Next Issue
Volume 9, February
Previous Issue
Volume 9, December

Table of Contents

Toxins, Volume 9, Issue 1 (January 2017)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Cover Story (view full-size image) The food toxicologists working on natural toxins should face in the next years the challenge of [...] Read more.
Order results
Result details
Select all
Export citation of selected articles as:
Open AccessArticle
Detoxification of Aflatoxin B1 by Zygosaccharomyces rouxii with Solid State Fermentation in Peanut Meal
Toxins 2017, 9(1), 42; https://doi.org/10.3390/toxins9010042 - 20 Jan 2017
Cited by 7 | Viewed by 2745
Abstract
Aflatoxins are highly carcinogenic, teratogenetic, and morbigenous secondary metabolites of Aspergillus flavus and A. parasiticus that can contaminate multiple staple foods, such as peanut, maize, and tree nuts. In this study, Zygosaccharomyces rouxii was screened out and identified from fermented soy paste—one kind [...] Read more.
Aflatoxins are highly carcinogenic, teratogenetic, and morbigenous secondary metabolites of Aspergillus flavus and A. parasiticus that can contaminate multiple staple foods, such as peanut, maize, and tree nuts. In this study, Zygosaccharomyces rouxii was screened out and identified from fermented soy paste—one kind of traditional Chinese food—to detoxify aflatoxin B1 (AFB1) by aerobic solid state fermentation in peanut meal. The optimal degradation condition was chosen from single factor experiment, and the most effective detoxification rate was about 97%. As for liquid fermentation, we tested the binding ability of Z. rouxii, and the highest binding rate reached was 74.3% (nonviable cells of Z. rouxii) in phosphate-buffered saline (PBS). Moreover, the biotransformation of AFB1 through fermentation of Z. rouxii in peanut meal was further verified by liquid chromatography/mass spectrometry (LC/MS). According to TIC scan, after fermentation by Z. rouxii, the AFB1 in peanut meal was prominently degraded to the lowering peaks of AFB1. Additionally, m/s statistics demonstrated that AFB1 may be degraded to some new products whose structural properties may be different from AFB1, or the degradation products may be dissolved in the aqueous phase rather than the organic phase. As far as we know, this is the first report indicating that the safe strain of Z. rouxii has the ability to detoxify AFB1. Full article
Show Figures

Figure 1

Open AccessArticle
Above and beyond C5a Receptor Targeting by Staphylococcal Leucotoxins: Retrograde Transport of Panton–Valentine Leucocidin and γ-Hemolysin
Toxins 2017, 9(1), 41; https://doi.org/10.3390/toxins9010041 - 20 Jan 2017
Viewed by 1886
Abstract
Various membrane receptors associated with the innate immune response have recently been identified as mediators of the cellular action of Staphylococcus aureus leucotoxins. Two of these, the Panton–Valentine leucotoxin LukS-PV/LukF-PV and the γ-hemolysin HlgC/HlgB, bind the C5a complement-derived peptide receptor. These leucotoxins utilize [...] Read more.
Various membrane receptors associated with the innate immune response have recently been identified as mediators of the cellular action of Staphylococcus aureus leucotoxins. Two of these, the Panton–Valentine leucotoxin LukS-PV/LukF-PV and the γ-hemolysin HlgC/HlgB, bind the C5a complement-derived peptide receptor. These leucotoxins utilize the receptor to induce intracellular Ca2+ release from internal stores, other than those activated by C5a. The two leucotoxins are internalized with the phosphorylated receptor, but it is unknown whether they divert retrograde transport of the receptor or follow another pathway. Immunolabeling and confocal microscopic techniques were used to analyze the presence of leucotoxins in endosomes, lysosomes, endoplasmic reticulum, and Golgi. The two leucotoxins apparently followed retrograde transport similar to that of the C5a peptide-activated receptor. However, HlgC/HlgB reached the Golgi network very early, whereas LukS-PV/LukF-PV followed slower kinetics. The HlgC/HlgB leucotoxin remained in neutrophils 6 h after a 10-min incubation of the cells in the presence of the toxin with no signs of apoptosis, whereas apoptosis was observed 3 h after neutrophils were incubated with LukS-PV/LukF-PV. Such retrograde transport of leucotoxins provides a novel understanding of the cellular effects initiated by sublytic concentrations of these toxins. Full article
(This article belongs to the collection Staphylococcus aureus Toxins)
Show Figures

