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Toxins
Volume 9
Issue 4
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Toxins, Volume 9, Issue 4 (April 2017) – 38 articles

Cover Story (view full-size image): TEM image of Helicobacter pylori attaching to the gastric epithelial cell line AGS. H. pylori is a class-I carcinogen which can lead to chronic inflammation, ulceration, MALT lymphoma and gastric cancer. In this special issue, different complex pathogen-host interactions were summarized shedding light on different H. pylori virulence factors that interfere with epithelial cells and cells from the immune system. View this paper
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762 KiB  
Review
Treatments for Latrodectism—A Systematic Review on Their Clinical Effectiveness
by Nicole M. Ryan, Nicholas A. Buckley and Andis Graudins
Toxins 2017, 9(4), 148; https://doi.org/10.3390/toxins9040148 - 21 Apr 2017
Cited by 21 | Viewed by 8463
Abstract
Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of [...] Read more.
Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of mild to moderate latrodectism is primarily supportive while severe cases have variously been treated with intravenous calcium, muscle relaxants, widow-spider antivenom and analgesic opioids. The object of this systematic review is to examine the literature on the clinical effectiveness of past and current treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched from 1946 to December 2016 to identify clinical studies on the treatment of latrodectism. Studies older than 40 years and not in English were not reviewed. There were only two full-publications and one abstract of placebo-controlled randomised trials on antivenom use for latrodectism. Another two randomised comparative trials compared the route of administration of antivenom for latrodectism. There were fourteen case series (including two abstracts), fourteen case reports and one letter investigating drug treatments for latrodectism with the majority of these also including antivenom for severe latrodectism. Antivenom with opioid analgesia is often the major treatment reported for latrodectism however; recent high quality evidence has cast doubt on the clinical effectiveness of this combination and suggests that other treatments need to be investigated. Full article
(This article belongs to the Special Issue Use of Antibodies/Antivenom Against Envenoming)
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Article
A Rapid Magnetic Solid Phase Extraction Method Followed by Liquid Chromatography-Tandem Mass Spectrometry Analysis for the Determination of Mycotoxins in Cereals
by Giorgia La Barbera, Anna Laura Capriotti, Chiara Cavaliere, Patrizia Foglia, Carmela Maria Montone, Riccardo Zenezini Chiozzi and Aldo Laganà
Toxins 2017, 9(4), 147; https://doi.org/10.3390/toxins9040147 - 21 Apr 2017
Cited by 32 | Viewed by 5456
Abstract
Mycotoxins can contaminate various food commodities, including cereals. Moreover, mycotoxins of different classes can co-contaminate food, increasing human health risk. Several analytical methods have been published in the literature dealing with mycotoxins determination in cereals. Nevertheless, in the present work, the aim was [...] Read more.
Mycotoxins can contaminate various food commodities, including cereals. Moreover, mycotoxins of different classes can co-contaminate food, increasing human health risk. Several analytical methods have been published in the literature dealing with mycotoxins determination in cereals. Nevertheless, in the present work, the aim was to propose an easy and effective system for the extraction of six of the main mycotoxins from corn meal and durum wheat flour, i.e., the main four aflatoxins, ochratoxin A, and the mycoestrogen zearalenone. The developed method exploited magnetic solid phase extraction (SPE), a technique that is attracting an increasing interest as an alternative to classical SPE. Therefore, the use of magnetic graphitized carbon black as a suitable extracting material was tested. The same magnetic material proved to be effective in the extraction of mycoestrogens from milk, but has never been applied to complex matrices as cereals. Ultra high–performance liquid chromatography tandem mass spectrometry was used for detection. Recoveries were >60% in both cereals, even if the matrix effects were not negligible. The limits of quantification of the method results were comparable to those obtained by other two magnetic SPE-based methods applied to cereals, which were limited to one or two mycotoxins, whereas in this work the investigated mycotoxins belonged to three different chemical classes. Full article
(This article belongs to the Section Mycotoxins)
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Article
Initial Spore Density Has an Influence on Ochratoxin A Content in Aspergillus ochraceus CGMCC 3.4412 in PDB and Its Interaction with Seeds
by Caiyan Li, Yanmin Song, Lu Xiong, Kunlun Huang and Zhihong Liang
Toxins 2017, 9(4), 146; https://doi.org/10.3390/toxins9040146 - 21 Apr 2017
Cited by 8 | Viewed by 5057
Abstract
The morphology and secondary metabolism of Aspergillus spp. are associated with initial spore density (ISD). Fatty acids (FA) are involved in the biosynthesis of aflatoxins (AF) through Aspergillus quorum sensing (QS). Here, we studied how ochratoxin A (OTA) was regulated by spore density [...] Read more.
The morphology and secondary metabolism of Aspergillus spp. are associated with initial spore density (ISD). Fatty acids (FA) are involved in the biosynthesis of aflatoxins (AF) through Aspergillus quorum sensing (QS). Here, we studied how ochratoxin A (OTA) was regulated by spore density in Aspergillus ochraceus CGMCC 3.4412. The results contribute to understanding the role of spore density in morphogenesis, OTA biosynthesis, and host–pathogen interactions. When A. ochraceus was grown in Potato Dextrose Broth (PDB) media at different spore densities (from 101 to 106 spores/mL), more OTA was produced when ISD were increased, but a higher level of ISD inhibited OTA biosynthesis. Seed infection studies showed that peanuts (Arachis hypogaea) and soybeans (Glycine max) with high FA content were more susceptible to OTA production when infected by A. ochraceus and reactive oxygen species (ROS)-induced OTA biosynthesis. These results suggested that FA was vital for OTA biosynthesis, and that oxidative stress was closely related to OTA biosynthesis in A. ochraceus. Full article
(This article belongs to the Collection Ochratoxins-Collection)
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Article
A Simple and Specific Noncompetitive ELISA Method for HT-2 Toxin Detection
by Henri O. Arola, Antti Tullila, Alexis V. Nathanail and Tarja K. Nevanen
Toxins 2017, 9(4), 145; https://doi.org/10.3390/toxins9040145 - 20 Apr 2017
Cited by 34 | Viewed by 8009
Abstract
We developed an HT-2 toxin-specific simple ELISA format with a positive read-out. The assay is based on an anti-immune complex (IC) scFv antibody fragment, which is genetically fused with alkaline phosphatase (AP). The anti-IC antibody specifically recognizes the IC between a primary anti-HT-2 [...] Read more.
