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Toxins, Volume 10, Issue 2 (February 2018)

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Open AccessArticle Effects of Zearalenone Exposure on the TGF-β1/Smad3 Signaling Pathway and the Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts
Toxins 2018, 10(2), 49; doi:10.3390/toxins10020049
Received: 11 December 2017 / Revised: 18 January 2018 / Accepted: 19 January 2018 / Published: 23 January 2018
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Abstract
Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium species, which is widely distributed and posed a great health risk to both humans and farm animals. Reproductive disorders associated with ZEA such as premature puberty, infertility and abortion have plagued the animal husbandry,
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Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium species, which is widely distributed and posed a great health risk to both humans and farm animals. Reproductive disorders associated with ZEA such as premature puberty, infertility and abortion have plagued the animal husbandry, but the molecular mechanism is unclear. Because transforming growth factor-β1 (TGF-β1) signaling pathway is involved in the proliferation and apoptosis of cells, proliferating cell nuclear antigen (PCNA), B-cell lymphoma/leukemia-2 (BCL-2) and BCL-2 associated X protein (BAX) that all play indispensable roles in the normal development of the uterus, it is hypothesized that ZEA induces reproductive disorders is closely related to the expression of these genes. The objective of this study was to assess the effects of dietary ZEA at the concentrations of 0.5 to 1.5 mg/kg on the mRNA and protein expression of these genes in the uteri of post-weaning gilts and to explore the possible molecular mechanism. Forty healthy post-weaning female piglets (Duroc × Landrace × Large White) aged 38 d were randomly allocated to basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d. Piglets were euthanized at the end of the experiment and samples were taken and subjected to immunohistochemistry, qRT-PCR and Western blot analyses. The relative mRNA expressions of PCNA, BCL-2 and Smad3 in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.05) as ZEA concentration increased in the diet. The relative protein expressions of PCNA, BAX, BCL-2, TGF-β1, Smad3, and phosphorylated Smad3 (p-Smad3) in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.001) with an increasing level of ZEA. The results showed that uterine cells in the ZEA (0.5–1.5 mg/kg) treatments were in a high proliferation state, indicating that ZEA could accelerate the proliferation of uteri and promote the development of the uteri. At the same time, the results suggested that ZEA activates the TGF-β1/Smad3 signaling pathway, suggesting it plays an important role in accelerating the development of the uterus. Full article
(This article belongs to the Special Issue Impact of Human Metabolism on the Toxicological Effects of Mycotoxins)
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Open AccessArticle Assessment of Urinary Deoxynivalenol Biomarkers in UK Children and Adolescents
Toxins 2018, 10(2), 50; doi:10.3390/toxins10020050
Received: 21 December 2017 / Revised: 11 January 2018 / Accepted: 17 January 2018 / Published: 23 January 2018
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Abstract
Deoxynivalenol (DON), the mycotoxin produced mainly by Fusarium graminearum and found in contaminated cereal-based foodstuff, has been consistently detected in body fluids in adults. Available data in children and adolescents are scarce. This study assessed urinary DON concentrations in children aged 3–9 years
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Deoxynivalenol (DON), the mycotoxin produced mainly by Fusarium graminearum and found in contaminated cereal-based foodstuff, has been consistently detected in body fluids in adults. Available data in children and adolescents are scarce. This study assessed urinary DON concentrations in children aged 3–9 years (n = 40) and adolescents aged 10–17 years (n = 39) in the UK. Morning urine samples were collected over two consecutive days and analysed for free DON (un-metabolised form), DON-glucuronides (DON-GlcA), deepoxy deoxynivalenol (DOM-1), and total DON (sum of free DON, DON-GlcA, and DOM-1). Total DON was detected in the urine of >95% of children and adolescents on both days. Mean total DON concentrations (ng/mg creatinine) were 41.6 and 21.0 for children and adolescents, respectively. The greatest total DON levels were obtained in female children on both days (214 and 219 ng/mg creatinine on days 1 and 2, respectively). Free DON and DON-GlcA were detected in most urine specimens, whereas DOM-1 was not present in any sample. Estimation of dietary DON exposure suggested that 33–63% of children and 5–46% of adolescents exceeded current guidance regarding the maximum provisional tolerable daily intake (PMTDI) for DON. Although moderate mean urinary DON concentrations were shown, the high detection frequency of urinary DON, the maximum biomarker concentrations, and estimated dietary DON exposure are concerning. Full article
(This article belongs to the collection Fusarium Toxins – Relevance for Human and Animal Health)
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Open AccessArticle Antimycobacterial Activity: A New Pharmacological Target for Conotoxins Found in the First Reported Conotoxin from Conasprella ximenes
Toxins 2018, 10(2), 51; doi:10.3390/toxins10020051
Received: 19 December 2017 / Revised: 11 January 2018 / Accepted: 17 January 2018 / Published: 23 January 2018
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Abstract
Mycobacterium tuberculosis is the etiological agent of tuberculosis, an airborne infectious disease that is a leading cause of human morbidity and mortality worldwide. We report here the first conotoxin that is able to inhibit the growth of M. tuberculosis at a concentration similar
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Mycobacterium tuberculosis is the etiological agent of tuberculosis, an airborne infectious disease that is a leading cause of human morbidity and mortality worldwide. We report here the first conotoxin that is able to inhibit the growth of M. tuberculosis at a concentration similar to that of two other drugs that are currently used in clinics. Furthermore, it is also the first conopeptide that has been isolated from the venom of Conasprella ximenes. The venom gland transcriptome of C. ximenes was sequenced to construct a database with 24,284 non-redundant transcripts. The conopeptide was purified from the venom using reverse phase high performance liquid chromatography (RP-HPLC) and was analyzed using electrospray ionization-mass spectrometry (ESI-MS/MS). No automatic identification above the identity threshold with 1% of the false discovery rate was obtained; however, a 10-amino-acid sequence tag, manually extracted from the MS/MS spectra, allowed for the identification of a conotoxin in the transcriptome database. Electron transfer higher energy collision dissociation (EThcD) fragmentation of the native conotoxin confirmed the N-terminal sequence (1–14), while LC-MS/MS analysis of the tryptic digest of the reduced and S-alkylated conotoxin confirmed the C-terminal region (15–36). The expected and experimental molecular masses corresponded, within sub-ppm mass error. The 37-mer peptide (MW 4109.69 Da), containing eight cysteine residues, was named I1_xm11a, according to the current nomenclature for this type of molecule. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessArticle Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in Uremic Serum-Exposed Human Rhabdomyosarcoma Cells
Toxins 2018, 10(2), 53; doi:10.3390/toxins10020053
Received: 29 November 2017 / Revised: 12 January 2018 / Accepted: 23 January 2018 / Published: 25 January 2018
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Abstract
Patients with end-stage kidney disease (ESKD) are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the
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Patients with end-stage kidney disease (ESKD) are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity of various trace elements in ESKD patients likely contribute as well. The purpose of this study is to determine the effect of trace elements on statin-induced toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells) for a long time. Cell viability, apoptosis, mRNA expression, and intracellular trace elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity than cells long-time exposed with normal serum (NS cells) (non-overlapping 95% confidence intervals). Intracellular levels of Mg, Mn, Cu, and Zn were significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01). Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated the distinction between both cells of simvastatin-induced cytotoxicity. These results suggest that Zn deficiencies may be involved in the increased risk for muscle complaints in ESKD patients. In conclusion, the increased severity of statin-induced rhabdomyolysis in ESKD patients may be partly due to trace elements deficiencies. Full article
(This article belongs to the Section Uremic Toxins)
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Open AccessArticle Data Analyses and Modelling for Risk Based Monitoring of Mycotoxins in Animal Feed
Toxins 2018, 10(2), 54; doi:10.3390/toxins10020054
Received: 20 December 2017 / Revised: 17 January 2018 / Accepted: 22 January 2018 / Published: 26 January 2018
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Abstract
Following legislation, European Member States should have multi-annual control programs for contaminants, such as for mycotoxins, in feed and food. These programs need to be risk based implying the checks are regular and proportional to the estimated risk for animal and human health.
