Pub Date : 2024-03-11DOI: 10.3103/s0096392523700219
T. B. Stanishneva-Konovalova, E. B. Pichkur, S. S. Kudryavtseva, I. A. Yaroshevich, A. N. Semenov, E. G. Maksimov, A. V. Moiseenko, O. I. Volokh, V. I. Muronets
Abstract
In this work, conditions were selected for obtaining a sample of eukaryotic chaperonin TRiC suitable for studying by cryo-electron microscopy. Using the method of differential scanning (time-resolved) fluorimetry, the temperature stability of protein samples at different concentrations of salt and glycerol was compared, and then the selected conditions were used to prepare the sample for microscopy. As a result, the structure of bovine TRiC in an open conformation was obtained at 4.42 Å resolution.
摘要 本研究选择了获得真核细胞伴侣蛋白 TRiC 样品的条件，以适合冷冻电镜研究。利用差示扫描（时间分辨）荧光测定法，比较了蛋白质样品在不同浓度的盐和甘油中的温度稳定性，然后利用选定的条件制备显微镜下的样品。结果以 4.42 Å 的分辨率获得了牛 TRiC 的开放构象结构。
{"title":"Cryo-EM Structure of Bovine Chaperonin TRiC/CCT in Open Conformation","authors":"T. B. Stanishneva-Konovalova, E. B. Pichkur, S. S. Kudryavtseva, I. A. Yaroshevich, A. N. Semenov, E. G. Maksimov, A. V. Moiseenko, O. I. Volokh, V. I. Muronets","doi":"10.3103/s0096392523700219","DOIUrl":"https://doi.org/10.3103/s0096392523700219","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>In this work, conditions were selected for obtaining a sample of eukaryotic chaperonin TRiC suitable for studying by cryo-electron microscopy. Using the method of differential scanning (time-resolved) fluorimetry, the temperature stability of protein samples at different concentrations of salt and glycerol was compared, and then the selected conditions were used to prepare the sample for microscopy. As a result, the structure of bovine TRiC in an open conformation was obtained at 4.42 Å resolution.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097478","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}
Pub Date : 2024-03-11DOI: 10.3103/s0096392523700153
L. V. Kordyukova, A. V. Moiseenko, T. A. Timofeeva, I. T. Fedyakina
Abstract
Cryo-electron microscopy (cryo-EM) is indispensable for the structural studies of enveloped viruses: dangerous pathogens of humans and animals. Yet, it requires highly specialized equipment as well as careful sample preparation. In this work, the capabilities of a JEOL JEM-2100 transmission electron microscope equipped with a cryo-transfer holder are used, and preliminary cryo-EM data for influenza A and B virus strains and SARS-CoV-2 inactivated with beta-propiolactone are presented. Image analysis allows us to (1) distinguish “empty” viral particles from “full” ones (containing nucleocapsid); (2) visualize the lipid bilayer of the viral envelope; (3) identify influenza virus surface antigens and the M1 protein layer combined with the inner lipid monolayer; and (4) distinguish different morphology of S-spikes on the surface of inactivated SARS-CoV-2 virions. The developed approach provides good image quality for both fundamental and applied research.