Graphical abstract

Open AccessArticle
A Survey of Aflatoxin-Producing Aspergillus sp. from Peanut Field Soils in Four Agroecological Zones of China
Toxins 2017, 9(1), 40; https://doi.org/10.3390/toxins9010040 - 20 Jan 2017
Cited by 4 | Viewed by 1815
Abstract
Peanut pods are easily infected by aflatoxin-producing Aspergillus sp.ecies from field soil. To assess the aflatoxin-producing Aspergillus sp. in different peanut field soils, 344 aflatoxin-producing Aspergillus strains were isolated from 600 soil samples of four agroecological zones in China (the Southeast coastal zone [...] Read more.
Peanut pods are easily infected by aflatoxin-producing Aspergillus sp.ecies from field soil. To assess the aflatoxin-producing Aspergillus sp. in different peanut field soils, 344 aflatoxin-producing Aspergillus strains were isolated from 600 soil samples of four agroecological zones in China (the Southeast coastal zone (SEC), the Yangtze River zone (YZR), the Yellow River zone (YR) and the Northeast zone (NE)). Nearly 94.2% (324/344) of strains were A. flavus and 5.8% (20/344) of strains were A. parasiticus. YZR had the highest population density of Aspergillus sp. and positive rate of aflatoxin production in isolated strains (1039.3 cfu·g−1, 80.7%), the second was SEC (191.5 cfu·g−1, 48.7%), the third was YR (26.5 cfu·g−1, 22.7%), and the last was NE (2.4 cfu·g−1, 6.6%). The highest risk of AFB1 contamination on peanut was in YZR which had the largest number of AFB1 producing isolates in 1g soil, followed by SEC and YR, and the lowest was NE. The potential risk of AFB1 contamination in peanuts can increase with increasing population density and a positive rate of aflatoxin-producing Aspergillus sp. in field soils, suggesting that reducing aflatoxigenic Aspergillus sp. in field soils could prevent AFB1 contamination in peanuts. Full article
(This article belongs to the Special Issue Exposure and Risk Assessment for Mycotoxins)
Show Figures

Figure 1

Open AccessEditor’s ChoiceLetter
Is the Insect World Overcoming the Efficacy of Bacillus thuringiensis?
Toxins 2017, 9(1), 39; https://doi.org/10.3390/toxins9010039 - 18 Jan 2017
Cited by 8 | Viewed by 2426
Abstract
The use of chemical pesticides revolutionized agriculture with the introduction of DDT (Dichlorodiphenyltrichloroethane) as the first modern chemical insecticide. However, the effectiveness of DDT and other synthetic pesticides, together with their low cost and ease of use, have led to the generation of [...] Read more.
The use of chemical pesticides revolutionized agriculture with the introduction of DDT (Dichlorodiphenyltrichloroethane) as the first modern chemical insecticide. However, the effectiveness of DDT and other synthetic pesticides, together with their low cost and ease of use, have led to the generation of undesirable side effects, such as pollution of water and food sources, harm to non-target organisms and the generation of insect resistance. The alternative comes from biological control agents, which have taken an expanding share in the pesticide market over the last decades mainly promoted by the necessity to move towards more sustainable agriculture. Among such biological control agents, the bacterium Bacillus thuringiensis (Bt) and its insecticidal toxins have been the most studied and commercially used biological control agents over the last 40 years. However, some insect pests have acquired field-evolved resistance to the most commonly used Bt-based pesticides, threatening their efficacy, which necessitates the immediate search for novel strains and toxins exhibiting different modes of action and specificities in order to perpetuate the insecticidal potential of this bacterium. Full article
(This article belongs to the Section Bacterial Toxins)
Show Figures

Graphical abstract

Open AccessEditor’s ChoiceReview
Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature
Toxins 2017, 9(1), 38; https://doi.org/10.3390/toxins9010038 - 18 Jan 2017
Cited by 66 | Viewed by 3526
Abstract
Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. [...] Read more.
Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future. Full article
(This article belongs to the Section Bacterial Toxins)
Show Figures

Figure 1

Open AccessEditorial
Announcing the 2017 Toxins Travel Awards for Post-Doctoral Fellows and Ph.D. Students
Toxins 2017, 9(1), 37; https://doi.org/10.3390/toxins9010037 - 17 Jan 2017
Viewed by 1793
Abstract
As Editor-in-Chief of Toxins, I am pleased to announce the winners of the Toxins Travel Awards for 2017.[...] Full article
Show Figures

Figure 1

Open AccessEditorial
Understanding the Snake Venom Metalloproteinases: An Interview with Jay Fox and José María Gutiérrez
Toxins 2017, 9(1), 33; https://doi.org/10.3390/toxins9010033 - 16 Jan 2017
Cited by 1 | Viewed by 1970
Abstract
Jay W. Fox and José María Gutiérrez recently finished editing a Special Issue on the topic “Snake Venom Metalloproteinases” in Toxins. The Special Issue covers a wide range of topics, including the molecular evolution and structure of snake venom metalloproteinases (SVMPs), the [...] Read more.
Jay W. Fox and José María Gutiérrez recently finished editing a Special Issue on the topic “Snake Venom Metalloproteinases” in Toxins. The Special Issue covers a wide range of topics, including the molecular evolution and structure of snake venom metalloproteinases (SVMPs), the mechanisms involved in the generation of diversity of SVMPs, the mechanism of action of SVMPs, and their role in the pathophysiology of envenomings, with implications for improving the therapy of envenomings. In this interview, we discussed with Jay W. Fox and José María Gutiérrez their research on the SVMPs and their perspectives on the future trends and challenges for studying snake venoms. Full article
(This article belongs to the Special Issue Snake Venom Metalloproteinases) Printed Edition available
Show Figures

