All pathogenicity island encoded virulence marker genes were detected in all (100%) isolates except nleA (47%), nleC (84%) and nleD (76%). Multidrug resistance was observed in 89% of isolates. PFGE revealed 34 profiles with eight distinct clusters that shared ≥80% intra-serotype similarity, regardless of the year of isolation. In conclusion, STEC isolates that were implicated in human disease between 2006 and 2013 in South Africa were mainly non-O157 strains which possessed virulence genes and markers commonly associated with STEC strains that have been incriminated in mild to severe human disease worldwide. Improved STEC monitoring and surveillance programs are needed in South Africa to control and prevent STEC disease in humans. Full article
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Open AccessArticle
Ciguatera-Causing Dinoflagellate Gambierdiscus spp. (Dinophyceae) in a Subtropical Region of North Atlantic Ocean (Canary Islands): Morphological Characterization and Biogeography
Received: 24 June 2019 / Revised: 16 July 2019 / Accepted: 17 July 2019 / Published: 19 July 2019
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Abstract
Dinoflagellates belonging to the genus Gambierdiscus produce ciguatoxins (CTXs), which are metabolized in fish to more toxic forms and subsequently cause ciguatera fish poisoning (CFP) in humans. Five species of Gambierdiscus have been described from the Canary Islands, where CTXs in fish have [...] Read more.
Dinoflagellates belonging to the genus Gambierdiscus produce ciguatoxins (CTXs), which are metabolized in fish to more toxic forms and subsequently cause ciguatera fish poisoning (CFP) in humans. Five species of Gambierdiscus have been described from the Canary Islands, where CTXs in fish have been reported since 2004. Here we present new data on the distribution of Gambierdiscus species in the Canary archipelago and specifically from two islands, La Palma and La Gomera, where the genus had not been previously reported. Gambierdiscus spp. concentrations were low, with maxima of 88 and 29 cells·g−1 wet weight in samples from La Gomera and La Palma, respectively. Molecular analysis (LSUrRNA gene sequences) revealed differences in the species distribution between the two islands: only G. excentricus was detected at La Palma whereas four species, G. australes, G. caribaeus, G. carolinianus, and G. excentricus, were identified from La Gomera. Morphometric analyses of cultured cells of the five Canary Islands species and of field specimens from La Gomera included cell size and a characterization of three thecal arrangement traits: (1) the shape of the 2′ plate, (2) the position of Po in the anterior suture of the 2′ plate, and (3) the length–width relationship of the 2″″ plate. Despite the wide morphological variability within the culture and field samples, the use of two or more variables allowed the discrimination of two species in the La Gomera samples: G. cf. excentricus and G. cf. silvae. A comparison of the molecular data with the morphologically based classification demonstrated important coincidences, such as the dominance of G. excentricus, but also differences in the species composition of Gambierdiscus, as G. caribaeus was detected in the study area only by using molecular methods. Full article
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Open AccessFeature PaperArticle
Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis
Received: 24 June 2019 / Revised: 15 July 2019 / Accepted: 16 July 2019 / Published: 19 July 2019
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Abstract
The genus Bitis comprises 18 species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor [...] Read more.
The genus Bitis comprises 18 species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor of the clade consisting of B. gabonica, B. nasicornis, B. parviocula and B. rhinoceros) induce an array of debilitating effects including anticoagulation, hemorrhagic shock and cytotoxicity, whilst the dwarf species B. atropos is known to have strong neurotoxic effects. However, the venom effects of the other species within the genus have not been explored in detail. A series of coagulation assays were implemented to assess the coagulotoxic venom effects of fourteen species within the genus. This study identified procoagulant venom as the ancestral condition, retained only by the basal dwarf species B. worthingtoni, suggesting anticoagulant venom is a derived trait within the Bitis genus and has been secondarily amplified on at least four occasions. A wide range of anticoagulant mechanisms were identified, such as pseudo-procoagulant and destructive activities upon fibrinogen in both giant and dwarf Bitis and the action of inhibiting the prothrombinase complex, which is present in a clade of dwarf Bitis. Antivenom studies revealed that while the procoagulant effects of B. worthingtoni were poorly neutralized, and thus a cause for concern, the differential mechanisms of anticoagulation in other species were all well neutralized. Thus, this study concludes there is a wide range of coagulotoxic mechanisms which have evolved within the Bitis genus and that clinical management strategies are limited for the procoagulant effects of B. worthingtoni, but that anticoagulant effects of other species are readily treated by the South African polyvalent antivenom. These results therefore have direct, real-work implications for the treatment of envenomed patients. Full article
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Open AccessArticle
Daphnia magna Exudates Impact Physiological and Metabolic Changes in Microcystis aeruginosa
Received: 21 May 2019 / Revised: 16 July 2019 / Accepted: 17 July 2019 / Published: 19 July 2019
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Abstract
While the intracellular function of many toxic and bioactive cyanobacterial metabolites is not yet known, microcystins have been suggested to have a protective role in the cyanobacterial metabolism, giving advantage to toxic over nontoxic strains under stress conditions. The zooplankton grazer Daphnia reduce [...] Read more.