{"title":"Cryo-Electron Microscopy of Enveloped Viruses Using an Upgraded Transmission Electron Microscope: Influenza Type A and B Viruses and SARS-CoV-2","authors":"L. V. Kordyukova, A. V. Moiseenko, T. A. Timofeeva, I. T. Fedyakina","doi":"10.3103/s0096392523700153","DOIUrl":"https://doi.org/10.3103/s0096392523700153","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Cryo-electron microscopy (cryo-EM) is indispensable for the structural studies of enveloped viruses: dangerous pathogens of humans and animals. Yet, it requires highly specialized equipment as well as careful sample preparation. In this work, the capabilities of a JEOL JEM-2100 transmission electron microscope equipped with a cryo-transfer holder are used, and preliminary cryo-EM data for influenza A and B virus strains and SARS-CoV-2 inactivated with beta-propiolactone are presented. Image analysis allows us to (1) distinguish “empty” viral particles from “full” ones (containing nucleocapsid); (2) visualize the lipid bilayer of the viral envelope; (3) identify influenza virus surface antigens and the M1 protein layer combined with the inner lipid monolayer; and (4) distinguish different morphology of S-spikes on the surface of inactivated SARS-CoV-2 virions. The developed approach provides good image quality for both fundamental and applied research.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097501","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}
Pub Date : 2024-03-11DOI: 10.3103/s0096392523700207
Y. F. Krupyanskii, N.G. Loiko, V. V. Kovalenko, A. A. Generalova, E. V. Tereshkin, A. V. Moiseenko, K. B. Tereshkina, A. N. Popov, O. S. Sokolova
Abstract
The architecture of DNA in the dormant cells was studied by synchrotron radiation diffraction and transmission electron microscopy. Diffraction experiments indicate the appearance of a periodic ordered organization of DNA. Transmission electron microscopy made it possible to visualize information about the type of DNA condensation. Intracellular nanocrystalline, liquid-crystalline and folded nucleosome-like structures of DNA have been found. Next, we studied changes in DNA architecture under stress of exposure to a chemical analogue of the anabiosis autoinducer (4-hexylresorcinol). Studies of the DNA architecture in the anabiotic and mummified states show the identity of the DNA structure in the anabiotic state and in the dormant state under starvation stress. The architecture of DNA in a mummified state is very different from that of DNA in an anabiotic state.
摘要 通过同步辐射衍射和透射电子显微镜研究了休眠细胞中 DNA 的结构。衍射实验表明，DNA出现了周期性的有序组织。透射电子显微镜可以直观地观察到DNA凝结类型的信息。我们发现了细胞内 DNA 的纳米晶、液晶和折叠核糖体状结构。接下来，我们研究了在暴露于无丝分裂自体诱导剂化学类似物（4-己基间苯二酚）的压力下 DNA 结构的变化。对缺氧状态和木乃伊化状态下的DNA结构的研究表明，缺氧状态下的DNA结构与饥饿胁迫下休眠状态下的DNA结构相同。木乃伊化状态下的 DNA 结构与无生物活性状态下的 DNA 结构截然不同。
{"title":"Condensed DNA Structure in Bacteria Subjected to Various Types of Stress","authors":"Y. F. Krupyanskii, N.G. Loiko, V. V. Kovalenko, A. A. Generalova, E. V. Tereshkin, A. V. Moiseenko, K. B. Tereshkina, A. N. Popov, O. S. Sokolova","doi":"10.3103/s0096392523700207","DOIUrl":"https://doi.org/10.3103/s0096392523700207","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The architecture of DNA in the dormant cells was studied by synchrotron radiation diffraction and transmission electron microscopy. Diffraction experiments indicate the appearance of a periodic ordered organization of DNA. Transmission electron microscopy made it possible to visualize information about the type of DNA condensation. Intracellular nanocrystalline, liquid-crystalline and folded nucleosome-like structures of DNA have been found. Next, we studied changes in DNA architecture under stress of exposure to a chemical analogue of the anabiosis autoinducer (4-hexylresorcinol). Studies of the DNA architecture in the anabiotic and mummified states show the identity of the DNA structure in the anabiotic state and in the dormant state under starvation stress. The architecture of DNA in a mummified state is very different from that of DNA in an anabiotic state.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097725","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}
Pub Date : 2024-03-11DOI: 10.3103/s0096392523700256
I. N. Levchenko, G. K. Vladimirov, I. V. Volodyaev, Y. A. Vladimirov
Abstract
The points of enzymatic activity, quantum yields, structure, functions of luminol chemiluminescence activated by physical activators natural dyes isoquinolysine coumarins C-334 and C-525 under the action of cytochrome c complex with cardiolipin in aqueous medium and in nonpolar environment were considered. It is shown: (1) the enzymatic activity points and quantum yields are significantly higher in the presence of the physical activator coumarin C-525 than in the case of its own unactivated luminescence or in the case of the physical activator C-334; (2) the enzymatic activity depends not only on the concentration of cytochrome c but also on the percentage ratio between the native form of cytochrome c with cardiolipin and the partially denatured one.
