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Low-frequency Oscillations of Functional Indicators of the Body 人体功能指标的低频振荡
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-07-04 DOI: 10.1134/S000635092470012X
O. V. Grishin, V. G. Grishin

It has been shown in a number of our studies that low-frequency (LF) oscillations in the functional parameters of the oxygen transport system are stable and synchronized with each other. The literature presents a large number of examples of LF oscillations of various functional indicators that are directly or indirectly related to energy metabolism. In parallel, for more than 40 years, artificially induced attenuated and constant spontaneous oscillations in the energization levels of mitochondria in the same LF range have been studied. The aim of this review is to consider a possible relationship between oscillations in the functional parameters of the oxygen transport system and the functional parameters of mitochondria in the very-low-frequency (VLF) range common to them (0.003–0.03 Hz). We believe that a common source for all these oscillations is the periodic dynamics of “energization” in mitochondria united in mitochondrial networks. The process of generating these oscillations proceeds in two phases. In the first phase, the inflow of Ca2+ into the mitochondria exceeds the outflow and enhances the activity of oxidative phosphorylation. In the second phase, the outflow of Ca2+ from the mitochondria prevails over the inflow and is accompanied by the inhibition of oxidative phosphorylation. The oscillations are of a constant spontaneous nature and are based on autocatalytic regulation based on the feedback principle. The inertia of the full cycle processes (first and second phases) lasting 1–3 min may be due to the capacity of the mitochondrial phosphate buffer. The mitochondrial networks of excitable tissues can be the structural basis for synchronizing oscillations at the tissue level. Synchronization at the body level between mitochondrial oscillations and oscillations in indicators related to energy metabolism can be carried out through a system of tunneling nanotubes.

我们的一些研究表明,氧运输系统功能参数的低频(LF)振荡是稳定的,并且相互同步。文献提供了大量与能量代谢直接或间接相关的各种功能指标的低频振荡实例。与此同时,40 多年来,在相同的低频范围内,线粒体能量水平的人工诱导衰减和恒定自发振荡也得到了研究。本综述旨在探讨氧运输系统的功能参数振荡与线粒体在其共同的极低频(0.003-0.03 Hz)范围内的功能参数振荡之间可能存在的关系。我们认为,所有这些振荡的共同来源是线粒体网络中线粒体的周期性动态 "能量化"。产生这些振荡的过程分为两个阶段。在第一阶段,进入线粒体的 Ca2+ 流入量超过流出量,氧化磷酸化活动增强。在第二阶段,线粒体中 Ca2+ 的流出量超过流入量,氧化磷酸化受到抑制。振荡具有恒定的自发性质,是基于反馈原理的自催化调节。全周期过程(第一和第二阶段)持续 1-3 分钟的惯性可能是线粒体磷酸盐缓冲器的能力所致。可兴奋组织的线粒体网络可以作为组织层面同步振荡的结构基础。线粒体振荡与能量代谢相关指标的振荡之间的身体同步可以通过隧道纳米管系统实现。
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引用次数: 0
Hafnium Complexes as Contrast Media and Dose Enhancing Agents for Radiology and Contrast-Enhanced Radiotherapy 铪复合物作为放射学和对比增强放射治疗的对比介质和剂量增强剂
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-07-04 DOI: 10.1134/S0006350924700167
A. A. Lipengolts, V. A. Skribitsky, Yu. A. Finogenova, A. T. Shulyak, M. A. Abakumov, A. Yu. Bykov, E. Yu. Grigorieva, A. V. Smirnova, K. E. Shpakova, K. Yu. Zhizhin

Hafnium is a promising element as contrast agent for diagnostic and therapeutic radiology. Currently there are no suitable hafnium drugs with renal excretion which can be used in radiology. In this work two new hafnium complexes with nitrilotriacetic acid (Hf-NTA) and 1,2-diaminocyclohexanetetraacetic acid (Hf-CDTA) were synthesized and studied for acute toxicity and biodistribution. Inorganic chemistry methods were used for Hf-NTA and Hf-CDTA synthesis. Acute toxicity was studied in female mice C57Bl/6. Median lethal dose (LD50) of Hf-CDTA was assessed as 408 ± 64 mg Hf/kg and of Hf-NTA less than 120 mg Hf/kg. Biodistribution and contrast properties studies of Hf-CDTA were performed in vivo using micro-CT in mice with transplanted subcutaneous mammary adenocarcinoma Ca755. CT imaging of mice intravenously injected with Hf-CDTA confirmed its renal excretion and contrast capability. CT imaging of tumor region with single intratumoral administration of Hf-CDTA showed promising hafnium concentration and retention in tumor for use in contrast-enhanced radiotherapy. Hf-CDTA showed acceptable toxicity and biodistribution in mice with subcutaneous tumors for biomedical application in radiology and radiotherapy. For diagnostic clinical application, the Hf-CDTA formulation must be improved to increase water solubility and decrease toxicity. Hf-NTA appeared to be unacceptably toxic for radiological application.