While the intracellular function of many toxic and bioactive cyanobacterial metabolites is not yet known, microcystins have been suggested to have a protective role in the cyanobacterial metabolism, giving advantage to toxic over nontoxic strains under stress conditions. The zooplankton grazer Daphnia reduce cyanobacterial dominance until a certain density, which may be supported by Daphnia exudates, affecting the cyanobacterial physiological state and metabolites’ production. Therefore, we hypothesized that D. magna spent medium will impact the production of cyanobacterial bioactive metabolites and affect cyanobacterial photosynthetic activity in the nontoxic, but not the toxic strain. Microcystin (MC-LR and des-MC-LR) producing M. aeruginosa PCC7806 and its non-microcystin producing mutant were exposed to spent media of different D. magna densities and culture durations. D. magna spent medium of the highest density (200/L) cultivated for the shortest time (24 h) provoked the strongest effect. D.magna spent medium negatively impacted the photosynthetic activity of M. aeruginosa PCC7806, as well as the dynamics of intracellular and extracellular cyanobacterial metabolites, while its mutant was unaffected. In the presence of Daphnia medium, microcystin does not appear to have a protective role for the strain. On the contrary, extracellular cyanopeptolin A increased in M. aeruginosa PCC7806 although the potential anti-grazing role of this compound would require further studies. Full article
(This article belongs to the Special Issue Environmental Drivers of Algal and Cyanobacterial Toxin Dynamics)
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Open AccessArticle
Fire Ant Venom Alkaloids Inhibit Biofilm Formation
Received: 18 May 2019 / Revised: 9 July 2019 / Accepted: 12 July 2019 / Published: 18 July 2019
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Abstract
Biofilm formation on exposed surfaces is a serious issue for the food industry and medical health facilities. There are many proposed strategies to delay, reduce, or even eliminate biofilm formation on surfaces. The present study focuses on the applicability of fire ant venom [...] Read more.
Biofilm formation on exposed surfaces is a serious issue for the food industry and medical health facilities. There are many proposed strategies to delay, reduce, or even eliminate biofilm formation on surfaces. The present study focuses on the applicability of fire ant venom alkaloids (aka ‘solenopsins’, from Solenopsis invicta) tested on polystyrene and stainless steel surfaces relative to the adhesion and biofilm-formation by the bacterium Pseudomonas fluorescens. Conditioning with solenopsins demonstrates significant reduction of bacterial adhesion. Inhibition rates were 62.7% on polystyrene and 59.0% on stainless steel surfaces. In addition, solenopsins drastically reduced cell populations already growing on conditioned surfaces. Contrary to assumptions by previous authors, solenopsins tested negative for amphipathic properties, thus understanding the mechanisms behind the observed effects still relies on further investigation. Full article
(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)
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Open AccessArticle
Perfringolysin O-Induced Plasma Membrane Pores Trigger Actomyosin Remodeling and Endoplasmic Reticulum Redistribution
Received: 1 July 2019 / Revised: 10 July 2019 / Accepted: 15 July 2019 / Published: 17 July 2019
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Abstract
Clostridium perfringens produces an arsenal of toxins that act together to cause severe infections in humans and livestock animals. Perfringolysin O (PFO) is a cholesterol-dependent pore-forming toxin encoded in the chromosome of virtually all C. perfringens strains and acts in synergy with other [...] Read more.
