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Biochemistry, Molecular Biology and Toxicology of Natural and Synthetic Toxins

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (28 April 2019) | Viewed by 89773

Special Issue Editors


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Guest Editor
Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic
Interests: antidotes for pesticide and nerve agent poisonings; Alzheimer’s disease treatment; detergents as disinfectants; nanoparticles; decontamination means; toxins; drug design and development; nanotechnology; IT; parallel computing; ANN; project management; scientific management; technology transfer; health economics and pharmacoeconomics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
College of Life Science, Yangtze University, Jingzhou, China
Interests: toxin; synthetic toxins; natural toxin; toxic industrial chemicals; chemical warfare agents; antidotes; signalling pathway; molecular biology; in vitro & in vivo; biochemistry
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Department for Experimental Toxicology and Pharmacology, National Poison Control Centre, Belgrade, Serbia
2. Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia
3. Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic
Interests: toxicology; pharmacology; toxicological pathology; non-clinical tests; GLP

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Guest Editor
1. Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Praça General Tibúrcio 80, Rio de Janeiro, RJ 22290-270, Brazil
2. Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003 Hradec Kralové, Czech Republic
Interests: Medicinal Chemistry; Chemical and Biological Defense; Molecular Modeling; Organic Synthesis; Drug Design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There are many chemical molecules of different origins—natural, semi-natural or synthetic. Year by year, many novel compounds are synthesized or isolated worldwide. Many of them influence biological systems. Some of them display their effects in a positive way, as promising drug candidates; on the other hand, other exert high toxicity to organisms.

This Special Issue will be focused on both synthetic and naturally-occurring toxins, their chemistry and biochemistry. Their effects will be solved at the molecular level (molecular biology and computer modelling). Finally, their toxic potential and possible antidotes used in case of their intoxications will be discussed.

Prof. Kamil Kuca
Assoc. Prof. Qinghua Wu
Prof. Vesna Jacevic
Prof. Tanos Celmar Costa Franca
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • toxin
  • synthetic toxins
  • natural toxin
  • toxic industrial chemicals
  • chemical warfare agents
  • antidotes
  • signalling pathway
  • molecular biology
  • in vitro and in vivo
  • biochemistry

Published Papers (15 papers)

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Editorial

Jump to: Research, Review

4 pages, 175 KiB  
Editorial
Immune Evasion, a Potential Mechanism of Trichothecenes: New Insights into Negative Immune Regulations
by Qinghua Wu, Wenda Wu, Tanos C. C. Franca, Vesna Jacevic, Xu Wang and Kamil Kuca
Int. J. Mol. Sci. 2018, 19(11), 3307; https://doi.org/10.3390/ijms19113307 - 24 Oct 2018
Cited by 23 | Viewed by 3389
Abstract
Days ago, the Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation”. This news has increased the attention on immunotoxicity and immune evasion [...] Read more.
Days ago, the Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation”. This news has increased the attention on immunotoxicity and immune evasion mechanisms, which are once again hot research topics. Actually, increasing lines of evidence show that trichothecene mycotoxins have a strong immunosuppressive effect. These mycotoxins suppress the host immunity and make them more sensitive to the infection of pathogens, including bacteria and viruses. However, the underlying mechanism(s) in this context is still poorly understood. Interestingly, recent work showed that an immune evasion mechanism might be involved in trichothecene immunotoxicity. In this work, we discuss the potential immune evasion mechanism in trichothecene immunotoxicity. More importantly, under these circumstances, we are pleased to compile a Special Issue entitled “Biochemistry, Molecular Biology, and Toxicology of Natural and Synthetic Toxins” for the International Journal of Molecular Sciences (IJMS). Researchers are encouraged to share their latest interesting findings with the readers of IJMS. Full article

