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Документ Відкритий доступ In silico the Ames mutagenicity predictive modelof environment(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Kislyak, Sergey V.; Duhan, Olexii M.; Yesypenko, Ruslana V.; Starosyla, Darya B.; Yalovenko, Olena I.Background.The classical in vitroand in vivo methods developed and widelyused in the past decades to as-sess the genetic effects of environmental factors are complex in view of their implementation, are expensive, long-lasting, have the problem of reproducibility of the results of experiment in different laboratories and may face ethical problems of using warm-blooded animals in experiments. Objective. Development, optimisation and testing of effective in silicomodels for assessment of Ames muta-genicity of environmental factors.Methods. The genetic assessment of the impact of environmental factors was carried out in accordance with a set of chemical compounds for which information on potential mutagenic activity was obtained experimen-tally, using the in vitroAmes Salmonella/microsome test.Four machine learning models were developed to solve the problem of binary classification to form two classes of xenobiotics (mutagen/non-mutagen).The total sampleis represented by a set of 8,083 xenobiotics. Results. We developed four machine learning models with 85% accuracy, matchingthe reproducibility of Ames test data across laboratories. In addition, we have proposed a binary classifier that subject to dimen-sionality reduction of the input data, taking into account the qualitative composition of molecular descrip-tors, allows us toimprove the accuracy of in silicoprediction of genotoxicity of chemicals. Conclusions.The necessity of updating and expanding the list of effective and more productive methods and approaches for assessing the genotoxic effects of environmental factors is substantiated, which allows avoi-ding the use of warm-blooded animals in the experiment, saving time and reducing the number of false-negative and false-positive results. The possibility of increase the accuracy of predictive machine learning models forassessing the genotoxic potential of environmental factors in conditions of dimensionality reduc-tion of the data set is presented.Документ Відкритий доступ Nhibition of cytochrome p450 activities by propoxazepam: safety assessment in context for potential drug interactions(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Larionov, Vitalii B.; Golovenko, Mykola Ya.; Valivodz, Iryna P.; Reder, Anatoliy S.Background.Propoxazepam is a new anelgetic agent of the benzodiazepine group, chemically known as 7-bromo-5-(o-chlorophenyl)-3-propyloxy-1,2-dihydro-3H-1,4-benzodiazepine-2-one. Propoxazepam is con-sidered a possible substrate of the CYP system, so its effect of on the CYP3A4 enzyme activity was investi-gated in vitrousing human liver microsomes.Objective.To evaluate the effects of propoxazepam on CYP3A4 activity in vitrousing testosterone and mida-zolam as markers of metabolic activity for CYP3A4 in human liver microsomes.Methods.Midazolam (1-hydroxylation reaction) and testosterone (6-hydroxylation reaction) were used as markers for CYP3A4-mediated activity. Ketoconazole (0.2 M) was used as a positive control for reversibleinhibition, and troleandomycin (50 M) for metabolism-dependent inhibition. For reversible inhibition, pro-poxazepam was added together with the corresponding substrate and cofactor (NADPH), while for metabo-lism-dependent inhibition, it was incubated with microsomes and cofactor for 30 minutes prior to substrate addition.Results.Propoxazepam at various concentrations (0 to 100 M) consistently inhibited CYP3A4 activities for both substrates, showing a similar "concentration–activity inhibition" dependence, with IC50values of 52.34.9M for midazolam and 46.1 9.2 M for testosterone. For metabolism-dependent inhibition, IC50values were 36.6 8.6 M for midazolam and 28.3 7.4 M for testosterone. Given that the binding of pro-poxazepam to microsomal protein under the experimental conditions, which reflected those in the IC50ex-periments, was low, no microsomal binding correction factor was applied to the reported IC50values.Conclusions.The highest predicted unbound Cmaxplasma concentration of propoxazepam, above which in-teractions can occur, is between 0.462 and 0.524 M, or 462 and 524 nM. This corresponds to concentra-tions of 188 to 214ng/mL (based on the molecular weight of propoxazepam, 414.73g/mol). According to pharmacokinetic data, these concentrations are not achievable after a single oral administration. Furtherstudies are required for multiple-dose administration.