摘要 研究了在水介质和非极性环境中，细胞色素 c 与心磷脂复合物作用下，由物理激活剂天然染料异喹啉香豆素 C-334 和 C-525 激活的鲁米诺化学发光的酶活性、量子产率、结构和功能。结果表明(1) 在物理激活剂香豆素 C-525 的存在下，酶活性点和量子产率明显高于其自身未激活发光或物理激活剂 C-334 的情况；(2) 酶活性不仅取决于细胞色素 c 的浓度，还取决于细胞色素 c 与心磷脂的原生形式和部分变性形式之间的百分比率。
{"title":"Peculiarities of Cytochrome c Enzymatic Activity with Cardiolipin","authors":"I. N. Levchenko, G. K. Vladimirov, I. V. Volodyaev, Y. A. Vladimirov","doi":"10.3103/s0096392523700256","DOIUrl":"https://doi.org/10.3103/s0096392523700256","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The points of enzymatic activity, quantum yields, structure, functions of luminol chemiluminescence activated by physical activators natural dyes isoquinolysine coumarins C-334 and C-525 under the action of cytochrome <i>c</i> complex with cardiolipin in aqueous medium and in nonpolar environment were considered. It is shown: (1) the enzymatic activity points and quantum yields are significantly higher in the presence of the physical activator coumarin C-525 than in the case of its own unactivated luminescence or in the case of the physical activator C-334; (2) the enzymatic activity depends not only on the concentration of cytochrome <i>c</i> but also on the percentage ratio between the native form of cytochrome <i>c</i> with cardiolipin and the partially denatured one.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097873","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}
Pub Date : 2024-03-11DOI: 10.3103/s0096392523700165
N. Yu. Mamaeva, N. I. Derkacheva, D. A. Gasanova, O. S. Sokolova, G. S. Glukhov
Abstract
A detergent-free protocol for purification of the coronavirus prefusion S-protein using styrene-maleic acid copolymer (SMA) was developed. Expression of the S-protein was carried out in HEK293T cells. Two solubilization methods were used to purify and prepare the S-protein for microscopy: in NP-40 detergent and as part of SMA. The resulting preparations were examined in an electron microscope, and the particles of purified S-proteins were classified. Analysis of two-dimensional projections of the particles showed that the use of lipodiscs for solubilization leads to lower mobility of the purified protein on the substrate compared to the protein in the detergent, which may further contribute to obtaining higher resolutions when studying the structure of membrane proteins.
摘要 利用苯乙烯-马来酸共聚物（SMA）开发了一种纯化冠状病毒预融合 S 蛋白的无洗涤剂方案。S 蛋白在 HEK293T 细胞中表达。使用两种溶解方法纯化和制备用于显微镜观察的 S 蛋白：在 NP-40 去污剂中和作为 SMA 的一部分。在电子显微镜下对制备结果进行检查，并对纯化的 S 蛋白颗粒进行分类。对颗粒二维投影的分析表明，与洗涤剂中的蛋白质相比，使用脂溶盘进行增溶会降低纯化蛋白质在基质上的流动性，这可能有助于在研究膜蛋白结构时获得更高的分辨率。
{"title":"Stabilization of Full-Length S-Protein of SARS-Cov-2 Coronavirus in SMA Polymer for Electron Microscopy Study","authors":"N. Yu. Mamaeva, N. I. Derkacheva, D. A. Gasanova, O. S. Sokolova, G. S. Glukhov","doi":"10.3103/s0096392523700165","DOIUrl":"https://doi.org/10.3103/s0096392523700165","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>A detergent-free protocol for purification of the coronavirus prefusion S-protein using styrene-maleic acid copolymer (SMA) was developed. Expression of the S-protein was carried out in HEK293T cells. Two solubilization methods were used to purify and prepare the S-protein for microscopy: in NP-40 detergent and as part of SMA. The resulting preparations were examined in an electron microscope, and the particles of purified S-proteins were classified. Analysis of two-dimensional projections of the particles showed that the use of lipodiscs for solubilization leads to lower mobility of the purified protein on the substrate compared to the protein in the detergent, which may further contribute to obtaining higher resolutions when studying the structure of membrane proteins.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097515","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}
Pub Date : 2024-03-11DOI: 10.3103/s0096392523700128
O. S. Sokolova, T. B. Stanishneva-Konovalova, M. P. Kirpichnikov
Abstract
The IV Russian International Conference on Cryo-Electron Microscopy (RICCEM-2023) was held at the Faculty of Biology of Lomonosov Moscow State University in a hybrid online and offline format and brought together more than 250 researchers from 10 countries. Following the conference, a special issue of the journal “Moscow University Biological Sciences Bulletin” was published. This article summarizes the main results of the conference and the content of the papers published in the special issue.
