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排序方式: 共有379条查询结果,搜索用时 15 毫秒
221.
Natalia Ka
mierczak Bartomiej Grygorcewicz Marta Roszak Beata Bochentyn Lidia Piechowicz 《International journal of molecular sciences》2022,23(3)
Problems connected with biofilm-related infections and antibiotic resistance necessitate the investigation and development of novel treatment strategies. Given their unique characteristics, one of the most promising alternatives to conventional antibiotics are bacteriophages. In the in vitro and in vivo larva model study, we demonstrate that phages vB_SauM-A, vB_SauM-C, and vB_SauM-D are effective antibiofilm agents. The exposure of biofilm to phages vB_SauM-A and vB_SauM-D led to 2–3 log reductions in the colony-forming unit number in most of the multidrug-resistant S. aureus strains. It was found that phage application reduced the formed biofilms independently of the used titer. Moreover, the study demonstrated that bacteriophages are more efficient in biofilm biomass removal and reduction in staphylococci count when compared to the antibiotics used. The scanning electron microscopy analysis results are in line with colony forming unit (CFU) counting but not entirely consistent with crystal violet (CV) staining. Additionally, phages vB_SauM-A, vB_SauM-C, and vB_SauM-D can significantly increase the survival rate and extend the survival time of Galleria mellonella larvae. 相似文献
222.
Jacek Rysz Beata Franczyk Magdalena Rysz-Grzyska Anna Gluba-Brzzka 《International journal of molecular sciences》2022,23(13)
The modifications in genomic DNA methylation are involved in the regulation of normal and pathological cellular processes. The epigenetic regulation stimulates biological plasticity as an adaptive response to variations in environmental factors. The role of epigenetic changes is vital for the development of some diseases, including atherogenesis, cancers, and chronic kidney disease (CKD). The results of studies presented in this review have suggested that altered DNA methylation can modulate the expression of pro-inflammatory and pro-fibrotic genes, as well those essential for kidney development and function, thus stimulating renal disease progression. Abnormally increased homocysteine, hypoxia, and inflammation have been suggested to alter epigenetic regulation of gene expression in CKD. Studies of renal samples have demonstrated the relationship between variations in DNA methylation and fibrosis and variations in estimated glomerular filtration rate (eGFR) in human CKD. The unravelling of the genetic–epigenetic profile would enhance our understanding of processes underlying the development of CKD. The understanding of multifaceted relationship between DNA methylation, genes expression, and disease development and progression could improve the ability to identify individuals at risk of CKD and enable the choice of appropriate disease management. 相似文献
223.
Magdalena Mizerska-Kowalska Sylwia Sowa Beata Donarska Wojciech Paziski Adrianna Sawiska-Brych Aleksandra Tomasik Anna Ziarkowska Krzysztof Z. czkowski Barbara Zdzisiska 《International journal of molecular sciences》2022,23(12)
Many organophosphorus compounds (OPs), especially various α-aminophosphonates, exhibit anti-cancer activities. They act, among others, as inhibitors of the proteases implicated in cancerogenesis. Thesetypes of inhibitors weredescribed, e.g., for neutral endopeptidase (NEP) expressed in different cancer cells, including osteosarcoma (OS). The aim of the present study isto evaluate new borane-protected derivatives of phosphonous acid (compounds 1–7) in terms of their drug-likeness properties, anti-osteosarcoma activities in vitro (against HOS and Saos-2 cells), and use as potential NEP inhibitors. The results revealed that all tested compounds exhibited the physicochemical and ADME properties typical for small-molecule drugs. However, compound 4 did not show capability of blood–brain barrier penetration (Lipiński and Veber rules;SwissAdme tool). Moreover, the α-aminophosphonite-boranes (compounds 4–7) exhibited stronger anti-proliferative activity against OS cells than the other phosphonous acid-borane derivatives (compounds 1–3),especially regarding HOS cells (MTT assay). The most promising compounds 4 and 6 induced apoptosis through the activation of caspase 3 and/or cell cycle arrest at the G2 phase (flow cytometry). Compound 4 inhibited the migration and invasiveness of highly aggressive HOS cells (wound/transwell and BME-coated transwell assays, respectively). Additionally, compound 4 and, to a lesser extent, compound 6 inhibited NEP activity (fluorometric assay). This activity of compound 4 was involved in its anti-proliferative potential (BrdU assay). The present study shows that compound 4 can be considered a potential anti-osteosarcoma agent and a scaffold for the development of new NEP inhibitors. 相似文献
224.
Przemysaw Czele Agnieszka Skotnicka Beata Szefler 《International journal of molecular sciences》2022,23(14)
Tumors are still one of the main causes of death; therefore, the search for new therapeutic agents that will enable the implementation of effective treatment is a significant challenge for modern pharmacy. One of the important factors contributing to the development of neoplastic diseases is the overexpression of enzymes responsible for the regulation of cell division processes such as cyclin-dependent kinases. Numerous studies and examples of already-developed drugs confirm that isatin is a convenient basis for the development of new groups of inhibitors for this class of enzyme. Therefore, in this work, a new group of potential inhibitors of the CDK2 enzyme, utilizing isatin derivatives and substituted benzoylhydrazines, has been designed based on the application of computational chemistry methods, such as docking and molecular dynamics, and their inhibiting ability was assessed. In the cases of the selected compounds, a synthesis method was developed, and the selected physicochemical properties of the newly synthesized derivatives were estimated. As part of the completed project, new compounds are developed which are potential inhibitors of the CDK2 enzyme. 相似文献
225.