We developed an HT-2 toxin-specific simple ELISA format with a positive read-out. The assay is based on an anti-immune complex (IC) scFv antibody fragment, which is genetically fused with alkaline phosphatase (AP). The anti-IC antibody specifically recognizes the IC between a primary anti-HT-2 toxin Fab fragment and an HT-2 toxin molecule. In the IC ELISA format, the sample is added together with the scFv-AP antibody to the ELISA plate coated with the primary antibody. After 15 min of incubation and a washing step, the ELISA response is read. A competitive ELISA including only the primary antibody recognizes both HT-2 and T-2 toxins. The anti-IC antibody makes the assay specific for HT-2 toxin, and the IC ELISA is over 10 times more sensitive compared to the competitive assay. Three different naturally contaminated matrices: wheat, barley and oats, were used to evaluate the assay performance with real samples. The corresponding limits of detection were 0.3 ng/mL (13 µg/kg), 0.1 ng/mL (4 µg/kg) and 0.3 ng/mL (16 µg/kg), respectively. The IC ELISA can be used for screening HT-2 toxin specifically and in relevant concentration ranges from all three tested grain matrices. Full article
(This article belongs to the Collection Biorecognition Assays for Mycotoxins)
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Article
Diabetogenic Effects of Ochratoxin A in Female Rats
by Firdevs Mor, Omur Sengul, Senay Topsakal, Mehmet Akif Kilic and Ozlem Ozmen
Toxins 2017, 9(4), 144; https://doi.org/10.3390/toxins9040144 - 19 Apr 2017
Cited by 11 | Viewed by 4741
Abstract
In this study, the diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated, and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into three [...] Read more.
In this study, the diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated, and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into three different study and control groups according to the duration of the OTA administration. The rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups were also used for the same time periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of the 6, 9 and 24 weeks. The plasma values of insulin, glucagon and glucose were determined for the study and control groups. Pancreatic lesions were evaluated via histopathological examination and insulin and glucagon expression in these lesions was subsequently determined using immunohistochemical methods. Statistically significant decreases in insulin levels were observed, in contrast to increases in blood glucagon and glucose levels. Histopathological examinations revealed slight to moderate degeneration in Langerhans islet cells in all OTA-treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in the Langerhans islet and predispose rats to DM. Full article
(This article belongs to the Special Issue Impact of Human Metabolism on the Toxicological Effects of Mycotoxins)
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Review
Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming
by Anjana Silva, Wayne C. Hodgson and Geoffrey K. Isbister
Toxins 2017, 9(4), 143; https://doi.org/10.3390/toxins9040143 - 19 Apr 2017
Cited by 45 | Viewed by 11675
Abstract
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the [...] Read more.
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this. Full article
(This article belongs to the Special Issue Use of Antibodies/Antivenom Against Envenoming)
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Comment
Comment on Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies. Toxins 2016, 8, 358
by Fellype C. Barreto, Daniela V. Barreto, Andrea E. M. Stinghen and Ziad A. Massy
Toxins 2017, 9(4), 142; https://doi.org/10.3390/toxins9040142 - 17 Apr 2017
Cited by 6 | Viewed by 3680
Abstract
Recently, the clinical and experimental evidences that support the toxic effects of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD) patients, has been discussed. In this panorama, the authors described several in vitro and in vivo studies, suggesting that indoxyl [...] Read more.
Recently, the clinical and experimental evidences that support the toxic effects of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD) patients, has been discussed. In this panorama, the authors described several in vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease. However, the discussion claims the need for relevant clinical studies in CKD patients whose bone turnover biomarkers and bone histomorphometry were assessed in order to demonstrate the association between serum levels of indoxyl sulfate and bone turnover. We would like to underline the availability of this clinical data to support the concept that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease in CKD patients. Full article
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
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Article
Modification of the Mycotoxin Deoxynivalenol Using Microorganisms Isolated from Environmental Samples
by Nina M. Wilson, Nicole McMaster, Dash Gantulga, Cara Soyars, Susan P. McCormick, Ken Knott, Ryan S. Senger and David G. Schmale
Toxins 2017, 9(4), 141; https://doi.org/10.3390/toxins9040141 - 15 Apr 2017
Cited by 18 | Viewed by 6061
Abstract
The trichothecene mycotoxin deoxynivalenol (DON) is a common contaminant of wheat, barley, and maize. New strategies are needed to reduce or eliminate DON in feed and food products. Microorganisms from plant and soil samples collected in Blacksburg, VA, USA, were screened by incubation [...] Read more.