摘要 铪是一种很有前途的放射诊断和治疗造影剂。目前,还没有合适的可通过肾脏排泄的铪药物可用于放射学。在这项工作中,合成了两种新的铪配合物,它们分别是氮基三乙酸(Hf-NTA)和1,2-二氨基环己烷四乙酸(Hf-CDTA),并对其急性毒性和生物分布进行了研究。Hf-NTA 和 Hf-CDTA 的合成采用了无机化学方法。对 C57Bl/6 雌性小鼠进行了急性毒性研究。经评估,Hf-CDTA 的中位致死剂量(LD50)为 408 ± 64 毫克 Hf/公斤,Hf-NTA 的中位致死剂量低于 120 毫克 Hf/公斤。在移植了皮下乳腺腺癌 Ca755 的小鼠体内,使用微型 CT 对 Hf-CDTA 进行了生物分布和对比度特性研究。对静脉注射 Hf-CDTA 的小鼠进行的 CT 成像证实了其肾脏排泄和造影能力。瘤内单次给药 Hf-CDTA 对肿瘤区域进行的 CT 成像显示,铪在肿瘤中的浓度和保留率有望用于造影剂增强放射治疗。Hf-CDTA 在小鼠皮下肿瘤中显示出可接受的毒性和生物分布,可用于放射学和放射治疗的生物医学应用。对于临床诊断应用,必须改进 Hf-CDTA 的配方,以增加水溶性和降低毒性。Hf-NTA 在放射学应用中似乎具有不可接受的毒性。
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引用次数: 0
Regularities of Induction and Growth of Tumors in Mice upon Irradiation of Ehrlich Carcinoma Cells Ex Vivo and In Vivo with a Pencil Scanning Beam of Protons 用铅笔扫描质子束照射小鼠体内和体外艾氏癌细胞时肿瘤诱发和生长的规律性
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-07-04 DOI: 10.1134/S0006350924700179
O. M. Rozanova, E. N. Smirnova, T. A. Belyakova, N. S. Strelnikova, A. V. Smirnov

The patterns of tumor induction and growth in mice under single irradiation ex vivo and in vivo of ascitic Ehrlich carcinoma (EAC) cells with a proton beam at doses of 30, 60, and 80 Gy are studied. It is shown that the frequency of tumor induction after the proton irradiation of EAC cells at a dose of 30 Gy under ex vivo irradiation was lower than after in vivo irradiation, and at doses of 60 Gy and 80 Gy, the number of tumors was the same. The temporal patterns of tumor occurrence in the ex vivo irradiation of EAC cells differed significantly from those after in vivo irradiation of the tumor: the time period during which the appearance of new tumors was recorded in the ex vivo groups was the same for all the studied doses, while when tumors were irradiated in vivo, this interval depended on the dose. The rate of tumor growth after the ex vivo and in vivo irradiation of cells does not depend on the dose, irradiation conditions, or time of their occurrence, but is significantly lower than in the control nonirradiated groups. The results obtained are of interest for understanding the mechanisms of potentially lethal damage to tumor cells, the role of the tumor microenvironment in inducing relapses, and ways to overcome them using the potential of proton therapy, as well as for developing biomedical models to find optimal targets for hadron cancer therapy.

研究了用 30、60 和 80 Gy 剂量的质子束对腹水艾氏癌(EAC)细胞进行体外和体内单次辐照后,小鼠肿瘤诱导和生长的模式。结果表明,质子束在体外照射 30 Gy 剂量的 EAC 细胞后,诱发肿瘤的频率低于体内照射,而在 60 Gy 和 80 Gy 剂量下,肿瘤数量相同。EAC细胞体外照射后肿瘤发生的时间模式与体内照射后肿瘤发生的时间模式明显不同:在所有研究剂量下,体外照射组记录到新肿瘤出现的时间段是相同的,而体内照射肿瘤时,这一间隔取决于剂量。细胞经体内外辐照后的肿瘤生长率与剂量、辐照条件或发生时间无关,但明显低于未受辐照的对照组。获得的结果对了解肿瘤细胞潜在致命损伤的机制、肿瘤微环境在诱导复发中的作用、利用质子疗法的潜力克服复发的方法以及开发生物医学模型以找到强子癌症疗法的最佳靶点都很有意义。
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引用次数: 0
Effect of the Pulsating Flow of Cerebrospinal Fluid on Spinal Pathologies 脑脊液脉动流对脊柱病变的影响
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-07-04 DOI: 10.1134/S0006350924700192
A. G. Zverev, Yu. N. Tokarev

Based on a dynamic parameter of the cerebrospinal fluid (CSF) flow, an original formula for estimating the pathology of the spinal motion segments of the spine is given. The graphs that clearly demonstrate a change in pathology depending on the depth of traumatization are given. The data obtained will be useful to specialists in computed tomography and magnetic resonance imaging, who are currently describing the pathology itself in a simplified way.