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Following legislation, European Member States should have multi-annual control programs for contaminants, such as for mycotoxins, in feed and food. These programs need to be risk based implying the checks are regular and proportional to the estimated risk for animal and human health. This study aimed to prioritize feed products in the Netherlands for deoxynivalenol and aflatoxin B1 monitoring. Historical mycotoxin monitoring results from the period 2007–2016 were combined with data from other sources. Based on occurrence, groundnuts had high priority for aflatoxin B1 monitoring; some feed materials (maize and maize products and several oil seed products) and complete/complementary feed excluding dairy cattle and young animals had medium priority; and all other animal feeds and feed materials had low priority. For deoxynivalenol, maize by-products had a high priority, complete and complementary feed for pigs had a medium priority and all other feed and feed materials a low priority. Also including health consequence estimations showed that feed materials that ranked highest for aflatoxin B1 included sunflower seed and palmkernel expeller/extracts and maize. For deoxynivalenol, maize products were ranked highest, followed by various small grain cereals (products); all other feed materials were of lower concern. Results of this study have proven to be useful in setting up the annual risk based control program for mycotoxins in animal feed and feed materials. Full article
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Open AccessArticle Botulinum Toxin A for Sialorrhoea Associated with Neurological Disorders: Evaluation of the Relationship between Effect of Treatment and the Number of Glands Treated
Toxins 2018, 10(2), 55; doi:10.3390/toxins10020055
Received: 21 December 2017 / Revised: 22 January 2018 / Accepted: 22 January 2018 / Published: 27 January 2018
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Abstract
Background: Sialorrhoea and drooling are disabling manifestations of different neurological disorders. The aim of this study was to evaluate the effects of botulinum neurotoxin type A (BoNT/A) injection on hypersalivation in 90 patients with neurological diseases of different aetiologies, and to define
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Background: Sialorrhoea and drooling are disabling manifestations of different neurological disorders. The aim of this study was to evaluate the effects of botulinum neurotoxin type A (BoNT/A) injection on hypersalivation in 90 patients with neurological diseases of different aetiologies, and to define the minimum number of injected salivary glands to reduce sialorrhoea. Determining the minimum number of glands that need to be engaged in order to have a significant reduction in drooling may be very useful for establishing the minimum total dosage of BoNT/A that may be considered effective in the treatment of hypersalivation. Methods: Twenty-five mouse units (MU) of BoNT/A (onabotulinumtoxin A, Botox; Allergan, Irvine, CA, USA; 100 MU/2 mL, 0.9% saline; or incobotulinumtoxin A, Xeomin; Merz Pharma, Germany; 100 MU/2 mL, 0.9% saline) were percutaneously injected into the parotid (p) glands and/or submandibular (s) glands under ultrasound control. On this basis, patients were divided into three groups. In group A (30 patients), BoNT/A injections were performed into four glands; in group B (30 patients), into three glands, and in group C (30 patients), into two glands. Patients treated in three glands (group B) were divided into two subgroups based on the treated glands (2 p + 1 s = 15 patients; 2 s + 1 p = 15 patients). Similarly, patients being injected in two glands (group C) were subdivided into three groups (2 p = 10 patients; 1 p + 1 s = 10 patients; 2 s = 10 patients). In patients who were injected in three and two salivary glands, saline solution was injected into the remaining one and two glands, respectively. Assessments were performed at baseline and at 2 weeks after the injections. Results: BoNT/A significantly reduced sialorrhoea in 82 out of 90 patients. The effect was more evident in patients who had four glands injected than when three or two glands were injected. The injections into three glands were more effective than injections into two glands. Conclusions: Our results have shown that BoNT/A injections induced a significant reduction in sialorrhoea in most patients (91%). In addition, we demonstrated that sialorrhoea associated with different neurological diseases was better controlled when the number of treated glands was higher. Full article
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Open AccessFeature PaperArticle Interacting Environmental Stress Factors Affects Targeted Metabolomic Profiles in Stored Natural Wheat and That Inoculated with F. graminearum
Toxins 2018, 10(2), 56; doi:10.3390/toxins10020056
Received: 20 December 2017 / Revised: 16 January 2018 / Accepted: 22 January 2018 / Published: 29 January 2018
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Abstract
Changes in environmental stress impact on secondary metabolite (SM) production profiles. Few studies have examined targeted SM production patterns in relation to interacting environmental conditions in stored cereals. The objectives were to examine the effect of water activity (aw; 0.95–0.90) x
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Changes in environmental stress impact on secondary metabolite (SM) production profiles. Few studies have examined targeted SM production patterns in relation to interacting environmental conditions in stored cereals. The objectives were to examine the effect of water activity (aw; 0.95–0.90) x temperature (10–25 °C) on SM production on naturally contaminated stored wheat and that inoculated with Fusarium graminearum. Samples were analysed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) on (a) total number of known SMs, (b) their concentrations and (c) changes under environmental stress. 24 Fusarium metabolites were quantified. Interestingly, statistical differences (ChisSq., p < 0.001) were observed in the number of SMs produced under different sets of interacting environmental conditions. The dominant metabolites in natural stored grain were deoxynivalenol (DON) and nivalenol (NIV) followed by a range of enniatins (A, A1, B, B1), apicidin and DON-3-glucoside at 10 °C. Increasing temperature promoted the biosynthesis of other SMs such as aurofusarin, moniliformin, zearalenone (ZEN) and their derivatives. Natural wheat + F. graminearum inoculation resulted in a significant increase in the number of metabolites produced (ChisSq., p < 0.001). For ZEN and its derivatives, more was produced under cooler storage conditions. Fusarin C was enhanced in contrast to that for the enniatin group. The relative ratios of certain groups of targeted SM changed with environmental stress. Both temperature and aw affected the amounts of metabolites present, especially of DON and ZEN. This study suggests that the dominant SMs produced in stored temperate cereals are the mycotoxins for which legislation exists. However, there are changes in the ratios of key metabolites which could influence the relative contamination with individual compounds. Thus, in the future, under more extreme environmental stresses, different dominant SMs may be formed which could make present legislation out of step with the future contamination which might occur. Full article
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Open AccessArticle Activation of Aflatoxin Biosynthesis Alleviates Total ROS in Aspergillus parasiticus
Toxins 2018, 10(2), 57; doi:10.3390/toxins10020057
Received: 9 November 2017 / Revised: 6 January 2018 / Accepted: 16 January 2018 / Published: 29 January 2018
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Abstract
An aspect of mycotoxin biosynthesis that remains unclear is its relationship with the cellular management of reactive oxygen species (ROS). Here we conduct a comparative study of the total ROS production in the wild-type strain (SU-1) of the plant pathogen and aflatoxin producer,
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An aspect of mycotoxin biosynthesis that remains unclear is its relationship with the cellular management of reactive oxygen species (ROS). Here we conduct a comparative study of the total ROS production in the wild-type strain (SU-1) of the plant pathogen and aflatoxin producer, Aspergillus parasiticus, and its mutant strain, AFS10, in which the aflatoxin biosynthesis pathway is blocked by disruption of its pathway regulator, aflR. We show that SU-1 demonstrates a significantly faster decrease in total ROS than AFS10 between 24 h to 48 h, a time window within which aflatoxin synthesis is activated and reaches peak levels in SU-1. The impact of aflatoxin synthesis in alleviation of ROS correlated well with the transcriptional activation of five superoxide dismutases (SOD), a group of enzymes that protect cells from elevated levels of a class of ROS, the superoxide radicals (O2). Finally, we show that aflatoxin supplementation to AFS10 growth medium results in a significant reduction of total ROS only in 24 h cultures, without resulting in significant changes in SOD gene expression. Our findings show that the activation of aflatoxin biosynthesis in A. parasiticus alleviates ROS generation, which in turn, can be both aflR dependent and aflatoxin dependent. Full article
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Open AccessArticle Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer
Toxins 2018, 10(2), 58; doi:10.3390/toxins10020058
Received: 28 November 2017 / Revised: 23 January 2018 / Accepted: 26 January 2018 / Published: 30 January 2018