The trichothecene mycotoxin deoxynivalenol (DON) is a common contaminant of wheat, barley, and maize. New strategies are needed to reduce or eliminate DON in feed and food products. Microorganisms from plant and soil samples collected in Blacksburg, VA, USA, were screened by incubation in a mineral salt media containing 100 μg/mL DON and analysis by gas chromatography mass spectrometry (GC/MS). Two mixed cultures derived from soil samples consistently decreased DON levels in assays using DON as the sole carbon source. Nuclear magnetic resonance (NMR) analysis indicated that 3-keto-4-deoxynivalenol was the major by-product of DON. Via 16S rRNA sequencing, these mixed cultures, including mostly members of the genera Acinetobacter, Leadbetterella, and Gemmata, were revealed. Incubation of one of these mixed cultures with wheat samples naturally contaminated with 7.1 μg/mL DON indicated nearly complete conversion of DON to the less toxic 3-epimer-DON (3-epi-DON). Our work extends previous studies that have demonstrated the potential for bioprospecting for microorganisms from the environment to remediate or modify mycotoxins for commercial applications, such as the reduction of mycotoxins in fuel ethanol co-products. Full article
(This article belongs to the Special Issue Promising Detoxification Strategies to Mitigate Mycotoxins in Food and Feed)
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Review
Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific Endoribonuclease Activity
by Hisako Masuda and Masayori Inouye
Toxins 2017, 9(4), 140; https://doi.org/10.3390/toxins9040140 - 14 Apr 2017
Cited by 52 | Viewed by 11672
Abstract
Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA [...] Read more.
Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA containing recognition sequences in the absence of ribosome in vitro. However, increasing evidence suggests that in vivo digestion may occur in association with ribosomes. Despite the prevalence of recognition sequences in many mRNA, preferential digestion seems to occur at specific positions within mRNA and also in certain reading frames. In this review, a variety of tools utilized to study the nuclease activities of toxins over the past 15 years will be reviewed. A recent adaptation of an RNA-seq-based technique to analyze entire sets of cellular RNA will be introduced with an emphasis on its strength in identifying novel targets and redefining recognition sequences. The differences in biochemical properties and postulated physiological roles will also be discussed. Full article
(This article belongs to the Section Bacterial Toxins)
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Article
Assessment of the Antimicrobial Activity and the Entomocidal Potential of Bacillus thuringiensis Isolates from Algeria
by Zahia Djenane, Farida Nateche, Meriam Amziane, Joaquín Gomis-Cebolla, Fairouz El-Aichar, Hassiba Khorf and Juan Ferré
Toxins 2017, 9(4), 139; https://doi.org/10.3390/toxins9040139 - 13 Apr 2017
Cited by 35 | Viewed by 9448
Abstract
This work represents the first initiative to analyze the distribution of B. thuringiensis in Algeria and to evaluate the biological potential of the isolates. A total of 157 isolates were recovered, with at least one isolate in 94.4% of the samples. The highest [...] Read more.
This work represents the first initiative to analyze the distribution of B. thuringiensis in Algeria and to evaluate the biological potential of the isolates. A total of 157 isolates were recovered, with at least one isolate in 94.4% of the samples. The highest Bt index was found in samples from rhizospheric soil (0.48) and from the Mediterranean area (0.44). Most isolates showed antifungal activity (98.5%), in contrast to the few that had antibacterial activity (29.9%). A high genetic diversity was made evident by the finding of many different crystal shapes and various combinations of shapes within a single isolate (in 58.4% of the isolates). Also, over 50% of the isolates harbored cry1, cry2, or cry9 genes, and 69.3% contained a vip3 gene. A good correlation between the presence of chitinase genes and antifungal activity was observed. More than half of the isolates with a broad spectrum of antifungal activity harbored both endochitinase and exochitinase genes. Interestingly, 15 isolates contained the two chitinase genes and all of the above cry family genes, with some of them harboring a vip3 gene as well. The combination of this large number of genes coding for entomopathogenic proteins suggests a putative wide range of entomotoxic activity. Full article
(This article belongs to the Special Issue The Insecticidal Bacterial Toxins in Modern Agriculture)
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Article
Suppression of Hepatic Epithelial-to-Mesenchymal Transition by Melittin via Blocking of TGFβ/Smad and MAPK-JNK Signaling Pathways
by Ji-Hyun Park, Byoungduck Park and Kwan-Kyu Park
Toxins 2017, 9(4), 138; https://doi.org/10.3390/toxins9040138 - 13 Apr 2017
Cited by 31 | Viewed by 5034
Abstract
Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, [...] Read more.
Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGFβ/Smad and TGFβ/nonSmad signaling pathways. MEL significantly inhibited TGF-β1-induced expression of EMT markers (E-cadherin reduction and vimentin induction) in vitro. These results were confirmed in CCl4-induced liver in vivo. Treatment with MEL almost completely blocked the phosphorylation of Smad2/3, translocation of Smad4 and phosphorylation of JNK in vitro and in vivo. Taken together, these results suggest that MEL suppresses EMT by inhibiting the TGFβ/Smad and TGFβ/nonSmad-c-Jun N-terminal kinase (JNK)/Mitogen-activated protein kinase (MAPK) signaling pathways. These results indicated that MEL possesses potent anti-fibrotic and anti-EMT properties, which may be responsible for its effects on liver diseases. Full article
(This article belongs to the Section Animal Venoms)
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Article
An On-Site, Ultra-Sensitive, Quantitative Sensing Method for the Determination of Total Aflatoxin in Peanut and Rice Based on Quantum Dot Nanobeads Strip
by Suiyan Ouyang, Zhaowei Zhang, Ting He, Peiwu Li, Qi Zhang, Xiaomei Chen, Du Wang, Hui Li, Xiaoqian Tang and Wen Zhang
Toxins 2017, 9(4), 137; https://doi.org/10.3390/toxins9040137 - 13 Apr 2017
Cited by 15 | Viewed by 5355
Abstract
An on-site, ultra-sensitive, and quantitative sensing method was developed based on quantum dot nanobeads (QDNBs) and a test strip for the determination of total aflatoxins (AFTs) in rice and peanuts. The monoclonal antibody against AFT (mAbAFT) was homemade and labeled with [...] Read more.