Research

Jump to: Editorial, Review

14 pages, 4168 KiB  
Article
Protective Effects of Salidroside against Carbon Tetrachloride (CCl4)-Induced Liver Injury by Initiating Mitochondria to Resist Oxidative Stress in Mice
by Shi-Yu Lin, Dan Xu, Xia-Xia Du, Chong-Lin Ran, Lu Xu, Shao-Jun Ren, Zi-Ting Tang, Li-Zi Yin, Chang-Liang He, Zhi-Xiang Yuan, Hua-Lin Fu, Xiao-Ling Zhao and Gang Shu
Int. J. Mol. Sci. 2019, 20(13), 3187; https://doi.org/10.3390/ijms20133187 - 28 Jun 2019
Cited by 47 | Viewed by 4827
Abstract
The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. [...] Read more.
The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl4-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl4-induced injury by resisting oxidative stress and protecting mitochondrial function. Full article
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21 pages, 3401 KiB  
Article
New Lectins from Mediterranean Flora. Activity against HT29 Colon Cancer Cells
by Isabel Oliveira, António Nunes, Ana Lima, Pedro Borralho, Cecília Rodrigues, Ricardo Boavida Ferreira and Ana Cristina Ribeiro
Int. J. Mol. Sci. 2019, 20(12), 3059; https://doi.org/10.3390/ijms20123059 - 22 Jun 2019
Cited by 13 | Viewed by 4189
Abstract
Experiments conducted in vitro and in vivo, as well as some preclinical trials for cancer therapeutics, support the antineoplastic properties of lectins. A screening of antitumoral activity on HT29 colon cancer cells, based on polypeptide characterization and specific lectin binding to HT29 cells [...] Read more.
Experiments conducted in vitro and in vivo, as well as some preclinical trials for cancer therapeutics, support the antineoplastic properties of lectins. A screening of antitumoral activity on HT29 colon cancer cells, based on polypeptide characterization and specific lectin binding to HT29 cells membrane receptors, was performed in order to assess the bioactivities present in four Mediterranean plant species: Juniperus oxycedrus subsp. oxycedrus, Juniperus oxycedrus subsp. badia, Arbutus unedo and Corema album. Total leaf proteins from each species were evaluated with respect to cell viability and inhibitory activities on HT29 cells (cell migration, matrix metalloproteinase –MMP proteolytic activities). A discussion is presented on a possible mechanism justifying the specific binding of lectins to HT29 cell receptors. All species revealed the presence of proteins with affinity to HT29 cell glycosylated receptors, possibly explaining the differential antitumor activity exhibited by the two most promising species, Juniperus oxycedrus subsp. badia and Arbutus unedo. Full article
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16 pages, 4274 KiB  
Article
Functional Analysis of Peptidyl-prolyl cis-trans Isomerase from Aspergillus flavus
by Saleem Ahmad, Sen Wang, Weizhong Wu, Kunlong Yang, YanFeng Zhang, Elisabeth Tumukunde, Shihua Wang and Yu Wang
Int. J. Mol. Sci. 2019, 20(9), 2206; https://doi.org/10.3390/ijms20092206 - 05 May 2019
Cited by 15 | Viewed by 4022
Abstract
Aspergillus flavus, a ubiquitous filamentous fungus found in soil, plants and other substrates has been reported not only as a pathogen for plants, but also a carcinogen producing fungus for human. Peptidyl-Prolyl Isomerase (PPIases) plays an important role in cell process such [...] Read more.