{"title":"Advances in Structural Research Using Electron Microscopy in Russia (Results of the Fourth International Conference RICCEM-2023)","authors":"O. S. Sokolova, T. B. Stanishneva-Konovalova, M. P. Kirpichnikov","doi":"10.3103/s0096392523700128","DOIUrl":"https://doi.org/10.3103/s0096392523700128","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The IV Russian International Conference on Cryo-Electron Microscopy (RICCEM-2023) was held at the Faculty of Biology of Lomonosov Moscow State University in a hybrid online and offline format and brought together more than 250 researchers from 10 countries. Following the conference, a special issue of the journal “Moscow University Biological Sciences Bulletin” was published. This article summarizes the main results of the conference and the content of the papers published in the special issue.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097729","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}
Pub Date : 2024-03-11DOI: 10.3103/s009639252370013x
K. V. Shaitan
Abstract
The current state of the protein folding problem and other biopolymers folding is discussed. The concept of a multidimensional potential energy surface and free energy surface for linear polymers is detailed, taking into account the topology of the configuration space and the presence of symmetry elements with respect to the rearrangement of identical monomer units. The presence of kinematic connections for conformational movements in a viscous medium leads to a tendency for the formation of helical structures of linear polymers. The dynamic effects of viscosity also lead to an almost uniform distribution of energy dissipation rates across the nodes of the chain. The combination of free energy surface topography and viscosity effects provides a physical basis for advancing folding theory toward interpreting a variety of experimental observations and elucidating principles of amino acid code formation for 3D protein structures. The relationship between the denaturation temperature of the folded state of the biopolymer and the energy of nonvalent interactions between monomers in the chain is analyzed.
{"title":"How Does a Biopolymer (Protein) Fold into a Unique 3D Structure?","authors":"K. V. Shaitan","doi":"10.3103/s009639252370013x","DOIUrl":"https://doi.org/10.3103/s009639252370013x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The current state of the protein folding problem and other biopolymers folding is discussed. The concept of a multidimensional potential energy surface and free energy surface for linear polymers is detailed, taking into account the topology of the configuration space and the presence of symmetry elements with respect to the rearrangement of identical monomer units. The presence of kinematic connections for conformational movements in a viscous medium leads to a tendency for the formation of helical structures of linear polymers. The dynamic effects of viscosity also lead to an almost uniform distribution of energy dissipation rates across the nodes of the chain. The combination of free energy surface topography and viscosity effects provides a physical basis for advancing folding theory toward interpreting a variety of experimental observations and elucidating principles of amino acid code formation for 3D protein structures. The relationship between the denaturation temperature of the folded state of the biopolymer and the energy of nonvalent interactions between monomers in the chain is analyzed.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097732","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}
Pub Date : 2024-03-01DOI: 10.3103/s0096392523700062
R. R. Yenikeyev, L. M. Zakharchuk
Abstract
Pure cultures of 19 strains of spore-forming bacteria were obtained from the equipment surfaces of the Russian segment of the International Space Station. The study of morphological, cultural, and physiological-biochemical properties of these bacteria allowed the authors to attribute all strains to the genus Bacillus. As a result of using MALDI-TOF methods and genome-wide sequencing, it was found that six of 19 bacillus strains belong to the species B. paralicheniformis, four to B. pumilus, four to B. subtilis, two to B. cereus, and one to B. amyloliquefaciens. In accordance with the requirements and norms of EUCAST 2023, the resistance of bacillus strains obtained from the Russian segment of the International Space Station to such antibiotics as imipenem, meropenem, ciprofloxacin, levofloxacin, norfloxacin, vancomycin, erythromycin, clindamycin, and linezolid was studied. Resistance to erythromycin was found in 11 strains of Bacillus, and five strains showed resistance to clindamycin. Only one strain showed resistance to imipenem, levofloxacin, and norfloxacin, respectively. Analysis of the complete genome of bacterial strains in which resistance to erythromycin and (or) clindamycin was found made it possible to establish that resistance to these antibiotics in B. paralicheniformis strains SE71, SE131, SE181, SE182, and SE183 provides the ermD antibiotic resistance gene. In B. cereus SE43, resistance to erythromycin encodes the mphL gene.