An on-site, ultra-sensitive, and quantitative sensing method was developed based on quantum dot nanobeads (QDNBs) and a test strip for the determination of total aflatoxins (AFTs) in rice and peanuts. The monoclonal antibody against AFT (mAbAFT) was homemade and labeled with QDNB. After the pre-coating of the AFT antigen on the test line (T line), the competitive immunoreactions were conducted between AFT and AFT antigen on the T line with QDNBs-mAbAFT. Under optimal conditions, this approach allowed a rapid response towards AFT with a considerable sensitivity of 1.4 pg/mL and 2.9 pg/mL in rice and peanut matrices, respectively. The put-in and put-out durations were within 10 min. The recoveries for AFT in rice and peanut sample matrices were recorded from 86.25% to 118.0%, with relative deviations (RSD) below 12%. The assay was further validated via the comparison between this QDNB strip and the conventional HPLC method using spiked samples. Thus, the design provided a potential alternative for on-site, ultra-sensitive, and quantitative sensing of AFT that could also be expanded to other chemical contaminants for food safety. Full article
(This article belongs to the Special Issue Selected papers from 1st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)
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Review
Sequence Polymorphism and Intrinsic Structural Disorder as Related to Pathobiological Performance of the Helicobacter pylori CagA Oncoprotein
by Hiroko Nishikawa and Masanori Hatakeyama
Toxins 2017, 9(4), 136; https://doi.org/10.3390/toxins9040136 - 13 Apr 2017
Cited by 21 | Viewed by 7127
Abstract
CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally associated with the development of gastrointestinal diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric epithelial cells via bacterial type IV secretion, CagA interacts with a [...] Read more.
CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally associated with the development of gastrointestinal diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric epithelial cells via bacterial type IV secretion, CagA interacts with a number of host proteins through the intrinsically disordered C-terminal tail, which contains two repeatable protein-binding motifs, the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif and the CagA multimerization (CM) motif. The EPIYA motif, upon phosphorylation by host kinases, binds and deregulates Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2), a bona fide oncoprotein, inducing pro-oncogenic mitogenic signaling and abnormal cell morphology. Through the CM motif, CagA inhibits the kinase activity of polarity regulator partitioning-defective 1b (PAR1b), causing junctional and polarity defects while inducing actin cytoskeletal rearrangements. The magnitude of the pathobiological action of individual CagA has been linked to the tandem repeat polymorphisms of these two binding motifs, yet the molecular mechanisms by which they affect disease outcome remain unclear. Recent studies using quantitative techniques have provided new insights into how the sequence polymorphisms in the structurally disordered C-terminal region determine the degree of pro-oncogenic action of CagA in the gastric epithelium. Full article
(This article belongs to the Special Issue H. pylori Virulence Factors in the Induction of Gastric Cancer)
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Article
Protein Discovery: Combined Transcriptomic and Proteomic Analyses of Venom from the Endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae)
by Zi-Wen Teng, Shi-Jiao Xiong, Gang Xu, Shi-Yu Gan, Xuan Chen, David Stanley, Zhi-Chao Yan, Gong-Yin Ye and Qi Fang
Toxins 2017, 9(4), 135; https://doi.org/10.3390/toxins9040135 - 12 Apr 2017
Cited by 39 | Viewed by 6671
Abstract
Many species of endoparasitoid wasps provide biological control services in agroecosystems. Although there is a great deal of information on the ecology and physiology of host/parasitoid interactions, relatively little is known about the protein composition of venom and how specific venom proteins influence [...] Read more.
Many species of endoparasitoid wasps provide biological control services in agroecosystems. Although there is a great deal of information on the ecology and physiology of host/parasitoid interactions, relatively little is known about the protein composition of venom and how specific venom proteins influence physiological systems within host insects. This is a crucial gap in our knowledge because venom proteins act in modulating host physiology in ways that favor parasitoid development. Here, we identified 37 possible venom proteins from the polydnavirus-carrying endoparasitoid Cotesia chilonis by combining transcriptomic and proteomic analyses. The most abundant proteins were hydrolases, such as proteases, peptidases, esterases, glycosyl hydrolase, and endonucleases. Some components are classical parasitoid venom proteins with known functions, including extracellular superoxide dismutase 3, serine protease inhibitor and calreticulin. The venom contains novel proteins, not recorded from any other parasitoid species, including tolloid-like proteins, chitooligosaccharidolytic β-N-acetylglucosaminidase, FK506-binding protein 14, corticotropin-releasing factor-binding protein and vascular endothelial growth factor receptor 2. These new data generate hypotheses and provide a platform for functional analysis of venom components. Full article
(This article belongs to the Section Animal Venoms)
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Review
Proteolysis in Helicobacter pylori-Induced Gastric Cancer
by Gernot Posselt, Jean E. Crabtree and Silja Wessler
Toxins 2017, 9(4), 134; https://doi.org/10.3390/toxins9040134 - 11 Apr 2017
Cited by 26 | Viewed by 9078
Abstract
Persistent infections with the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the [...] Read more.
Persistent infections with the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the epithelium is a hallmark of H. pylori-associated disorders and requires extensive modulation of epithelial cell surface structures. Hence, the complex network of controlled proteolysis which facilitates tissue homeostasis in healthy individuals is deregulated and crucially contributes to the induction and progression of gastric cancer through processing of extracellular matrix (ECM) proteins, cell surface receptors, membrane-bound cytokines, and lateral adhesion molecules. Here, we summarize the recent reports on mechanisms how H. pylori utilizes a variety of extracellular proteases, involving the proteases Hp0169 and high temperature requirement A (HtrA) of bacterial origin, and host matrix-metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and tissue inhibitors of metalloproteinases (TIMPs). H. pylori-regulated proteases represent predictive biomarkers and attractive targets for therapeutic interventions in gastric cancer. Full article
(This article belongs to the Special Issue H. pylori Virulence Factors in the Induction of Gastric Cancer)
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Article
Differences in Ribosome Binding and Sarcin/Ricin Loop Depurination by Shiga and Ricin Holotoxins
by Xiao-Ping Li and Nilgun E. Tumer
Toxins 2017, 9(4), 133; https://doi.org/10.3390/toxins9040133 - 11 Apr 2017
Cited by 20 | Viewed by 5243
Abstract
Both ricin and Shiga holotoxins display no ribosomal activity in their native forms and need to be activated to inhibit translation in a cell-free translation inhibition assay. This is because the ribosome binding site of the ricin A chain (RTA) is blocked by [...] Read more.