Документ Відкритий доступ Biosafety aspects of hybridoma technology: nature of risks and approaches to their management(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Shevchuk, Kateryna M.; Baranovska, Anastasia V.; Chernetskyi, Andrii S.; Shchotkina, Nataliia V.; Besarab, Alexander B.This study investigates the biosafety aspects of hybridoma technology, focusing on the identification and management of associated risks. Monoclonal antibodies, essential tools in immunology, biotechnology, and medicine, are primarily produced through hybridoma technology. This process involves fusing B lymphocytes from immunized animals with myeloma cells to create hybridomas, which are then cultured to produce spe-cific antibodies. The research highlights significant contamination risks, particularly from rodent-borne virus-es and other pathogens, during both in vivoand in vitrocultivation. It systematically analyzes existing strate-gies for identifying and mitigating these risks at various stages of monoclonal antibody production, including hybridoma identification, cell fusion, and antibody purification. The study underscores the importance of stringent biosafety protocols and optimized purification methodologies to ensure the production of high-quality, contaminant-free monoclonal antibodies. Additionally, it emphasizes the necessity of comprehensive risk assessments and the implementation of advanced contamination control systems in laboratories. The conclusions drawn from this study provide valuable insights into enhancing the safety and efficacy of monoc-lonal antibody production. By addressing these biosafety concerns, the research supports the widespread ap-plication of monoclonal antibodies in scientific and medical fields, ensuring their reliability and effectiveness in various diagnostic and therapeutic contexts.Документ Відкритий доступ Optimization of parameters of saline sodium citrate buffer for stability of colloidal gold nanoparticles usedin dna hybridization biosensor(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Sobolevskyi, Maksym S.; Holubiev, Illia Iu.; Lopatynskyi, Andrii М.; Samoylov, Anton V.; Dorozinsky, Glib V.; Lyapin, Oleksandr M.; Khrystosenko, Roman V.; Chegel, Volodymyr І.; Dzyadevych, Sergiy V.; Soldatkin, Oleksandr O.Background.The use of optical biosensors based on surface plasmon resonance (SPR) spectrometry have long been established as a viable alternative tothe traditional molecular biological methods, such as immu-nostainingor ELISA. Its capacity to perform real-time quantitative measurements is complemented with the possibility for the enhancement of the sensor signal with the use of optically active colloidal nanoparticles. On the other hand, few such nanoparticle-containing DNA biosensors have been developed, owing to poor colloidal stability of nanoparticles in chemical conditions suitable for hybridization of nucleic acid sequences.Objective.This study investigates the possibility of using gold nanoparticles (AuNPs) modified with thiolated oligonucleotides, 6-mercapto-1-hexanol, and lipoic acid as part of a hybridization system for biosensor de-tection of DNA sequences in order to improve its main analytical characteristics.Methods.Astudy of the colloidal stability of nanoparticlesinSSC (saline sodium citrate)media of differentmultiplicitybefore and after modification was carried out in order to select the best environment for the op-eration of the biosensor system.Aggregation of modified AuNPs was facilitated by their centrifugation, after which pelleted nanoparticles were resuspended and investigated by spectrophotometry. The conclusions re-garding the colloidal stability of AuNPs were based on the drop in concentration of colloidal AuNPs after each centrifugation.Results.The possibility of using the studied NPs in biosensor analysis was shown, and0.1SSC buffer solu-tion was determined to bethe optimal mediumfor their operational stability. Approbation of the nanoparticle-containingDNA hybridizationbiosensor based on SPR spectrometry was carried outin 2.0SSC medium.Conclusions.The prospective use ofthestudiedNPs as components of DNA hybridization systems for the detection of genetic markers has been provenДокумент Невідомий Антиадгезивні властивості 4-(адамантил-1)-1-(1-амінобутил)бензолу щодо staphylococcus aureus(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Гуменюк, Наталія І.