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1.
Weronika Gonciarz ukasz Lechowicz Mariusz Urbaniak Wiesaw Kaca Magdalena Chmiela 《International journal of molecular sciences》2021,22(1)
Infections due to Gram-negative bacteria Helicobacter pylori may result in humans having gastritis, gastric or duodenal ulcer, and even gastric cancer. Investigation of quantitative changes of soluble biomarkers, correlating with H. pylori infection, is a promising tool for monitoring the course of infection and inflammatory response. The aim of this study was to determine, using an experimental model of H. pylori infection in guinea pigs, the specific characteristics of infrared spectra (IR) of sera from H. pylori infected (40) vs. uninfected (20) guinea pigs. The H. pylori status was confirmed by histological, molecular, and serological examination. The IR spectra were measured using a Fourier-transform (FT)-IR spectrometer Spectrum 400 (PerkinElmer) within the range of wavenumbers 3000–750 cm−1 and converted to first derivative spectra. Ten wavenumbers correlated with H. pylori infection, based on the chi-square test, were selected for a K-nearest neighbors (k-NN) algorithm. The wavenumbers correlating with infection were identified in the W2 and W3 windows associated mainly with proteins and in the W4 window related to nucleic acids and hydrocarbons. The k-NN for detection of H. pylori infection has been developed based on chemometric data. Using this model, animals were classified as infected with H. pylori with 100% specificity and 97% sensitivity. To summarize, the IR spectroscopy and k-NN algorithm are useful for monitoring experimental H. pylori infection and related inflammatory response in guinea pig model and may be considered for application in humans. 相似文献
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Mariusz Ciesielski Bohdan Mochnacki 《International Journal of Cast Metals Research》2019,32(4):213-220
The thermal processes proceeding in the casting-mould system are analysed. Solidification process can be described in the different ways. One of them consists in the application of the Fourier–Kirchhoff equation in which the source function controlling the phase change is introduced. In this paper, two approaches to the modelling of pure metals solidification, i.e. the solidification proceeding at the constant temperature and in the artificially introduced interval of temperature are considered. Numerical model used at the stage of computations is constructed using the Control Volume Method in which the principle of conservation of energy (taking also into account the release of latent heat of solidification) is applied to each control volume ensuring the correctness of the model. The use of Voronoi/Thiessen tessellation to the discretization of the casting-mould system can accurately reproduce the shape of each sub-domain. In the final part of the paper, the examples of computations are shown. 相似文献
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Dr. Eric M. Lewandowski Dr. Łukasz Szczupak Dr. Aleksandra Kowalczyk Dr. Gracia Mendoza Prof. Manuel Arruebo Lian M. C. Jacobs Prof. Paweł Stączek Prof. Yu Chen Prof. Konrad Kowalski 《Chembiochem : a European journal of chemical biology》2020,21(15):2187-2195
The conjugation of organometallic groups to current β-lactam antibiotics is a field of increasing study due to the ability of certain organometallic groups to enhance the antibiotic potency of these drugs. Herein, we report the antibacterial properties of two metallocenyl (ferrocenyl and ruthenocenyl) 7-aminocephalosporanic acid (7-ACA) antibiotic conjugates. Continuing a trend we found in our previous studies, the ruthenocenyl conjugate showed greater antibacterial activity than its ferrocenyl counterpart. Compared with the previously published 7-aminodesacetoxycephalosporanic acid (7-ADCA) conjugates, the 3-acetyloxymethyl group significantly improved the compounds’ activity. Furthermore, the Rc-7-ACA compound was more active against clinical Staphylococcus aureus isolates than the ampicillin reference. Noticeably, neither of the two new compounds showed an undesirable toxic effect in HeLa and L929 cells at the concentrations at which they displayed strong antibacterial effects. The antibacterial activity of the two metallocenyl 7-ACA derivatives was further confirmed by scanning electron microscopy (SEM). SEM micrographs showed that bacteria treated with metallocenyl 7-ACA derivatives feature cell wall damage and morphology changes. Using a CTX-M-14 β-lactamase competition assay based on nitrocefin hydrolysis, we showed that the Rc-7-ACA bound more favorably to CTX-M-14 than its ferrocenyl counterpart, again confirming the superiority of the ruthenocenyl moiety over the ferrocenyl one in interacting with proteins. We also report a 1.47 Å resolution crystal structure of Rc-7-ACA in complex with the CTX-M-14 E166A mutant, an enzyme sharing a similar active site configuration with penicillin-binding proteins, the molecular target of β-lactam antibiotics. These results strengthen the case for the antibacterial utility of the Rc and Fc groups. 相似文献
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Pazera Marcin Buciakowski Mariusz Witczak Marcin Mrugalski Marcin 《Neural computing & applications》2020,32(2):379-389
Neural Computing and Applications - The paper is devoted to the problem of a neural network-based robust simultaneous actuator and sensor faults estimator design for the purpose of the fault... 相似文献
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Dr. Tomasz Ratajczyk Prof. Dr. Gerd Buntkowsky Dr. Torsten Gutmann Dr. Bartłomiej Fedorczyk Dr. Adam Mames Dr. Mariusz Pietrzak Zuzanna Puzio Piotr Grzegorz Szkudlarek 《Chembiochem : a European journal of chemical biology》2021,22(5):855-860
The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H2 results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the 1H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan 1H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide. 相似文献
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Monika K. Nisiewicz Agata Kowalczyk Anna Sobiepanek Agata Jagielska Barbara Wagner Julita Nowakowska Marianna Gniadek Ireneusz P. Grudzinski Tomasz Kobiela Anna M. Nowicka 《International journal of molecular sciences》2021,22(1)
Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas. 相似文献
10.
Anna Mroczek Joanna Zawitkowska Jerzy Kowalczyk Monika Lejman 《International journal of molecular sciences》2021,22(2)
Acute lymphoblastic leukaemia (ALL) is a relevant form of childhood neoplasm, as it accounts for over 80% of all leukaemia cases. T-cell ALL constitutes a genetically heterogeneous cancer derived from T-lymphoid progenitors. The diagnosis of T-ALL is based on morphologic, immunophenotypic, cytogenetic, and molecular features, thus the results are used for patient stratification. Due to the expression of surface and intracellular antigens, several subtypes of T-ALL can be distinguished. Although the aetiology of T-ALL remains unclear, a wide spectrum of rearrangements and mutations affecting crucial signalling pathways has been described so far. Due to intensive chemotherapy regimens and supportive care, overall cure rates of more than 80% in paediatric T-ALL patients have been accomplished. However, improved knowledge of the mechanisms of relapse, drug resistance, and determination of risk factors are crucial for patients in the high-risk group. Even though some residual disease studies have allowed the optimization of therapy, the identification of novel diagnostic and prognostic markers is required to individualize therapy. The following review summarizes our current knowledge about genetic abnormalities in paediatric patients with T-ALL. As molecular biology techniques provide insights into the biology of cancer, our study focuses on new potential therapeutic targets and predictive factors which may improve the outcome of young patients with T-ALL. 相似文献