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MECHANISMS OF ANTIVIRAL ACTIVITY OF FLAVONOIDS 黄酮类化合物的抗病毒机制
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.034
O. I. Golembiovska
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.
文章探讨了广泛分布于植物界的黄酮类化合物抗病毒活性的多方面机制。这项工作的目的是回顾有关类黄酮抗病毒活性机制的文献资料。方法。根据PubMed(https://pubmed.ncbi.nlm.nih.gov/)数据库选取了2015-2023年发表的文献。其中包括有关类黄酮抗病毒活性机制的信息。结果。文件从类黄酮结构概述开始,介绍了类黄酮与病毒生命周期各个阶段之间错综复杂的相互作用。通过对体外和体内研究的全面分析,综述强调了类黄酮抑制病毒进入、复制和释放的多种方式。根据其抗病毒机制,黄酮类化合物可作为预防性抑制剂、治疗性抑制剂或通过影响免疫系统的间接抑制剂。结论。这些综合信息不仅有助于推动抗病毒研究,还为开发针对各种病毒感染的新型治疗干预措施奠定了基础。
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引用次数: 0
POLARIZED ACTIVATION OF HUMAN PERIPHERAL BLOOD PHAGOCYTES BY BACTERIOPHAGE–DERIVED DOUBLESTRANDED RNA (LARIFAN) in vitro 细菌衍生的双链核糖核酸(LARIFAN)在体外对人类表皮血液噬菌体的极化激活作用
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.069
R. Dovhyi
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.
研究目的本研究旨在探讨 Larifan 对体外人体血液单核细胞和粒细胞代谢特征的影响。研究方法研究招募了四名 21-26 岁的健康成年男性作为献血者。通过吞噬活性、活性氧生成、一氧化氮生成和精氨酸酶活性评估人血单核细胞和粒细胞的代谢特征。通过流式细胞术评估了 FITC 标记的灭活金黄色葡萄球菌的吞噬能力和活性氧的产生。精氨酸酶活性在细胞裂解液中进行评估,一氧化氮的生成在上清液中使用格里斯反应进行检测。结果用 Larifan 处理的人血单核细胞和粒细胞的吞噬指数和活性氧生成都较低。该药物可导致一氧化氮产生量的增加以及血液单核细胞精氨酸酶活性的降低。结论。我们的研究结果表明 Larifan 能够增强静止吞噬细胞的抗病毒特性,同时抑制氧化应激的发展。
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引用次数: 0
BIOMEDICAL APPLICATION OF K5 PLASMINOGEN FRAGMENT K5 血浆蛋白酶片段的生物医学应用
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.005
L. G. Kapustianenko
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.
目的Plasminogen kringle 5 是一种内源性血管生成抑制剂。本综述旨在强调 Kringle 5 在调节血管生成和肿瘤生长方面的潜在生物医学应用。方法。血管生成是一个复杂的过程,涉及内皮细胞增殖、迁移、基底膜降解和新生血管组织。由于新血管不受控制的生长会导致许多常见疾病的恶化,首先是肿瘤疾病、自身免疫性疾病、眼部新生血管损伤等,因此使用血管紧张素可以成为预防和辅助治疗这些病症的一种很有前景的药物治疗方法。应用血管紧张素的优势在于,即使使用高剂量也无毒性、无免疫原性、靶细胞对其作用缺乏耐受性。血管紧张素包括一组含环的蛋白水解衍生纤溶酶原/纤溶酶原片段,可作为内皮增殖和迁移的强效抑制介质。在所有已知的血管生长抑素种类中,分离出的 K5 血浆纤溶酶原片段通过触发多种信号通路,导致细胞死亡,从而抑制血管生成,对内皮细胞的增殖具有最强的抑制活性。结果。目前的文献数据表明,人纤溶酶原的 Kringle 结构域 5 除了对内皮细胞和某些类型的肿瘤细胞具有表达性和高度特异性的细胞毒性外,还具有作为抗血管生成和抗肿瘤调节剂的其他优势,包括其特异性抑制活性,这种活性只影响活化、增殖的内皮细胞,因此对其他类型的正常细胞无毒性。作为一种在人体机体内形成的内源性蛋白质,K5 不会引起免疫反应。K5 作为一种结构稳定的小多肽分子,可在大肠杆菌细胞中获得重组蛋白,也可用于定向给药和缓释的药代动力学系统。结论K5有望成功用作治疗剂,以控制与血管生成失调相关的病理过程,因此有必要开发和改进其生产方法,并进一步测试其合理的多生物活性。
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引用次数: 0
COMPLEXATION OF CURCUMIN WITH BOVINE SERUM ALBUMIN AND DIPHTHERIA TOXOID CRM197 姜黄素与牛血清白蛋白和白喉类毒素 crm197 的复合物
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.076
D.A. Zhukova
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.