Clostridium perfringens produces an arsenal of toxins that act together to cause severe infections in humans and livestock animals. Perfringolysin O (PFO) is a cholesterol-dependent pore-forming toxin encoded in the chromosome of virtually all C. perfringens strains and acts in synergy with other toxins to determine the outcome of the infection. However, its individual contribution to the disease is poorly understood. Here, we intoxicated human epithelial and endothelial cells with purified PFO to evaluate the host cytoskeletal responses to PFO-induced damage. We found that, at sub-lytic concentrations, PFO induces a profound reorganization of the actomyosin cytoskeleton culminating into the assembly of well-defined cortical actomyosin structures at sites of plasma membrane (PM) remodeling. The assembly of such structures occurs concomitantly with the loss of the PM integrity and requires pore-formation, calcium influx, and myosin II activity. The recovery from the PM damage occurs simultaneously with the disassembly of cortical structures. PFO also targets the endoplasmic reticulum (ER) by inducing its disruption and vacuolation. ER-enriched vacuoles were detected at the cell cortex within the PFO-induced actomyosin structures. These cellular events suggest the targeting of the endothelium integrity at early stages of C. perfringens infection, in which secreted PFO is at sub-lytic concentrations. Full article
(This article belongs to the Section Bacterial Toxins)
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Open AccessReview
Rapid Detection of Botulinum Neurotoxins—A Review
Received: 25 June 2019 / Revised: 15 July 2019 / Accepted: 15 July 2019 / Published: 17 July 2019
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Abstract
A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to [...] Read more.
A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent. Full article
(This article belongs to the Special Issue New Challenges in Foodborne Botulism Outbreaks)
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Open AccessReview
Assays for Determining Pertussis Toxin Activity in Acellular Pertussis Vaccines
Received: 16 June 2019 / Revised: 12 July 2019 / Accepted: 13 July 2019 / Published: 17 July 2019
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Abstract
Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This [...] Read more.
Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This toxin is responsible for many physiological effects on the host, but it is also immunogenic and in its detoxified form is the main component of all ACVs. In producing toxoid for vaccines, it is vital to achieve a balance between sufficiently detoxifying PTx to render it safe while maintaining enough molecular structure that it retains its protective immunogenicity. To ensure that the first part of this balancing act has been successfully achieved, assays are required to accurately measure residual PTx activity in ACV products accurately. Quality control assays are also required to ensure that the detoxification procedures are robust and stable. This manuscript reviews the methods that have been used to achieve this aim, or may have the potential to replace them, and highlights their continuing requirement as vaccines that induce a longer lasting immunity are developed to prevent the re-occurrence of outbreaks that have been observed recently. Full article
(This article belongs to the Special Issue Pertussis Toxin)
Open AccessReview
The ADP-Ribosylating Toxins of Salmonella
Received: 17 June 2019 / Revised: 10 July 2019 / Accepted: 12 July 2019 / Published: 16 July 2019
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Abstract
A number of pathogenic bacteria utilize toxins to mediate disease in a susceptible host. The foodborne pathogen Salmonella is one of the most important and well-studied bacterial pathogens. Recently, whole genome sequence characterizations revealed the presence of multiple novel ADP-ribosylating toxins encoded by [...] Read more.
A number of pathogenic bacteria utilize toxins to mediate disease in a susceptible host. The foodborne pathogen Salmonella is one of the most important and well-studied bacterial pathogens. Recently, whole genome sequence characterizations revealed the presence of multiple novel ADP-ribosylating toxins encoded by a variety of Salmonella serovars. In this review, we discuss both the classical (SpvB) and novel (typhoid toxin, ArtAB, and SboC/SeoC) ADP-ribosylating toxins of Salmonella, including the structure and function of these toxins and our current understanding of their contributions to virulence. Full article
(This article belongs to the Special Issue ADP-Ribosylating Toxin)
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Open AccessMeeting Report
Report of the IVth Workshop of the Spanish National Network on Mycotoxins and Toxigenic Fungi and Their Decontamination Processes (MICOFOOD), Held in Pamplona, Spain, 29–31 May 2019
Received: 5 July 2019 / Accepted: 12 July 2019 / Published: 16 July 2019
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Abstract
The present publication collects the communications presented in the IV Workshop of the Spanish National Network on Mycotoxins and Toxigenic Fungi and their Decontamination Processes (MICOFOOD), held in the School of Pharmacy and Nutrition of the Universidad de Navarra (Pamplona, Spain) from the [...] Read more.