Aspergillus flavus, a ubiquitous filamentous fungus found in soil, plants and other substrates has been reported not only as a pathogen for plants, but also a carcinogen producing fungus for human. Peptidyl-Prolyl Isomerase (PPIases) plays an important role in cell process such as protein secretion cell cycle control and RNA processing. However, the function of PPIase has not yet been identified in A. flavus. In this study, the PPIases gene from A. flavus named ppci1 was cloned into expression vector and the protein was expressed in prokaryotic expression system. Activity of recombinant ppci1 protein was particularly inhibited by FK506, CsA and rapamycin. 3D-Homology model of ppci1 has been constructed with the template, based on 59.7% amino acid similarity. The homologous recombination method was used to construct the single ppci1 gene deletion strain Δppci1. We found that, the ppci1 gene plays important roles in A. flavus growth, conidiation, and sclerotia formation, all of which showed reduction in Δppci1 and increased in conidiation compared with the wild-type and complementary strains in A. flavus. Furthermore, aflatoxin and peanut seeds infection assays indicated that ppci1 contributes to virulence of A. flavus. Furthermore, we evaluated the effect of PPIase inhibitors on A. flavus growth, whereby these were used to treat wild-type strains. We found that the growths were inhibited under every inhibitor. All, these results may provide valuable information for designing inhibitors in the controlling infections of A. flavus. Full article
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19 pages, 5088 KiB  
Article
Low-Luminance Blue Light-Enhanced Phototoxicity in A2E-Laden RPE Cell Cultures and Rats
by Cheng-Hui Lin, Man-Ru Wu, Wei-Jan Huang, Diana Shu-Lian Chow, George Hsiao and Yu-Wen Cheng
Int. J. Mol. Sci. 2019, 20(7), 1799; https://doi.org/10.3390/ijms20071799 - 11 Apr 2019
Cited by 27 | Viewed by 6747
Abstract
N-retinylidene-N-retinylethanolamine (A2E) and other bisretinoids are components of lipofuscin and accumulate in retinal pigment epithelial (RPE) cells—these adducts are recognized in the pathogenesis of retinal degeneration. Further, blue light-emitting diode (LED) light (BLL)-induced retinal toxicity plays an important role in retinal degeneration. Here, [...] Read more.
N-retinylidene-N-retinylethanolamine (A2E) and other bisretinoids are components of lipofuscin and accumulate in retinal pigment epithelial (RPE) cells—these adducts are recognized in the pathogenesis of retinal degeneration. Further, blue light-emitting diode (LED) light (BLL)-induced retinal toxicity plays an important role in retinal degeneration. Here, we demonstrate that low-luminance BLL enhances phototoxicity in A2E-laden RPE cells and rats. RPE cells were subjected to synthetic A2E, and the effects of BLL on activation of apoptotic biomarkers were examined by measuring the levels of cleaved caspase-3. BLL modulates the protein expression of zonula-occludens 1 (ZO-1) and paracellular permeability in A2E-laden RPE cells. Early inflammatory and angiogenic genes were also screened after short-term BLL exposure. In this study, we developed a rat model for A2E treatment with or without BLL exposure for 21 days. BLL exposure caused fundus damage, decreased total retinal thickness, and caused neuron transduction injury in the retina, which were consistent with the in vitro data. We suggest that the synergistic effects of BLL and A2E accumulation in the retina increase the risk of retinal degeneration. These outcomes help elucidate the associations between BLL/A2E and angiogenic/apoptotic mechanisms, as well as furthering therapeutic strategies. Full article
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17 pages, 5296 KiB  
Article
Wnt/β-Catenin Pathway Is Involved in Cadmium-Induced Inhibition of Osteoblast Differentiation of Bone Marrow Mesenchymal Stem Cells
by Lu Wu, Qinzhi Wei, Yingjian Lv, Junchao Xue, Bo Zhang, Qian Sun, Tian Xiao, Rui Huang, Ping Wang, Xiangyu Dai, Haibo Xia, Junjie Li, Xingfen Yang and Qizhan Liu
Int. J. Mol. Sci. 2019, 20(6), 1519; https://doi.org/10.3390/ijms20061519 - 26 Mar 2019
Cited by 36 | Viewed by 6180
Abstract
