Innovative Biosystems and Bioengineering: international scientific e-journal, Vol. 7, No. 4
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Документ Відкритий доступ The influence of flavonoid compositions on Nrf2 transcription factor expression in case of infections triggered by influenza a virus and transmissible gastroenteritis coronavirus(Igor Sikorsky Kyiv Polytechnic Institute, 2023) Arkhypova, М.; Deriabin, О.; Trokhymchuk, Т.; Starosyla, D.; Atamaniuk, V.; Zavelevich, М.; Vialykh, Zh.; Rybalko, S.; Galkin, A.Background. Viral infections trigger transcription factors, including Nrf2, which regulate the expression of genes related to cytokines, chemokines, and more. Nuclear factor erythroid 2-related factor 2 (Nrf2) participates in complex regulatory networks controlling the expression of cytoprotective genes and immune responses. Recently, new roles have been attributed to Nrf2, including the regulation of antiviral responses. Objective. The aim of the study was to analyze Nrf2 activation in influenza virus infection in vivo and in transmissible gastroenteritis coronavirus (TGEV) infection in vitro, as well as the effects of the flavonoid compositions Proteflazidum and Protoil on the Nrf2 expression in these two experimental models of viral infection. Methods. Outbred white mice were infected with influenza A virus (A/FM/1/47/H1N1 strain). Jurkat cells were infected with TGEV, previously adapted to these cells. Flavonoid compositions Proteflazidum and Protoil (Ecopharm, Ukraine), containing the mixture of tricin, luteolin, apigenin, quercetin, and rhamnosin, were used in corresponding dilutions. Real-Time PCR was employed to analyze Nrf2 RNA expression in the lungs of mice and in both uninfected and virus-infected cells. Additionally, ELISA was used to assess the expression of Nrf2 peptide. Results. The Nrf2 expression in the lungs of influenza virus-infected mice showed a tendency to increase within a 100-fold range. In virus-infected mice treated with Proteflazidum or Protoil, the level of Nrf2 expression in the lungs decreased about 10-fold compared to infected untreated mice. TGEV infection resulted in 100-fold increase in Nrf2 expression in Jurkat cells. Both Proteflazidum and Protoil decreased Nrf2 expression in TGEV-infected cells, while their effects on Nrf2 expression in the intact cells on Day 1 were not detected. Conclusions. Flavonoid compositions have only a slight effect on Nrf2 expression in intact cells. However, in case of virus infection, both in vivo and in vitro, they counteract the extensive up-regulation of Nrf2 expression due to viral infection.Документ Відкритий доступ In silico analysis of anti-cervical cancer drug off-target effects on diverse protein isoforms for enhanced therapeutic strategies(Igor Sikorsky Kyiv Polytechnic Institute, 2023) Azhar, Iqbal; Faisal, Ali; Shanza, Choudhary; Adiba, Qayyum; Fiza, Arshad; Sara, Ashraf; Moawaz, Aziz; Asad, Ullah Shakil; Momina, Hussain; Muhammad, Sajid; Sheikh, Arslan SehgalBackground. Cervical cancer is a serious medical condition that affects hundreds of thousands of individuals worldwide annually. The selection and analysis of suitable gene targets in the early stages of drug design are crucial for combating this disease. However, overlooking the presence of various protein isoforms may result in unwanted therapeutic or harmful side effects. Objective. This study aimed to provide a computational analysis of the interactions between cervical cancer drugs and their targets, influenced by alternative splicing. Methods. Using open-access databases, we targeted 45 FDA-approved cervical cancer drugs that target various genes having more than two distinct protein-coding isoforms. To check the conservation of binding pocket in isoforms of the genes, multiple sequence analysis was performed. To better understand the associations between proteins and FDA-approved drugs at the isoform level, we conducted molecular docking analysis. Results. The study reveals that many drugs lack potential targets at the isoform level. Further examination of various isoforms of the same gene revealed distinct ligand-binding pocket configurations, including differences in size, shape, electrostatic characteristics, and structure. Conclusions. This study highlights the potential risks of focusing solely on the canonical isoform, and ignoring the impact of cervical cancer drugs on- and off-target effects at the isoform level. These findings emphasize the importance of considering interactions between drugs and their targets at the isoform level to promote effective treatment outcomes.