Figure 1

Open AccessEditor’s ChoiceArticle
Novel Aflatoxin-Degrading Enzyme from Bacillus shackletonii L7
Toxins 2017, 9(1), 36; https://doi.org/10.3390/toxins9010036 - 14 Jan 2017
Cited by 10 | Viewed by 2498
Abstract
Food and feed contamination by aflatoxin (AF)B1 has adverse economic and health consequences. AFB1 degradation by microorganisms or microbial enzymes provides a promising preventive measure. To this end, the present study tested 43 bacterial isolates collected from maize, rice, and soil [...] Read more.
Food and feed contamination by aflatoxin (AF)B1 has adverse economic and health consequences. AFB1 degradation by microorganisms or microbial enzymes provides a promising preventive measure. To this end, the present study tested 43 bacterial isolates collected from maize, rice, and soil samples for AFB1-reducing activity. The higher activity was detected in isolate L7, which was identified as Bacillus shackletonii. L7 reduced AFB1, AFB2, and AFM1 levels by 92.1%, 84.1%, and 90.4%, respectively, after 72 h at 37 °C. The L7 culture supernatant degraded more AFB1 than viable cells and cell extracts; and the degradation activity was reduced from 77.9% to 15.3% in the presence of proteinase K and sodium dodecyl sulphate. A thermostable enzyme purified from the boiled supernatant was designated as Bacillus aflatoxin-degrading enzyme (BADE). An overall 9.55-fold purification of BADE with a recovery of 39.92% and an activity of 3.85 × 103 U·mg−1 was obtained using chromatography on DEAE-Sepharose. BADE had an estimated molecular mass of 22 kDa and exhibited the highest activity at 70 °C and pH 8.0, which was enhanced by Cu2+ and inhibited by Zn2+, Mn2+, Mg2+, and Li+. BADE is the major protein involved in AFB1 detoxification. This is the first report of a BADE isolated from B. shackletonii, which has potential applications in the detoxification of aflatoxins during food and feed processing. Full article
Show Figures

Figure 1

Open AccessArticle
Unravelling the Diversity of the Cyclopiazonic Acid Family of Mycotoxins in Aspergillus flavus by UHPLC Triple-TOF HRMS
Toxins 2017, 9(1), 35; https://doi.org/10.3390/toxins9010035 - 13 Jan 2017
Cited by 16 | Viewed by 2013
Abstract
Cyclopiazonic acid (α-cyclopiazonic acid, α-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures approximately 40 years ago, its contribution to the A. flavus mycotoxin [...] Read more.
Cyclopiazonic acid (α-cyclopiazonic acid, α-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures approximately 40 years ago, its contribution to the A. flavus mycotoxin burden is consistently minimized by our focus on the more potent carcinogenic aflatoxins also produced by this fungus. Here, we report the screening and identification of several CPA-type alkaloids not previously found in A. flavus cultures. Our identifications of these CPA-type alkaloids are based on a dereplication strategy involving accurate mass high resolution mass spectrometry data and a careful study of the α-CPA fragmentation pattern. In total, 22 CPA-type alkaloids were identified in extracts from the A. flavus strains examined. Of these metabolites, 13 have been previously reported in other fungi, though this is the first report of their existence in A. flavus. Two of our metabolite discoveries, 11,12-dehydro α-CPA and 3-hydroxy-2-oxo CPA, have never been reported for any organism. The conspicuous presence of CPA and its numerous derivatives in A. flavus cultures raises concerns about the long-term and cumulative toxicological effects of these fungal secondary metabolites and their contributions to the entire A. flavus mycotoxin problem. Full article
Show Figures

Figure 1

Open AccessArticle
Distinct Neurotoxicity Profile of Listeriolysin O from Listeria monocytogenes
Toxins 2017, 9(1), 34; https://doi.org/10.3390/toxins9010034 - 13 Jan 2017
Cited by 5 | Viewed by 1723
Abstract
Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, Streptococcus pneumoniae and Listeria [...] Read more.
Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, Streptococcus pneumoniae and Listeria monocytogenes, cause fatal bacterial meningitis, and both produce toxins of the CDC family—pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death. We utilized primary glial cultures and acute mouse brain slices to examine the neuropathological effects of listeriolysin O and to compare it to pneumolysin with identical hemolytic activity. In cultures, listeriolysin O permeabilized cells slower than pneumolysin did but still initiated non-lytic astrocytic cell shape changes, just as pneumolysin did. In an acute brain slice culture system, listeriolysin O produced dendritic varicosities in an NMDA-dependent manner but failed to cause dendritic spine collapse and cortical astrocyte reorganization. Thus, listeriolysin O demonstrated slower cell permeabilization and milder glial cell remodeling ability than did pneumolysin and lacked dendritic spine collapse capacity but exhibited equivalent dendritic pathology. Full article
(This article belongs to the Section Bacterial Toxins)
Show Figures

