Репозиторий Университета

© 2020 Elsevier B.V. Ecosystems are facing increased pressure due to the emission of many classes of emerging contaminants. However, very little is known about the interactions of these pollutants, such as bisphenols (BPs), plasticizers or pharmaceuticals. By employing bioluminescent bacteria (Microtox assay), we were able to define interactions between selected emerging pollutants (namely BPA, BPS, BPF, BADGE, BADGE·2HCl, DEP, DBP) in ternary mixtures, at environmentally relevant concentration levels (down to as low as 1.89, 1.42, 3.08, and 0.326 μM for, respectively, BPA, BPF, BPS and BADGE·2HCl). We provide the first systematic analysis of bisphenols and phthalates in three component mixtures. Using this system, we performed toxicity modelling with concentration addition (CA) and independent action (IA) approaches, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. Interestingly, we mathematically and experimentally confirmed a novel synergy between BPA, BADGE and BADGE·2HCl. The synergy of BPA, BADGE and BADGE·2HCl is distinct, with both models suggesting these analytes have a similar mode of action (MOA). Moreover, we unexpectedly found a strong antagonistic impact with DEP, in mixtures containing BPA and BADGE analogues, which is confirmed with both mathematical models. Our study also shows that the impact of BPS and BPF in many mixtures is highly concentration dependent, justifying the necessity to perform mixture studies using wide concentration ranges. Overall, this study demonstrates that bioluminescent bacteria are a relevant model for detecting the synergistic and antagonist actions of environmental pollutants in mixtures, and highlights the importance of analyzing combinations of pollutants in higher order mixtures.

© 2020 Elsevier B.V. Bioactive compounds from endophytic fungi exhibit diverse biological activities which include anticancer effect. Capitalising on the abundance of unexplored endophytes that reside within marine plants, this study assessed the anticancer potential of ethyl acetate endophytic fungal extracts (i.e. MBFT Tip 2.1, MBL 1.2, MBS 3.2, MKS 3 and MKS 3.1) derived from leaves, stem and fruits of marine plants that grow along Morib Beach, Malaysia. For identification of endophytic fungi, EF 4/ EF 3 and ITS 1/ ITS 4 PCR primer pairs were used to amplify the fungal 18S rDNA sequence and ITS region sequence, respectively. The resultant sequences were subjected to similarity search via the NCBI GenBank database. High-performance thin layer chromatography (HPTLC) hyphenated with bioassays was used to characterise the extracts in terms of their phytochemical profiles and bioactivity. Microchemical derivatisation was used to assess polyphenolic and phytosterol/ terpenoid content whereas biochemical derivatisation was used to establish antioxidant activities and α-amylase enzyme inhibition. The sulforhodamine B (SRB) assay was used to assess the anticancer effect of the extracts against HCT116 (a human colorectal cancer cell line). The present results indicated MBS 3.2 (Penicillium decumbens) as the most potent extract against HCT116 (IC50 = 0.16 μg/mL), approximately 3-times more potent than 5-flurouracil (IC50 = 0.46 μg/mL). Stepwise multiple regression method suggests that the anticancer effect of MBS 3.2 could be associated with high polyphenolic content and antioxidant potential. Nonlinear regression analysis confirmed that low to moderate α-amylase inhibition exhibits maximum anticancer activity. Current findings warrant further in-depth mechanistic studies.