Cadmium is a common environmental pollutant that causes bone damage. However, the effects of cadmium on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) and its mechanism of action in this process are unclear. Here, we determined the effects of cadmium [...] Read more.
Cadmium is a common environmental pollutant that causes bone damage. However, the effects of cadmium on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) and its mechanism of action in this process are unclear. Here, we determined the effects of cadmium chloride (CdCl2) on the osteogenic differentiation of BMMSCs and the potential mechanism involved in this process. As determined in the present investigation, CdCl2, in a concentration-dependent manner, affected the viability of BMMSCs and their cytoskeletons. Exposure to 0.1 or 0.2 µM CdCl2 inhibited osteogenic differentiation of BMMSCs, which was reflected in the down-regulation of osteoblast-related genes (ALP, OCN, Runx2, OSX, and OPN); in suppression of the protein expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2); and in decreased ALP activity and capacity for mineralization. Moreover, mRNA microarray was performed to determine the roles of these factors in BMMSCs treated with CdCl2 in comparison to control BMMSCs. As determined with the microarrays, the Wingless-type (Wnt), mothers against decapentaplegic and the C. elegans gene Sam (SMAD), and Janus kinase-Signal Transducers and Activators of Transcription (JAK-STAT) signaling pathways were involved in the effects caused by CdCl2. Moreover, during differentiation, the protein levels of Wnt3a, β-catenin, lymphoid enhancer factor 1 (LEF1), and T-cell factor 1 (TCF1) were reduced by CdCl2. The current research shows that CdCl2 suppresses the osteogenesis of BMMSCs via inhibiting the Wnt/β-catenin pathway. The results establish a previously unknown mechanism for bone injury induced by CdCl2. Full article
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15 pages, 3118 KiB  
Article
Metabolomics Characterizes the Effects and Mechanisms of Quercetin in Nonalcoholic Fatty Liver Disease Development
by Yan Xu, Jichun Han, Jinjin Dong, Xiangcheng Fan, Yuanyuan Cai, Jing Li, Tao Wang, Jia Zhou and Jing Shang
Int. J. Mol. Sci. 2019, 20(5), 1220; https://doi.org/10.3390/ijms20051220 - 11 Mar 2019
Cited by 55 | Viewed by 5371
Abstract
As metabolomics is widely used in the study of disease mechanisms, an increasing number of studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin [...] Read more.
As metabolomics is widely used in the study of disease mechanisms, an increasing number of studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with an HFD for 30 and 50 days. The results indicated quercetin exhibited hepatoprotective activity in 30-day HFD-induced NAFLD rats by regulating fatty acid related metabolites (adrenic acid, etc.), inflammation-related metabolites (arachidonic acid, etc.), oxidative stress-related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin did not improve NAFLD in the 50-day HFD; perhaps quercetin was unable to reverse the inflammation induced by a long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD in early stages. Furthermore, combining metabolomics and experimental approaches opens avenues to study the effects and mechanisms of drugs for complex diseases. Full article
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16 pages, 2637 KiB  
Article
Transcriptomic Analysis for Indica and Japonica Rice Varieties under Aluminum Toxicity
by Peng Zhang, Zhuoran Ding, Zhengzheng Zhong and Hanhua Tong
Int. J. Mol. Sci. 2019, 20(4), 997; https://doi.org/10.3390/ijms20040997 - 25 Feb 2019
Cited by 13 | Viewed by 4380
Abstract
Aluminum (Al) at high concentrations inhibits root growth, damage root systems, and causes significant reductions in rice yields. Indica and Japonica rice have been cultivated in distinctly different ecological environments with different soil acidity levels; thus, they might have different mechanisms of Al-tolerance. [...] Read more.