Figure 1

Open AccessArticle
Auranofin Inhibits the Enzyme Activity of Pasteurella multocida Toxin PMT in Human Cells and Protects Cells from Intoxication
Toxins 2017, 9(1), 32; https://doi.org/10.3390/toxins9010032 - 13 Jan 2017
Cited by 2 | Viewed by 2432
Abstract
The AB-type protein toxin from Pasteurella multocida (PMT) contains a functionally important disulfide bond within its catalytic domain, which must be cleaved in the host cell cytosol to render the catalytic domain of PMT into its active conformation. Here, we found that the [...] Read more.
The AB-type protein toxin from Pasteurella multocida (PMT) contains a functionally important disulfide bond within its catalytic domain, which must be cleaved in the host cell cytosol to render the catalytic domain of PMT into its active conformation. Here, we found that the reductive potential of the cytosol of target cells, and more specifically, the activity of the thioredoxin reductase (TrxR) is crucial for this process. This was demonstrated by the strong inhibitory effect of the pharmacological TrxR inhibitor auranofin, which inhibited the intoxication of target cells with PMT, as determined by analyzing the PMT-catalyzed deamidation of GTP-binding proteins (G-proteins) in the cytosol of cells. The amount of endogenous substrate levels modified by PMT in cells pretreated with auranofin was reduced compared to cells treated with PMT alone. Auranofin had no inhibitory effect on the activity of the catalytic domain of constitutively active PMT in vitro, demonstrating that auranofin did not directly inhibit PMT activity, but interferes with the mode of action of PMT in cells. In conclusion, the results show that TrxR is crucial for the mode of action of PMT in mammalian cells, and that the drug auranofin can serve as an efficient inhibitor, which might be a starting point for novel therapeutic options against toxin-associated diseases. Full article
(This article belongs to the Special Issue Pasteurella multocida and Its Virulence Factors)
Show Figures

Figure 1

Open AccessArticle
The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress
Toxins 2017, 9(1), 31; https://doi.org/10.3390/toxins9010031 - 13 Jan 2017
Cited by 3 | Viewed by 2130
Abstract
A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. [...] Read more.
A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σB operon in L. monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a ΔmazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus, we found that the mazEF locus did not affect transcription of genes within the σB operon, but MazEF effected the expression of the σB-dependent genes opuCA and lmo0880, with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus, suggesting a novel mode of action for MazEF in L. monocytogenes. Full article
(This article belongs to the Section Bacterial Toxins)
Show Figures

Figure 1

Open AccessEditorial
Acknowledgement to Reviewers of Toxins in 2016
Toxins 2017, 9(1), 30; https://doi.org/10.3390/toxins9010030 - 11 Jan 2017
Viewed by 1346
Abstract
The editors of Toxins would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article
Open AccessArticle
RnlB Antitoxin of the Escherichia coli RnlA-RnlB Toxin–Antitoxin Module Requires RNase HI for Inhibition of RnlA Toxin Activity
Toxins 2017, 9(1), 29; https://doi.org/10.3390/toxins9010029 - 11 Jan 2017
Cited by 1 | Viewed by 1614
Abstract
The Escherichia coli RnlA-RnlB toxin–antitoxin system is related to the anti-phage mechanism. Under normal growth conditions, an RnlA toxin with endoribonuclease activity is inhibited by binding of its cognate RnlB antitoxin. After bacteriophage T4 infection, RnlA is activated by the disappearance of RnlB, [...] Read more.
The Escherichia coli RnlA-RnlB toxin–antitoxin system is related to the anti-phage mechanism. Under normal growth conditions, an RnlA toxin with endoribonuclease activity is inhibited by binding of its cognate RnlB antitoxin. After bacteriophage T4 infection, RnlA is activated by the disappearance of RnlB, resulting in the rapid degradation of T4 mRNAs and consequently no T4 propagation when T4 dmd encoding a phage antitoxin against RnlA is defective. Intriguingly, E. coli RNase HI, which plays a key role in DNA replication, is required for the activation of RnlA and stimulates the RNA cleavage activity of RnlA. Here, we report an additional role of RNase HI in the regulation of RnlA-RnlB system. Both RNase HI and RnlB are associated with NRD (one of three domains of RnlA). The interaction between RnlB and NRD depends on RNase HI. Exogenous expression of RnlA in wild-type cells has no effect on cell growth because of endogenous RnlB and this inhibition of RnlA toxicity requires RNase HI and NRD. These results suggest that RNase HI recruits RnlB to RnlA through NRD for inhibiting RnlA toxicity and thus plays two contrary roles in the regulation of RnlA-RnlB system. Full article
(This article belongs to the Section Bacterial Toxins)
Show Figures

Figure 1

Open AccessArticle
The Antagonistic Effect of Mycotoxins Deoxynivalenol and Zearalenone on Metabolic Profiling in Serum and Liver of Mice
Toxins 2017, 9(1), 28; https://doi.org/10.3390/toxins9010028 - 10 Jan 2017
Cited by 12 | Viewed by 2009
Abstract
Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg [...] Read more.
Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP) > 1, t-test p value < 0.05. The metabolic pathway analysis was performed with MetaMapp and drawn by CytoScape. Results show that the combined DON and ZEN treatment has an obvious “antagonistic effect” in serum and liver tissue metabolic profiling of mice. The blood biochemical indexes, like alkaline phosphatase, alanine transaminase, and albumin (ALB)/globulin (GLO), reveal a moderated trend in the combined DON + ZEN treatment group, which is consistent with histopathological examination. The metabolic pathway analysis demonstrated that the combined DON and ZEN treatment could down-regulate the valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, and O-glycosyl compounds related glucose metabolism in liver tissue. The metabolic profiling in serum confirmed the finding that the combined DON and ZEN treatment has an “antagonistic effect” on liver metabolism of mice. Full article
Show Figures

