Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood–brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC—pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks. 相似文献
Effect of chemical composition of Mg-xCu based alloys (x = 9.94–58.00 wt %) modified by KCl upon their hydrogen storage performance was studied. Kinetic curves and pressure-concentration isotherms were measured in the ranges up to 60 bar and 388 °C, respectively. It was observed that desorption rate dc/dt is not significantly influenced by the composition. Unknown Cu-rich phase was detected that has shown a catalytic effect on desorption from a mixture with other phases. Activation energy of hydrogen desorption decreased with increasing x from 180 kJ/mol down to 98 kJ/mol. Average hydride dissociation enthalpy, ΔH, for the lowest plateau was 75 kJ/mol which is equal to literature value for pure Mg. Slightly lover average value, 67 kJ/mol was obtained for the second plateau and ΔH for the third one decreased from 70 kJ/mol for the lowest to 49 kJ/mol for the highest x. 相似文献
In recent years, there has been an increasing interest in investigating the carcinogenicity of mycotoxins in humans. This systematic review aims to provide an overview of data linking exposure to different mycotoxins with human cancer risk. Publications (2019 and earlier) of case–control or longitudinal cohort studies were identified in PubMed and EMBASE. These articles were then screened by independent reviewers and their quality was assessed according to the Newcastle–Ottawa scale. Animal, cross‐sectional, and molecular studies satisfied criteria for exclusion. In total, 14 articles were included: 13 case–control studies and 1 longitudinal cohort study. Included articles focused on associations of mycotoxin exposure with primary liver, breast, and cervical cancer. Overall, a positive association between the consumption of aflatoxin‐contaminated foods and primary liver cancer risk was verified. Two case–control studies in Africa investigated the relationship between zearalenone and its metabolites and breast cancer risk, though conflicting results were reported. Two case–control studies investigated the association between hepatocellular carcinoma and fumonisin B1 exposure, but no significant associations were observed. This systematic review incorporates several clear observations of dose‐dependent associations between aflatoxins and liver cancer risk, in keeping with IARC Monograph conclusions. Only few human epidemiological studies investigated the associations between mycotoxin exposures and cancer risk. To close this gap, more in‐depth research is needed to unravel evidence for other common mycotoxins, such as deoxynivalenol and ochratoxin A. The link between mycotoxin exposures and cancer risk has mainly been established in experimental studies, and needs to be confirmed in human epidemiological studies to support the evidence‐based public health strategies. 相似文献
Gasoline engine emissions have been classified as possibly carcinogenic to humans and represent a significant health risk. In this study, we used MucilAir™, a three-dimensional (3D) model of the human airway, and BEAS-2B, cells originating from the human bronchial epithelium, grown at the air-liquid interface to assess the toxicity of ordinary gasoline exhaust produced by a direct injection spark ignition engine. The transepithelial electrical resistance (TEER), production of mucin, and lactate dehydrogenase (LDH) and adenylate kinase (AK) activities were analyzed after one day and five days of exposure. The induction of double-stranded DNA breaks was measured by the detection of histone H2AX phosphorylation. Next-generation sequencing was used to analyze the modulation of expression of the relevant 370 genes. The exposure to gasoline emissions affected the integrity, as well as LDH and AK leakage in the 3D model, particularly after longer exposure periods. Mucin production was mostly decreased with the exception of longer BEAS-2B treatment, for which a significant increase was detected. DNA damage was detected after five days of exposure in the 3D model, but not in BEAS-2B cells. The expression of CYP1A1 and GSTA3 was modulated in MucilAir™ tissues after 5 days of treatment. In BEAS-2B cells, the expression of 39 mRNAs was affected after short exposure, most of them were upregulated. The five days of exposure modulated the expression of 11 genes in this cell line. In conclusion, the ordinary gasoline emissions induced a toxic response in MucilAir™. In BEAS-2B cells, the biological response was less pronounced, mostly limited to gene expression changes. 相似文献
Magnesium (Mg) as a potential material for biodegradable implants is attractive due to its mechanical similarity to the bone tissue and nontoxic corrosion products. However, the rapid corrosion rate of bare magnesium is associated with hydrogen release, which may complicate the healing process. The corrosion rate may be reduced by suitable alloying, but concurrently the biocompatibility of such alloy might be deteriorated. Another way of reduction of the corrosion rate is coating. Hydroxyapatite (HA)-based coating is considered to improve biocompatibility as well as decrease the corrosion rate by the barrier effect. In this study, ultrathin (150 nm) HA and HA containing Sr coatings are deposited via pulsed electron ablation technique on pure Mg. The microstructure of the coating was assessed by scanning electron microscopy. Electrochemical methods were used to investigate the corrosion properties of prepared coatings. The materials covered by this layer were characterized by superior corrosion behavior, with corrosion rates of coated samples up to five times lower as compared with the uncoated ones. Such coating is the thinnest coating found in the literature sources. 相似文献
The role of starch aerogel (St-AG) and carboxymethyl cellulose (CMC) as biolgical active compounds, when they subjected for complexation with metal ions, is assessed in this work. The complexation is carried out with palladium(II) and copper(II) ions, in solid state. Different tools of analysis are carried out to characterize and elucidate the structures of these complexes, namely: elemental analysis, IR, thermal analysis, magnetic measurement and molar conductance techniques. All synthesized complexes are formed with 1:2 (metal:ligand) stoichiometry except the case of aerogel starch 1:1 (Pd:starch). All isolated complexes show a satisfactory cytotoxic effect results against colon cancer cell lines HCT11. Additionally, these complexes are screened for their antibacterial activities against two types of Gram positive and negative bacteria. Molecular docking investigation confirmed the cytotoxicity and antibacterial results. Proton–ligands association constants and their complex formation constants with some bivalent metal ions, using potentiometric method show that the complexes formed in solution have a stoichiometry of 1:1 [metal:ligand]. The effects of metal ion, ionic radius, electronegativity and nature of ligand on the formation constants are discussed. The formation constants of the complexes with 3D transition metals followed the order Mn2+ < Co2+ < Ni2+ < Cu2+ > Zn2+. 相似文献
The paper presents a system for monitoring and assessment the speech quality in the IP telephony infrastructures using modular probes. The probes are placed at key nodes in the network where aggregating packet loss data. The system dynamically measures speech quality and results are collected on a central server. For data analysis we applied four-state Markov model for modeling the impact of network impairments on speech quality, afterwards, the resilient back propagation (Rprop) algorithm was used to train a neural network. Information about the speech quality are displayed in the form of automatically generated graphs and tables. The proposed solution has been tested with selected codecs and further generalizes the already presented concepts of the speech quality estimation in the IP environment.