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Abstract
Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex
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Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50) (−log [ETA]) of 6.66 ± 0.17 M). Although sample preparation time affected contractile response (p < 0.001), pre-myograph incubation temperature (39 vs. 21 °C, 1 h) had no effect (p > 0.05). Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92) for both polymers, with no significant difference between polymers (p > 0.05). No significant differences in maximum inhibitory (p = 0.96) and IC50 responses (p = 0.163) between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01), for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessFeature PaperArticle An Improved Method for the Sensitive Detection of Shiga Toxin 2 in Human Serum
Toxins 2018, 10(2), 59; doi:10.3390/toxins10020059
Received: 18 November 2017 / Revised: 12 January 2018 / Accepted: 29 January 2018 / Published: 31 January 2018
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Abstract
Shiga toxins (Stx) released by Stx-producing E. coli (STEC) are virulence factors that are most closely associated with hemolytic uremic syndrome (HUS), a life-threatening complication of intestinal infections by STEC. Stx have to enter into the circulatory system before they are delivered to
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Shiga toxins (Stx) released by Stx-producing E. coli (STEC) are virulence factors that are most closely associated with hemolytic uremic syndrome (HUS), a life-threatening complication of intestinal infections by STEC. Stx have to enter into the circulatory system before they are delivered to target organs and cause damage. The presence of Stx in sera could be a risk indicator for HUS development. However, the detection of Stx, particularly Stx2, has been difficult due to the presence of Stx2-binding components in human serum. Here, we report new ELISA-based methods for the detection of Stx1 and Stx2 in human serum and the effect of guanidinium chloride on enhancing the sensitivity for the detection of Stx2. The recovery rate for Stx2 was 62% when Stx2-spiked serum samples were treated with guanidinium chloride at a concentration of 200 mM, in contrast to 17% without guanidinium chloride treatment. The effectiveness of guanidinium chloride treatment for the detection of Stx2 in human serum was validated using sera from STEC-infected patients. Coimmunoprecipitation results indicated a specific physical interaction between Stx2 and the human serum amyloid P component (HuSAP) in human serum samples. Our in vitro study demonstrated that the inhibition from HuSAP alone for the detection of Stx2 was only 20%, much less than 69.6% from human serum at Stx2 level 10 ng/mL, suggesting that there may be other factors that bind Stx2 in human serum. This study indicates that treatment of serum samples with guanidinium chloride may be useful for the early and sensitive detection of Stx2 in sera of STEC-infected patients, so preventive measures can be adopted in a timely manner. Full article
(This article belongs to the collection Rapid Detection of Bacterial Toxins)
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Open AccessArticle Fatal Neurotoxicosis in Dogs Associated with Tychoplanktic, Anatoxin-a Producing Tychonema sp. in Mesotrophic Lake Tegel, Berlin
Toxins 2018, 10(2), 60; doi:10.3390/toxins10020060
Received: 22 December 2017 / Revised: 19 January 2018 / Accepted: 22 January 2018 / Published: 31 January 2018
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Abstract
In May 2017, at least 12 dogs showed signs of acute neurotoxicosis after swimming in or drinking from Lake Tegel, a mesotrophic lake in Berlin, Germany, and several of the affected dogs died shortly afterwards despite intensive veterinary treatment. Cyanobacterial blooms were not
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In May 2017, at least 12 dogs showed signs of acute neurotoxicosis after swimming in or drinking from Lake Tegel, a mesotrophic lake in Berlin, Germany, and several of the affected dogs died shortly afterwards despite intensive veterinary treatment. Cyanobacterial blooms were not visible at the water surface or the shorelines. However, detached and floating water moss (Fontinalis antipyretica) with high amounts of Tychonema sp., a potential anatoxin-a (ATX) producing cyanobacterium, was found near the beaches where the dogs had been swimming and playing. Necropsies of two of the dogs revealed no specific lesions beside the anamnestic neurotoxicosis. ATX was detected in concentrations up to 8700 µg L−1 in the stomach contents, while other (neuro)toxic substances were not found. In the aqueous fraction of Fontinalis/Tychonema clumps sampled after the casualties, ATX was found in concentrations up to 1870 µg L−1. This is the first report of a dense population of Tychonema sp. in stands of Fontinalis resulting in high ATX contents. This case emphasizes the need for further investigation of potentially toxic, non-bloom forming cyanobacteria in less eutrophic water bodies and underlines the novel challenge of developing appropriate surveillance schemes for respective bathing sites. Full article
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Open AccessArticle Survey of Candidate Genes for Maize Resistance to Infection by Aspergillus flavus and/or Aflatoxin Contamination
Toxins 2018, 10(2), 61; doi:10.3390/toxins10020061
Received: 21 December 2017 / Revised: 20 January 2018 / Accepted: 24 January 2018 / Published: 31 January 2018
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Abstract
Many projects have identified candidate genes for resistance to aflatoxin accumulation or Aspergillus flavus infection and growth in maize using genetic mapping, genomics, transcriptomics and/or proteomics studies. However, only a small percentage of these candidates have been validated in field conditions, and their
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Many projects have identified candidate genes for resistance to aflatoxin accumulation or Aspergillus flavus infection and growth in maize using genetic mapping, genomics, transcriptomics and/or proteomics studies. However, only a small percentage of these candidates have been validated in field conditions, and their relative contribution to resistance, if any, is unknown. This study presents a consolidated list of candidate genes identified in past studies or in-house studies, with descriptive data including genetic location, gene annotation, known protein identifiers, and associated pathway information, if known. A candidate gene pipeline to test the phenotypic effect of any maize DNA sequence on aflatoxin accumulation resistance was used in this study to determine any measurable effect on polymorphisms within or linked to the candidate gene sequences, and the results are published here. Full article
(This article belongs to the collection Aflatoxins)
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Open AccessArticle Development and Validation of a UPLC-MS/MS and UPLC-HR-MS Method for the Determination of Fumonisin B1 and Its Hydrolysed Metabolites and Fumonisin B2 in Broiler Chicken Plasma
Toxins 2018, 10(2), 62; doi:10.3390/toxins10020062
Received: 14 December 2017 / Revised: 26 January 2018 / Accepted: 29 January 2018 / Published: 31 January 2018
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Abstract
A sensitive and specific method for the quantitative determination of Fumonisin B1 (FB1), its partially hydrolysed metabolites pHFB1a+b and hydrolysed metabolite HFB1, and Fumonisin B2 (FB2) in broiler chicken plasma using ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) was developed. The
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A sensitive and specific method for the quantitative determination of Fumonisin B1 (FB1), its partially hydrolysed metabolites pHFB1a+b and hydrolysed metabolite HFB1, and Fumonisin B2 (FB2) in broiler chicken plasma using ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) was developed. The sample preparation was rapid, straightforward and consisted of a deproteinization and phospholipid removal step using an Oasis® OstroTM 96-well plate. Chromatography was performed on an Acquity HSS-T3 column, using 0.3% formic acid and 10 mM ammonium formate in water, and acetonitrile as mobile phases. The MS/MS instrument was operated in the positive electrospray ionization mode and the two multiple reaction monitoring transitions were monitored for each component for quantification and identification, respectively. The method was validated in-house: matrix-matched calibration graphs were prepared and good linearity (r ≥ 0.99) was achieved over the concentration ranges tested (1–500 ng/mL for FB1 and FB2; 0.86–860 ng/mL for pHFB1a; 0.72–1430 ng/mL for pHFB1b and 2.5–2500 ng/mL for HFB1). Limits of quantification (LOQ) and detection (LOD) in plasma ranged between 0.72 to 2.5 ng/mL and 0.03 to 0.17 ng/mL, respectively. The results for the within-day and between-day precision and accuracy fell within the specified ranges. Moreover, the method was transferred to an UPLC high-resolution mass spectrometry (HR-MS) instrument in order to determine potential metabolites of HFB1, such as N-acyl-HFB1s and phase II metabolites. The method has been successfully applied to investigate the toxicokinetics and biotransformation of HFB1 in broiler chickens. Full article
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Open AccessFeature PaperArticle Validation of a Method for Cylindrospermopsin Determination in Vegetables: Application to Real Samples Such as Lettuce (Lactuca sativa L.)