Figure 1

Open AccessArticle
Advanced Oxidation Protein Products-Modified Albumin Induces Differentiation of RAW264.7 Macrophages into Dendritic-Like Cells Which Is Modulated by Cell Surface Thiols
Toxins 2017, 9(1), 27; https://doi.org/10.3390/toxins9010027 - 10 Jan 2017
Cited by 6 | Viewed by 2119
Abstract
Local accumulation of Advanced Oxidation Protein Products (AOPP) induces pro-inflammatory and pro-fibrotic processes in kidneys and is an independent predictor of renal fibrosis and of rapid decline of eGFR in patients with chronic kidney disease (CKD). In addition to kidney damage, circulating AOPP [...] Read more.
Local accumulation of Advanced Oxidation Protein Products (AOPP) induces pro-inflammatory and pro-fibrotic processes in kidneys and is an independent predictor of renal fibrosis and of rapid decline of eGFR in patients with chronic kidney disease (CKD). In addition to kidney damage, circulating AOPP may be regarded as mediators of systemic oxidative stress and, in this capacity, they might play a role in the progression of atherosclerotic damage of arterial walls. Atherosclerosis is a chronic inflammatory disease that involves activation of innate and adaptive immunity. Dendritic cells (DCs) are key cells in this process, due to their role in antigen presentation, inflammation resolution and T cell activation. AOPP consist in oxidative modifications of proteins (such as albumin and fibrinogen) that mainly occur through myeloperoxidase (MPO)-derived hypochlorite (HOCl). HOCl modified proteins have been found in atherosclerotic lesions. The oxidizing environment and the shifts in cellular redox equilibrium trigger inflammation, activate immune cells and induce immune responses. Thus, surface thiol groups contribute to the regulation of immune functions. The aims of this work are: (1) to evaluate whether AOPP-proteins induce activation and differentiation of mature macrophages into dendritic cells in vitro; and (2) to define the role of cell surface thiol groups and of free radicals in this process. AOPP-proteins were prepared by in vitro incubation of human serum albumin (HSA) with HOCl. Mouse macrophage-like RAW264.7 were treated with various concentrations of AOPP-HSA with or without the antioxidant N-acetyl cysteine (NAC). Following 48 h of HSA-AOPP treatment, RAW264.7 morphological changes were evaluated by microscopic observation, while markers of dendritic lineage and activation (CD40, CD86, and MHC class II) and allogeneic T cell proliferation were evaluated by flow cytometry. Cell surface thiols were measured by AlexaFluor-maleimide binding, and ROS production was assessed as DCF fluorescence by flow cytometry. HSA-AOPP induced the differentiation of RAW264.7 cells into a dendritic-like phenotype, as shown by morphological changes, by increased CD40, CD86 and MHC class II surface expression and by induction of T cell proliferation. The cell surface thiols dose dependently decreased following HSA-AOPP treatment, while ROS production increased. NAC pre-treatment enhanced the amount of cell surface thiols and prevented their reduction due to treatment with AOPP. Both ROS production and RAW264.7 differentiation into DC-like cells induced by HSA-AOPP were reduced by NAC. Our results highlight that oxidized plasma proteins modulate specific immune responses of macrophages through a process involving changes in the thiol redox equilibrium. We suggest that this mechanism may play a role in determining the rapid progression of the atherosclerotic process observed in CKD patients. Full article
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
Show Figures

Figure 1

Open AccessReview
The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin
Toxins 2017, 9(1), 26; https://doi.org/10.3390/toxins9010026 - 10 Jan 2017
Cited by 9 | Viewed by 1867
Abstract
Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of [...] Read more.
Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin. Full article
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
Show Figures

Graphical abstract

Open AccessReview
Impact of Indoxyl Sulfate on Progenitor Cell-Related Neovascularization of Peripheral Arterial Disease and Post-Angioplasty Thrombosis of Dialysis Vascular Access
Toxins 2017, 9(1), 25; https://doi.org/10.3390/toxins9010025 - 07 Jan 2017
Cited by 6 | Viewed by 1696
Abstract
Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention [...] Read more.
Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair. Clinically, indoxyl sulfate is associated with total and cardiovascular mortality in patients with CKD. Recent studies have indicated that in addition to coronary and cerebral arteries, indoxyl sulfate plays a role in peripheral artery disease (PAD) and dialysis graft thrombosis. Emerging evidence suggests that indoxyl sulfate is implicated via novel mechanisms, including progenitor cell-related neovascularization and tissue factor-related hypercoagulability. These findings raise the possibility that strategies targeting serum indoxyl sulfate may have the potential to improve the outcomes of PAD and dialysis vascular access in patients with CKD. Full article
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
Show Figures

Figure 1

Open AccessArticle
Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon
Toxins 2017, 9(1), 24; https://doi.org/10.3390/toxins9010024 - 07 Jan 2017
Cited by 4 | Viewed by 1654
Abstract
This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5′- and 3′-end of MB were labeled with [...] Read more.
This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5′- and 3′-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A2-coralyne-A2 coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs. Full article
(This article belongs to the Section Animal Venoms)
Show Figures