{"title":"Bacteria of the Genus Bacillus on the Russian Segment of the International Space Station","authors":"R. R. Yenikeyev, L. M. Zakharchuk","doi":"10.3103/s0096392523700062","DOIUrl":"https://doi.org/10.3103/s0096392523700062","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Pure cultures of 19 strains of spore-forming bacteria were obtained from the equipment surfaces of the Russian segment of the International Space Station. The study of morphological, cultural, and physiological-biochemical properties of these bacteria allowed the authors to attribute all strains to the genus <i>Bacillus</i>. As a result of using MALDI-TOF methods and genome-wide sequencing, it was found that six of 19 bacillus strains belong to the species <i>B. paralicheniformis</i>, four to <i>B. pumilus</i>, four to <i>B. subtilis</i>, two to <i>B. cereus</i>, and one to <i>B. amyloliquefaciens</i>. In accordance with the requirements and norms of EUCAST 2023, the resistance of bacillus strains obtained from the Russian segment of the International Space Station to such antibiotics as imipenem, meropenem, ciprofloxacin, levofloxacin, norfloxacin, vancomycin, erythromycin, clindamycin, and linezolid was studied. Resistance to erythromycin was found in 11 strains of <i>Bacillus</i>, and five strains showed resistance to clindamycin. Only one strain showed resistance to imipenem, levofloxacin, and norfloxacin, respectively. Analysis of the complete genome of bacterial strains in which resistance to erythromycin and (or) clindamycin was found made it possible to establish that resistance to these antibiotics in <i>B. paralicheniformis</i> strains SE71, SE131, SE181, SE182, and SE183 provides the <i>ermD</i> antibiotic resistance gene. In <i>B. cereus</i> SE43, resistance to erythromycin encodes the <i>mphL</i> gene.</p>","PeriodicalId":19004,"journal":{"name":"Moscow University Biological Sciences Bulletin","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140005436","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}
Pub Date : 2024-03-01DOI: 10.3103/s0096392523700049
A. N. Pavlyuchenkova, I. A. Kutyrev, A. V. Fedorov, M. A. Chelombitko, O. E. Mazur, Z. N. Dugarov
Abstract
In this work, the anti-inflammatory potential of secretory-excretory products (SEP) of gull-tapeworm Dibothriocephalus dendriticus and Ligula Ligula interrupta plerocercoids was studied for the first time in an in vitro model of LPS-induced activation of macrophages. A monocyte cell line derived from a patient with acute monocytic leukemia, THP-1, was used as a macrophage model. The anti-inflammatory properties of SEP were determined by the content of tumor necrosis factor (TNF) and interleukin-6 cytokines in the incubation medium using commercial kits for enzyme immunoassay. The results of our study indicated that SEP from L. interrupta plerocercoids have a pronounced anti-inflammatory effect, while SEP from D. dendriticus plerocercoids did not have such an effect. The authors next investigated the anti-inflammatory properties of L. interrupta SEP in a carrageenan-induced air-sac inflammation model in mice. A significant decrease in the volume of inflammatory exudate under the influence of L. interrupta SEP was found as well as an increase in the level of the interleukin-6 cytokine. At the same time, SEP of L. interrupta had no effect on the number of cells per 1 mL of exudate or the level of the proinflammatory cytokine TNF. The low molecular weight fraction of L. interrupta SEP also increased the level of the anti-inflammatory cytokine interleukin-10, which indicates a more pronounced anti-inflammatory effect compared to the high molecular weight fraction. The results obtained, in general, indicate the anti-inflammatory properties of the SEP of L. interrupta plerocercoids. However, the mechanism of anti-inflammatory action has not been elucidated and requires further research.