Toxins 2018, 10(2), 63; doi:10.3390/toxins10020063
Received: 11 January 2018 / Revised: 19 January 2018 / Accepted: 1 February 2018 / Published: 1 February 2018
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Abstract
Reports on the occurrence of the cyanobacterial toxin cylindrospermopsin (CYN) have increased worldwide because of CYN toxic effects in humans and animals. If contaminated waters are used for plant irrigation, these could represent a possible CYN exposure route for humans. For the first
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Reports on the occurrence of the cyanobacterial toxin cylindrospermopsin (CYN) have increased worldwide because of CYN toxic effects in humans and animals. If contaminated waters are used for plant irrigation, these could represent a possible CYN exposure route for humans. For the first time, a method employing solid phase extraction and quantification by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) of CYN was optimized in vegetables matrices such as lettuce (Lactuca sativa). The validated method showed a linear range, from 5 to 500 ng CYN g−1 of fresh weight (f.w.), and detection and quantitation limits (LOD and LOQ) of 0.22 and 0.42 ng CYN g−1 f.w., respectively. The mean recoveries ranged between 85 and 104%, and the intermediate precision from 12.7 to 14.7%. The method showed to be robust for the three different variables tested. Moreover, it was successfully applied to quantify CYN in edible lettuce leaves exposed to CYN-contaminated water (10 µg L−1), showing that the tolerable daily intake (TDI) in the case of CYN could be exceeded in elderly high consumers. The validated method showed good results in terms of sensitivity, precision, accuracy, and robustness for CYN determination in leaf vegetables such as lettuce. More studies are needed in order to prevent the risks associated with the consumption of CYN-contaminated vegetables. Full article
(This article belongs to the Special Issue Selected Papers from the 5th Iberoamerican Cyanotoxins Meeting)
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Open AccessArticle Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain
Toxins 2018, 10(2), 64; doi:10.3390/toxins10020064
Received: 27 December 2017 / Revised: 26 January 2018 / Accepted: 31 January 2018 / Published: 2 February 2018
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Abstract
Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.5. If the DIIS3-S4 linker of Nav1.5 is substituted by the correspond
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Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.5. If the DIIS3-S4 linker of Nav1.5 is substituted by the correspond linker of Nav1.7, the sensitivity of Nav1.5 to JZTX-34 extremely increases to 1.05 µM. Meanwhile, a mutant D816R in the DIIS3-S4 linker of Nav1.7 decreases binding affinity of Nav1.7 to JZTX-34 about 32-fold. The reverse mutant R800D at the corresponding position in Nav1.5 greatly increased its binding affinity to JZTX-34. This implies that JZTX-34 binds to DIIS3-S4 linker of Nav1.7 and the critical residue of Nav1.7 is D816. Unlike β-scorpion toxin trapping sodium channel in an open state, activity of JZTX-34 requires the sodium channel to be in a resting state. JZTX-34 exhibits an obvious analgesic effect in a rodent pain model. Especially, it shows a longer duration and is more effective than morphine in hot pain models. In a formalin-induced pain model, JZTX-34 at dose of 2 mg/kg is equipotent with morphine (5 mg/kg) in the first phase and several-fold more effective than morphine in second phase. Taken together, our data indicate that JZTX-34 releases pain by selectively binding to the domain II voltage sensor of Nav1.7 in a closed configuration. Full article
(This article belongs to the Special Issue Toxins and Ion Channels)
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Open AccessArticle The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats
Toxins 2018, 10(2), 66; doi:10.3390/toxins10020066
Received: 23 November 2017 / Revised: 31 January 2018 / Accepted: 31 January 2018 / Published: 2 February 2018
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Abstract
(1) Background: The botulinum toxin A (BoNT-A) heavy chain (HC) can stimulate the growth of primary motor neurites. (2) Methods: A recombinant BoNT/A HC was injected locally plus interval intrathecal catheter of BoNT/A HC to rats with ipsilateral semi-dissociated lumbar spinal cord injuries
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(1) Background: The botulinum toxin A (BoNT-A) heavy chain (HC) can stimulate the growth of primary motor neurites. (2) Methods: A recombinant BoNT/A HC was injected locally plus interval intrathecal catheter of BoNT/A HC to rats with ipsilateral semi-dissociated lumbar spinal cord injuries (SCIs). First, 2D gel with a silver nitrate stain was applied to detect the general pattern of protein expression. Growth associated protein 43 (GAP-43) and superior cervical ganglion 10 (SCG10) were chosen to represent the altered proteins, based on their molecular weight and pI, and were used to further detect their expression. Meanwhile, the neuronal processes were measured. The measurements of thermal hyperalgesia and grasp power at the ipsilateral hindlimb were used to evaluate spinal sensory and motor function, respectively. (3) Results: The local injection of BoNT/A HC followed by its intrathecal catheter intervally altered the spinal protein expression pattern after an SCI; protein expression was similar to normal levels or displayed a remarkable increase. The changes in the expression and distribution of phosphorylated growth associated protein 43(p-GAP 43) and superior cervical ganglion 10 (SCG 10) indicated that the administration of BoNT/A HC to the SCI significantly amplified the expression of p-GAP43 and SCG10 (p < 0.05). Meanwhile, the positive immunofluorescent staining for both p-GAP43 and SCG10 was mainly present near the rostral aspect of the injury, both in the cytoplasm and the neuronal processes. Moreover, the outgrowth of neurites was stimulated by the BoNT/A HC treatment; this was evident from the increase in neurite length, number of branches and the percentage of cells with neuronal processes. The results from the spinal function tests suggested that the BoNT/A HC did not affect sensation, but had a large role in improving the ipsilateral hindlimb grasp power (p < 0.05). (4) Conclusions: The local injection with the intermittent intrathecal administration of BoNT/A heavy chain to rats with SCI increased the local expression of GAP-43 and SCG 10, which might be affiliated with the regeneration of neuronal processes surrounding the injury, and might also be favorable to the relief of spinal motor dysfunction. Full article
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Open AccessArticle Control of Fusarium verticillioides (Sacc.) Nirenberg and Fumonisins by Using a Combination of Crop Protection Products and Fertilization
Toxins 2018, 10(2), 67; doi:10.3390/toxins10020067
Received: 3 December 2017 / Revised: 10 January 2018 / Accepted: 1 February 2018 / Published: 2 February 2018
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Abstract
Fusarium verticillioides is the most common fungal pathogen associated with maize ear rot in Tanzania. In a two-year trial, we investigated the efficacy of crop protection (insecticide and/or fungicide) and fertilizer (nitrogen and/or phosphorus) treatments in reducing the occurrence of F. verticillioides and
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Fusarium verticillioides is the most common fungal pathogen associated with maize ear rot in Tanzania. In a two-year trial, we investigated the efficacy of crop protection (insecticide and/or fungicide) and fertilizer (nitrogen and/or phosphorus) treatments in reducing the occurrence of F. verticillioides and its mycotoxins in maize grown in Tanzania. Seasonal differences were seen to have a substantial influence on the incidence and severity of insect infestation, Fusarium ear and kernel rot, biomass of F. verticillioides and contamination with fumonisins. With regard to the application of fertilizers, it was concluded that the impact on maize stalk borer injury, Fusarium symptoms and fumonisin levels was not significant, whereas crop protection significantly reduced maize damage. The application of an insecticide was most effective in reducing insect injury and as a result of the reduced insect injury the insecticide treatment also resulted in a significant decrease in Fusarium symptoms. In 2014, fumonisin levels were also significantly lower in maize treated with an insecticide. Additionally, significant positive correlations between insect damage and Fusarium symptoms were observed. In conclusion, this study clearly shows that application of an insecticide alone or in combination with a fungicide at anthesis significantly reduces insect damage and consequently reduces F. verticillioides infection and associated fumonisin contamination. Full article
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Open AccessArticle Candidacidal Activity of a Novel Killer Toxin from Wickerhamomyces anomalus against Fluconazole-Susceptible and -Resistant Strains
Toxins 2018, 10(2), 68; doi:10.3390/toxins10020068
Received: 1 December 2017 / Revised: 30 January 2018 / Accepted: 1 February 2018 / Published: 3 February 2018
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Abstract
The isolation and characterization from the sand fly Phlebotomus perniciosus of a Wickerhamomyces anomalus yeast strain (Wa1F1) displaying the killer phenotype was recently reported. In the present work, the killer toxin (KT) produced by Wa1F1 was purified and characterized, and
