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781.
Alicja Chrzanowska Marta Struga Piotr Roszkowski Micha Koliski Sebastian Kmiecik Karolina Jabrzykowska Anna Zabost Joanna Stefaska Ewa Augustynowicz-Kope Magorzata Wrzosek Anna Bielenica 《International journal of molecular sciences》2022,23(11)
Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (1m–16m) were synthesized with good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. They were the most effective for prostate cancer cells with an IC50 below 5 µM for respective conjugates with sorbic (2m), oleic (4m), 6-heptenoic (10m), linoleic (11m), caprylic (15m), and stearic (16m) acids. All derivatives were evaluated against a panel of standard and clinical bacterial strains, as well as towards mycobacteria. The highest activity towards standard isolates was observed for the acetic acid derivative 14m, followed by conjugates of unsaturated crotonic (1m) and sorbic (2m) acids. The activity of conjugates tested against an expanded panel of clinical coagulase-negative staphylococci showed that the compound (14m) was recognized as a leading structure with an MIC of 0.5 μg/mL denoted for all quinolone-susceptible isolates. In the group of CP derivatives, sorbic (2) and geranic (3) acid amides exhibited the highest bactericidal potential against clinical strains. The M. tuberculosis Spec. 210 strain was the most sensitive to sorbic (2m) conjugate and to conjugates with medium- and long-chain polyunsaturated acids. To establish the mechanism of antibacterial action, selected CP and MXF conjugates were examined in both topoisomerase IV decatenation assay and the DNA gyrase supercoiling assay, followed by suitable molecular docking studies. 相似文献
782.
Henry H. L. Wu Ewa M. Goldys Carol A. Pollock Sonia Saad 《International journal of molecular sciences》2022,23(14)
Chronic kidney disease (CKD) is a global health issue, affecting more than 10% of the worldwide population. The current approach for formal diagnosis and prognostication of CKD typically relies on non-invasive serum and urine biomarkers such as serum creatinine and albuminuria. However, histological evidence of tubulointerstitial fibrosis is the ‘gold standard’ marker of the likelihood of disease progression. The development of novel biomedical technologies to evaluate exfoliated kidney cells from urine for non-invasive diagnosis and prognostication of CKD presents opportunities to avoid kidney biopsy for the purpose of prognostication. Efforts to apply these technologies more widely in clinical practice are encouraged, given their potential as a cost-effective approach, and no risk of post-biopsy complications such as bleeding, pain and hospitalization. The identification of biomarkers in exfoliated kidney cells from urine via western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence techniques, measurement of cell and protein-specific messenger ribonucleic acid (mRNA)/micro-RNA and other techniques have been reported. Recent innovations such as multispectral autofluorescence imaging and single-cell RNA sequencing (scRNA-seq) have brought additional dimensions to the clinical application of exfoliated kidney cells from urine. In this review, we discuss the current evidence regarding the utility of exfoliated proximal tubule cells (PTC), podocytes, mesangial cells, extracellular vesicles and stem/progenitor cells as surrogate markers for the early diagnosis and prognostication of CKD. Future directions for development within this research area are also identified. 相似文献
783.
Ewa Tomaszewska Halyna Rudyk Izabela
wietlicka Monika Huas-Stasiak Janine Donaldson Marta Arczewska Siemowit Muszyski Piotr Dobrowolski Maria Mielnik-Baszczak Marcin Bartomiej Arciszewski Volodymyr Kushnir Oksana Brezvyn Viktor Muzyka Ihor Kotsyumbas 《International journal of molecular sciences》2021,22(22)
Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. The rats were randomly allocated to either a control group (n = 6), not treated with FBs, or to one of the two groups intoxicated with FBs (either at 60 mg FB/kg b.w. or at 90 mg FB/kg b.w. Numerous negative, offspring sex-dependent effects of maternal FB exposure were observed with regards to the histomorphometry of trabecular bone. These effects were due to FB-inducted alterations in bone metabolism, as indicated by changes in the expression of selected proteins involved in bone development: tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF). The immunolocalization of MMPs and TIMP-2 was performed in trabecular and compact bone, as well as articular and growth plate cartilages. Based on the results, it can be concluded that the exposure of pregnant dams to FB negatively affected the expression of certain proteins responsible for bone matrix degradation in newborns prenatally exposed to FB in a dose- and sex-dependent manner. 相似文献
784.