Both ricin and Shiga holotoxins display no ribosomal activity in their native forms and need to be activated to inhibit translation in a cell-free translation inhibition assay. This is because the ribosome binding site of the ricin A chain (RTA) is blocked by the B subunit in ricin holotoxin. However, it is not clear why Shiga toxin 1 (Stx1) or Shiga toxin 2 (Stx2) holotoxin is not active in a cell-free system. Here, we compare the ribosome binding and depurination activity of Stx1 and Stx2 holotoxins with the A1 subunits of Stx1 and Stx2 using either the ribosome or a 10-mer RNA mimic of the sarcin/ricin loop as substrates. Our results demonstrate that the active sites of Stx1 and Stx2 holotoxins are blocked by the A2 chain and the B subunit, while the ribosome binding sites are exposed to the solvent. Unlike ricin, which is enzymatically active, but cannot interact with the ribosome, Stx1 and Stx2 holotoxins are enzymatically inactive but can interact with the ribosome. Full article
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
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Review
Helicobacter pylori Strains and Gastric MALT Lymphoma
by Pauline Floch, Francis Mégraud and Philippe Lehours
Toxins 2017, 9(4), 132; https://doi.org/10.3390/toxins9040132 - 8 Apr 2017
Cited by 62 | Viewed by 6577
Abstract
This article summarizes the main findings concerning Helicobacter pylori associated with gastric MALT lymphoma (GML). Considered together, GML strains based on their virulence factor profile appear to be less virulent than those associated with peptic ulcers or gastric adenocarcinoma. A particular Lewis antigen [...] Read more.
This article summarizes the main findings concerning Helicobacter pylori associated with gastric MALT lymphoma (GML). Considered together, GML strains based on their virulence factor profile appear to be less virulent than those associated with peptic ulcers or gastric adenocarcinoma. A particular Lewis antigen profile has been identified in GML strains and could represent an alternative adaptive mechanism to escape the host immune response thereby allowing continuous antigenic stimulation of infiltrating lymphocytes. Full article
(This article belongs to the Special Issue H. pylori Virulence Factors in the Induction of Gastric Cancer)
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Article
Insights into the Structure of the Vip3Aa Insecticidal Protein by Protease Digestion Analysis
by Yolanda Bel, Núria Banyuls, Maissa Chakroun, Baltasar Escriche and Juan Ferré
Toxins 2017, 9(4), 131; https://doi.org/10.3390/toxins9040131 - 7 Apr 2017
Cited by 52 | Viewed by 7067
Abstract
Vip3 proteins are secretable proteins from Bacillus thuringiensis whose mode of action is still poorly understood. In this study, the activation process for Vip3 proteins was closely examined in order to better understand the Vip3Aa protein stability and to shed light on its [...] Read more.
Vip3 proteins are secretable proteins from Bacillus thuringiensis whose mode of action is still poorly understood. In this study, the activation process for Vip3 proteins was closely examined in order to better understand the Vip3Aa protein stability and to shed light on its structure. The Vip3Aa protoxin (of 89 kDa) was treated with trypsin at concentrations from 1:100 to 120:100 (trypsin:Vip3A, w:w). If the action of trypsin was not properly neutralized, the results of SDS-PAGE analysis (as well as those with Agrotis ipsilon midgut juice) equivocally indicated that the protoxin could be completely processed. However, when the proteolytic reaction was efficiently stopped, it was revealed that the protoxin was only cleaved at a primary cleavage site, regardless of the amount of trypsin used. The 66 kDa and the 19 kDa peptides generated by the proteases co-eluted after gel filtration chromatography, indicating that they remain together after cleavage. The 66 kDa fragment was found to be extremely resistant to proteases. The trypsin treatment of the protoxin in the presence of SDS revealed the presence of secondary cleavage sites at S-509, and presumably at T-466 and V-372, rendering C-terminal fragments of approximately 29, 32, and 42 kDa, respectively. The fact that the predicted secondary structure of the Vip3Aa protein shows a cluster of beta sheets in the C-terminal region of the protein might be the reason behind the higher stability to proteases compared to the rest of the protein, which is mainly composed of alpha helices. Full article
(This article belongs to the Special Issue The Insecticidal Bacterial Toxins in Modern Agriculture)
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611 KiB  
Review
Strategies and Methodologies for Developing Microbial Detoxification Systems to Mitigate Mycotoxins
by Yan Zhu, Yousef I. Hassan, Dion Lepp, Suqin Shao and Ting Zhou
Toxins 2017, 9(4), 130; https://doi.org/10.3390/toxins9040130 - 7 Apr 2017
Cited by 97 | Viewed by 9801
Abstract
Mycotoxins, the secondary metabolites of mycotoxigenic fungi, have been found in almost all agricultural commodities worldwide, causing enormous economic losses in livestock production and severe human health problems. Compared to traditional physical adsorption and chemical reactions, interest in biological detoxification methods that are [...] Read more.