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The isolation and characterization from the sand fly Phlebotomus perniciosus of a Wickerhamomyces anomalus yeast strain (Wa1F1) displaying the killer phenotype was recently reported. In the present work, the killer toxin (KT) produced by Wa1F1 was purified and characterized, and its antimicrobial activity in vitro was investigated against fluconazole- susceptible and -resistant clinical isolates and laboratory strains of Candida albicans and C. glabrata displaying known mutations. Wa1F1-KT showed a differential killing ability against different mutant strains of the same species. The results may be useful for the design of therapeutic molecules based on Wa1F1-KT and the study of yeast resistance mechanisms. Full article
(This article belongs to the Special Issue Yeast Killer Toxins)
Open AccessFeature PaperArticle Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping
Toxins 2018, 10(2), 69; doi:10.3390/toxins10020069
Received: 27 November 2017 / Revised: 30 January 2018 / Accepted: 2 February 2018 / Published: 6 February 2018
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Abstract
Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the
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Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessArticle In Vitro Study of the Cytotoxic, Cytostatic, and Antigenotoxic Profile of Hemidesmus indicus (L.) R.Br. (Apocynaceae) Crude Drug Extract on T Lymphoblastic Cells
Toxins 2018, 10(2), 70; doi:10.3390/toxins10020070
Received: 22 December 2017 / Revised: 31 January 2018 / Accepted: 1 February 2018 / Published: 6 February 2018
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Abstract
In traditional Indian medicine, the crude drug Hemidesmus indicus root—commonly known as Indian sarsaparilla—is used alone or in poly-herbal preparations for the treatment of a wide range of diseases. The present study focuses on the cancer chemopreventive and therapeutic potential of H. indicus
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In traditional Indian medicine, the crude drug Hemidesmus indicus root—commonly known as Indian sarsaparilla—is used alone or in poly-herbal preparations for the treatment of a wide range of diseases. The present study focuses on the cancer chemopreventive and therapeutic potential of H. indicus extracts on an acute lymphoblastic leukemia cell line (CCRF-CEM). With this aim in mind, we subjected H. indicus roots to two subsequent extractions (hydro-alcoholic extraction and soxhlet extraction). As DNA damage is an important prerequisite for the induction of mutations/cancer by genotoxic carcinogens, cancer chemoprevention may be achieved by preventing genotoxicity. Through an integrated experimental approach, we explored the genoprotective potential of the soxhlet H. indicus extract against different mutagenic compounds and its cytotoxic, proapoptotic, and cytostatic properties. In our experimental conditions, H. indicus induced a cytotoxic effect involving the activation of both intrinsic and extrinsic apoptotic pathways and blocked the cell cycle in the S phase. Moreover, the antigenotoxicity results showed that the extract was able to mitigate DNA damage, an essential mechanism for its applicability as a chemopreventive agent, via either the modulation of extracellular and intracellular events involved in DNA damage. These data add to the growing body of evidence that H. indicus can represent a noteworthy strategy to target early and late stages of cancer. Full article
(This article belongs to the Section Plant Toxins)
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Open AccessArticle Chemometric Analysis of the Volatile Compounds Generated by Aspergillus carbonarius Strains Isolated from Grapes and Dried Vine Fruits
Toxins 2018, 10(2), 71; doi:10.3390/toxins10020071
Received: 6 November 2017 / Revised: 1 February 2018 / Accepted: 3 February 2018 / Published: 6 February 2018
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Abstract
Ochratoxin A (OTA) contamination in grape production is an important problem worldwide. Microbial volatile organic compounds (MVOCs) have been demonstrated as useful tools to identify different toxigenic strains. In this study, Aspergillus carbonarius strains were classified into two groups, moderate toxigenic strains (MT)
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Ochratoxin A (OTA) contamination in grape production is an important problem worldwide. Microbial volatile organic compounds (MVOCs) have been demonstrated as useful tools to identify different toxigenic strains. In this study, Aspergillus carbonarius strains were classified into two groups, moderate toxigenic strains (MT) and high toxigenic strains (HT), according to OTA-forming ability. The MVOCs were analyzed by GC-MS and the data processing was based on untargeted profiling using XCMS Online software. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was performed using extract ion chromatogram GC-MS datasets. For contrast, quantitative analysis was also performed. Results demonstrated that the performance of the OPLS-DA model of untargeted profiling was better than the quantitative method. Potential markers were successfully discovered by variable importance on projection (VIP) and t-test. (E)-2-octen-1-ol, octanal, 1-octen-3-one, styrene, limonene, methyl-2-phenylacetate and 3 unknown compounds were selected as potential markers for the MT group. Cuparene, (Z)-thujopsene, methyl octanoate and 1 unknown compound were identified as potential markers for the HT groups. Finally, the selected markers were used to construct a supported vector machine classification (SVM-C) model to check classification ability. The models showed good performance with the accuracy of cross-validation and test prediction of 87.93% and 92.00%, respectively. Full article
(This article belongs to the collection Ochratoxins-Collection)
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Open AccessArticle PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer
Toxins 2018, 10(2), 72; doi:10.3390/toxins10020072
Received: 22 January 2018 / Revised: 1 February 2018 / Accepted: 2 February 2018 / Published: 7 February 2018
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Abstract
Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of
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Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC) inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM), and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG) neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessArticle Bacillus subtilis Type I antitoxin SR6 Promotes Degradation of Toxin yonT mRNA and Is Required to Prevent Toxic yoyJ Overexpression
Toxins 2018, 10(2), 74; doi:10.3390/toxins10020074
Received: 18 January 2018 / Revised: 30 January 2018 / Accepted: 4 February 2018 / Published: 7 February 2018
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Abstract
yonT/SR6 is the second type I toxin-antitoxin (TA) system encoded on prophage SPβ in the B. subtilis chromosome. The yonT ORF specifying a 58 aa toxin is transcribed on a polycistronic mRNA under control of the yonT promoter. The antitoxin SR6 is
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yonT/SR6 is the second type I toxin-antitoxin (TA) system encoded on prophage SPβ in the B. subtilis chromosome. The yonT ORF specifying a 58 aa toxin is transcribed on a polycistronic mRNA under control of the yonT promoter. The antitoxin SR6 is a 100 nt antisense RNA that overlaps yonT at its 3′ end and the downstream gene yoyJ encoding a second, much weaker, toxin at its 5′ end. SR6 displays a half-life of >60 min, whereas yonT mRNA is less stable with a half-life of ≈8 min. SR6 is in significant excess over yonT mRNA except in minimal medium with glucose. It interacts with the 3′ UTR of yonT mRNA, thereby promoting its degradation by RNase III. By contrast, SR6 does not affect the amount or half-life of yoyJ mRNA. However, in its absence, a yoyJ overexpression plasmid could not be established in Bacillus subtilis suggesting that SR6 inhibits yoyJ translation by directly binding to its ribosome-binding site. While the amounts of both yonT RNA and SR6 were affected by vancomycin, manganese, heat-shock and ethanol stress as well as iron limitation, oxygen stress decreased only the amount of SR6. Full article
(This article belongs to the Section Bacterial Toxins)
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Open AccessArticle Preparation of Monoclonal Antibody for Brevetoxin 1 and Development of Ic-ELISA and Colloidal Gold Strip to Detect Brevetoxin 1
Toxins 2018, 10(2), 75; doi:10.3390/toxins10020075
Received: 26 December 2017 / Revised: 28 January 2018 / Accepted: 1 February 2018 / Published: 8 February 2018
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Abstract
Brevetoxin-1 (BTX-1), a marine toxin mostly produced by the dinoflagellatae Karenia brevis, has caused the death of marine organisms and has had numerous toxicological effects on human health. Hence, it is very necessary to develop a rapid, economical, and reliable immunoassay method