The present publication collects the communications presented in the IV Workshop of the Spanish National Network on Mycotoxins and Toxigenic Fungi and their Decontamination Processes (MICOFOOD), held in the School of Pharmacy and Nutrition of the Universidad de Navarra (Pamplona, Spain) from the 29 to the 31 May 2019. More than 70 professionals from academia, the industry and public services have participated. The scientific program included: five sessions: sponsors (presentation and services), toxigenic fungi, toxicology, analysis and control, and reduction and prevention strategies. In total, 18 oral communications and 24 posters were presented. It is worth mentioning the high participation and quality of the communications from PhD students. The invited conference, entitled: “Mycotoxins within the framework of exposure assessment: past present and future”, was given by Dr. Barbara de Santis (Istituto Superiore di Sanità, Rome, Italy). The meeting ended with the roundtable: “From feed to fork: safe food without mycotoxins”, where representatives of feed and agrofood companies and public administrations discussed about the current situation and problems related with mycotoxins. Different prizes were awarded for the best oral presentation (Effect of Staphylococcus xylosus on the growth of toxigenic moulds in meat substrates, by E. Cebrian et al., University of Extremadura), and the best posters (Combined toxicity of aflatoxins and ochratoxin A: A systematic review by M. Alonso-Jaúregui et al., Universidad de Navarra; and Application of natamycin in products affected by toxigenic fungi by Torrijos et al., Universitat de València). The participants had the opportunity to learn about the history and gastronomy of Pamplona. Situated in the north of Spain, Pamplona is a city of Roman origin featuring a large gothic cathedral complex and a Vauban citadel of the 16th century. Full article
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Open AccessArticle
Reduction of Deoxynivalenol in Wheat with Superheated Steam and Its Effects on Wheat Quality
Received: 16 May 2019 / Revised: 12 July 2019 / Accepted: 15 July 2019 / Published: 16 July 2019
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Abstract
Deoxynivalenol (DON) is the most commonly found mycotoxin in scabbed wheat. In order to reduce the DON concentration in scabbed wheat with superheated steam (SS) and explore the feasibility to use the processed wheat as crisp biscuit materials, wheat kernels were treated with [...] Read more.
Deoxynivalenol (DON) is the most commonly found mycotoxin in scabbed wheat. In order to reduce the DON concentration in scabbed wheat with superheated steam (SS) and explore the feasibility to use the processed wheat as crisp biscuit materials, wheat kernels were treated with SS to study the effects of SS processing on DON concentration and the quality of wheat. Furthermore, the wheat treated with SS were used to make crisp biscuits and the texture qualities of biscuits were measured. The results showed that DON in wheat kernels could be reduced by SS effectively. Besides, the reduction rate raised significantly with the increase of steam temperature and processing time and it was also affected significantly by steam velocity. The reduction rate in wheat kernels and wheat flour could reach 77.4% and 60.5% respectively. In addition, SS processing might lead to partial denaturation of protein and partial gelatinization of starch, thus affecting the rheological properties of dough and pasting properties of wheat flour. Furthermore, the qualities of crisp biscuits were improved at certain conditions of SS processing. Full article
(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)
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Open AccessEditorial
Dinophysis Toxins: Distribution, Fate in Shellfish and Impacts
Received: 9 July 2019 / Accepted: 11 July 2019 / Published: 16 July 2019
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Abstract
Several planktonic dinoflagellate species of the genus Dinophysis produce one or two groups of lipophilic toxins: (i) okadaic acid (OA) and its derivatives, the dinophysistoxins (DTXs), and (ii) pectenotoxins (PTXs) [...] Full article
(This article belongs to the Special Issue Dinophysis Toxins: Distribution, Fate in Shellfish and Impacts)
Open AccessReview
Phobalysin: Fisheye View of Membrane Perforation, Repair, Chemotaxis and Adhesion
Received: 29 May 2019 / Revised: 4 July 2019 / Accepted: 11 July 2019 / Published: 16 July 2019
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Abstract
Phobalysin P (PhlyP, for photobacterial lysin encoded on a plasmid) is a recently described small β-pore forming toxin of Photobacterium damselae subsp. damselae (Pdd). This organism, belonging to the family of Vibrionaceae, is an emerging pathogen of fish and various marine animals, which [...] Read more.