Mycotoxins, the secondary metabolites of mycotoxigenic fungi, have been found in almost all agricultural commodities worldwide, causing enormous economic losses in livestock production and severe human health problems. Compared to traditional physical adsorption and chemical reactions, interest in biological detoxification methods that are environmentally sound, safe and highly efficient has seen a significant increase in recent years. However, researchers in this field have been facing tremendous unexpected challenges and are eager to find solutions. This review summarizes and assesses the research strategies and methodologies in each phase of the development of microbiological solutions for mycotoxin mitigation. These include screening of functional microbial consortia from natural samples, isolation and identification of single colonies with biotransformation activity, investigation of the physiological characteristics of isolated strains, identification and assessment of the toxicities of biotransformation products, purification of functional enzymes and the application of mycotoxin decontamination to feed/food production. A full understanding and appropriate application of this tool box should be helpful towards the development of novel microbiological solutions on mycotoxin detoxification. Full article
(This article belongs to the Special Issue Promising Detoxification Strategies to Mitigate Mycotoxins in Food and Feed)
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3879 KiB  
Article
Adsorption of Ten Microcystin Congeners to Common Laboratory-Ware Is Solvent and Surface Dependent
by Stefan Altaner, Jonathan Puddick, Susanna A. Wood and Daniel R. Dietrich
Toxins 2017, 9(4), 129; https://doi.org/10.3390/toxins9040129 - 6 Apr 2017
Cited by 26 | Viewed by 5106
Abstract
Cyanobacteria can produce heptapetides called microcystins (MC) which are harmful to humans due to their ability to inhibit cellular protein phosphatases. Quantitation of these toxins can be hampered by their adsorption to common laboratory-ware during sample processing and analysis. Because of their structural [...] Read more.
Cyanobacteria can produce heptapetides called microcystins (MC) which are harmful to humans due to their ability to inhibit cellular protein phosphatases. Quantitation of these toxins can be hampered by their adsorption to common laboratory-ware during sample processing and analysis. Because of their structural diversity (>100 congeners) and different physico-chemical properties, they vary in their adsorption to surfaces. In this study, the adsorption of ten different MC congeners (encompassing non-arginated to doubly-arginated congeners) to common laboratory-ware was assessed using different solvent combinations. Sample handling steps were mimicked with glass and polypropylene pipettes and vials with increasing methanol concentrations at two pH levels, before analysis by liquid chromatography-tandem mass spectrometry. We demonstrated that MC adsorb to polypropylene surfaces irrespective of pH. After eight successive pipet actions using polypropylene tips ca. 20% of the MC were lost to the surface material, which increased to 25%–40% when solutions were acidified. The observed loss was alleviated by changing the methanol (MeOH) concentration in the final solvent. The required MeOH concentration varied depending on which congener was present. Microcystins only adsorbed to glass pipettes (loss up to 30% after eight pipet actions) when in acidified aqueous solutions. The latter appeared largely dependent on the presence of ionizable groups, such as arginine residues. Full article
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Review
Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins
by Robert Frangež, Dušan Šuput, Jordi Molgó and Evelyne Benoit
Toxins 2017, 9(4), 128; https://doi.org/10.3390/toxins9040128 - 5 Apr 2017
Cited by 8 | Viewed by 4739
Abstract
Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar [...] Read more.
Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity. Full article
(This article belongs to the Section Bacterial Toxins)
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Article
Baseline Susceptibility of Field Populations of Helicoverpa armigera to Bacillus thuringiensis Vip3Aa Toxin and Lack of Cross-Resistance between Vip3Aa and Cry Toxins
by Yiyun Wei, Shuwen Wu, Yihua Yang and Yidong Wu
Toxins 2017, 9(4), 127; https://doi.org/10.3390/toxins9040127 - 5 Apr 2017
Cited by 27 | Viewed by 5092
Abstract
The cotton bollworm Helicoverpa armigera (Hübner) is one of the most damaging cotton pests worldwide. In China, control of this pest has been dependent on transgenic cotton producing a single Bacillus thuringiensis (Bt) protein Cry1Ac since 1997. A small, but significant, increase in [...] Read more.
The cotton bollworm Helicoverpa armigera (Hübner) is one of the most damaging cotton pests worldwide. In China, control of this pest has been dependent on transgenic cotton producing a single Bacillus thuringiensis (Bt) protein Cry1Ac since 1997. A small, but significant, increase in H. armigera resistance to Cry1Ac was detected in field populations from Northern China. Since Vip3Aa has a different structure and mode of action than Cry proteins, Bt cotton pyramids containing Vip3Aa are considered as ideal successors of Cry1Ac cotton in China. In this study, baseline susceptibility of H. armigera to Vip3Aa was evaluated in geographic field populations collected in 2014 from major cotton-producing areas of China. The LC50 values of 12 field populations ranged from 0.053 to 1.311 μg/cm2, representing a 25-fold range of natural variation among populations. It is also demonstrated that four laboratory strains of H. armigera with high levels of resistance to Cry1Ac or Cry2Ab have no cross-resistance to Vip3Aa protein. The baseline susceptibility data established here will serve as a comparative reference for detection of field-evolved resistance to Vip3Aa in H. armigera after future deployment of Bt cotton pyramids in China. Full article
(This article belongs to the Special Issue The Insecticidal Bacterial Toxins in Modern Agriculture)
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Article
Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi
by Slavica Janevska, Birgit Arndt, Leonie Baumann, Lisa Helene Apken, Lucas Maciel Mauriz Marques, Hans-Ulrich Humpf and Bettina Tudzynski
Toxins 2017, 9(4), 126; https://doi.org/10.3390/toxins9040126 - 5 Apr 2017
Cited by 35 | Viewed by 6546
Abstract
The PKS-NRPS-derived tetramic acid equisetin and its N-desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus. The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum, a species distantly [...] Read more.