Проблематика. Staphylococcusaureusвіднесенідобактерійізвисокимрівнемстійкостідоантимік-робнихпрепаратів, однієюзпричинякоїєздатністьмікроорганізмівформуватибіоплівки. Перспек-тивноюстратегієюантимікробноїтерапіїупацієнтівзінфекційнимизахворюваннями, пов’язанимизбіоплівками, євпливнапершіетапиплівкоутворення.Мета.Встановити здатність 4-(адамантил-1)-1-(1-амінобутил)бензолу впливати на формування біо-плівок S.aureusта експресію генів плівкоутворення.Методика реалізації.Мінімальну інгібуючу концентрацію (МІК) 4-(адамантил-1)-1-(1-амінобутил)бензолу(шифр АМ-166) щодо метицилінрезистентного штаму S.aureus222визначали методом серійних мікро-розведень. Антибіоплівкову активність сполуки АМ-166 досліджували за методикою O’Toole, оцінку інтенсивності утворення біоплівки S.aureusвизначали згідно зіStepanovic.Вплив АМ-166 на експре-сію генів досліджували за допомогою полімеразної ланцюгової реакції (ПЛР) уреальному часі.Результати. МІК сполуки АМ-166 щодо S.aureus222 становить 5мкг/мл. За дії АМ-166 за 0,25та 0,5МІК здатність S.aureusдо плівкоутворення змінюється з середньої (контроль) до слабкої, за 5,0МІКштам втрачає здатність формувати біоплівку. Встановлено, що сполука в концентрації 0,5МІК збіль-шує експресію генаicaRта знижує транскрипційну активність генів icaA, clfB, fib,fnbB, ebpS, eno,якіберуть участь у плівкоутворенні йадгезії.Висновки.Похідне адамантану АМ-166 порушує формування біоплівок MRSA, змінює транскрипційнуактивність генів icaлокусу, пригнічує прикріпленняS.aureusдо біотичної поверхні через вплив на експресію генів.Документ Невідомий The effect of lyophilized and frozen umbilicalcord cryoextract on L929 cell culture(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Kaverinska, A. I.; Shevchenko, N. O.; Osetsky, A. I.; Sukhodub, L. B.; Lazurenko, V. V.; Zhelezniakov, O. Yu.; Prokopiuk, V. Yu.Background.The human umbilical cord is a promising source of biologically active substances with regenera-tive properties. However,the potential of lyophilized cryoextract from the umbilical cord for regenerative medicine, which could facilitate storage and transportation, remains unexplored. Therefore, it is important to study the effect of such cryoextracts using a cellular model.Objective.To evaluate the effect of lyophilized and frozen umbilical cord cryoextracts on the L929 cell line to assess their therapeutic potential.Methods.This study was conducted on L929 cell cultures. Cryoextracts from the human umbilical cord were obtained through cryoextraction and lyophilized forms at 80 and 20C. These extracts were added to Dul-becco's Modified EagleMedium(DMEM) at three concentrations: 0.1, 0.5, and 1.0mg/ml. The control groups included cells cultured in DMEM with and without fetal bovine serum. Cell morphology and mono-layer confluency were observed. To assess the impact of the cryoextracts, several assays were performed: cell viability (adhesion), migration activity (scratch test), pinocytosis activity (neutral red uptake assay), metabol-ic activity (MTT assay), and (proliferation) population doubling time.Results. The addition of umbilical cord cryoextract and its lyophilized form at 80C was non-toxic to the cells. The most effective concentration was 0.1mg/ml, which significantly stimulated cell adhesion and pro-liferation compared to the culture medium without fetal serum. The lyophilized cryoextract at 20C did not enhance cell viability but did increase pinocytosis activity.Conclusions. These findings suggest that umbilical cord cryoextract and its lyophilized form at 80C can be used as growth factors in cell line cultivation. The lyophilized cryoextract shows promise for use in condi-tions where specialized storage equipment is not available. However, the lyophilized form at 20C primarily stimulates pinocytosis activity and inhibits proliferation.