Phobalysin P (PhlyP, for photobacterial lysin encoded on a plasmid) is a recently described small β-pore forming toxin of Photobacterium damselae subsp. damselae (Pdd). This organism, belonging to the family of Vibrionaceae, is an emerging pathogen of fish and various marine animals, which occasionally causes life-threatening soft tissue infections and septicemia in humans. By using genetically modified Pdd strains, PhlyP was found to be an important virulence factor. More recently, in vitro studies with purified PhlyP elucidated some basic consequences of pore formation. Being the first bacterial small β-pore forming toxin shown to trigger calcium-influx dependent membrane repair, PhlyP has advanced to a revealing model toxin to study this important cellular function. Further, results from co-culture experiments employing various Pdd strains and epithelial cells together with data on other bacterial toxins indicate that limited membrane damage may generally enhance the association of bacteria with target cells. Thereby, remodeling of plasma membrane and cytoskeleton during membrane repair could be involved. In addition, a chemotaxis-dependent attack-and track mechanism influenced by environmental factors like salinity may contribute to PhlyP-dependent association of Pdd with cells. Obviously, a synoptic approach is required to capture the regulatory links governing the interaction of Pdd with target cells. The characterization of Pdd’s secretome may hold additional clues because it may lead to the identification of proteases activating PhlyP’s pro-form. Current findings on PhlyP support the notion that pore forming toxins are not just killer proteins but serve bacteria to fulfill more subtle functions, like accessing their host. Full article
(This article belongs to the Special Issue Pore-Forming Toxins (PFTs): Never Out of Fashion)
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Open AccessReview
Understanding Mycotoxin Contamination Across the Food Chain in Brazil: Challenges and Opportunities
Received: 23 May 2019 / Revised: 26 June 2019 / Accepted: 28 June 2019 / Published: 15 July 2019
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Abstract
Brazil is one of the largest food producers and exporters in the world. In the late 20th century, the European Union program for the harmonization of regulations for contaminants in food, including mycotoxins, led to the examination of mycotoxin contamination in foods at [...] Read more.
Brazil is one of the largest food producers and exporters in the world. In the late 20th century, the European Union program for the harmonization of regulations for contaminants in food, including mycotoxins, led to the examination of mycotoxin contamination in foods at a global level. The problem of the rejection of food by the European Union and other countries became a Brazilian national priority because of economic and food safety aspects. Ochratoxin A in coffee and cocoa and aflatoxins in Brazil nuts are examples of the impact of technical trade barriers on Brazilian foods. To overcome these threats, several strategies were undertaken by Brazilian and international organizations. In this context, the Codex Commission on Food Contaminants (CCCF) has emerged as a forum to discuss with more transparency issues related to mycotoxins, focusing on establishing maximum levels and codes of practices for some commodities and mycotoxins to ensure fair trade and food safety. Our experience in investigating and understanding mycotoxin contamination across the food chains in Brazil has contributed nationally and internationally to providing some answers to these issues. Full article
(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)
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Open AccessPerspective
Aflatoxin Binders in Foods for Human Consumption—Can This be Promoted Safely and Ethically?
Received: 2 June 2019 / Revised: 6 July 2019 / Accepted: 12 July 2019 / Published: 14 July 2019
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Abstract
Aflatoxins continue to be a food safety problem globally, especially in developing regions. A significant amount of effort and resources have been invested in an attempt to control aflatoxins. However, these efforts have not substantially decreased the prevalence nor the dietary exposure to [...] Read more.
Aflatoxins continue to be a food safety problem globally, especially in developing regions. A significant amount of effort and resources have been invested in an attempt to control aflatoxins. However, these efforts have not substantially decreased the prevalence nor the dietary exposure to aflatoxins in developing countries. One approach to aflatoxin control is the use of binding agents in foods, and lactic acid bacteria (LAB) have been studied extensively for this purpose. However, when assessing the results comprehensively and reviewing the practicality and ethics of use, risks are evident, and concerns arise. In conclusion, our review suggests that there are too many issues with using LAB for aflatoxin binding for it to be safely promoted. Arguably, using binders in human food might even worsen food safety in the longer term. Full article
(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)
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Open AccessArticle
AFM1 Detection in Milk by Fab’ Functionalized Si3N4 Asymmetric Mach–Zehnder Interferometric Biosensors
Received: 27 May 2019 / Revised: 11 July 2019 / Accepted: 11 July 2019 / Published: 14 July 2019
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Abstract
Aflatoxins (AF) are naturally occurring mycotoxins, produced by many species of Aspergillus. Among aflatoxins, Aflatoxin M1 (AFM1) is one of the most frequent and dangerous for human health. The acceptable maximum level of AFM1 in milk according to EU regulation is 50 ppt, [...] Read more.