The PKS-NRPS-derived tetramic acid equisetin and its N-desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus. The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum, a species distantly related to the notorious rice pathogen Fusarium fujikuroi. Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi. Bioinformatic analysis revealed that this cluster does not contain the equisetin N-methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi. Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22, led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23, encoding a second Zn(II)2Cys6 TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T. TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus. Full article
(This article belongs to the Collection Evolutionary/Phylogenetic Studies of Mycotoxin Biosynthetic Pathways)
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3034 KiB  
Article
Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration
by José M. Rojas, Tomás Arán-Sekul, Emmanuel Cortés, Romina Jaldín, Kely Ordenes, Patricio R. Orrego, Jorge González, Jorge E. Araya and Alejandro Catalán
Toxins 2017, 9(4), 125; https://doi.org/10.3390/toxins9040125 - 5 Apr 2017
Cited by 23 | Viewed by 5866
Abstract
Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration [...] Read more.
Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active) and rLlPLD2 (inactive) isoforms induce interleukin (IL)-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1) expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism. Full article
(This article belongs to the Section Animal Venoms)
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Article
Patterns of Gene Expression in Western Corn Rootworm (Diabrotica virgifera virgifera) Neonates, Challenged with Cry34Ab1, Cry35Ab1 and Cry34/35Ab1, Based on Next-Generation Sequencing
by Haichuan Wang, Seong-il Eyun, Kanika Arora, Sek Yee Tan, Premchand Gandra, Etsuko Moriyama, Chitvan Khajuria, Jessica Jurzenski, Huarong Li, Maia Donahue, Ken Narva and Blair Siegfried
Toxins 2017, 9(4), 124; https://doi.org/10.3390/toxins9040124 - 30 Mar 2017
Cited by 15 | Viewed by 5715
Abstract
With Next Generation Sequencing technologies, high-throughput RNA sequencing (RNAseq) was conducted to examine gene expression in neonates of Diabrotica virgifera virgifera (LeConte) (Western Corn Rootworm, WCR) challenged with individual proteins of the binary Bacillus thuringiensis insecticidal proteins, Cry34Ab1 and Cry35Ab1, and the combination [...] Read more.
With Next Generation Sequencing technologies, high-throughput RNA sequencing (RNAseq) was conducted to examine gene expression in neonates of Diabrotica virgifera virgifera (LeConte) (Western Corn Rootworm, WCR) challenged with individual proteins of the binary Bacillus thuringiensis insecticidal proteins, Cry34Ab1 and Cry35Ab1, and the combination of Cry34/Cry35Ab1, which together are active against rootworm larvae. Integrated results of three different statistical comparisons identified 114 and 1300 differentially expressed transcripts (DETs) in the Cry34Ab1 and Cry34/35Ab1 treatment, respectively, as compared to the control. No DETs were identified in the Cry35Ab1 treatment. Putative Bt binding receptors previously identified in other insect species were not identified in DETs in this study. The majority of DETs (75% with Cry34Ab1 and 68.3% with Cry34/35Ab1 treatments) had no significant hits in the NCBI nr database. In addition, 92 DETs were shared between Cry34Ab1 and Cry34/35Ab1 treatments. Further analysis revealed that the most abundant DETs in both Cry34Ab1 and Cry34/35Ab1 treatments were associated with binding and catalytic activity. Results from this study confirmed the nature of these binary toxins against WCR larvae and provide a fundamental profile of expression pattern of genes in response to challenge of the Cry34/35Ab1 toxin, which may provide insight into potential resistance mechanisms. Full article
(This article belongs to the Special Issue The Insecticidal Bacterial Toxins in Modern Agriculture)
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1845 KiB  
Review
Extensive Evolution of Cereal Ribosome-Inactivating Proteins Translates into Unique Structural Features, Activation Mechanisms, and Physiological Roles
by Jeroen De Zaeytijd and Els J. M. Van Damme
Toxins 2017, 9(4), 123; https://doi.org/10.3390/toxins9040123 - 29 Mar 2017
Cited by 20 | Viewed by 6457
Abstract
Ribosome-inactivating proteins (RIPs) are a class of cytotoxic enzymes that can depurinate rRNAs thereby inhibiting protein translation. Although these proteins have also been detected in bacteria, fungi, and even some insects, they are especially prevalent in the plant kingdom. This review focuses on [...] Read more.
Ribosome-inactivating proteins (RIPs) are a class of cytotoxic enzymes that can depurinate rRNAs thereby inhibiting protein translation. Although these proteins have also been detected in bacteria, fungi, and even some insects, they are especially prevalent in the plant kingdom. This review focuses on the RIPs from cereals. Studies on the taxonomical distribution and evolution of plant RIPs suggest that cereal RIPs have evolved at an enhanced rate giving rise to a large and heterogeneous RIP gene family. Furthermore, several cereal RIP genes are characterized by a unique domain architecture and the lack of a signal peptide. This advanced evolution of cereal RIPs translates into distinct structures, activation mechanisms, and physiological roles. Several cereal RIPs are characterized by activation mechanisms that include the proteolytic removal of internal peptides from the N-glycosidase domain, a feature not documented for non-cereal RIPs. Besides their role in defense against pathogenic fungi or herbivorous insects, cereal RIPs are also involved in endogenous functions such as adaptation to abiotic stress, storage, induction of senescence, and reprogramming of the translational machinery. The unique properties of cereal RIPs are discussed in this review paper. Full article
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
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2167 KiB  
Article
A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus) Venoms
by Janeyuth Chaisakul, Muhamad Rusdi Ahmad Rusmili, Wayne C. Hodgson, Panadda Hatthachote, Kijja Suwan, Anjaree Inchan, Lawan Chanhome, Iekhsan Othman and Krongkarn Chootip
Toxins 2017, 9(4), 122; https://doi.org/10.3390/toxins9040122 - 29 Mar 2017
Cited by 13 | Viewed by 4410
Abstract
Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this [...] Read more.
Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the in vivo and in vitro cardiovascular effects of B. candidus venoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. B. candidus venoms (50 µg/kg–100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg–100 µg/ml) induced concentration-dependent relaxation (EC50 = 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration–response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by B. candidus venoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors. Full article
(This article belongs to the Section Animal Venoms)
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1354 KiB  
Article
Use of Carabids for the Post-Market Environmental Monitoring of Genetically Modified Crops
by Oxana Skoková Habuštová, Zdeňka Svobodová, Ľudovít Cagáň and František Sehnal
Toxins 2017, 9(4), 121; https://doi.org/10.3390/toxins9040121 - 29 Mar 2017
Cited by 4 | Viewed by 5510
Abstract
Post-market environmental monitoring (PMEM) of genetically modified (GM) crops is required by EU legislation and has been a subject of debate for many years; however, no consensus on the methodology to be used has been reached. We explored the suitability of carabid beetles [...] Read more.
Post-market environmental monitoring (PMEM) of genetically modified (GM) crops is required by EU legislation and has been a subject of debate for many years; however, no consensus on the methodology to be used has been reached. We explored the suitability of carabid beetles as surrogates for the detection of unintended effects of GM crops in general PMEM surveillance. Our study combines data on carabid communities from five maize field trials in Central Europe. Altogether, 86 species and 58,304 individuals were collected. Modeling based on the gradual elimination of the least abundant species, or of the fewest categories of functional traits, showed that a trait-based analysis of the most common species may be suitable for PMEM. Species represented by fewer than 230 individuals (all localities combined) should be excluded and species with an abundance higher than 600 should be preserved for statistical analyses. Sixteen species, representing 15 categories of functional traits fulfill these criteria, are typical dominant inhabitants of agroecocoenoses in Central Europe, are easy to determine, and their functional classification is well known. The effect of sampling year is negligible when at least four samples are collected during maize development beginning from 1 April. The recommended methodology fulfills PMEM requirements, including applicability to large-scale use. However, suggested thresholds of carabid comparability should be verified before definitive conclusions are drawn. Full article
(This article belongs to the Special Issue The Insecticidal Bacterial Toxins in Modern Agriculture)
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1978 KiB  
Article
Changes in the Fusarium Head Blight Complex of Malting Barley in a Three-Year Field Experiment in Italy
by Giovanni Beccari, Antonio Prodi, Francesco Tini, Umberto Bonciarelli, Andrea Onofri, Souheib Oueslati, Marwa Limayma and Lorenzo Covarelli
Toxins 2017, 9(4), 120; https://doi.org/10.3390/toxins9040120 - 29 Mar 2017
Cited by 43 | Viewed by 6578
Abstract
In this study, conducted for three years on eleven malting barley varieties cultivated in central Italy, the incidence of different mycotoxigenic fungal genera, the identification of the Fusarium species associated with the Fusarium Head Blight (FHB) complex, and kernels contamination with deoxynivalenol (DON) [...] Read more.
In this study, conducted for three years on eleven malting barley varieties cultivated in central Italy, the incidence of different mycotoxigenic fungal genera, the identification of the Fusarium species associated with the Fusarium Head Blight (FHB) complex, and kernels contamination with deoxynivalenol (DON) and T-2 mycotoxins were determined. The influence of climatic conditions on Fusarium infections and FHB complex composition was also investigated. Fusarium species were always present in the three years and the high average and maximum temperatures during anthesis mainly favored their occurrence. The FHB complex was subject to changes during the three years and the main causal agents were F. poae, F. avenaceum, F. tricinctum and F. graminearum, which, even if constantly present, never represented the principal FHB agent. The relative incidence of Fusarium species changed because of climatic conditions occurring during the seasons. The FHB complex was composed of many different Fusarium species and some of them were associated with a specific variety and/or with specific weather parameters, indicating that the interaction between a certain plant genotype and climatic conditions may influence the presence of Fusarium spp. causing infections. With regard to mycotoxin contamination, T-2 toxin, in some cases, was found in kernels at levels that exceeded EU recommended values. Full article
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Review
NF‐κB Signaling in Gastric Cancer
by Olga Sokolova and Michael Naumann
Toxins 2017, 9(4), 119; https://doi.org/10.3390/toxins9040119 - 28 Mar 2017
Cited by 177 | Viewed by 9918
Abstract
Gastric cancer is a leading cause of cancer death worldwide. Diet, obesity, smoking and chronic infections, especially with Helicobacter pylori, contribute to stomach cancer development. H. pylori possesses a variety of virulence factors including encoded factors from the cytotoxin‐associated gene pathogenicity island (cagPAI) [...] Read more.
Gastric cancer is a leading cause of cancer death worldwide. Diet, obesity, smoking and chronic infections, especially with Helicobacter pylori, contribute to stomach cancer development. H. pylori possesses a variety of virulence factors including encoded factors from the cytotoxin‐associated gene pathogenicity island (cagPAI) or vacuolating cytotoxin A (VacA). Most of the cagPAI‐encoded products form a type 4 secretion system (T4SS), a pilus‐like macromolecular transporter, which translocates CagA into the cytoplasm of the host cell. Only H. pylori strains carrying the cagPAI induce the transcription factor NF‐κB, but CagA and VacA are dispensable for direct NF‐κB activation. NF‐κB‐driven gene products include cytokines/chemokines, growth factors, anti‐apoptotic factors, angiogenesis regulators and metalloproteinases. Many of the genes transcribed by NF‐κB promote gastric carcinogenesis. Since it has been shown that chemotherapy‐caused cellular stress could elicit activation of the survival factor NF‐κB, which leads to acquisition of chemoresistance, the NF‐κB system is recommended for therapeutic targeting. Research is motivated for further search of predisposing conditions, diagnostic markers and efficient drugs to improve significantly the overall survival of patients. In this review, we provide an overview about mechanisms and consequences of NF‐κB activation in gastric mucosa in order to understand the role of NF‐κB in gastric carcinogenesis. Full article
(This article belongs to the Special Issue H. pylori Virulence Factors in the Induction of Gastric Cancer)
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