{"title":"MECHANISMS OF ANTIVIRAL ACTIVITY OF FLAVONOIDS","authors":"O. I. Golembiovska","doi":"10.15407/biotech16.06.034","DOIUrl":"https://doi.org/10.15407/biotech16.06.034","url":null,"abstract":"The article examines the multifaceted mechanisms underlying the antiviral activity of flavonoids, compounds widely distributed in the plant kingdom. The aim of the work was to review literature data on mechanisms of antiviral activity of flavonoids. Methods. Publications were selected based on the PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases published in 2015–2023. They include information on mechanisms of antiviral activity of flavonoids. Results. Beginning with an overview of flavonoid structures, the document navigates through the intricate interactions between flavonoids and various stages of the viral life cycle. Drawing upon a comprehensive analysis of in vitro and in vivo studies, the review highlights the diverse ways in which flavonoids inhibit viral entry, replication, and release. Depending on their antiviral mechanisms, flavonoids can serve as preventive inhibitors, therapeutic inhibitors, or indirect inhibitors by influencing the immune system. Conclusion. The synthesized information not only contributes to the advancement of antiviral research but also lays the foundation for the development of novel therapeutic interventions against a spectrum of viral infections.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"69 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139006587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"POLARIZED ACTIVATION OF HUMAN PERIPHERAL BLOOD PHAGOCYTES BY BACTERIOPHAGE–DERIVED DOUBLESTRANDED RNA (LARIFAN) in vitro","authors":"R. Dovhyi","doi":"10.15407/biotech16.06.069","DOIUrl":"https://doi.org/10.15407/biotech16.06.069","url":null,"abstract":"Aim. This study aimed to examine the effect of Larifan on metabolic characteristics of human blood monocytes and granulocytes in vitro. Methods. Four healthy adult men aged 21–26 years were recruited to participate in the study as blood donors. The metabolic profile of human blood monocytes and granulocytes was evaluated by phagocytic activity, reactive oxygen species production, nitric oxide generation, and arginase activity. Phagocytosis of FITC-labeled inactivated Staphylococcus aureus and reactive oxygen species generation were estimated by flow cytometry. Arginase activity was assessed in cell lysates, and nitric oxide generation in supernatants was examined using the Griess reaction. Results. Phagocytic index and reactive oxygen species generation were found to be lower in both human blood monocytes and granulocytes treated with Larifan. The drug caused a dose-dependent increase in nitric oxide production, as well as a decrease in the arginase activity of blood monocytes. Conclusions. Our results indicate the ability of Larifan to reinforce the antiviral properties of resting phagocytes along with containment of oxidative stress development.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139008278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BIOMEDICAL APPLICATION OF K5 PLASMINOGEN FRAGMENT","authors":"L. G. Kapustianenko","doi":"10.15407/biotech16.06.005","DOIUrl":"https://doi.org/10.15407/biotech16.06.005","url":null,"abstract":"Aim. Plasminogen kringle 5 is an endogenous angiogenic inhibitor. The purpose of the present review was to highlight the potential biomedical application of kringle 5 in the regulation of angiogenesis and tumor growth. Methods. Angiogenesis is a complex process that involves endothelial cell proliferation, migration, basement membrane degradation, and neovessel organization. Since the uncontrolled growth of new blood vessels causes the progression of many common diseases, first of all, oncological diseases, autoimmune disorders, neovascular damage of the eye, the use of angiostatins can be a promising pharmacotherapeutic approach to the prevention and adjuvant therapy of these pathological conditions. The advantages of angiostatins application are their non-toxicity even at high doses, non-immunogenicity, lack of tolerance of target cells to their action. Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which act as potent inhibitory mediators of endothelial proliferation and migration. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Results. Current literature data suggest that in addition to expressed and highly specific cytotoxicity in relation to endotheliocytes and some types of tumor cells, the kringle domain 5 of human plasminogen has other advantages as an antiangiogenic and antitumor regulator, including its specific inhibitory activity, which affects only activated, proliferating endothelial cells, and therefore is non-toxic to other types of normal cells. As an endogenous protein, which is formed in the human organism, K5 does not provoke an immune response. K5 as a small polypeptide molecule with a stable structure can be obtained as a recombinant protein in E. coli cells, and can also be used in pharmacokinetic systems of targeted delivery and sustained release. Conclusions. The prospect of successful use of K5 as a therapeutic agent to manage pathological processes associated with dysregulation of angiogenesis makes it necessary to develop and improve methods of its production and to further test its plausible pleiotropic biological activities.