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Brevetoxin-1 (BTX-1), a marine toxin mostly produced by the dinoflagellatae Karenia brevis, has caused the death of marine organisms and has had numerous toxicological effects on human health. Hence, it is very necessary to develop a rapid, economical, and reliable immunoassay method for BTX-1 detection. In this study, two kinds of complete antigen were synthesized using the succinic anhydride and isobutyl chloroformate two-step methods. Conjugate BTX-1-OVA was used as an antigen for mice immunization, and BTX-1-BSA for measuring the titer of the produced antibodies. A hybridoma cell line 6C6 stably secreting monoclonal antibody (mAb) against BTX-1 was obtained by fusing SP2/0 myeloma cells with the spleen cells from the immunized mouse. The hybridoma 6C6 was injected into the abdomen of BALB/c mice to obtain ascites, and the anti-BTX-1 mAb was harvested from ascites by precipitation with caprylic acid/ammonium sulfate (CA-AS). The anti-BTX-1 mAb was identified as an IgG1 subtype, and the cross-reactivity results showed that anti-BTX-1 mAb was highly specific to BTX-1 with the affinity of 1.06 × 108 L/mol. The indirect competitive ELISA results indicated that the linear range for BTX-1 detection was 14–263 ng/mL with IC50 of 60 ng/mL, and a detection limit of 14 ng/mL. The average recovery rate from the spiked samples was 88 ± 2% in intra-assay and 89 ± 2% in inter-assay. The limit of detection (LOD) using the colloidal gold strip was 200 ng/mL with high specificity. Therefore, the anti-BTX-1 mAb can be used to detect BTX-1 in shellfish and other related samples. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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Open AccessArticle Multiple Mycotoxins in Rice: Occurrence and Health Risk Assessment in Children and Adults of Punjab, Pakistan
Toxins 2018, 10(2), 77; doi:10.3390/toxins10020077
Received: 12 December 2017 / Revised: 4 February 2018 / Accepted: 7 February 2018 / Published: 10 February 2018
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Abstract
Mycotoxin contamination in rice can create a health risk for the consumers. In this study, the measurement of 23 mycotoxins in rice samples (n = 180) was performed using a validated LC–MS/MS method. A food frequency questionnaire was used to get rice
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Mycotoxin contamination in rice can create a health risk for the consumers. In this study, the measurement of 23 mycotoxins in rice samples (n = 180) was performed using a validated LC–MS/MS method. A food frequency questionnaire was used to get rice consumption data for the assessment of mycotoxin dietary exposure, before calculating the health risk in adults and children of north and south regions of the Pakistani Punjab province. The prevalence of aflatoxin B1 (56%), aflatoxin B2 (48%), nivalenol (28%), diacetoxyscirpenol (23%), fumonisin B1 (42%), zearalenone (15%), HT-2 toxin (10%), deoxynivalenol (8%), and ochratoxin A (6%) was estimated in samples with a mean concentration range between 0.61 and 22.98 µg/kg. Aflatoxin degradation by traditional Pakistani cooking recipes was evaluated and observed to be 41–63%. The dietary exposure to aflatoxins exceeded the tolerable daily intake at all levels, and ochratoxin A and zearalenone posed health risk at high contamination and high consumption levels. The margin of aflatoxin B1 exposure ranged between 10 and 69 in adults and 10 and 62 in children. The mean cancer risk by aflatoxin B1 exposure was 0.070 (adults) and 0.071 (children) cases/year/100,000 people in South Punjab population, and 0.122 (adults) and 0.127 (children) cases/year/100,000 people in North Punjab population. This study will provide new insights for the planning and management of mycotoxins in Pakistan. Full article
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Open AccessArticle Natural Contamination with Mycotoxins Produced by Fusarium graminearum and Fusarium poae in Malting Barley in Argentina
Toxins 2018, 10(2), 78; doi:10.3390/toxins10020078
Received: 30 October 2017 / Revised: 14 December 2017 / Accepted: 16 January 2018 / Published: 11 February 2018
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Abstract
Two of the most common species of toxin-producing Fusarium contaminating small cereal grains are Fusarium graminearum and F. poae; with both elaborating diverse toxins, especially deoxynivalenol (DON) and nivalenol (NIV), respectively. The objective of our work during the 2012–2014 growing seasons was
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Two of the most common species of toxin-producing Fusarium contaminating small cereal grains are Fusarium graminearum and F. poae; with both elaborating diverse toxins, especially deoxynivalenol (DON) and nivalenol (NIV), respectively. The objective of our work during the 2012–2014 growing seasons was to screen crops for the most commonly isolated Fusarium species and to quantify DON and NIV toxins in natural malting-barley samples from different producing areas of Argentina. We identified 1180 Fusarium isolates in the 119 samples analyzed, with 51.2% being F. graminearum, 26.2% F. poae and 22.6% other species. We found high concentrations of mycotoxins, at maximum values of 12 μg/g of DON and 7.71 μg/g of NIV. Of the samples, 23% exhibited DON at an average of 2.36 μg/g, with 44% exceeding the maximum limits (average of 5.24 μg/g); 29% contained NIV at an average of 2.36 μg/g; 7% contained both DON and NIV; and 55% were without DON or NIV. Finally, we report the mycotoxin contamination of the grain samples produced by F. graminearum and F. poae, those being the most frequent Fusarium species present. We identified the main Fusarium species affecting natural malting-barley grains in Argentina and documented the presence of many samples with elevated concentrations of DON and NIV. To our knowledge, the investigation reported here was the first to quantify the contamination by Fusarium and its toxins in natural samples of malting barley in Argentina. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessArticle Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells
Toxins 2018, 10(2), 79; doi:10.3390/toxins10020079
Received: 22 December 2017 / Revised: 1 February 2018 / Accepted: 7 February 2018 / Published: 11 February 2018
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Abstract
Pulmonary permeability edema is characterized by reduced alveolar Na+ uptake capacity and capillary barrier dysfunction and is a potentially lethal complication of listeriosis. Apical Na+ uptake is mainly mediated by the epithelial sodium channel (ENaC) and initiates alveolar liquid clearance. Here
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Pulmonary permeability edema is characterized by reduced alveolar Na+ uptake capacity and capillary barrier dysfunction and is a potentially lethal complication of listeriosis. Apical Na+ uptake is mainly mediated by the epithelial sodium channel (ENaC) and initiates alveolar liquid clearance. Here we examine how listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, impairs the expression and activity of ENaC. To that purpose, we studied how sub-lytic concentrations of LLO affect negative and positive regulators of ENaC expression in the H441 airway epithelial cell line. LLO reduced expression of the crucial ENaC-α subunit in H441 cells within 2 h and this was preceded by activation of PKC-α, a negative regulator of the channel’s expression. At later time points, LLO caused a significant reduction in the phosphorylation of Sgk-1 at residue T256 and of Akt-1 at residue S473, both of which are required for full activation of ENaC. The TNF-derived TIP peptide prevented LLO-mediated PKC-α activation and restored phospho-Sgk-1-T256. The TIP peptide also counteracted the observed LLO-induced decrease in amiloride-sensitive Na+ current and ENaC-α expression in H441 cells. Intratracheally instilled LLO caused profound pulmonary edema formation in mice, an effect that was prevented by the TIP peptide; thus indicating the therapeutic potential of the peptide for the treatment of pore-forming toxin-associated permeability edema. Full article
(This article belongs to the Section Bacterial Toxins)
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Open AccessArticle Novel Phage Display-Derived Anti-Abrin Antibodies Confer Post-Exposure Protection against Abrin Intoxication
Toxins 2018, 10(2), 80; doi:10.3390/toxins10020080
Received: 15 January 2018 / Revised: 6 February 2018 / Accepted: 8 February 2018 / Published: 13 February 2018
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Abstract
Abrin toxin is a type 2 ribosome inactivating glycoprotein isolated from the seeds of Abrus precatorius (jequirity pea). Owing to its high toxicity, relative ease of purification and accessibility, it is considered a biological threat agent. To date, there is no effective post-exposure
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Abrin toxin is a type 2 ribosome inactivating glycoprotein isolated from the seeds of Abrus precatorius (jequirity pea). Owing to its high toxicity, relative ease of purification and accessibility, it is considered a biological threat agent. To date, there is no effective post-exposure treatment for abrin poisoning and passive immunization remains the most effective therapy. However, the effectiveness of anti-abrin monoclonal antibodies for post-exposure therapy following abrin intoxication has not been demonstrated. The aim of this study was to isolate high affinity anti-abrin antibodies that possess potent toxin-neutralization capabilities. An immune scFv phage-display library was constructed from an abrin-immunized rabbit and a panel of antibodies (six directed against the A subunit of abrin and four against the B subunit) was isolated and expressed as scFv-Fc antibodies. By pair-wise analysis, we found that these antibodies target five distinct epitopes on the surface of abrin and that antibodies against all these sites can bind the toxin simultaneously. Several of these antibodies (namely, RB9, RB10, RB28 and RB30) conferred high protection against pulmonary intoxication of mice, when administered six hours post exposure to a lethal dose of abrin. The data presented in this study demonstrate for the first time the efficacy of monoclonal antibodies in treatment of mice after pulmonary intoxication with abrin and promote the use of these antibodies, one or several, for post-exposure treatment of abrin intoxication. Full article