Документ Невідомий Antifungal activity and cytotoxicity of imidazole- and morpholine-based lysosomotropic detergents(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Hodyna, D.; Kovalishyn, V.; Shulha, Yu.; Trokhimenko, O.; Aksenovska, O.; Rogalsky, S.; Metelytsia, L.Background. The spread of infectious diseases caused by drug-resistant bacteria and fungi, especially nosocomial strains, is currently considered a serious medical problem. It is known that the fungus Candida albicans is the most common causative agent of candidal infection, including the severe type. The emergence and rapid formation of drug resistance, as a risk factor in the treatment of oncological diseases burdened by candidal infection, requires new therapeutic approaches, including the study of synthetic bioregulators with antifungal and anticancer efficacy. Objective. To synthesize and to determine the antifungal activity and cytotoxicity of imidazole- and morpholine-based lysosomotropic detergents (LDs) comprising both dodecyl radicals and ester-functionalized long alkyl chains. Methods. To develop the QSAR models by the OCHEM platform, machine learning methods such as Transformer Convolutional Neural Network (Trans-CNN), Transformer Convolutional Neural Fingerprint (TransCNF), and Random Forest (RF) were used. Imidazole- and morpholine-based lysosomotropic detergents comprising both dodecyl radicals and ester-functionalized long alkyl chains were synthesized and characterized by 1H Nuclear Magnetic Resonance spectroscopy. The antifungal properties of studied compounds were estimated by the disc diffusion method against the С. albicans ATCC 10231, С. albicans, С. glаbrata and С. krusei clinical isolates. The in vitro cytotoxic activity of LDs was evaluated by IC50 value against the throat cancer HEp-2 cell lines. AutoDock Vina software was used for the evaluation of the synthesis compounds as ligands of several antifungal targets. Results. The identified and synthesized imidazole- and morpholine-based LDs showed high antifungal potential against all Candida spp., specifically against the fluconazole-resistant С. albicans, С. glаbrata, and С. krusei clinical isolates. Imidazole-based LD 1 (IM-C12) and morpholine-based LD 4 (Mor-C12) were the most active against tested fungal strains. Molecular docking results suggest that the antifungal mechanisms of the compounds may be related to the inhibition of fungal lanosterol 14-demethylase. The cytotoxic results of the synthesized compounds against the HEp-2 cell line demonstrated that morpholine-based LDs are less cytotoxic compared to imidazole-based. Conclusions. It was found that LD IM-C12 (1) is the most promising cytostatic and antifungal agent based on the obtained results. LDs IM-CH2COOC10 (2) and Mor-C12 (4), which, under conditions of chemical modification, including through the carbon chain, may also be interesting for developing potential anticancer agents.Документ Невідомий Effect of mesenchymal stromal cells of different origin on DNA fragmentation in rat hippocampal neuronal nuclei after ischemia-reperfusion(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Konovalov, S. V.; Moroz, V. M.; Yoltukhivskyi, M. V.; Husakova, I. V.; Deryabina, O. G.; Tochilovskyi, A. A.; Kordium, V. A.Background. The treatment of cerebral blood circulation disorders remains a pressing issue due to their prevalence in the elderly. Brain tissue ischemia caused by such disorders leads to necrotic and neuroapoptotic changes. To mitigate neuroapoptosis in the ischemic zone during the subacute period of the process, neuroprotectors are used. In recent years, the neuroprotective properties of mesenchymal stromal cells (MSCs) have been actively studied. Objective. To compare effect of MSCs of different origin and the cell lysate of human MSCs from Wharton's jelly (hWJ-MSC) on neuroapoptotic changes in the hippocampus of the rat brain after ischemia-reperfusion (IR). Methods. A 20-minute bilateral transient IR of the internal carotid arteries was performed on 165 four - month-old male Wistar rats. Following IR modeling, MSCs derived from hWJ-MSCs, as well as human and rat adipose tissue, were injected intravenously into the femoral vein of the rats. Other groups of rats received intravenous injections of fetal rat fibroblasts and cell lysate from hWJ-MSCs. Only an intravenous injection of physiological solution was administered to the control group of rats. The level of DNA fragmentation in the nuclei of hippocampal neurons on the 7th day after IR was assessed via flow cytometry. Results. Experimental IR caused a 4.9-fold increase in the level of fragmented DNA in the operated rats compared to the sham-operated animals. The use of MSCs of various origins and hWJ-MSC lysate reduces the intensity of DNA fragmentation in the nuclei of rat hippocampal neurons, with the most pronounced effects observed in groups treated with rat fetal fibroblasts (by 4.8 times), human adipose tissue MSCs (by 2.5 times), and hWJ-MSC cell lysate (by 2 times). Conclusions. A persistent focus of necrotic and apoptotic death of neurons in the hippocampus of rats is formed after experimental 20-minute IR of rats' brain, as evidenced by increased levels of fragmented DNA. Intravenous transplantation of MSCs of various origin and cell lysate from hWJ-MSC demonstrated a significant effect in the IR model: neurodestruction and neuroapoptosis at the area of the ischemic brain damage get less intensive. MSCs derived from human adipose tissue demonstrated superior neuroprotective potential compared to rat adipose tissue MSCs in the IR model of the rat brain.