Ewa Fuc Dagmara Złotkowska Emilia Stachurska Barbara Wróblewska 《Journal of dairy science》2018,101(12):10703-10713
The aim of this study was to evaluate the ex vivo and in vivo studies immune potential of α- and κ-casein. Ex vivo, naïve mouse splenocytes were stimulated with α- or κ-casein. After 120 h of culture, the proliferation index (PI), determined by 3-(4,5 dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and carboxyfluorescein diacetate N-succinimidyl ester (CFSE) staining, did not vary for either antigen, suggesting similar ex vivo immunogenic potential of both casein fractions. In vivo, BALB/ccmdb mice were sensitized with α- or κ-casein and then gavaged with primary antigen. Mice immunized with α-casein had higher levels of IgG (216.33) and IgA (210.22) in serum at the end of the experiment compared with mice immunized with κ-casein (215 and 29.3 for IgG and IgA, respectively). The use of α-casein for mouse immunization and ex vivo lymphocyte stimulation resulted in higher concentrations of secreted cytokines (IL-4, IL-10) compared with κ-casein stimulation. This is consistent with increasing regulatory T cell (Treg) lymphocyte populations, independent of the antigen used for stimulation. In summary, the immunogenic potential of α- and κ-casein was similar. Humoral and cellular immune responses confirmed their strong, independent potential to induce B and T cells. We propose that the lymphocyte proliferation index be used as an initial screening for protein immunogenicity. 相似文献
785.
Vonnahme KA Redmer DA Borowczyk E Bilski JJ Luther JS Johnson ML Reynolds LP Grazul-Bilska AT 《Reproduction (Cambridge, England)》2006,131(6):1115-1126
Corpora lutea and blood samples were collected from superovulated ewes 0, 4, 8, 12 and 24 h after prostaglandin F(2alpha) (PGF) analog injection on day 10 of the estrous cycle. Changes in vascular cell and fibroblast composition, apoptosis and mRNA expression for several angiogenic factors in the corpus luteum (CL) were determined. While peripheral progesterone concentration decreased at 24 h after PGF injection, CL weight did not change. The area of positive BS-1 lectin staining (endothelial cell marker), smooth muscle cell actin (SMCA; pericyte and SMC marker), collagen type 1 (fibroblast marker), and the rate of cell death changed in luteal tissues after PGF treatment. In association with these cellular changes, mRNA for several angiogenic factors including vascular endothelial growth factor (VEGF) and receptors (Flt and KDR), basic fibroblast growth factor (FGF2) and receptor, angiopoietin (ANGPT) 1 and receptor Tie-2, endothelial nitric oxide synthase (NOS3), and angiotensin II receptor 1 (AT1) were altered. Changes in endothelial cell marker expression were positively correlated with changes in VEGF and NO systems. In addition, changes in mRNA expression for VEGF, Flt and KDR were positively correlated with changes in ANGPT2, Tie-2, and NOS3, indicating a functional relationship. This data demonstrates that after an initial increase, the endothelial component of the vascular bed decreases during PGF-induced luteal regression. However, SMCA expression remained high during luteal regression, potentially indicating a role of pericytes and vascular SMC in luteolysis, likely to regulate tissue remodeling and to maintain the integrity of larger blood vessels. Further, it appears that early regression may increase collagen type 1 production and/or expression by fibroblasts. Expression of angiogenic factors is influenced by PGF-induced luteolysis and may serve to maintain vascular structure in order to aid luteal regression. 相似文献
786.
Paula Ossowicz-Rupniewska Joanna Klebeko Ewelina
witek Karolina Bilska Anna Nowak Wiktoria Duchnik ukasz Kucharski ukasz Struk Karolina Wenelska Adam Klimowicz Ewa Janus 《International journal of molecular sciences》2022,23(8)
Modifications of (RS)-2-[4-(2-methylpropyl)phenyl] propanoic acid with amino acid isopropyl esters were synthesised using different methods via a common intermediate. The main reaction was the esterification of the carboxyl group of amino acids with isopropanol and chlorination of the amino group of the amino acid, followed by an exchange or neutralisation reaction and protonation. All of the proposed methods were very efficient, and the compounds obtained have great potential to be more effective drugs with increased skin permeability compared with ibuprofen. In addition, it was shown how the introduction of a modification in the form of an ion pair affects the properties of the obtained compound. 相似文献
787.
Dominik Tarabasz Pawe Szczeblewski Tomasz Laskowski Wojciech Paziski Ewa Baranowska-Wjcik Dominik Szwajgier Wirginia Kukula-Koch Henry O. Meissner 《International journal of molecular sciences》2022,23(9)
The aim of the study was to present the fingerprint of different Lepidium peruvianum tuber extracts showing glucosinolates-containing substances possibly playing an important role in preventinting dementia and other memory disorders. Different phenotypes of Lepidium peruvianum (Brassicaceae) tubers were analysed for their glucosinolate profile using a liquid chromatograph coupled with mass spectrometer (HPLC-ESI-QTOF-MS/MS platform). Qualitative analysis in 50% ethanolic extracts confirmed the presence of ten compounds: aliphatic, indolyl, and aromatic glucosinolates, with glucotropaeolin being the leading one, detected at levels between 0–1.57% depending on phenotype, size, processing, and collection site. The PCA analysis showed important variations in glucosinolate content between the samples and different ratios of the detected compounds. Applied in vitro activity tests confirmed inhibitory properties of extracts and single glucosinolates against acetylcholinesterase (AChE) (15.3–28.9% for the extracts and 55.95–57.60% for individual compounds) and butyrylcholinesterase (BuChE) (71.3–77.2% for the extracts and 36.2–39.9% for individual compounds). The molecular basis for the activity of glucosinolates was explained through molecular docking studies showing that the tested metabolites interacted with tryptophan and histidine residues of the enzymes, most likely blocking their active catalytic side. Based on the obtained results and described mechanism of action, it could be concluded that glucosinolates exhibit inhibitory properties against two cholinesterases present in the synaptic cleft, which indicates that selected phenotypes of L. peruvianum tubers cultivated under well-defined environmental and ecological conditions may present a valuable plant material to be considered for the development of therapeutic products with memory-stimulating properties. 相似文献
788.