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"21 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138977127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"COMPLEXATION OF CURCUMIN WITH BOVINE SERUM ALBUMIN AND DIPHTHERIA TOXOID CRM197","authors":"D.A. Zhukova","doi":"10.15407/biotech16.06.076","DOIUrl":"https://doi.org/10.15407/biotech16.06.076","url":null,"abstract":"Aim. The goal of the study is to demonstrate the binding sites for curcumin on the protein carriers - bovine serum albumin and diphtheria toxoid CRM197. BSA was chosen as a potential non-specific protein carrier because of its widely used in medicine as a drug carrier. Methods. In the investigation, both spectrophotometric and molecular docking methods were used. Results. Two stable binding sites were demonstrated for BSA to bind curcumin. CRM197 was taken as a well-studied carrier protein with its own antitumor activity and has been investigated as a specific carrier with a high affinity for cancer cells with overexpression of epidermal growth factor receptor. Our results showed one possible curcumin binding site, making CRM197 an ideal specific curcumin delivery platform that provides at least an additive effect in anticancer therapies. Conclusions. In conclusion, both studied proteins form stable complexes with curcumin that can lay in base of the commercial drug application.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139006510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"INFLUENCE OF BIOLOGICAL INDUCTORS ON THE SYNTHESIS AND BIOLOGICAL ACTIVITY OF MICROBIAL METABOLITES","authors":"T.P. Pirog","doi":"10.15407/biotech16.06.017","DOIUrl":"https://doi.org/10.15407/biotech16.06.017","url":null,"abstract":"The increasing antibiotic resistance is a severe concern for humanity. Co-cultivation of microorganisms is a promising method for obtaining new secondary antimicrobial metabolites. An effective strategy for co-cultivation of microorganisms involves the usage of certain biological inductors. The aim of this review is to summarize existing scientific research in the literature related to the influence of physiologically different types of biological inductors on the synthesis and biological activity of microbial secondary metabolites. An analysis of the literature has shown that in such studies, either live or inactivated cells of the inductor are added to the culture medium at significantly lower concentrations compared to the producer cells of the final metabolites, or the supernatant (filtrate) after cultivation of a competitive microorganism is used as an inductor. According to the literature and our own experimental studies, the using inductors is an effective approach not only for intensifying the synthesis of bacteriocins, surfactants, and antibiotics, but also for increasing their biological activity. Additionally, it often leads to the production of novel antimicrobial compounds that are not typical for the producer. However, the mechanisms of effect of inductors on the synthesis of biologically active secondary metabolites require further research, as the literature suggests that their introduction into the cultivation medium of producer does not always lead to an intensification of the synthesis of the final product. Moreover, the biological activity of secondary metabolites depends on the cultivation conditions of the producer, including the presence of biological inductors in the culture medium. Therefore, it is essential to conduct further research on the interaction between producers and competitive microorganisms to regulate the biological activity of the synthesised metabolites. In addition, there is a necessity to search for more cost-effective substrates for the biosynthesis of secondary metabolites, optimize the composition of the culture medium and expand the range of both pro- and eukaryotic inductors.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"52 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139007019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DYNAMICS OF THE PHENOLIC CONSTITUENTS AND ANTIOXIDANT ACTIVITY IN SUBMERGED CULTURES OF Xylaria SPECIES","authors":"A. Atamanchuk","doi":"10.15407/biotech16.06.082","DOIUrl":"https://doi.org/10.15407/biotech16.06.082","url":null,"abstract":"Purpose. This study was conducted to enhance comprehension of the dynamic process of synthesis of phenolic compounds by representatives of the genus Xylaria, and the correlation between phenol content and antioxidant properties found in biomass and culture liquid during submerged cultivation. Methods. Cultivation of Xylaria polymorpha and Xylaria longipes fungal strains from the IBK Mushroom Culture Collection was carried out on a glucose-yeast-peptone nutrient medium under submerged conditions. Harvesting of both biomass and culture liquid was done on the 