1,721,048 research outputs found
Mechanisms of Fumonisin B1 Toxicity: A Computational Perspective beyond the Ceramide Synthases Inhibition
No full textFumonisins are mycotoxins produced by Fusarium fujikuroi species complex that may contaminate food and feed threatening human and animal health. Among the fumonisins group, fumonisin B1 is the most widespread and best characterized in terms of toxicity, while additional toxicological data on its congeners, such as N-acylated and hydrolyzed forms, need to be collected to support the group-based risk assessment. The inhibition of ceramide synthase has been identified as the key molecular mechanism of fumonisins toxicity resulting in modifications of sphingolipids rheostat. However, the existence of ancillary mechanisms and biological targets are likely to occur given the growing number of evidence reporting the multitarget mechanisms of mycotoxins toxicity. Therefore, in the framework of the early warning analysis of multitarget toxicity of fumonisins group, the present study aimed at searching potential targets for future hazard characterization studies of fumonisin B1 and its hydrolyzed and N-acetylated forms. In particular, on the basis of structural analogies with known inhibitors, the molecular interaction between N-acylated and hydrolyzed forms of fumonisin B1 and either ceramide transfer protein or sphingosine kinase I was assessed with a molecular modeling study. Our results pointed out that the molecular features of N-acylated hydrolyzed fumonisin B1 and hydrolyzed fumonisin B1 may allow the interaction with the ceramide transfer protein and with the sphingosine kinase I enzyme, respectively. Overall, our results identified such proteins as relevant targets that might take part in fumonisins group toxicity, adding plausible mechanistic insights to better understand fumonisins toxicity. Moreover, possible divergences in the mechanisms of action of fumonisin B1 and its modified forms were identified pointing out the need to assess their relevance with high priority to enhance the understanding of group toxicity
In silico analysis sheds light on the structural basis underlying the ribotoxicity of trichothecenes—A tool for supporting the hazard identification process
No full textAn in silico perspective on the toxicodynamic of tetrodotoxin and analogues – A tool for supporting the hazard identification
No full textA computational study toward the “personalized” activity of alternariol – Does it matter for safe food at individual level?
No full textMycotoxins in food may threat public health at a global scale. However, for most of them, the current body of knowledge does not support a proper risk assessment and more data are needed to clarify their toxicity. In particular, the assessment of “personalized” action may succeed in understanding and counteracting the effects of many toxicants. Therefore, the assessment of “personalized” toxicology of mycotoxins might deserve attention to foster the understanding of their mechanisms of toxicity and to eventually improve the assessment of risk. This work dealt with the early warning analysis of possible differences in eliciting androgenic stimuli by alternariol, a widespread mycotoxin produce by Alternaria species, when mutations on the androgen receptor occur. It was applied a computational study based on docking simulations, pharmacophore modeling and molecular dynamics to assess the capability of alternariol to interact with the androgen receptor bearing the M749I substitution – which confers insensitivity to androgens stimulation. The results collected pointed to possible “protective” effects against alternariol suggesting: i) the likely existence of inter-individual responses to alternariol stimulation; ii) the meaningfulness of collecting data on “personalized” response to mycotoxins toward a more precise paradigm addressing the risk assessment at the individual level
Application of lactic acid fermentation to elderberry juice: Changes in acidic and glucidic fractions
No full textIntegrated In Silico – In Vitro Study Investigating Dipeptides as Chorismate Synthase Modulators: Spotlight on Its Mechanism of Action
No full textCampylobacter jejuni is a widespread foodborne pathogen causing campylobacteriosis, a disease leading to diarrhea, fever, and gastroenteritis, able to adapt to many niches. Here, we present a hybrid in silico/in vitro study investigating the modulation of C. jejuni chorismate synthase by peptides. This enzyme belongs to the shikimate pathway, and it is an interesting target for selective growth modulation, being crucial for bacteria but not present in animals. To account for the identification of "natural" modulators, a library of 400 dipeptides is screened in silico through docking and molecular dynamics simulations to identify possible inhibiting sequences. The dipeptide glutamate-aspartate (ED) stood out, emulating the pharmacophoric fingerprint and interaction of the enzyme's natural substrate. Serendipitously, in vitro trials revealed ED as an activity enhancer. Considering the growth of C. jejuni in protein-rich matrices, this outlined a possibly relevant matrix-dependent effect worthy of dedicated investigations. The underpinning mechanisms are computationally investigated, describing possible ED-dependent effects on substrate/product turnover and enzyme structural stability. This study deepened the understanding of chorismate synthase and opened new directions in designing food-grade peptide-based modulators. This may provide ground to improve controlling bacterial growth in diverse contexts, including food safety and environmental/agricultural hygiene
Analytical issue related to fumonisins: A matter of sample comminution?
No full textThe aim of the present work was to evaluate the effect of sample particle size on fumonisins recovery during the extraction step. Four maize samples were ground and the resulted flours were separated in six different fractions according to their particle size (1000-250 μm). Fumonisin B1 and B2 were quantified on each fraction, as well as on the unfractionated sample by HPLC-MS/MS. Furthermore, the proximate analysis was carried out to exclude the influence of macro-constituent on the mycotoxins distribution. Although the six maize fractions were found to be characterized by the same macro-constituent composition, a significant increase (p < 0.000) of fumonisins content was observed in all the analysed samples. Extraction yields up to five times higher were found in the finer flours. From the above, it is clear that the sample particle size has a significant impact on the fumonisins recovery. The outcomes suggest that sample granulometry should be standardized for ensuring accuracy and reliability of the analysis results. Overall, the results of this study, although still preliminary, may offer a reliable analytical solution to finally address the “hidden fumonisin issue”
Polyphenol profiling and concentration in peach fruits subjected to UV-B irradiation in post-harvest
No full textGroup detection of DON and its modified forms by an ELISA kit
No full textDeoxynivalenol (DON) and its modified forms (3-, and 15-acetyl-DON, DON-3-glucoside) are commonly analysed by chromatographic methods. Indeed, coupled with proper extraction and clean-up, LC-MS represents the best approach for multi-mycotoxin measurements. On the other hand, immunochemistry-based methods are possibly able to detect a family of structurally related compounds, although the determination of single contributions is not possible so far. However, ELISA methods often lead to an apparent overestimation of the mycotoxins content because modified forms and matrix components can potentially cross-react with the antibodies (designed for the parent toxin). Several data about the possible cross-reactivity of commercial DON-detecting ELISA kit are reported in the literature so far. Data are commonly obtained in buffer solutions or in matrix-matched solutions, but comparison of a set of naturally incurred samples has never been reported. In the present work the accuracy of a commercial DON-detecting ELISA kit was evaluated on naturally incurred soft wheat (n = 15) and maize (n = 15), taking into account the matrix effect. Recovery was calculated considering the DON concentration found by LC-MS/MS and the total DON concentration, expressed as the sum of DON and its modified forms found by LC-MS/MS. The obtained data clearly show that, when 3-modified forms of DON occur in the sample, the ELISA kit does actually detect them, thus returning an apparent overestimation if only DON content is considered. When the ELISA recovery is calculated on the total DON content, the accuracy of the analysis increases and the variability decreases. According to our data, the ELISA kit seems to be a promising group detection tool for the accurate evaluation of DON and its modified forms, expressed as sum of DON, DON-3Glc and 3Ac-DON, for soft wheat and maize samples.</p
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