Graphical abstract

Open AccessArticle
Analysis of MicroRNA Expression Profiling Involved in MC-LR-Induced Cytotoxicity by High-Throughput Sequencing
Toxins 2017, 9(1), 23; https://doi.org/10.3390/toxins9010023 - 07 Jan 2017
Cited by 11 | Viewed by 1730
Abstract
In recent years, microRNAs (miRNAs) in toxicology have attracted great attention. However, the underlying mechanism of miRNAs in the cytotoxicity of microcystin-LR (MC-LR) is lacking. The objective of this study is to analyze miRNA profiling in HepG2 cells after 24 h of MC-LR-exposure [...] Read more.
In recent years, microRNAs (miRNAs) in toxicology have attracted great attention. However, the underlying mechanism of miRNAs in the cytotoxicity of microcystin-LR (MC-LR) is lacking. The objective of this study is to analyze miRNA profiling in HepG2 cells after 24 h of MC-LR-exposure to affirm whether and how miRNAs were involved in the cytotoxicity of MC-LR. The results showed that totally 21 and 37 miRNAs were found to be significantly altered in the MC-LR treated cells at concentrations of 10 and 50 μM, respectively, when compared to the control cells. In these two groups, 37,566 and 39,174 target genes were predicted, respectively. The further analysis showed that MC-LR-exposure promoted the expressions of has-miR-149-3p, has-miR-449c-5p, and has-miR-454-3p while suppressed the expressions of has-miR-4286, has-miR-500a-3p, has-miR-500a-5p, and has-miR-500b-5p in MC-LR-treated groups when compared to the control group. Moreover, the result of qPCR confirmed the above result, suggesting that these miRNAs may be involved in MC-LR-hepatotoxicity and they may play an important role in the hepatitis and liver cancer caused by MC-LR. The target genes for differentially expressed miRNAs in MC-LR treatment groups were significantly enriched to totally 23 classes of GO, in which three were significantly enriched in both 10 and 50 μM MC-LR groups. Moreover, the results of KEGG pathway analysis showed that MC-LR-exposure altered some important signaling pathways such as MAPK, biosynthesis of secondary metabolites, and pyrimidine and purine metabolism, which were possibly negatively regulated by the corresponding miRNAs and might play important role in MC-LR-mediated cytotoxicity in HepG2 cells. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
Show Figures

Figure 1

Open AccessEditor’s ChoiceArticle
Bioactivity of Natural and Engineered Antimicrobial Peptides from Venom of the Scorpions Urodacus yaschenkoi and U. manicatus
Toxins 2017, 9(1), 22; https://doi.org/10.3390/toxins9010022 - 06 Jan 2017
Cited by 11 | Viewed by 1675
Abstract
The spread of multidrug-resistant human pathogens has drawn attention towards antimicrobial peptides (AMPs), which are major players in the innate immune systems of many organisms, including vertebrates, invertebrates, plants and microbes. Scorpion venom is an abundant source of novel and potent AMPs. Here, [...] Read more.
The spread of multidrug-resistant human pathogens has drawn attention towards antimicrobial peptides (AMPs), which are major players in the innate immune systems of many organisms, including vertebrates, invertebrates, plants and microbes. Scorpion venom is an abundant source of novel and potent AMPs. Here, we investigated natural and engineered AMPs from the scorpions Urodacus yaschenkoi and U. manicatus to determine their antimicrobial spectra as well as their hemolytic/cytotoxic activity. None of the AMPs were active against fungi, but many of them were active at low concentrations (0.25–30 µM) against seven different bacteria. Hemolytic and cytotoxic activities were determined using pig erythrocytes and baby hamster kidney cells, respectively. The amino acid substitutions in the engineered AMPs did not inhibit cytotoxicity, but reduced hemolysis and therefore increased the therapeutic indices. The phylogenetic analysis of scorpion AMPs revealed they are closely related and the GXK motif is highly conserved. The engineered scorpion AMPs offer a promising alternative for the treatment of multidrug-resistant bacterial infections and could be modified further to reduce their hemolytic/cytotoxic activity. Full article
(This article belongs to the Section Animal Venoms)
Show Figures

Figure 1

Open AccessArticle
High Uric Acid Ameliorates Indoxyl Sulfate-Induced Endothelial Dysfunction and Is Associated with Lower Mortality among Hemodialysis Patients
Toxins 2017, 9(1), 20; https://doi.org/10.3390/toxins9010020 - 06 Jan 2017
Cited by 8 | Viewed by 2282
Abstract
High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatable with regard to the association between high UA and poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD [...] Read more.
High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatable with regard to the association between high UA and poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of <6.1 mg/dL was associated with a higher risk of all-cause mortality compared with a UA level of >8.1 mg/dL [HR, 1.20, 95% CI (1.10–1.31)] adjusting for baseline demographic and biochemical parameters. Moreover, a UA level of <6.1 mg/dL was associated with greater risks of cardiovascular mortality [HR, 1.26, 95% CI (1.13–1.41)] and stroke-related mortality [HR, 1.59, 95% CI (1.12–2.25)], respectively. In vitro experiments further showed an increase in oxidative stress and an inhibition nitric oxide synthesis by indoxyl sulfate (IS) in human aortic endothelial cells, which were significantly attenuated by UA in a dose-dependent manner. We concluded that higher UA in serum was associated with lower risk of all-cause and cardiovascular mortality among HD patients probably through its antioxidant property in ameliorating the IS-related vascular toxicity. Full article
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
Show Figures