Aflatoxins (AF) are naturally occurring mycotoxins, produced by many species of Aspergillus. Among aflatoxins, Aflatoxin M1 (AFM1) is one of the most frequent and dangerous for human health. The acceptable maximum level of AFM1 in milk according to EU regulation is 50 ppt, equivalent to 152 pM, and 25 ppt, equivalent to 76 pM, for adults and infants, respectively. Here, we study a photonic biosensor based on Si 3 N 4 asymmetric Mach–Zehnder Interferometers (aMZI) functionalized with Fab’ for AFM1 detection in milk samples (eluates). The minimum concentration of AFM1 detected by our aMZI sensors is 48 pM (16.8 pg/mL) in purified and concentrated milk samples. Moreover, the real-time detection of the ligand-analyte binding enables the study of the kinetics of the reaction. We measured the kinetic rate constants of the Fab’-AFM1 interaction. Full article
(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)
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Open AccessArticle
Paralytic Shellfish Toxins and Ocean Warming: Bioaccumulation and Ecotoxicological Responses in Juvenile Gilthead Seabream (Sparus aurata)
Received: 4 June 2019 / Revised: 5 July 2019 / Accepted: 9 July 2019 / Published: 13 July 2019
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Abstract
Warmer seawater temperatures are expected to increase harmful algal blooms (HABs) occurrence, intensity, and distribution. Yet, the potential interactions between abiotic stressors and HABs are still poorly understood from ecological and seafood safety perspectives. The present study aimed to investigate, for the first [...] Read more.
Warmer seawater temperatures are expected to increase harmful algal blooms (HABs) occurrence, intensity, and distribution. Yet, the potential interactions between abiotic stressors and HABs are still poorly understood from ecological and seafood safety perspectives. The present study aimed to investigate, for the first time, the bioaccumulation/depuration mechanisms and ecotoxicological responses of juvenile gilthead seabream (Sparus aurata) exposed to paralytic shellfish toxins (PST) under different temperatures (18, 21, 24 °C). PST were detected in fish at the peak of the exposure period (day five, 0.22 µg g−1 N-sulfocarbamoylGonyautoxin-1-2 (C1 and C2), 0.08 µg g−1 Decarbamoylsaxitoxin (dcSTX) and 0.18 µg g−1 Gonyautoxin-5 (B1)), being rapidly eliminated (within the first 24 h of depuration), regardless of exposure temperature. Increased temperatures led to significantly higher PST contamination (275 µg STX eq. kg−1). During the trial, fish antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; glutathione S-transferase, GST) in both muscle and viscera were affected by temperature, whereas a significant induction of heat shock proteins (HSP70), Ubiquitin (Ub) activity (viscera), and lipid peroxidation (LPO; muscle) was observed under the combination of warming and PST exposure. The differential bioaccumulation and biomarker responses observed highlight the need to further understand the interactive effects between PST and abiotic stressors, to better estimate climate change impacts on HABs events, and to develop mitigation strategies to overcome the potential risks associated with seafood consumption. Full article
(This article belongs to the Special Issue Marine Biotoxins and Seafood Poisoning)
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Open AccessArticle
Development and Characterization of Monoclonal Antibodies to Botulinum Neurotoxin Type E
Received: 29 May 2019 / Revised: 9 July 2019 / Accepted: 12 July 2019 / Published: 13 July 2019
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Abstract
Botulism is a devastating disease caused by botulinum neurotoxins (BoNTs) secreted primarily by Clostridium botulinum. Mouse bioassays without co-inoculation with antibodies are the standard method for the detection of BoNTs, but are not capable of distinguishing between the different serotypes (A–G). Most [...] Read more.