© 2020 Background: The sprouts of Brassica vegetables are known from their nutritional and chemopreventive values. Moreover, sprouts fortification with some trace elements, like selenium, may increase their importance in human diet. Thus, the aim of our study was to examine if selenium enrichment of kale and kohlrabi sprouts may influence their biochemical properties (phenolic acids and L-tryptophan content, antioxidant potential) or cytotoxic activity. Additional aim of the study was to evaluate the profile of selenium compounds and to describe the multidimensional interactions between the mentioned parameters. Methods: Selenium content in the sprouts was evaluated by double-channel atomic fluorescence spectrometer AFS-230 with the flow hydride-generation system. Separation of selenium species in water soluble fraction was performed by size-exclusion LC-ICP-MS. The identification and quantification of phenolic acids and L-tryptophan was performed by HPLC. For antioxidant activity DPPH and FRAP methods were used. Cytotoxic activity of the sprouts extracts on a panel of human metastatic carcinoma cells was evaluated by MTT test. Results: Selenium content in the fortified sprouts was several orders of magnitude higher than in the unfortified ones. Only small percentage of supplemented selenium (ca. 10 %) was incorporated into the sprouts as seleno-L-methionine, while the other detected selenium species remained unidentified. Selenium fortification differently stimulated the production of phenolic acids (sinapic, chlorogenic, isochlorogenic and caffeic acid) in the tested sprouts, depending on the particular species, selenium dose and the investigated compound. PCA analysis revealed strong correlation between antioxidant parameters and phenolic acids and L-tryptophan, while Se correlated only with caffeic acid. The sprouts extracts (≥1 mg/mL) showed cytotoxic potency to all the studied cancer cell lines (SW480, SW620, HepG2, SiHa), regardless the selenium supplementation. Conclusion: Se-fortified kale and kohlrabi sprouts are good candidates for functional food ingredients. Moreover, these results indicate that the sprouts enriched with sodium selenite show higher nutritional value, without significant changes in their cytotoxic activity.

© 2019 Institution of Chemical Engineers Enabling technologies have led to the design of new extraction protocols for naturally occurring compounds that are fast, sustainable and have low energy demands. Ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have been used, in this study, for the recovery of valuable nutraceuticals and primary metabolites from pumpkin seeds (Curcubita sp.) and have been compared with conventional methods. In order to optimise extraction parameters and conditions, we have compared yields, total phenolic content, antioxidant activity, as well as fatty-acid and lipid profiles. The best yield, in both lipophilic and hydrophilic compounds, was achieved under UAE with a ternary solvent mixture (hexane/ethanol/water - 30:49:21). However, the highest phenolic content and antioxidant capacity were obtained using MAE under subcritical conditions with good extraction yields. The oil composition, as obtained using GC-FID analyses, showed a prevalence for unsaturated fatty acids; mainly linoleic and oleic acids. The use of UAE with ternary mixtures presented the highest lipid content and a slightly higher percentage of unsaturated compounds. Preliminary tests to verify the scalability of UAE with a ternary mixture showed that the extraction performance was maintained when using larger volumes (factor 10). This study will pave the road for the potential exploitation of UAE as a fast and efficient procedure for the simultaneous recovery of lipophilic and hydrophilic compounds from pumpkin seeds.

© 2018 Fedoros et al. Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties. The results of diversity assay demonstrate that BP-Cx-1 has multiple biological effects on neurotransmitters receptors, ligand-gated ion channels and transporters. Of particular importance is that the major part of identified molecular targets are involved in modulation of inflammation and immune response and might be related to tumorigenesis. Characterization of molecular composition of BP-Cx-1 with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and subsequent identification of possible active components by searching for molecular matches in silico in ChEMBL indicated polyphenolic components, nominally, flavonoids, sapogenins, phenanthrenes, as the major carriers of biological activity of BP-Cx-1. In vitro and in silico target screening yielded overlapping lists of proteins: adenosine receptors, dopamine receptor DRD4, glucocorticoid receptor, serotonin receptor 5-HT1, prostaglandin receptors, muscarinic cholinergic receptor, GABAA receptor. The pleiotropic molecular activities of polyphenolic components are beneficial in treatment of multifactorial disorders such as diseases associated with chronic inflammation and cancer.