Figure 1

Open AccessArticle
Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring
Toxins 2017, 9(1), 21; https://doi.org/10.3390/toxins9010021 - 05 Jan 2017
Cited by 18 | Viewed by 2379
Abstract
Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. [...] Read more.
Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0–21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1) and 3β-hydroxysteroid dehydrogenase (HSD) in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr), and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1) in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females. Full article
(This article belongs to the Special Issue Exposure and Risk Assessment for Mycotoxins)
Show Figures

Figure 1

Open AccessReview
The Status of Fusarium Mycotoxins in Sub-Saharan Africa: A Review of Emerging Trends and Post-Harvest Mitigation Strategies towards Food Control
Toxins 2017, 9(1), 19; https://doi.org/10.3390/toxins9010019 - 05 Jan 2017
Cited by 28 | Viewed by 2022
Abstract
Fusarium fungi are common plant pathogens causing several plant diseases. The presence of these molds in plants exposes crops to toxic secondary metabolites called Fusarium mycotoxins. The most studied Fusarium mycotoxins include fumonisins, zearalenone, and trichothecenes. Studies have highlighted the economic impact of [...] Read more.
Fusarium fungi are common plant pathogens causing several plant diseases. The presence of these molds in plants exposes crops to toxic secondary metabolites called Fusarium mycotoxins. The most studied Fusarium mycotoxins include fumonisins, zearalenone, and trichothecenes. Studies have highlighted the economic impact of mycotoxins produced by Fusarium. These arrays of toxins have been implicated as the causal agents of wide varieties of toxic health effects in humans and animals ranging from acute to chronic. Global surveillance of Fusarium mycotoxins has recorded significant progress in its control; however, little attention has been paid to Fusarium mycotoxins in sub-Saharan Africa, thus translating to limited occurrence data. In addition, legislative regulation is virtually non-existent. The emergence of modified Fusarium mycotoxins, which may contribute to additional toxic effects, worsens an already precarious situation. This review highlights the status of Fusarium mycotoxins in sub-Saharan Africa, the possible food processing mitigation strategies, as well as future perspectives. Full article
(This article belongs to the collection Leading Opinions (Closed))
Open AccessEditor’s ChoiceReview
Forthcoming Challenges in Mycotoxins Toxicology Research for Safer Food—A Need for Multi-Omics Approach
Toxins 2017, 9(1), 18; https://doi.org/10.3390/toxins9010018 - 04 Jan 2017
Cited by 16 | Viewed by 2878
Abstract
The presence of mycotoxins in food represents a severe threat for public health and welfare, and poses relevant research challenges in the food toxicology field. Nowadays, food toxicologists have to provide answers to food-related toxicological issues, but at the same time they should [...] Read more.
The presence of mycotoxins in food represents a severe threat for public health and welfare, and poses relevant research challenges in the food toxicology field. Nowadays, food toxicologists have to provide answers to food-related toxicological issues, but at the same time they should provide the appropriate knowledge in background to effectively support the evidence-based decision-making in food safety. Therefore, keeping in mind that regulatory actions should be based on sound scientific findings, the present opinion addresses the main challenges in providing reliable data for supporting the risk assessment of foodborne mycotoxins. Full article
(This article belongs to the collection Leading Opinions (Closed))
Show Figures

Graphical abstract

Open AccessEditor’s ChoiceArticle
Degradation of Aflatoxins by Means of Laccases from Trametes versicolor: An In Silico Insight
Toxins 2017, 9(1), 17; https://doi.org/10.3390/toxins9010017 - 01 Jan 2017
Cited by 12 | Viewed by 2913
Abstract
Mycotoxins are secondary metabolites of fungi that contaminate food and feed, and are involved in a series of foodborne illnesses and disorders in humans and animals. The mitigation of mycotoxin content via enzymatic degradation is a strategy to ensure safer food and feed, [...] Read more.
Mycotoxins are secondary metabolites of fungi that contaminate food and feed, and are involved in a series of foodborne illnesses and disorders in humans and animals. The mitigation of mycotoxin content via enzymatic degradation is a strategy to ensure safer food and feed, and to address the forthcoming issues in view of the global trade and sustainability. Nevertheless, the search for active enzymes is still challenging and time-consuming. The in silico analysis may strongly support the research by providing the evidence-based hierarchization of enzymes for a rational design of more effective experimental trials. The present work dealt with the degradation of aflatoxin B1 and M1 by laccase enzymes from Trametes versicolor. The enzymes–substrate interaction for various enzyme isoforms was investigated through 3D molecular modeling techniques. Structural differences among the isoforms have been pinpointed, which may cause different patterns of interaction between aflatoxin B1 and M1. The possible formation of different products of degradation can be argued accordingly. Moreover, the laccase gamma isoform was identified as the most suitable for protein engineering aimed at ameliorating the substrate specificity. Overall, 3D modeling proved to be an effective analytical tool to assess the enzyme–substrate interaction and provided a solid foothold for supporting the search of degrading enzyme at the early stage. Full article
Show Figures