(This article belongs to the Section Plant Toxins)
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Open AccessArticle Natural Occurrence of Nivalenol, Deoxynivalenol, and Deoxynivalenol-3-Glucoside in Polish Winter Wheat
Toxins 2018, 10(2), 81; doi:10.3390/toxins10020081
Received: 18 January 2018 / Revised: 9 February 2018 / Accepted: 10 February 2018 / Published: 13 February 2018
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Abstract
The presence of mycotoxins in cereal grain is a very important food safety factor. The occurrence of “masked” mycotoxins has been intensively investigated in recent years. In this study, the occurrence of nivalenol, deoxynivalenol-3-glucoside, and deoxynivalenol in 92 samples of winter wheat from
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The presence of mycotoxins in cereal grain is a very important food safety factor. The occurrence of “masked” mycotoxins has been intensively investigated in recent years. In this study, the occurrence of nivalenol, deoxynivalenol-3-glucoside, and deoxynivalenol in 92 samples of winter wheat from Polish cultivars was determined. The frequency of the occurrence of deoxynivalenol and nivalenol in the samples was 83% and 70%, respectively. The average content of the analytes was: for deoxynivalenol 140.2 µg/kg (10.5–1265.4 µg/kg), for nivalenol 35.0 µg/kg (5.1–372.5 µg/kg). Deoxynivalenol-3-glucoside, the formation of which is connected with the biotransformation pathway in plants, was present in 27% of tested wheat samples; its average content was 41.9 µg/kg (15.8–137.5 µg/kg). The relative content of deoxynivalenol-3-glucoside (DON-3G) compared to deoxynivalenol (DON) in positive samples was 4–37%. Despite the high frequency of occurrence of these mycotoxins, the quality of wheat from the 2016 season was good. The maximum content of DON, as defined in EU regulations (1250 µg/kg), was exceeded in only one sample. Nevertheless, the presence of a glycosidic derivative of deoxynivalenol can increase the risk to food safety, as it can be hydrolyzed by intestinal microflora. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessArticle A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A
Toxins 2018, 10(2), 84; doi:10.3390/toxins10020084 (registering DOI)
Received: 14 December 2017 / Revised: 5 February 2018 / Accepted: 13 February 2018 / Published: 15 February 2018
PDF Full-text (757 KB) | Supplementary Files
Abstract
The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody
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The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination. Full article
(This article belongs to the Special Issue Botulinum Neurotoxins Antibody and Vaccine)
Open AccessArticle Characterization of the Venom of C. d. cumanesis of Colombia: Proteomic Analysis and Antivenomic Study
Toxins 2018, 10(2), 85; doi:10.3390/toxins10020085 (registering DOI)
Received: 29 November 2017 / Revised: 6 February 2018 / Accepted: 13 February 2018 / Published: 17 February 2018
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Abstract
The Colombian rattlesnake Crotalus durissus cumanensis is distributed in three geographic zones of the country: the Atlantic Coast, the upper valley of the Magdalena River, and the eastern plains of the Colombian Orinoquía. Its venom induces neurological symptoms, such as eyelid ptosis, myasthenic
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The Colombian rattlesnake Crotalus durissus cumanensis is distributed in three geographic zones of the country: the Atlantic Coast, the upper valley of the Magdalena River, and the eastern plains of the Colombian Orinoquía. Its venom induces neurological symptoms, such as eyelid ptosis, myasthenic facies, and paralysis of the respiratory muscles, which can lead to death. Identification and analysis of C. d. cumanensis showed nine groups of proteins responsible for the neurotoxic effect, of which the crotoxin complex was the most abundant (64.71%). Immunorecognition tests of C. d. cumanensis showed that the use of a commercial antivenom manufactured in Mexico resulted in immunoreactivity. Full article
(This article belongs to the Section Animal Venoms)
Open AccessArticle Fusarium graminearum in Stored Wheat: Use of CO2 Production to Quantify Dry Matter Losses and Relate This to Relative Risks of Zearalenone Contamination under Interacting Environmental Conditions
Toxins 2018, 10(2), 86; doi:10.3390/toxins10020086 (registering DOI)
Received: 12 January 2018 / Revised: 8 February 2018 / Accepted: 14 February 2018 / Published: 17 February 2018
PDF Full-text (716 KB) | Supplementary Files
Abstract
Zearalenone (ZEN) contamination from Fusarium graminearum colonization is particularly important in food and feed wheat, especially during post-harvest storage with legislative limits for both food and feed grain. Indicators of the relative risk from exceeding these limits would be useful. We examined the
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Zearalenone (ZEN) contamination from Fusarium graminearum colonization is particularly important in food and feed wheat, especially during post-harvest storage with legislative limits for both food and feed grain. Indicators of the relative risk from exceeding these limits would be useful. We examined the effect of different water activities (aw; 0.95–0.90) and temperature (10–25 °C) in naturally contaminated and irradiated wheat grain, both inoculated with F. graminearum and stored for 15 days on (a) respiration rate; (b) dry matter losses (DML); (c) ZEN production and (d) relationship between DML and ZEN contamination relative to the EU legislative limits. Gas Chromatography was used to measure the temporal respiration rates and the total accumulated CO2 production. There was an increase in temporal CO2 production rates in wetter and warmer conditions in all treatments, with the highest respiration in the 25 °C × 0.95 aw treatments + F. graminearum inoculation. This was reflected in the total accumulated CO2 in the treatments. The maximum DMLs were in the 0.95 aw/20–25 °C treatments and at 10 °C/0.95 aw. The DMLs were modelled to produce contour maps of the environmental conditions resulting in maximum/minimum losses. Contamination with ZEN/ZEN-related compounds were quantified. Maximum production was at 25 °C/0.95–0.93 aw and 20 °C/0.95 aw. ZEN contamination levels plotted against DMLs for all the treatments showed that at ca <1.0% DML, there was a low risk of ZEN contamination exceeding EU legislative limits, while at >1.0% DML, the risk was high. This type of data is important in building a database for the development of a post-harvest decision support system for relative risks of different mycotoxins. Full article
Open AccessArticle An On-Site Simultaneous Semi-quantification of Aflatoxin B1, Zearalenone, and T-2 Toxin in Maize- and Cereal-based Feed via Multicolor Immunochromatographic Assay
Toxins 2018, 10(2), 87; doi:10.3390/toxins10020087 (registering DOI)
Received: 9 January 2018 / Revised: 8 February 2018 / Accepted: 15 February 2018 / Published: 17 February 2018
PDF Full-text (606 KB) | Supplementary Files
Abstract
Multiple-mycotoxin contamination has been frequently found in the agro-food monitoring due to the coexistence of fungi. However, many determination methods focused on a single mycotoxin, highlighting the demand for on-site determination of multiple mycotoxins in a single run. We develop a multicolor-based immunochromatographic
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Multiple-mycotoxin contamination has been frequently found in the agro-food monitoring due to the coexistence of fungi. However, many determination methods focused on a single mycotoxin, highlighting the demand for on-site determination of multiple mycotoxins in a single run. We develop a multicolor-based immunochromatographic strip (ICS) for simultaneous determination of aflatoxin B1 (AFB1), zearalenone (ZEN) and T-2 toxin in maize- and cereal-based animal feeds. The nanoparticles with different colors are conjugated with three monoclonal antibodies, which serve as the immunoassay probes. The decrease in color intensity is observed by the naked eyes, providing simultaneous quantification of three mycotoxins. The visible limits of detection for AFB1, ZEN and T-2 are estimated to be 0.5, 2, and 30 ng/mL, respectively. The cut-off values are 1, 10, and 50 ng/mL, respectively. Considerable specificity and stability are found using real samples. The results are in excellent agreement with those from high-performance liquid chromatography/tandem mass spectrometry. The multi-color ICS boasts sensitive and rapid visual differentiation and simultaneous semi-quantification of aflatoxin B1, zearalenone and T-2 toxin in maize- and cereal-based feed samples within 20 min. Full article
(This article belongs to the Special Issue Advanced Sensors for Toxins)

Review

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Open AccessFeature PaperReview Toxicodynamics of Mycotoxins in the Framework of Food Risk Assessment—An In Silico Perspective
Toxins 2018, 10(2), 52; doi:10.3390/toxins10020052
Received: 26 November 2017 / Revised: 16 January 2018 / Accepted: 20 January 2018 / Published: 23 January 2018
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Abstract
Mycotoxins severely threaten the health of humans and animals. For this reason, many countries have enforced regulations and recommendations to reduce the dietary exposure. However, even though regulatory actions must be based on solid scientific knowledge, many aspects of their toxicological activity are