研究目的本研究的目的是证明姜黄素在牛血清白蛋白和白喉类毒素 CRM197 这两种蛋白质载体上的结合位点。之所以选择牛血清白蛋白作为潜在的非特异性蛋白质载体,是因为它在医学中被广泛用作药物载体。研究方法采用分光光度法和分子对接法进行研究。结果。证明了 BSA 与姜黄素有两个稳定的结合位点。CRM197 是一种经过充分研究的载体蛋白,具有自身的抗肿瘤活性,并已被研究为一种对表皮生长因子受体过度表达的癌细胞具有高亲和力的特异性载体。我们的研究结果显示了一个可能的姜黄素结合位点,这使得 CRM197 成为一种理想的特异性姜黄素递送平台,在抗癌疗法中至少能提供一种叠加效应。结论总之,所研究的两种蛋白质都能与姜黄素形成稳定的复合物,为商业药物应用奠定了基础。
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引用次数: 0
INFLUENCE OF BIOLOGICAL INDUCTORS ON THE SYNTHESIS AND BIOLOGICAL ACTIVITY OF MICROBIAL METABOLITES 生物诱导剂对微生物代谢物的合成和生物活性的影响
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.017
T.P. Pirog
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.
抗生素耐药性的不断增加是人类严重关切的问题。微生物的协同培养是获得新的次级抗菌代谢物的一种很有前景的方法。微生物协同培养的有效策略是使用某些生物诱导剂。本综述旨在总结现有文献中关于不同生理类型的生物诱导剂对微生物次生代谢物的合成和生物活性的影响的科学研究。文献分析表明,在这些研究中,要么在培养基中加入浓度明显低于最终代谢物产生细胞的诱导体活细胞或灭活细胞,要么使用竞争性微生物培养后的上清液(滤液)作为诱导体。根据文献和我们自己的实验研究,使用诱导剂是一种有效的方法,不仅可以强化细菌素、表面活性剂和抗生素的合成,还可以提高它们的生物活性。此外,它还经常导致生产出对生产者来说并不常见的新型抗菌化合物。然而,诱导剂对具有生物活性的次生代谢物合成的影响机制还需要进一步研究,因为文献表明,在生产者的培养基中引入诱导剂并不总能加强最终产物的合成。此外,次生代谢物的生物活性取决于生产者的培养条件,包括培养基中是否存在生物诱导剂。因此,必须进一步研究生产者与竞争微生物之间的相互作用,以调节合成代谢物的生物活性。此外,还有必要为次生代谢物的生物合成寻找更具成本效益的底物,优化培养基的成分,并扩大原核和真核诱导剂的范围。
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引用次数: 0
DYNAMICS OF THE PHENOLIC CONSTITUENTS AND ANTIOXIDANT ACTIVITY IN SUBMERGED CULTURES OF Xylaria SPECIES Xylaria 菌种混合培养液中酚类成分和抗氧化剂活性的动态变化
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.082
A. Atamanchuk
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.