© 2017 Informa UK Limited, trading as Taylor  &  Francis Group. Background: Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal guideline-recommended drug; omalizumab, has limited effect, side effects or is too expensive or unavailable. Herein, we systematically review the evidence for the use of the nonbiologic treatments in antihistamine-refractory chronic urticaria. Methods: We performed a systematic review of the literature using PubMed and Webofscience and identified studies that reported use of one or more of the nonbiological, nonantihistamine treatment options for chronic urticaria. The studies were evaluated based on study design, number of patients, effect of treatment and safety. Results: We identified 118 studies or case series with 13 different treatments (azathioprine, chloroquine, colchicine, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate, montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a paucity of controlled trials for most of the treatments reviewed albeit the strongest evidence in favor of a beneficial effect in chronic urticaria was, apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed by IVIG. Conclusion: The treatment options reviewed should be seen as potential alternatives in treatment-resistant chronic urticaria where guideline-based selections have failed. However, larger controlled trials are warranted to advance the level of evidence, possibly supporting some treatments’ future recommendation in selected patients.

© 2018 Nutritec. All Rights Reserved.  The aim of this study was to examine the effect of polyphenol quercetin on morphological changes in nonalcoholic fatty liver disease (NAFLD) in rats fed high-fructose diet. Material and methods. For 20 weeks animals (n=8 in each group) of the 1 st group were given standard diet and water; the 2 nd group - standard diet and 20% fructose solution; the 3 rd group - standard diet with quercetin supplementation (0.1%) and 20% fructose solution. Formalin-fixed and paraffin-embedded liver samples were sectioned, stained (hematoxilin and eosin, Van Gieson's stain), evaluated with the use of the SAF and NAS scales. Results and discussion. Histological assessment did not reveal pathology in the structure of the liver of the 1 st group rats (SOAOFO; NAS - 0, fibrosis - 0). The 2 nd group rat livers disclosed micro-, mid- and macrovesicular steatosis, inflammation without ballooning, pericellular and periportal fibrosis (S2A1F2; NAS - 3, fibrosis - 2). Quercetin-treated rats exhibited in liver significantly less steatosis without significant changes in inflammation and fibrosis features (S1A1F2; NAS - 2, fibrosis - 2) compared with rats of the 2 nd group. Conclusion. The data obtained demonstrate the ability of quercetin to inhibit the development of NAFLD in rats fed a diet with a high content of fructose, by reducing the severity of hepatostatosis.

© Izdatel'stvo Meditsina. All rights reserved. In the article, an overview of the information on the method and application technology of SWOT (Strengths, Weaknesses Opportunities, Threats) analysis is presented. The specific characters of the method, the object domain of its application, the task, the methodology are disclosed. An interesting idea is the scheme of the options used to achieve more complete benefit from the method. The strengths and the shortcomings of the SWOT analysis noted by experts in the field of its application are given. Further on, the authors propose an innovative technology for using the SWOT model to develop personalized forecasting, preservation, development, and management of health, based on the provisions of the functional direction of genetics - phenomics. The advantages of technology, the urgency of its application are revealed. The new technology is based on provisions of the development of the theory of the essential adaptation. To ensure the state of health the functioning level of the body's systems must be consistent with the optimality, namely with their response norms, which determine the individual phenotype. In the process of the organism adaptation to the conditions of the external environment, the central nervous system (it's a known fact) and the significant body system (the system with the maximum response norm), determining, respectively, the specific and nonspecific responses of the organism will be released by their activity. In the interaction of body systems, it is important to take the ordering into consideration. Dominant systems can actively involve other systems of the body to the process of adaptation according to the principle of the interaction with them, by strengthening or decreasing their activity. Taking into account the direction of interaction (inhibition, toning), this fact becomes important for understanding the pathogenesis of diseases, their targeted prevention, and treatment. A comprehensive record of the mechanisms of the formation of a specific and nonspecific reaction is used in the interest of identifying and effectively preventing functional disorders in the body. The SWOT analysis technology of personalized forecasting, preservation, development and health management eliminates the main drawbacks of SWOT analysis. On the other hand, the SWOT analysis technology helps to expand the range of application of phenomics, depending on the opportunities and threats of the environment.