Aluminum (Al) at high concentrations inhibits root growth, damage root systems, and causes significant reductions in rice yields. Indica and Japonica rice have been cultivated in distinctly different ecological environments with different soil acidity levels; thus, they might have different mechanisms of Al-tolerance. In the present study, transcriptomic analysis in the root apex for Al-tolerance in the seedling stage was carried out within Al-tolerant and -sensitive varieties belonging to different subpopulations (i.e., Indica, Japonica, and mixed). We found that there were significant differences between the gene expression patterns of Indica Al-tolerant and Japonica Al-tolerant varieties, while the gene expression patterns of the Al-tolerant varieties in the mixed subgroup, which was inclined to Japonica, were similar to the Al-tolerant varieties in Japonica. Moreover, after further GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses of the transcriptomic data, we found that eight pathways, i.e., “Terpenoid backbone biosynthesis”, “Ribosome”, “Amino sugar and nucleotide sugar metabolism”, “Plant hormone signal transduction”, “TCA cycle”, “Synthesis and degradation of ketone bodies”, and “Butanoate metabolism” were found uniquely for Indica Al-tolerant varieties, while only one pathway (i.e., “Sulfur metabolism”) was found uniquely for Japonica Al-tolerant varieties. For Al-sensitive varieties, one identical pathway was found, both in Indica and Japonica. Three pathways were found uniquely in “Starch and sucrose metabolism”, “Metabolic pathway”, and “Amino sugar and nucleotide sugar metabolism”. Full article
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12 pages, 2201 KiB  
Article
Construction of Electrochemical Immunosensor Based on Gold-Nanoparticles/Carbon Nanotubes/Chitosan for Sensitive Determination of T-2 Toxin in Feed and Swine Meat
by Yanxin Wang, Liyun Zhang, Dapeng Peng, Shuyu Xie, Dongmei Chen, Yuanhu Pan, Yanfei Tao and Zonghui Yuan
Int. J. Mol. Sci. 2018, 19(12), 3895; https://doi.org/10.3390/ijms19123895 - 05 Dec 2018
Cited by 28 | Viewed by 3390
Abstract
T-2 toxin (T-2) is one of major concern mycotoxins acknowledged as an unavoidable contaminant in human foods, animal feeds and also agriculture products. Thus, a facile and sensitive method is essential for accurate T-2 toxin detection. In our work, a specific electrochemical immunosensor [...] Read more.
T-2 toxin (T-2) is one of major concern mycotoxins acknowledged as an unavoidable contaminant in human foods, animal feeds and also agriculture products. Thus, a facile and sensitive method is essential for accurate T-2 toxin detection. In our work, a specific electrochemical immunosensor based on gold nanoparticles/carboxylic group-functionalized single-walled carbon nanotubes/chitosan (AuNPs/cSWNTs/CS) composite was established. The mechanism of the electrochemical immunosensor was an indirect competitive binding to a given amount of anti-T-2 between free T-2 and T-2-bovine serum albumin, which was conjugated on covalently functionalized cSWNTs decorated on the glass carbon electrode. Afterwards, the alkaline phosphatase labeled anti-mouse secondary antibody was bound to the electrode surface by reacting with the primary antibody. Lastly, alkaline phosphatase catalyzed the hydrolysis of the substrate α-naphthyl phosphate, which produced an electrochemical signal. Compared with conventional methods, the established immunosensor was more sensitive and simpler. Under optimal conditions, this method could quantitatively detect T-2 from 0.01 to 100 μg·L−1 with a detection limit of 0.13 μg·L−1 and favorable recovery 91.42–102.49%. Moreover, the immunosensor was successfully applied to assay T-2 in feed and swine meat, which showed good correlation with the results obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS). Full article