研究目的本研究旨在进一步了解木鳖子属植物合成酚类化合物的动态过程,以及沉水培养过程中生物质和培养液中酚含量与抗氧化特性之间的相关性。研究方法在浸没条件下,用葡萄糖-酵母-蛋白胨营养培养基培养来自 IBK 蘑菇培养物保藏中心的 Xylaria polymorpha 和 Xylaria longipes 真菌菌株。在培养的第 3 天、第 5 天、第 7 天和第 9 天收获生物量和培养液,然后用乙酸乙酯提取。用 Folin-Ciocalteu 法测定提取物中的总酚含量,并用 DPPH 法评估其抗氧化潜力。结果研究结果表明,木虱属真菌物种的酚类化合物积累是根据菌株水平而定的。值得注意的是,与 X. polymorpha 相比,X. longipes 菌株的酚类成分产量更高,并在特定的培养时间表现出更强的抗氧化活性。此外,菌丝体生物量和培养液中多酚积累的动态与抗氧化活性之间建立了很强的相关性。结论从所研究菌株的生物质和培养液中提取出了具有抗氧化特性的天然酚类化合物。与培养液相比,生物质中的酚类化合物浓度和抗氧化活性值明显更高。研究结果表明,培养时间越晚并不一定会产生更多的酚类物质,因此有必要对这些化合物的积累情况进行全面评估,并对相关参数进行动态研究。
{"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}
引用次数: 0
RADIATION AND HYPOXIA STUDIES: EFFECTS OF HIGH-ENERGY ATMOSPHERIC PARTICLES ON BIOLOGICAL ORGANISMS AND POSSIBILITIES OF THEIR REHABILITATION 辐射和缺氧研究:高能大气粒子对生物有机体的影响及其恢复的可能性
Pub Date : 2023-12-12 DOI: 10.15407/biotech16.06.048
O. M. Klyuchko
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.
观测了宇宙辐射对地球大气层中原子和分子的影响,以及随后原子和气体分子的变化,以及生物体缺氧状态的发展,并提出了一些纠正这种失调的方法。这项工作的目的是研究电离层中的辐射效应,以及随后在地球表面以上不同高度的原子、气体分子的高能量转化;一些高能量大气粒子与海平面(a.s.l.)以上 5.500 米近地生物物体的相互作用,以及氧气在生物有机体辐照后果中的作用。方法。乌克兰国家科学院 EMBS 研究站在山区条件下进行的调查:使用标准实验室方法、综合方法技术对病人进行长期观察的结果进行比较分析:呼吸系统、心血管系统的临床、生理研究;血液学、免疫学状态;高级神经活动的功能状态、精神和神经状态;抗低氧血症药物的使用、组织化学、生物物理方法、数学建模等。结果。介绍了卫星大气探测期间获得的最新数据:对大气中原子、分子结构的影响、从电离层到地球表面的气体浓度、光化学过程、光离子化等现象的研究。根据文章中描述的现象,讨论了 "信息 "这一概念。乌克兰医生和科学家在山区条件下对切尔诺贝利辐照病人的检查和康复结果补充了对气体微粒变化、生物体缺氧(缺氧状态)的研究。结论观察了太阳辐射对地球大气层中原子、分子和分子复合物的影响现象。主要注意力集中在研究不同高度的气体浓度,以及氧气在生物体辐照和康复后果中的作用。对病人的医疗和康复提出了切实可行的建议。
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引用次数: 0
KAN0438757: A NOVEL PFKFB3 INHIBITOR THAT INDUCES PROGRAMMED CELL DEATH AND SUPPRESSES CELL MIGRATION IN NON-SMALL CELL LUNG CARCINOMA CELLS KAN0438757:一种新型 pfkfb3 抑制剂,可诱导细胞程序性死亡并抑制非小细胞肺癌细胞的迁移
Pub Date : 2023-10-31 DOI: 10.15407/biotech16.05.034
Özdemir Deniz
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.