Graphical abstract

Open AccessArticle
Deoxynivalenol (DON) Contamination of Feed and Grinding Fineness: Are There Interactive Implications on Stomach Integrity and Health of Piglets?
Toxins 2017, 9(1), 16; https://doi.org/10.3390/toxins9010016 - 01 Jan 2017
Cited by 2 | Viewed by 1659
Abstract
The common feed contaminant deoxynivalenol (DON) was reported to influence the morphology of the pars nonglandularis (PN) of porcine stomach. Moreover, finely ground feed is known to trigger the development of ulcers and other pathologies of PN while coarsely ground feed protects from [...] Read more.
The common feed contaminant deoxynivalenol (DON) was reported to influence the morphology of the pars nonglandularis (PN) of porcine stomach. Moreover, finely ground feed is known to trigger the development of ulcers and other pathologies of PN while coarsely ground feed protects from such lesions. The interactions between grinding fineness and DON contamination of feed were not examined so far. Therefore, both finely and coarsely ground feeds were tested either in the absence or presence of a DON contaminated wheat on growth performance and health of rearing piglets, including stomach integrity. DON contamination significantly reduced feed intake and serum albumin concentration with this effect being more pronounced after feeding the coarsely ground feed. Albeit at a higher level, albumin concentration was also reduced after feeding the finely ground and uncontaminated feed. Finely ground and DON-contaminated feed caused a significantly more pronounced lymphoplasmacytic infiltration both of PN and pars glandularis, partly paralleled by lymph follicle formation and detritus filled foveolae and tubes suggesting a local immune response probably triggered by epithelial lesions. It is concluded that DON contamination of feed exacerbates the adverse effects of finely ground feed on stomach mucosal integrity. Full article
(This article belongs to the Section Mycotoxins)
Show Figures

Figure 1

Open AccessArticle
Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
Toxins 2017, 9(1), 15; https://doi.org/10.3390/toxins9010015 - 30 Dec 2016
Cited by 9 | Viewed by 2606
Abstract
Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for [...] Read more.
Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs): RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS) approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs) were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation. Full article
(This article belongs to the Special Issue Snake Venom Metalloproteinases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
The Anatomical Basis of Paradoxical Masseteric Bulging after Botulinum Neurotoxin Type A Injection
Toxins 2017, 9(1), 14; https://doi.org/10.3390/toxins9010014 - 30 Dec 2016
Cited by 5 | Viewed by 3093
Abstract
The aim of this study was to determine the detailed anatomical structures of the superficial part of the masseter and to elucidate the boundaries and locations of the deep tendon structure within the superficial part of the masseter. Forty-four hemifaces from Korean and [...] Read more.
The aim of this study was to determine the detailed anatomical structures of the superficial part of the masseter and to elucidate the boundaries and locations of the deep tendon structure within the superficial part of the masseter. Forty-four hemifaces from Korean and Thai embalmed cadavers were used in this study. The deep tendon structure was located deep in the lower third of the superficial part of the masseter. It was observed in all specimens and was designated as a deep inferior tendon (DIT). The relationship between the masseter and DIT could be classified into three types according to the coverage pattern: Type A, in which areas IV and V were covered by the DIT (27%, 12/44); Type B, in which areas V and VI were covered by the DIT (23%, 10/44); and Type C, in which areas IV, V, and VI were covered by the DIT (50%, 22/44). The superficial part of the masseter consists of not only the muscle belly but also the deep tendon structure. Based on the results obtained in this morphological study, we recommend performing layer-by-layer retrograde injections into the superficial and deep muscle bellies of the masseter. Full article
(This article belongs to the collection Botulinum Toxins on Human Pain)
Show Figures

Figure 1

Open AccessArticle
Variations of Growth and Toxin Yield in Cylindrospermopsis raciborskii under Different Phosphorus Concentrations
Toxins 2017, 9(1), 13; https://doi.org/10.3390/toxins9010013 - 29 Dec 2016
Cited by 6 | Viewed by 1983
Abstract
The bloom-forming cyanobacteria, Cylindrospermopsis raciborskii, is a producer of the cytotoxic cylindrospermopsin (CYN). In this study, the growth, toxin yield, and expression of CYN biosynthesis genes of C. raciborskii were examined under varying phosphorus (P) concentrations. The results show the cell number [...] Read more.
The bloom-forming cyanobacteria, Cylindrospermopsis raciborskii, is a producer of the cytotoxic cylindrospermopsin (CYN). In this study, the growth, toxin yield, and expression of CYN biosynthesis genes of C. raciborskii were examined under varying phosphorus (P) concentrations. The results show the cell number at 0.00 and 0.01 mg·L−1 P was significantly lower than that at higher P concentrations (≥0.5 mg·L−1). The chlorophyll a content, filament length, heterocyst, and akinete numbers at P ≤ 0.05 mg·L−1 were also significantly reduced. The intracellular and extracellular CYN concentrations and the extracellular proportions increased during the culture period, and larger values were observed at higher P concentrations. Total CYN content reached 45.34–63.83 fg·cell−1 and extracellular CYN proportion reached 11.49%–20.44% at the stationary growth phase. A significantly positive correlation was observed between CYN production and cell growth rate. Three cyr genes were expressed constantly even at P-deficient conditions. The transcription of cyr genes at P-replete conditions or after P supplementation increased from 1.18-fold to 8.33-fold. In conclusion, C. raciborskii may rapidly reorganize metabolic processes as an adaptive response to environmental P fluctuations. CYN production and cyr gene expression were constitutive metabolic processes in toxic C. raciborskii. Full article
(This article belongs to the collection Marine and Freshwater Toxins)
Show Figures

Graphical abstract

Previous Issue
Next Issue
Back to TopTop