Mateusz Mieczkowski Beata Mrozikiewicz-Rakowska Micha Kowara Marcin Kleibert Leszek Czupryniak 《International journal of molecular sciences》2022,23(14)
Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement). 相似文献
226.
Ramon van der Vlag M. Yagiz Unver Dr. Tommaso Felicetti Dr. Aleksandra Twarda-Clapa Fatima Kassim Cagdas Ermis Dr. Constantinos G. Neochoritis Dr. Bogdan Musielak Beata Labuzek Prof. Dr. Alexander Dömling Prof. Dr. Tad A. Holak Prof. Dr. Anna K. H. Hirsch 《ChemMedChem》2020,15(4):370-375
Innovative and efficient hit-identification techniques are required to accelerate drug discovery. Protein-templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein-templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists. Herein, we present our attempts to use a protein-templated reductive amination to target protein-protein interactions (PPIs), a challenging class of drug targets. We address a flexible pocket, which is difficult to achieve by structure-based drug design. After careful analysis we did not find one of the possible products in the kinetic target-guided synthesis (KTGS) approach, however subsequent synthesis and biochemical evaluation of each library member demonstrated that all the obtained molecules inhibit MDM2. The most potent library member (Ki=0.095 μm ) identified is almost as active as Nutlin-3, a potent inhibitor of the p53-MDM2 PPI. 相似文献
227.
Leszek Rydzak Agnieszka Sagan Dariusz Andrejko Agnieszka Starek Beata Ślaska-Grzywna Agata Blicharz-Kania Zbigniew Kobus Marcin Natoniewski 《Food and Bioprocess Technology》2017,10(11):1997-2004
This study aims to provide comprehensive information on the process of vacuum impregnation of wheat grains. Vacuum impregnation, saturating materials with additional liquid components, is a well-known process originally developed to ensure leak tightness or reduce the porosity of various materials. We describe its potential uses in the food processing industry relating to the impregnation of grains and leguminous plant seeds. The objective of the study was to determine the influence of impregnation and infrared heating of wheat grains on flour efficiency, moisture content and particle size distribution in the resulting flour and bran. The experimental material comprised three varieties of wheat. The results showed that the method of preparing the wheat grains for milling combined with impregnation had a significant impact on the particle size distribution of bran but not on the particle size distribution of flour. A more complete view of the process characteristics requires further investigation of factors related to the structural and textural properties of the impregnated material, factors which are highly varied in the case of food materials and food products. 相似文献
228.
The thickness, the refractive index, and the optical anisotropy of thin sulfonated poly(ether ether ketone) films, prepared by spin-coating or solvent deposition, have been investigated with spectroscopic ellipsometry. For not too high polymer concentrations (≤5 wt%) and not too low spin speeds (≥2000 rpm), the thicknesses of the films agree well with the scaling predicted by the model of Meyerhofer, when methanol or ethanol are used as solvent. The films exhibit uniaxial optical anisotropy with a higher in-plane refractive index, indicating a preferred orientation of the polymer chains in this in-plane direction. The radial shear forces that occur during the spin-coating process do not affect the refractive index and the extent of anisotropy. The anisotropy is due to internal stresses within the thin confined polymer film that are associated with the preferred orientations of the polymer chains. The internal stresses are reduced in the presence of a plasticizer, such as water or an organic solvent, and increase to their original value upon removal of such a plasticizer. 相似文献
229.
Lesław Juszczak Mariusz Witczak Teresa Fortuna Beata Solarz 《International Journal of Food Properties》2013,16(6):1364-1372
The study investigates the viscosity of clarified beetroot juice as dependent on temperature and soluble solids content. Rheological research was carried out using a rotational rheometer with a system of coaxial cylinders. Flow curves were obtained in the temperature range from 10 to 60°C and at the soluble solids content of 50° to 67.1°Bx. The concentrate under study showed a Newtonian behaviour. Dynamic viscosity ranged from 5.2 to 320 mPa·s and depended on soluble solids content and temperature of measurement. The effect of temperature was described using an Arrhenius equation. Activation energy values were between 24.68 and 39.96 kJ/mol. The effect of soluble solids content was described employing a power-law function and an exponential function. In addition, two equations were proposed to describe the combined effect of temperature and soluble solids content on the viscosity of beetroot juice concentrate. 相似文献
230.
Katarzyna Bartkowska Krzysztof Turlejski Beata Tepper Leszek Rychlik Peter Vogel Ruzanna Djavadian 《International journal of molecular sciences》2021,22(14)
Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10–22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew’s brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures. 相似文献