目的PFKFB3 是一种糖酵解激活剂,在人类肺癌中过度表达,在多种细胞功能(包括细胞程序性死亡)中发挥着关键作用。尽管有许多小分子化合物被描述为 PFKFB3 抑制剂,但其中一些在体外和体内显示出令人失望的结果。KAN0438757 是一种选择性强的小分子抑制剂。然而,KAN0438757 对非小细胞肺癌细胞的影响仍然未知。在此,我们试图破解 KAN0438757 对非小细胞肺癌细胞的增殖、迁移、DNA 损伤和程序性细胞死亡的影响。研究方法通过WST-1、实时细胞分析、彗星试验、伤口愈合迁移试验、MMP/JC-1和AO/ER双重染色试验以及Western印迹分析,检测KAN0438757对非小细胞肺癌细胞活力、增殖、DNA损伤、迁移、凋亡和自噬的影响。结果我们的研究结果表明,KAN0438757 能显著抑制 A549 和 H1299 细胞的活力和增殖,并抑制 A549 细胞的迁移。更重要的是,KAN0438757 能导致 DNA 损伤并引发细胞凋亡,同时伴随着 A549 细胞中 PARP 的上调。此外,用 KAN0438757 处理会导致 LC3 II 和 Beclin1 的增加,这表明 KAN0438757 能刺激自噬。结论总之,用 KAN0438757 靶向 PFKFB3 可能是一种很有前景的有效治疗方法,需要进一步对 KAN0438757 作为非小细胞肺癌细胞疗法进行体外和体内评估。
{"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}
引用次数: 0
BIOCATALYTIC CARBON DIOXIDE CAPTURE PROMOTED BY CARBONIC ANHYDRASE 碳酸酐酶促进的生物催化二氧化碳捕获
Pub Date : 2023-10-31 DOI: 10.15407/biotech16.05.005
O. K. Zolotareva
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.
二氧化碳是大气中最丰富的温室气体,其浓度的快速、稳定增长导致了极端天气和气候事件的发生。由于化石燃料(石油、煤炭和天然气)的燃烧,近几十年来空气中的二氧化碳浓度每年增加 2ppm 以上,仅去年一年就增加了 3.29ppm。为了防止出现气候变化的 "最坏 "情况,需要通过碳管理立即大幅减少二氧化碳排放量。目标。分析在环境脱碳计划中使用碳酸酐酶的研究现状和前景。结果。碳酸酐酶(CA)是一种酶,可将溶液中 CO2 和 HCO3 的交换速度提高 104 至 106 倍。迄今为止,已在不同生物体内发现了 7 种 CA。CA 需要为体内的各种代谢途径快速提供 CO2 和 HCO3,这也解释了 CA 在进化过程中的多重独立起源。利用碳酸酐酶(CA)对从细菌和哺乳动物组织中分离出来的酶进行了二氧化碳封存项目测试。研究最多的是人类 KAz 的一种异构体--hCAII--最活跃的天然酶。它的缺点是长期不稳定、对温度高度敏感、对污染物(如硫化合物)的耐受性低以及无法重复使用。分子建模和酶固定化方法被用来克服这些局限性。结果表明,固定化可提供更高的热稳定性和储存稳定性,并提高可重复使用性。结论。利用碳酸酐酶(CA)捕获二氧化碳是减缓全球变暖的最具成本效益的方法之一,其发展需要在提高 CA 的稳定性和热稳定性方面做出巨大努力。
{"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}
引用次数: 0
EFFECT OF PHENYLALANINE AND LIGHT ON THE GROWTH OF HAIRY ROOTS OF Artemisia tilesii LEDEB 苯丙氨酸和光照对艾蒿毛根生长的影响
Pub Date : 2023-10-31 DOI: 10.15407/biotech16.05.061
Т. Bohdanovych
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.
目的分析分别或联合使用不同浓度的苯丙氨酸和不同光照模式来促进两个品系的毛根蒿生物量积累和黄酮类化合物生物合成的可能性。研究方法在含有高浓度(1 毫摩尔)和低浓度(0.05 和 0.1 毫摩尔)苯丙氨酸的固化培养基上,在光照(3000 lx,16 小时)和黑暗条件下培养毛细根。培养四周后,按照标准测试方法测定增重、黄酮含量和 DPPH 清除活性。结果在光照下生长的根呈绿色,分枝较多,较粗,而在黑暗中生长的根则更加细长。添加 1 mM 苯丙氨酸会抑制所有样品的生长。不同品系对较低浓度的耐受性不同。无论苯丙氨酸的浓度如何,两个品系所有样品的类黄酮含量在光照下都更高(高达 3.14 倍)。在光照下生长的根的抗氧化活性也更高,EC50 值与类黄酮含量相关。结论光照促进了两种毛细根系所有样本中黄酮类化合物的合成和抗氧化活性。添加苯丙氨酸对生物量积累和类黄酮生物合成的影响具有品系特异性。
{"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}
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Biotechnologia Acta
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