Ewa Stodolak-Zych Ewa Dzierzkowska Sara Matwally Maciej Mikołajczyk Marcin Gajek Alicja Rapacz-Kmita 《国际聚合物材料杂志》2019,68(1-3):19-26
AbstractThe paper describes the results of research on obtaining porous membranes produced from polylactide fibers (PLA) by electrospinning, additionally modified with gentamicin antibiotic (GM) at the stage of preparing a spinning solution to provide bactericidal properties. Both solid (1oPNF) and porous (2oPNF 3oPNF) polymer fibers were obtained, and the control of fiber porosity was achieved using various solvent systems: dichloromethane (DCM), dimethylformamide (DMF), chloroform (CHL) and dimethyl sulfoxide (DMSO). Three types of fibers differing in morphology (fiber diameter) and mean pore size were obtained. Physicochemical properties of porous and solid drug-containing fibers were examined, determining their surface free energy (SFE) and wetting angle (CA), and the effectiveness of modification with the drug was confirmed in spectroscopic studies (FTIR-ATR). Antibacterial activity of the prepared drug-modified nonwovens was confirmed by the disk diffusion method against Gram-negative Escherichia coli bacteria strain. The results of tests have shown that depending on the type of solvents used at the electrospinning stage, porous fibers can be obtained from polylactide. The addition of gentamicin affected antibacterial properties, and the pore size determined the rate of drug release monitored by the ion coupled plasma method (ICP). 相似文献
789.
Low‐concentrated acidic electrolysed water treatment of pork: inactivation of surface microbiota and changes in product quality 下载免费PDF全文
Ewa Brychcy Magdalena Malik Piotr Drożdżewski Natalia Ulbin‐Figlewicz Andrzej Jarmoluk 《International Journal of Food Science & Technology》2015,50(11):2340-2350
The study analysed the effect of low‐concentrated acidic electrolysed water (LCAEW) treatment on meat. Microbiological analysis and colour and sensory quality testing during storage were performed on Longissimus thoracis. FT‐IR and FT‐Raman spectroscopy were used to detect eventual changes in the structure of meat after treatment. Meat samples were sprayed for 120 s with LCAEW (0.001%, 0.01% or 0.1% NaCl solution were electrolysed for 0, 5 or 10 min). The highest reduction in total number of micro‐organisms (3.25 log reduction), yeast and moulds (2.68 log reduction) and psychrotrophs (3.10 log reduction) was observed after spraying the meat samples with 0.1% NaCl electrolysed for 10 min. LCAEW caused a decrease in deoxymyoglobin and metmyoglobin concentration in unstored meat samples. The preliminary sensory studies proved that colour changes are not significant for consumers. The IR and Raman spectra indicate that the structure of compounds of meat tissues are not affected by chlorine and chlorine compounds (LCAEW components). LCAEW has no influence on denaturation of meat protein. 相似文献
790.
Research in cognitive neuroscience and in brain–computer interfaces (BCI) is frequently concerned with finding evidence that a given brain area processes, or encodes, given stimuli. Experiments based on neuroimaging techniques consist of a stimulation protocol presented to a subject while his or her brain activity is being recorded. The question is then whether there is enough evidence of brain activity related to the stimuli within the recorded data. Finding a link between brain activity and stimuli has recently been proposed as a classification task, called brain decoding. A classifier that can accurately predict which stimuli were presented to the subject provides support for a positive answer to the question. However, it is only the answer for a given data set and the question still remains whether it is a general rule that will apply also to new data. In this paper we try to reliably answer the neuroscientific question about the presence of a significant link between brain activity and stimuli once we have the classification results. The proposed method is based on a Beta-Binomial model for the population of generalization errors of classifiers from multi-subject studies within the Bayesian hypothesis testing framework. We present an application on nine brain decoding investigations from a real functional magnetic resonance imaging (fMRI) experiment about the relation between mental calculation and eye movements. 相似文献