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8 pages, 5753 KiB  
Communication
Integration of a Gold-Specific Whole E. coli Cell Sensing and Adsorption Based on BioBrick
by Li Yan, Peiqing Sun, Yun Xu, Shanbo Zhang, Wei Wei and Jing Zhao
Int. J. Mol. Sci. 2018, 19(12), 3741; https://doi.org/10.3390/ijms19123741 - 24 Nov 2018
Cited by 5 | Viewed by 3348
Abstract
Detection and recovery of heavy metals from environmental sources is a major task in environmental protection and governance. Based on previous research into cell-based visual detection and biological adsorption, we have developed a novel system combining these two functions by the BioBrick technique. [...] Read more.
Detection and recovery of heavy metals from environmental sources is a major task in environmental protection and governance. Based on previous research into cell-based visual detection and biological adsorption, we have developed a novel system combining these two functions by the BioBrick technique. The gold-specific sensory gol regulon was assembled on the gold-chaperone GolB (Gold-specific binding protein), which is responsible for selectively absorbing gold ions, and this led to an integration system with increased probe tolerance for gold. After being incorporated into E. coli, this system featured high-selective detection and recycling of gold ions among multi-metal ions from the environment. It serves as an efficient method for biological detection and recovery of various heavy metals. We have developed modular methods for cell-based detection and adsorption of heavy metals, and these offer a quick and convenient tool for development in this area. Full article
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11 pages, 2719 KiB  
Article
T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production
by Ji Wang, Chenglin Yang, Zhihang Yuan, Jine Yi and Jing Wu
Int. J. Mol. Sci. 2018, 19(11), 3360; https://doi.org/10.3390/ijms19113360 - 27 Oct 2018
Cited by 18 | Viewed by 3790
Abstract
Although mTOR (the mammalian target of rapamycin) can regulate intracellular free Ca2+concentration in normal cultured podocytes, it remains elusive as to how mTORC2/AKT-mediated Ca2+participates in the process of T-2 toxin-induced apoptosis. The potential signaling responsible for intracellular Ca2+ [...] Read more.
Although mTOR (the mammalian target of rapamycin) can regulate intracellular free Ca2+concentration in normal cultured podocytes, it remains elusive as to how mTORC2/AKT-mediated Ca2+participates in the process of T-2 toxin-induced apoptosis. The potential signaling responsible for intracellular Ca2+ concentration changes was investigated using immunoblot assays in an in vitro model of TM3 cell injury induced by T-2 toxin. Changes in Ca2+ were assessed using the Ca2+-sensitive fluorescent indictor dye Fura 2-AM. The cytotoxicity of TM3 cells was assessed with an MTT bioassay, and apoptosis was measured using Annexin V-FITC staining. Following T-2 toxin treatment, the growth of cells, phospho-mTORSer2481, phospho-mTORSer2448, and phospho-AktSer473 were significantly decreased in a time-dependent manner, whereas Ca2+ and apoptosis were increased. T-2 toxin-induced apoptosis was prevented by BAPTA-AM (a Ca2+chelator) and MHY1485 (an mTOR activator), and the application of mTOR activator MHY1485 also prevented the increase of intracellular free Ca2+concentration in TM3 cells. Our results strongly suggest that T-2 toxin exposure induces apoptosis in TM3 cells by inhibiting mTORC2/AKT to promote Ca2+ production. Full article
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Review