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Mycotoxins severely threaten the health of humans and animals. For this reason, many countries have enforced regulations and recommendations to reduce the dietary exposure. However, even though regulatory actions must be based on solid scientific knowledge, many aspects of their toxicological activity are still poorly understood. In particular, deepening knowledge on the primal molecular events triggering the toxic stimulus may be relevant to better understand the mechanisms of action of mycotoxins. The present work presents the use of in silico approaches in studying the mycotoxins toxicodynamics, and discusses how they may contribute in widening the background of knowledge. A particular emphasis has been posed on the methods accounting the molecular initiating events of toxic action. In more details, the key concepts and challenges of mycotoxins toxicology have been introduced. Then, topical case studies have been presented and some possible practical implementations of studying mycotoxins toxicodynamics have been discussed. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessReview A Review of Current Methods for Analysis of Mycotoxins in Herbal Medicines
Toxins 2018, 10(2), 65; doi:10.3390/toxins10020065
Received: 13 December 2017 / Revised: 30 January 2018 / Accepted: 30 January 2018 / Published: 2 February 2018
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Abstract
The presence of mycotoxins in herbal medicines is an established problem throughout the entire world. The sensitive and accurate analysis of mycotoxin in complicated matrices (e.g., herbs) typically involves challenging sample pretreatment procedures and an efficient detection instrument. However, although numerous reviews have
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The presence of mycotoxins in herbal medicines is an established problem throughout the entire world. The sensitive and accurate analysis of mycotoxin in complicated matrices (e.g., herbs) typically involves challenging sample pretreatment procedures and an efficient detection instrument. However, although numerous reviews have been published regarding the occurrence of mycotoxins in herbal medicines, few of them provided a detailed summary of related analytical methods for mycotoxin determination. This review focuses on analytical techniques including sampling, extraction, cleanup, and detection for mycotoxin determination in herbal medicines established within the past ten years. Dedicated sections of this article address the significant developments in sample preparation, and highlight the importance of this procedure in the analytical technology. This review also summarizes conventional chromatographic techniques for mycotoxin qualification or quantitation, as well as recent studies regarding the development and application of screening assays such as enzyme-linked immunosorbent assays, lateral flow immunoassays, aptamer-based lateral flow assays, and cytometric bead arrays. The present work provides a good insight regarding the advanced research that has been done and closes with an indication of future demand for the emerging technologies. Full article
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Open AccessFeature PaperReview Pharmacokinetics of Snake Venom
Toxins 2018, 10(2), 73; doi:10.3390/toxins10020073
Received: 9 December 2017 / Revised: 31 January 2018 / Accepted: 3 February 2018 / Published: 7 February 2018
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Abstract
Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and
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Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present) and Medline (1946–present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessFeature PaperReview Mitigating Toxic Planktonic Cyanobacterial Blooms in Aquatic Ecosystems Facing Increasing Anthropogenic and Climatic Pressures
Toxins 2018, 10(2), 76; doi:10.3390/toxins10020076
Received: 20 December 2017 / Revised: 2 February 2018 / Accepted: 5 February 2018 / Published: 8 February 2018
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Abstract
Toxic planktonic cyanobacterial blooms are a pressing environmental and human health problem. Blooms are expanding globally and threatening sustainability of our aquatic resources. Anthropogenic nutrient enrichment and hydrological modifications, including water diversions and reservoir construction, are major drivers of bloom expansion. Climatic change,
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Toxic planktonic cyanobacterial blooms are a pressing environmental and human health problem. Blooms are expanding globally and threatening sustainability of our aquatic resources. Anthropogenic nutrient enrichment and hydrological modifications, including water diversions and reservoir construction, are major drivers of bloom expansion. Climatic change, i.e., warming, more extreme rainfall events, and droughts, act synergistically with human drivers to exacerbate the problem. Bloom mitigation steps, which are the focus of this review, must consider these dynamic interactive factors in order to be successful in the short- and long-term. Furthermore, these steps must be applicable along the freshwater to marine continuum connecting streams, lakes, rivers, estuarine, and coastal waters. There is an array of physical, chemical, and biological approaches, including flushing, mixing, dredging, application of algaecides, precipitating phosphorus, and selective grazing, that may arrest and reduce bloom intensities in the short-term. However, to ensure long term, sustainable success, targeting reductions of both nitrogen and phosphorus inputs should accompany these approaches along the continuum. Lastly, these strategies should accommodate climatic variability and change, which will likely modulate and alter nutrient-bloom thresholds. Full article
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Open AccessReview Strategies to Improve the Clinical Utility of Saporin-Based Targeted Toxins
Toxins 2018, 10(2), 82; doi:10.3390/toxins10020082
Received: 16 December 2017 / Revised: 29 January 2018 / Accepted: 11 February 2018 / Published: 13 February 2018
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Abstract
Plant Ribosome-inactivating proteins (RIPs) including the type I RIP Saporin have been used for the construction of Immunotoxins (ITxs) obtained via chemical conjugation of the toxic domain to whole antibodies or by generating genetic fusions to antibody fragments/targeting domains able to direct the
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Plant Ribosome-inactivating proteins (RIPs) including the type I RIP Saporin have been used for the construction of Immunotoxins (ITxs) obtained via chemical conjugation of the toxic domain to whole antibodies or by generating genetic fusions to antibody fragments/targeting domains able to direct the chimeric toxin against a desired sub-population of cancer cells. The high enzymatic activity, stability and resistance to conjugation procedures and especially the possibility to express recombinant fusions in yeast, make Saporin a well-suited tool for anti-cancer therapy approaches. Previous clinical work on RIPs-based Immunotoxins (including Saporin) has shown that several critical issues must be taken into deeper consideration to fully exploit their therapeutic potential. This review focuses on possible combinatorial strategies (chemical and genetic) to augment Saporin-targeted toxin efficacy. Combinatorial approaches may facilitate RIP escape into the cytosolic compartment (where target ribosomes are), while genetic manipulations may minimize potential adverse effects such as vascular-leak syndrome or may identify T/B cell epitopes in order to decrease the immunogenicity following similar strategies as those used in the case of bacterial toxins such as Pseudomonas Exotoxin A or as for Type I RIP Bouganin. This review will further focus on strategies to improve recombinant production of Saporin-based chimeric toxins. Full article
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Open AccessReview Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans
Toxins 2018, 10(2), 83; doi:10.3390/toxins10020083 (registering DOI)
Received: 22 December 2017 / Revised: 6 February 2018 / Accepted: 8 February 2018 / Published: 14 February 2018
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Abstract
The neurotoxin β-N-methylamino-l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC). The ubiquitous
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The neurotoxin β-N-methylamino-l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC). The ubiquitous presence of BMAA in aquatic environments and organisms along the food chain potentially makes it public health concerns. However, the BMAA-associated human health risk remains difficult to rigorously assess due to analytical challenges associated with the detection and quantification of BMAA and its natural isomers, 2,4-diamino butyric acid (DAB), β-amino-N-methyl-alanine (BAMA) and N-(2-aminoethyl) glycine (AEG). This systematic review, reporting the current knowledge on the presence of BMAA and isomers in aquatic environments and human food sources, was based on a selection and a score numbering of the scientific literature according to various qualitative and quantitative criteria concerning the chemical analytical methods used. Results from the best-graded studies show that marine bivalves are to date the matrix containing the higher amount of BMAA, far more than most fish muscles, but with an exception for shark cartilage. This review discusses the available data in terms of their use for human health risk assessment and identifies knowledge gaps requiring further investigations. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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