Документ Невідомий Assessing the ethanologenic potential of xylose-fermenting yeasts Scheffersomyces stipitis UCM Y-2810(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Hretskyi, I.; Mokrousova, O.; Oleshko, A.; Budyakova, O.; Antonenko, D.; Fomina, M.Background. Enhancing the efficiency of second-generation (2G) bioethanol production from lignocellulosic biomass is crucial for advancing sustainable biofuel technologies. However, the conversion of biomass into 2G bioethanol faces substantial challenges, necessitating a comprehensive investigation of microbial agents. Objective. To evaluate the effect of glucose and xylose concentrations, as well as cultivation duration, on the efficiency of ethanologenesis using the model organism Scheffersomyces stipitis UCM Y-2810, and to determine the optimal conditions for achieving maximum ethanol yield. Methods. The effects of glucose and xylose concentrations and cultivation time on ethanologenesis efficiency were evaluated using S. stipitis UCM Y-2810 as a model organism. The experimental design included three levels of factors: xylose concentration (3, 16.5, and 30 g/l), glucose concentration (1, 5.5, and 10 g/l), and cultivation durations (1, 2, and 3 days). Statistical analysis of the experimental data was conducted using a three-factor, three-level Box–Behnken design. Results. Under submerged cultivation of the strain of S. stipitis UCM Y-2810 in model media, optimization of the ethanologenesis process resulted in a maximum ethanol yield of 7.74 g/l. The optimal conditions for this yield were identified as follows: xylose concentration of 16.5 g/l, glucose concentration of 7.75 g/l, and a cultivation time of 3 days. Conclusions. The application of the Box–Behnken design revealed that the statistically significant factors influencing ethanologenesis efficiency were xylose concentration, yeast cultivation duration, and the linearquadratic interaction between these two factors.Документ Невідомий Morphometric changes in rat periwound skin during healing of excisional wounds after exposure to chronic social stress(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Makyeyeva, L. V.; Frolov, O. K.; Aliyeva, O. G.Background. Chronic stress is the most common systemic factor that negatively affects the body's overall resistance, including wound healing. While many aspects of skin recovery after a surgical wound are well defined, the involvement of cells in the periwound rarea emains unsufficiently studied. Objective. To determine the morphological features of the periwound skin at different stages of the healing process after exposure to chronic social stress. Methods. Chronic social stress was modeled through long-term psychoemotional exposure in Wistar laboratory rats of the experimental group. Animals in both control and experimental groups were wounded in the interscapular area by skin excision. The material of the periwounds was collected on the 1st, 3rd, 7th, 14th and 30th days of wound healing and processed according to standard histological methods. Results. Exposure to chronic social stress led to thinning of the skin layers even before wounding. Visual wound healing was delayed. The main reparative processes by phases (inflammation, proliferation, and remodulation) also occurred with significant delays. Conclusions. Aggressive-dominant social stress is a rather strong damaging factor for susceptible animals, leading to impaired physiological skin regeneration. This was evident in the thinning of skin layers observed in histological samples even before wound application, resulting from reduced proliferation and differentiation processes. The negative consequences of chronic social stress were further manifested in the healing of a surgical wound: the repair processes during the main phases, in particular inflammation and proliferation, were delayed, which ultimately led to the chronicity of reparative regeneration.Документ Невідомий Biosafety Management: Emphasis on Medicine, Pharmacy, and Biotechnology(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Galkin, Alexander