Jump to: Editorial, Research

14 pages, 569 KiB  
Review
Progress in Mycotoxins Affecting Intestinal Mucosal Barrier Function
by Zhihua Ren, Chaoyue Guo, Shumin Yu, Ling Zhu, Ya Wang, Hui Hu and Junliang Deng
Int. J. Mol. Sci. 2019, 20(11), 2777; https://doi.org/10.3390/ijms20112777 - 06 Jun 2019
Cited by 78 | Viewed by 4556
Abstract
Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, [...] Read more.
Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, immune barrier, and biological barrier. Firstly, mycotoxins can disrupt the mechanical barrier function of the intestinal mucosa, by destroying the morphology and tissue integrity of the intestinal epithelium. Secondly, mycotoxins can cause changes in the composition of mucin monosaccharides and the expression of intestinal mucin, which in turn affects mucin function. Thirdly, mycotoxins can cause damage to the intestinal mucosal immune barrier function. Finally, the microbiotas of animals closely interact with ingested mycotoxins. Based on existing research, this article reviews the effects of mycotoxins on the intestinal mucosal barrier and its mechanisms. Full article
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36 pages, 2387 KiB  
Review
Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
by Jowita Nowakowska-Gołacka, Hanna Sominka, Natalia Sowa-Rogozińska and Monika Słomińska-Wojewódzka
Int. J. Mol. Sci. 2019, 20(6), 1307; https://doi.org/10.3390/ijms20061307 - 15 Mar 2019
Cited by 30 | Viewed by 7221
Abstract
Several bacterial and plant AB-toxins are delivered by retrograde vesicular transport to the endoplasmic reticulum (ER), where the enzymatically active A subunit is disassembled from the holotoxin and transported to the cytosol. In this process, toxins subvert the ER-associated degradation (ERAD) pathway. ERAD [...] Read more.
Several bacterial and plant AB-toxins are delivered by retrograde vesicular transport to the endoplasmic reticulum (ER), where the enzymatically active A subunit is disassembled from the holotoxin and transported to the cytosol. In this process, toxins subvert the ER-associated degradation (ERAD) pathway. ERAD is an important part of cellular regulatory mechanism that targets misfolded proteins to the ER channels, prior to their retrotranslocation to the cytosol, ubiquitination and subsequent degradation by a protein-degrading complex, the proteasome. In this article, we present an overview of current understanding of the ERAD-dependent transport of AB-toxins to the cytosol. We describe important components of ERAD and discuss their significance for toxin transport. Toxin recognition and disassembly in the ER, transport through ER translocons and finally cytosolic events that instead of overall proteasomal degradation provide proper folding and cytotoxic activity of AB-toxins are discussed as well. We also comment on recent reports presenting medical applications for toxin transport through the ER channels. Full article
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10 pages, 3203 KiB  
Review
Novichoks: The Dangerous Fourth Generation of Chemical Weapons
by Tanos C. C. Franca, Daniel A. S. Kitagawa, Samir F. de A. Cavalcante, Jorge A. V. da Silva, Eugenie Nepovimova and Kamil Kuca
Int. J. Mol. Sci. 2019, 20(5), 1222; https://doi.org/10.3390/ijms20051222 - 11 Mar 2019
Cited by 85 | Viewed by 13406
Abstract
“Novichoks” is the name given to the controversial chemical weapons supposedly developed in the former Soviet Union between the 1970s and the 1990s. Designed to be undetectable and untreatable, these chemicals became the most toxic of the nerve agents, being very attractive for [...] Read more.
“Novichoks” is the name given to the controversial chemical weapons supposedly developed in the former Soviet Union between the 1970s and the 1990s. Designed to be undetectable and untreatable, these chemicals became the most toxic of the nerve agents, being very attractive for both terrorist and chemical warfare purposes. However, very little information is available in the literature, and the Russian government did not acknowledge their development. The intent of this review is to provide the IJMS readers with a general overview on what is known about novichoks today. We briefly tell the story of the secret development of these agents, and discuss their synthesis, toxicity, physical-chemical properties, and possible ways of treatment and neutralization. In addition, we also wish to call the attention of the scientific community to the great risks still represented by nerve agents worldwide, and the need to keep constant investments in the development of antidotes and ways to protect against such deadly compounds. Full article
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18 pages, 2124 KiB  
Review
Biological Toxins as the Potential Tools for Bioterrorism
by Edyta Janik, Michal Ceremuga, Joanna Saluk-Bijak and Michal Bijak
Int. J. Mol. Sci. 2019, 20(5), 1181; https://doi.org/10.3390/ijms20051181 - 08 Mar 2019
Cited by 96 | Viewed by 13465
Abstract
Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as “Chemicals produced by living organisms that have toxic properties for another organism”. Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is [...] Read more.
Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as “Chemicals produced by living organisms that have toxic properties for another organism”. Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is that many biological toxins can be obtained very easily. Simple bacterial culturing systems and extraction equipment dedicated to plant toxins are cheap and easily available, and can even be constructed at home. Many toxins affect the nervous systems of mammals by interfering with the transmission of nerve impulses, which gives them their high potential in bioterrorist attacks. Others are responsible for blockage of main cellular metabolism, causing cellular death. Moreover, most toxins act very quickly and are lethal in low doses (LD50 < 25 mg/kg), which are very often lower than chemical warfare agents. For these reasons we decided to prepare this review paper which main aim is to present the high potential of biological toxins as factors of bioterrorism describing the general characteristics, mechanisms of action and treatment of most potent biological toxins. In this paper we focused on six most danger toxins: botulinum toxin, staphylococcal enterotoxins, Clostridium perfringens toxins, ricin, abrin and T-2 toxin. We hope that this paper will help in understanding the problem of availability and potential of biological toxins. Full article
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