Botulism is a devastating disease caused by botulinum neurotoxins (BoNTs) secreted primarily by Clostridium botulinum. Mouse bioassays without co-inoculation with antibodies are the standard method for the detection of BoNTs, but are not capable of distinguishing between the different serotypes (A–G). Most foodborne intoxications are caused by serotypes BoNT/A and BoNT/B. BoNT/E outbreaks are most often observed in northern coastal regions and are associated with eating contaminated marine animals and other fishery products. Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of BoNT/E3. Monoclonal antibodies (mAbs) were generated against BoNT/E3 by immunizing with recombinant peptide fragments of the light and heavy chains of BoNT/E3. In all, 12 mAbs where characterized for binding to both the recombinant peptides and holotoxin, as well as their performance in Western blots and sandwich ELISAs. The most sensitive sandwich assay, using different mAbs for capture and detection, exhibited a limit of detection of 0.2 ng/ml in standard buffer matrix and 10 ng/mL in fish product matrices. By employing two different mAbs for capture and detection, a more standardized sandwich assay was constructed. Development of sensitive and selective mAbs to BoNT/E would help in the initial screening of potential food contamination, speeding diagnosis and reducing use of laboratory animals. Full article
(This article belongs to the Special Issue Characterization and Quantitative Analysis of Botulinum Neurotoxin)
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Open AccessArticle
The Activity of Isoquinoline Alkaloids and Extracts from Chelidonium majus against Pathogenic Bacteria and Candida sp.
Received: 13 June 2019 / Revised: 8 July 2019 / Accepted: 11 July 2019 / Published: 12 July 2019
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Abstract
Chelidonium majus (Papaveraceae) extracts exhibit antimicrobial activity due to the complex alkaloid composition. The aim of the research was to evaluate the antimicrobial potential of extracts from wild plants and in vitro cultures, as well as seven major individual alkaloids. Plant [...] Read more.
Chelidonium majus (Papaveraceae) extracts exhibit antimicrobial activity due to the complex alkaloid composition. The aim of the research was to evaluate the antimicrobial potential of extracts from wild plants and in vitro cultures, as well as seven major individual alkaloids. Plant material derived from different natural habitats and in vitro cultures was used for the phytochemical analysis and antimicrobial tests. The composition of alkaloids was analyzed using chromatographic techniques (HPLC with DAD detection). The results have shown that roots contained higher number and amounts of alkaloids in comparison to aerial parts. All tested plant extracts manifested antimicrobial activity, related to different chemical structures of the alkaloids. Root extract used at 31.25–62.5 mg/L strongly reduced bacterial biomass. From the seven individually tested alkaloids, chelerythrine was the most effective against P. aeruginosa (MIC at 1.9 mg/L), while sanguinarine against S. aureus (MIC at 1.9 mg/L). Strong antifungal activity was observed against C. albicans when chelerythrine, chelidonine, and aerial parts extract were used. The experiments with plant extracts, individually tested alkaloids, and variable combinations of the latter allowed for a deeper insight into the potential mechanisms affecting the activity of this group of compounds. Full article
(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)
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Open AccessArticle
αD-Conotoxins in Species of the Eastern Pacific: The Case of Conus princeps from Mexico
Received: 12 June 2019 / Revised: 9 July 2019 / Accepted: 10 July 2019 / Published: 12 July 2019
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Abstract
Conus snails produce venoms containing numerous peptides such as the α-conotoxins (α-CTXs), which are well-known nicotinic acetylcholine receptor (nAChR) antagonists. Thirty-eight chromatographic fractions from Conus princeps venom extract were isolated by RP-HPLC. The biological activities of 37 fractions (0.07 µg/µL) were assayed by [...] Read more.
Conus snails produce venoms containing numerous peptides such as the α-conotoxins (α-CTXs), which are well-known nicotinic acetylcholine receptor (nAChR) antagonists. Thirty-eight chromatographic fractions from Conus princeps venom extract were isolated by RP-HPLC. The biological activities of 37 fractions (0.07 µg/µL) were assayed by two-electrode voltage clamp on human α7 nAChRs expressed in Xenopus laevis oocytes. Fractions F7 and F16 notably inhibited the response elicited by acetylcholine by 52.7 ± 15.2% and 59.6 ± 2.5%, respectively. Fraction F7 was purified, and an active peptide (F7-3) was isolated. Using a combination of Edman degradation, mass spectrometry, and RNASeq, we determined the sequence of peptide F7-3: AVKKTCIRSTOGSNWGRCCLTKMCHTLCCARSDCTCVYRSGKGHGCSCTS, with one hydroxyproline (O) and a free C-terminus. The average mass of this peptide, 10,735.54 Da, indicates that it is a homodimer of identical subunits, with 10 disulfide bonds in total. This peptide is clearly similar to αD-CTXs from species of the Indo-Pacific. Therefore, we called it αD-PiXXA. This toxin slowly and reversibly inhibited the ACh-induced response of the hα7 nAChR subtype, with an IC50 of 6.2 μM, and it does not affect the hα3β2 subtype at 6.5 μM. Full article
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Open AccessArticle
Prophylactic Effects of Bee Venom Phospholipase A2 in Lipopolysaccharide-Induced Pregnancy Loss
Received: 21 June 2019 / Revised: 11 July 2019 / Accepted: 11 July 2019 / Published: 12 July 2019
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Abstract
Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal [...] Read more.
Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal loss, including viable implants, the fetal resorption rate, and the fetal weight, were measured after LPS and bvPLA2 treatment. The levels of serum and tissue inflammatory cytokines were determined. To investigate the involvement of the Treg population in bvPLA2-mediated protection against fetal loss, the effect of Treg depletion was evaluated following bvPLA2 and LPS treatment. The results clearly revealed that bvPLA2 can prevent fetal loss accompanied by growth restriction in the remaining viable fetus. When the LPS-induced abortion mice were treated with bvPLA2, Treg cells were significantly increased compared with those in the non-pregnant, PBS, and LPS groups. After LPS injection, the levels of proinflammatory cytokines were markedly increased compared with those in the PBS mouse group, while bvPLA2 treatment showed significantly decreased TNF-α and IFN-γ expression compared with that in the LPS group. The protective effects of bvPLA2 treatment were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 has protective effects in the LPS-induced abortion mouse model by regulating Treg populations. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessArticle
Prodigiosin Promotes Nrf2 Activation to Inhibit Oxidative Stress Induced by Microcystin-LR in HepG2 Cells
Received: 24 June 2019 / Revised: 8 July 2019 / Accepted: 9 July 2019 / Published: 12 July 2019
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Abstract
Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR [...] Read more.
Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR is still undetermined. This study aimed to examine the effect of prodigiosin against oxidative stress induced by MC-LR in HepG2 cells. Ros was generated after cells were treated with MC-LR and was significantly inhibited with treatment of prodigiosin. In prodigiosin-treated cells, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-related phase II enzyme heme oxygenase-1 (HO-1) were increased. Besides, prodigiosin contributed to enhance nuclear Nrf2 level and repressed ubiquitination. Furthermore, prodigiosin promoted Nrf2 protein level and inhibited ROS in Nrf2 knocked down HepG2 cells. Results indicated that prodigiosin reduced ROS induced by MC-LR by enhancing Nrf2 translocation into the nucleus in HepG2 cells. The finding presents new clues for the potential clinical applications of prodigiosin for inhibiting MC-LR-induced oxidative injury in the future. Full article
(This article belongs to the collection Toxicological Challenges of Aquatic Toxins)
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Open AccessArticle
Toxic Flatworm Egg Plates Serve as a Possible Source of Tetrodotoxin for Pufferfish
Received: 28 June 2019 / Revised: 9 July 2019 / Accepted: 10 July 2019 / Published: 11 July 2019
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Abstract
The pufferfish Takifugu niphobles (at present Takifugu alboplumbeus) possesses highly concentrated tetrodotoxin (TTX), an extremely potent neurotoxin that provides effective protection from predators, at least at the larval stages. However, the source of the toxin has remained unclear. Recently, DNA from the [...] Read more.
The pufferfish Takifugu niphobles (at present Takifugu alboplumbeus) possesses highly concentrated tetrodotoxin (TTX), an extremely potent neurotoxin that provides effective protection from predators, at least at the larval stages. However, the source of the toxin has remained unclear. Recently, DNA from the toxic flatworm Planocera multitentaculata was detected in the intestinal contents of juveniles and young of the pufferfish, suggesting that the flatworm contributes to its toxification at various stages of its life. In this study, we describe the behavior of the pufferfish in the intertidal zone that appears to contribute to its toxification before and during its spawning period: pufferfish were found to aggregate and ingest flatworm egg plates by scraping them off the surface of rocks. DNA analysis based on 28S rRNA and cytochrome c oxidase subunit I (COI) genes identified the egg plates as those of P. multitentaculata. Liquid chromatography with tandem mass spectrometry analysis revealed that the egg plates contain highly concentrated TTX. The feeding behavior of the pufferfish on the flatworm egg plates was also observed in the aquarium. These results suggest that pufferfish feed on the flatworm egg plate, which enables them to acquire toxicity themselves while providing their offspring with the protective shield of TTX. Full article
(This article belongs to the Special Issue Isolation and Characterization of Marine Toxins)
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