Документ Відкритий доступ Antibacterial activity of 1-dodecylpyridinium tetrafluoroborate and its inclusion complex with sulfobutyl ether-B-cyclodextrin against mdr acinetobacter baumannii strains(Igor Sikorsky Kyiv Polytechnic Institute, 2023) Rogalsky, S.; Hodyna, D.; Semenyuta, I.; Frasinyuk, M.; Tarasyuk, O.; Riabov, S.; Kobrina, L.; Tetko, I.; Metelytsia, L.Background.The bacterial pathogen Acinetobacter baumanniiis one of the most dangerous multi-drug-resistant (MDR) microorganisms, which causes numerous bacterial infections. Nowadays, there is an urgent need for new broad-spectrum antibacterial agents with specific molecular mechanisms of action. Long-chain 1-alkylpyridinium salts are efficient cationic biocides which can inhibit enzymes involved in the biosynthesis of bacterial fatty acids.Incorporating these compounds into inclusion complexes with cyclic oligosaccharide B-cyclodextrin can reduce their relatively high acute toxicity.Objective. The aim of this research was to develop new anti-A.baumanniiagents based on hydrophobic 1-alkylpyridinium salt and its inclusion complex with sulfobutyl ether B-cyclodextrin (SBECD). Methods. Hydrophobiccationic biocide 1-dodecylpyridinium tetrafluoroborate (PyrC12-BF4) and its inclu-sion complex with SBECD have been synthesized. The structure of the SBECD/PyrC12-BF4complex was characterized by 1H Nuclear Magnetic Resonance spectroscopy, as well as UV spectroscopy. In vitroanti-bacterial activity of the synthesized compounds was estimated against MDR clinical isolates of A. baumanniiusing standard disc diffusion method. Acute toxicity studies were performed on Daphnia magnamodel hydro-biont.Molecular docking was performed using the crystal structure of the A.baumannii3-oxoacyl-[acyl-carrier-protein] reductase(FabG).Документ Відкритий доступ Viability of nodule bacteria Bradyrhizobium japonicum on soybean seeds by treatment with fungicides during extended storage(Igor Sikorsky Kyiv Polytechnic Institute, 2023) Vorobey, N. A.; Kukol, K. P.; Kots, S. Ya.; Pukhtaievych, P. P.; Patyka, V. P.Background. With the increase in soybean cultivation areas, inoculants are becoming increasingly sought after. They are not only compatible with the original preparations for seed treatment of soybean but also offer the possibility of applying them for several days or even months before sowing into the soil. Objective. The viability of new strains of nodule bacteria Bradyrhizobium japonicum (strain PC07 and strain B78) was investigated on the surface of soybean seeds treated with fungicides Fever and Maxim XL during the extended storage of inoculated seeds. Additionally, their ability for nitrogen fixation under symbiotic conditions was evaluated. Methods. Сultivation, serial dilution method, determination of bacterial titer of inoculants, quantification of colony forming units (CFU), gas chromatography. Results. In laboratory conditions, on the soybean seeds of Almaz and Vasylkivska varieties, the viability of the nodule bacteria B. japonicum PC07 and B78, which are more resistant to the active substances of these fungicides in pure culture, decreased. This reduction was dependent on the storage period, the fungicide used, and the strain of inoculant. One day after inoculation on the seeds without the use of fungicide, 68.6–75.4% CFU of the initial number was retained. Seeds treated with the fungicide Fever contained 36.5–38.3% CFU, and those treated with Maxim XL contained 26.2–27.0% CFU.Документ Відкритий доступ Effect of zinc supplementation to diluent boar semen on sperm characteristics and activity of antioxidant enzymes(Igor Sikorsky Kyiv Polytechnic Institute, 2023) Slyvchuk, O. Yu.; Shtapenko, O. V.; Yaremchuk, I. M.; Kornyat, S. B.; Dzen, Ye. O.Background. Zinc is essential for male reproductive function as it is necessary for spermatozoa maturation, capacitation, acrosome reaction, and fertilization. It has been established that the use of chelates compounds of metals with amino acids, nucleotides, peptides, and carbohydrates is not only more effective but also economically justified. Objective. The aim of this study was to evaluate and compare the effect of different concentrations of Zn glutamic amino acid chelate (ZnGlu) on boar spermatozoa motility, viability parameters, and prooxidantantioxidant homeostasis during in vitro incubation. Methods. Freshly ejaculated boar semen, after the addition of "Ecosperm" diluent, was divided into groups: a control group and three experimental groups. Zinc glutamate was supplemented to the experimental samples at concentrations of 1.0, 2.0, and 5.0 µg/ml, respectively. Semen samples were stored at 18 C for 4 days. Every 24 hours, sperm motility and viability and the antioxidant status were assessed by the level of diene conjugates (DC), concentration of malondialdehydere (MDA), and the activities of catalase and superoxide dismutase. Results. It was observed that boar sperm motility decreased with the extension of storage time, while the addition of 2.0 and 5.0 µg ZnGlu significantly improved sperm total motility and the percentage of vitality spermatozoa during 48–96 hours of incubation. Our studies also demonstrate that ZnGlu possess a protective effect in alleviating oxidative stress in boar sperm in vitro.