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Pub Date : 2024-03-01DOI: 10.3103/s0096392523700104
A. N. Khokhlov
Abstract
The history of research into the fundamental mechanisms of the pathogenesis of Alzheimer’s disease (AD) is briefly reviewed. Concepts in which a decisive role in the development of this disease was attributed to aluminum or free radicals are analyzed. The lack of reliable data to date to support these concepts is highlighted. The author’s point of view is stated, according to which almost all the results indicating the advisability of using antioxidants (as well as other potential drugs for AD) for the prevention and treatment of AD were obtained in model animals with certain pathologies (for example, with severe oxidative stress), which contribute to the formation of symptoms similar to those of AD in humans. In this regard, parallels with experimental gerontological work aimed at studying the effect of calorie-restricted nutrition on aging and life span are drawn. It is noted that these studies also used animals that were either not completely normal or were in unfavorable conditions. According to the author, the lack of serious success in the development of effective geroprotectors or drugs for the prevention/treatment of AD is due to the ignorance by most specialists of the principles of classical gerontology, in particular, the definitions of aging and age-related diseases, as well as correct approaches to the selection of control objects for their studies. It is emphasized that humans, unfortunately, cannot use the freshwater hydra method to combat aging and age-related diseases. Under certain conditions, it continuously renews all cells (including nerve cells) of its body and thereby ensures its “immortality.” In humans, replacing “old” neurons can lead to loss of personality/individuality, and “repairing” these cells seems impossible today. In this regard, the author considers it advisable to conduct studies of the aging of postmitotic cells in experiments on stationary cell cultures, which can accelerate, in particular, elucidation of the mechanisms of accumulation of beta-amyloid and senile pigments, such as lipofuscin, in neurons. The need to conduct clinical studies of AD as complementary to experimental work is noted, although the former are much more expensive and time-consuming. Only confirmation in human studies of the effectiveness of drugs developed in experiments on model animals will allow them to be recommended for clinical use.
摘要 本文简要回顾了阿尔茨海默病（AD）发病基本机制的研究历史。其中分析了铝或自由基在该病发展中起决定性作用的概念。重点指出了迄今为止缺乏支持这些概念的可靠数据。作者阐述了自己的观点，即几乎所有表明使用抗氧化剂（以及其他可能用于治疗注意力缺失症的药物）预防和治疗注意力缺失症的可取性的结果，都是在患有某些病症（例如，严重氧化应激）的模型动物身上获得的，这些病症会导致形成与人类注意力缺失症类似的症状。在这方面，与旨在研究限制卡路里营养对衰老和寿命影响的老年学实验工作有相似之处。值得注意的是，这些研究使用的动物要么不完全正常，要么处于不利条件下。作者认为，在开发有效的老年保护剂或预防/治疗注意力缺失症的药物方面之所以没有取得重大成功，是因为大多数专家不了解经典老年学的原理，特别是对衰老和老年相关疾病的定义，以及选择研究对照对象的正确方法。需要强调的是，遗憾的是，人类无法使用淡水水螅的方法来对抗衰老和老年疾病。在特定条件下，淡水九头蛇会不断更新其身体的所有细胞（包括神经细胞），从而确保其 "永生"。对于人类来说，更换 "老 "的神经细胞会导致人格/个性的丧失，而 "修复 "这些细胞在今天看来是不可能的。在这方面，作者认为最好在静止细胞培养实验中对有丝分裂后细胞的衰老进行研究，这尤其能加速阐明神经元中β-淀粉样蛋白和脂褐素等老年色素的积累机制。我们注意到，有必要开展 AD 临床研究，作为实验工作的补充，尽管前者更为昂贵和耗时。只有在人体研究中确认在模式动物实验中开发的药物的有效性，才能建议将其用于临床。
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