3rd, 5th, 7th, and 9th day of cultivation, followed by extraction with ethyl acetate. The total phenol content of extracts was determined using the Folin–Ciocalteu method and the antioxidant potential was evaluated through the DPPH assay. Results. Findings revealed that the accumulation of phenolic compounds by fungal species of the Xylaria genus was specified on a strain level. Notably, X. longipes strains exhibited higher production of phenolic constituents compared to X. polymorpha and demonstrated superior antioxidant activity at a specific time of cultivation. Furthermore, a strong correlation was established between the dynamics of polyphenol accumulation and antioxidant activity in both mycelial biomass and culture liquid. Conclusions. Natural phenolic compounds with antioxidant properties were extracted from the biomass and culture liquid of the studied strains. Significantly higher concentrations of phenolic compounds and values of antioxidant activity were found in the biomass compared to the culture liquid. The results indicate that a later day of cultivation is not necessarily equivalent to the production of more phenols, emphasizing the need for a comprehensive assessment of the accumulation of these compounds and the dynamic study of related parameters.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"22 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139007593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RADIATION AND HYPOXIA STUDIES: EFFECTS OF HIGH-ENERGY ATMOSPHERIC PARTICLES ON BIOLOGICAL ORGANISMS AND POSSIBILITIES OF THEIR REHABILITATION","authors":"O. M. Klyuchko","doi":"10.15407/biotech16.06.048","DOIUrl":"https://doi.org/10.15407/biotech16.06.048","url":null,"abstract":"The influences of cosmic radiation on atoms and molecules in the Earth's atmosphere were observed with subsequent transformation of atoms, molecules of gases, as well as development of states of oxygen deficiency (hypoxic) in biological organisms, some recommended ways of such disorders correction. Purposes of this work were to study radiation effects in ionosphere with subsequent high-energy transformations of atoms, molecules of gases at different heights above the Earth surface; interaction of some high-energy atmospheric particles with biological objects at near Earth's heights up to 5.500 m above sea level (a.s.l.), and oxygen roles in consequences of biological organisms’ irradiation. Methods. Analysis of results of satellite and rocket observations of the Earth atmosphere gases exploring at different altitudes a.s.l. Investigations in mountain conditions at EMBS research station of the National Academy of Sciences of Ukraine: comparative analysis of results of long-term observation of patients using standard laboratory methods, complex of methodological techniques: clinical, physiological studies of respiratory, cardiovascular systems; hematological, immunological states; functional state of higher nervous activity, mental and neurotic state; antihypoxants use, histochemical, biophysical methods, math modelling, others. Results. The last data obtained during the satellites atmosphere exploring were presented: studies of influences on the structure of atoms, molecules in atmosphere, concentrations of gases from ionosphere to the Earth surface, such phenomena as photochemical processes, photoionization. The notion “information” was discussed basing on phenomena, described in the article. Described studies of gases particles modification, oxygen deficiency in organisms (hypoxic states) were supplemented with the results of irradiated Chernobyl patients’ examinations, rehabilitation by Ukrainian doctors, scientists in mountain conditions. Conclusions. Phenomena of solar radiation influence on atoms, molecules and molecular complexes in the Earth's atmosphere were observed. The main attention was concentrated on the studies of gases concentrations at different heights with linked effects of oxygen roles in consequences of organisms’ irradiation and rehabilitation. Practical recommendations for patients’ medical care and rehabilitation were done.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"9 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139007681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KAN0438757: A NOVEL PFKFB3 INHIBITOR THAT INDUCES PROGRAMMED CELL DEATH AND SUPPRESSES CELL MIGRATION IN NON-SMALL CELL LUNG CARCINOMA CELLS","authors":"Özdemir Deniz","doi":"10.15407/biotech16.05.034","DOIUrl":"https://doi.org/10.15407/biotech16.05.034","url":null,"abstract":"Aim. PFKFB3 is glycolytic activators that is overexpressed in human lung cancer and plays a crucial role in multiple cellular functions including programmed cell death. Despite the many small molecules described as PFKFB3 inhibitors, some of them have shown disappointing results in vitro and in vivo. On the other hand KAN0438757, selective and potent, small molecule inhibitor has been developed. However, the effects of KAN0438757, in non-small cell lung carcinoma cells remain unknown. Herein, we sought to decipher the effect of KAN0438757 on proliferation, migration, DNA damage, and programmed cell death in non-small cell lung carcinoma cells. Methods. The effects of KAN0438757 on cell viability, proliferation, DNA damage, migration, apoptosis, and autophagy in in non-small cell lung carcinoma cells was tested by WST-1, real-time cell analysis, comet assay, wound-healing migration test, and MMP/JC-1 and AO/ER dual staining assays as well as western blot analysis. Results. Our results revealed that KAN0438757 significantly suppressed the viability and proliferation of A549 and H1299 cells and inhibited migration of A549 cells. More importantly, KAN0438757 caused DNA damage and triggered apoptosis and this was accompanied by the up-regulation of cleaved PARP in A549 cells. Furthermore, treatment with KAN0438757 resulted in increased LC3 II and Beclin1, which indicated that KAN0438757 stimulated autophagy. Conclusions. Overall, targeting PFKFB3 with KAN0438757 may be a promising effective treatment approach, requiring further in vitro and in vivo evaluation of KAN0438757 as a therapy in non-small cell lung carcinoma cells.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139308663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BIOCATALYTIC CARBON DIOXIDE CAPTURE PROMOTED BY CARBONIC ANHYDRASE","authors":"O. K. Zolotareva","doi":"10.15407/biotech16.05.005","DOIUrl":"https://doi.org/10.15407/biotech16.05.005","url":null,"abstract":"The rapid and steady increase in the concentration of CO2, the most abundant greenhouse gas in the atmosphere, leads to extreme weather and climate events. Due to the burning of fossil fuels (oil, coal and natural gas), the concentration of CO2 in the air has been increasing in recent decades by more than 2 ppm per year, and in the last year alone - by 3.29 ppm. To prevent the \"worst\" scenarios of climate change, immediate and significant reductions in CO2 emissions through carbon management are needed. Aim. Analysis of the current state of research and prospects for the use of carbonic anhydrase in environmental decarbonization programs. Results. Carbonic anhydrase (CA) is an enzyme that accelerates the exchange of CO2 and HCO3 in solution by a factor of 104 to 106. To date, 7 types of CAs have been identified in different organisms. CA is required to provide a rapid supply of CO2 and HCO3 for various metabolic pathways in the body, explaining its multiple independent origins during evolution. Enzymes isolated from bacteria and mammalian tissues have been tested in CO2 sequestration projects using carbonic anhydrase (CA). The most studied is one of the isoforms of human KAz - hCAII - the most active natural enzyme. Its drawbacks have been instability over time, high sensitivity to temperature, low tolerance to contaminants such as sulphur compounds and the impossibility of reuse. Molecular modelling and enzyme immobilisation methods were used to overcome these limitations. Immobilisation was shown to provide greater thermal and storage stability and increased reusability. Conclusions. Capturing carbon dioxide using carbonic anhydrase (CA) is one of the most cost-effective methods to mitigate global warming, the development of which requires significant efforts to improve the stability and thermal stability of CAs.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139307249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"EFFECT OF PHENYLALANINE AND LIGHT ON THE GROWTH OF HAIRY ROOTS OF Artemisia tilesii LEDEB","authors":"Т. Bohdanovych","doi":"10.15407/biotech16.05.061","DOIUrl":"https://doi.org/10.15407/biotech16.05.061","url":null,"abstract":"Aim. To analyze the possibility of using phenylalanine of various concentrations and different lighting modes separately and in combination to boost the biomass accumulation and biosynthesis of flavonoids in two lines of Artemisia tilesii Ledeb. hairy roots. Methods. The roots were grown on solidified medium with phenylalanine at high (1mM) and low concentrations (0.05 and 0.1 mM) with lighting (3000 lx, 16 h) and in darkness. After four weeks cultivation, weight gain, flavonoid content and DPPH-scavenging activity were determined according to the standard tests. Results. Roots grown in light were greenish in color, more branched and thick, yet the roots were more elongated after maintenance in the dark. Addition of 1 mM phenylalanine has led to inhibition of growth of all samples. The tolerance to lower concentrations varied among the lines. The flavonoid content for all samples of both lines was higher in the light (up to 3.14 times), regardless of the concentration of phenylalanine. The antioxidant activity was as well higher for the roots grown in light and the values of EC50 correlated with the flavonoid content. Conclusions. Illumination boosted the synthesis of flavonoids and antioxidant activity in all samples of both hairy root lines. The effect of phenylalanine addition on biomass accumulation and flavonoid biosynthesis was line-specific.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"137 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139309050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}