根据脑脊液(CSF)流的动态参数,给出了估算脊柱运动节段病理的独创公式。图表清楚地显示了病理变化取决于创伤深度。所获得的数据将对计算机断层扫描和磁共振成像专家有所帮助,因为他们目前正在以简化的方式描述病理本身。
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引用次数: 0
Spatial Structure of the Casoxin C Molecule Casoxin C 分子的空间结构
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-07-04 DOI: 10.1134/S0006350924700052
N. A. Akhmedov, L. N. Agaeva, R. M. Abbasli, L. I. Ismailova

A theoretical conformational analysis was performed to study the conformational possibilities for the casoxin C molecule (Tyr1–Ile2–Pro3–Ile4–Gln5–Tyr6–Val7–Leu8–Ser9–Arg10–OH). The potential function of the system was chosen as a sum of non-valence, electrostatic, and torsion interactions, and the energy of hydrogen bonds. The low-energy conformations of the casoxin C molecule were found, the values of dihedral angles of the main and side chains of the amino acid residues that make up the molecule were determined, and the energy of intra- and interresidual interactions was estimated. It has been shown that the spatial structure of the casoxin C molecule is represented by conformations of eight shapes of the peptide backbone. The results obtained can be used to elucidate the structural and structural-functional organization of casoxin molecules.

为了研究 casoxin C 分子(Tyr1-Ile2-Pro3-Ile4-Gln5-Tyr6-Val7-Leu8-Ser9-Arg10-OH)的构象可能性,我们进行了理论构象分析。系统的势函数被选为非价、静电和扭转相互作用以及氢键能量的总和。找到了 Casoxin C 分子的低能构象,确定了组成分子的氨基酸残基主链和侧链的二面角值,并估算了残基内和残基间相互作用的能量。结果表明,卡索辛 C 分子的空间结构由肽骨架的八种构象表示。所获得的结果可用于阐明 casoxin 分子的结构和结构功能组织。
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引用次数: 0
Interaction of Magnesium Ions with Semiquinone Radicals of Tiron, an Indicator of Reactive Oxygen Species 镁离子与铁酮的半醌自由基(一种活性氧指示剂)的相互作用
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-18 DOI: 10.1134/S0006350923060192
L. Yu. Ustynyuk, V. A. Medvedeva, S. O. Liubimovskii, E. K. Ruuge, A. N. Tikhonov

It has been shown using experimental (electron paramagnetic resonance) and quantum chemical (density functional theory) research methods that the previously observed changes in the electron paramagnetic resonance spectrum of the semiquinone Tiron radical in seawater are due to its interaction with Mg2+ ions. The formation of a complex between Mg2+ and the Tiron radical is due to the electrostatic attraction of ions carrying large charges of the opposite sign (+2 and –3), on the one hand, and the ability of Mg2+ ions to bind effectively to bidentate oxygen-containing ligands, on the other hand. The formation of tight contact ion pairs leads to a redistribution of the electron and spin density in the Tiron radical, which can be judged by the observed changes in the electron paramagnetic resonance spectrum of this radical.

摘要 利用实验(电子顺磁共振)和量子化学(密度泛函理论)研究方法表明,以前观察到的海水中半醌铁龙自由基电子顺磁共振谱的变化是由于它与 Mg2+ 离子的相互作用引起的。Mg2+ 与铁氧自由基之间形成复合物,一方面是由于携带相反符号(+2 和 -3)大电荷的离子之间的静电吸引,另一方面是由于 Mg2+ 离子能够有效地与双齿含氧配体结合。紧密接触离子对的形成导致铁龙自由基中电子和自旋密度的重新分布,这可以从观察到的该自由基电子顺磁共振谱的变化中判断出来。
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引用次数: 0
What Is the Reason that Gaseous Nitric Oxide Inhalation Does Not Affect Systemic Arterial Pressure in Humans and Animals? 吸入气态一氧化氮不会影响人类和动物全身动脉压的原因是什么?
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-18 DOI: 10.1134/S0006350923060209
A. F. Vanin, A. A. Abramov, A. B. Vagapov, A. A. Timoshin, A. V. Pekshev, V. L. Lakomkin, E. K. Ruuge

The reason for the lack of the hypotensive effect of gaseous NO, as introduced by inhalation into the bodies of animals and humans, has been identified. Since this defect was completely eliminated by inhalation of NO simultaneous with intravenous administration of low molecular mass thiol solutions to animals (rats), it is concluded that gaseous NO entering through the lungs into the blood circulating in a large circle of blood circulation converts into nitrosonium cation (NO+) as a result of single-electron oxidation, which is unable to exert vasodilating and thereby hypotensive effects on animals and humans. The binding of NO+ to low molecular mass thiols leads to its transformation into S-nitrosothiols, followed by the release of this nitrosyl agent in the form of neutral NO molecules characterized by hypotensive activity. The formation of dinitrosyl iron complexes with thiol-containing ligands in the blood and tissues of organs of experimental animals in these experiments, which could cause a hypotensive effect, was not detected. The hypotensive effect of inhaled NO, which was found in the lungs, could be due to the penetration of NO through the outer wall of blood vessels with subsequent activation of the enzyme guanylate cyclase, an inducer of vasodilation and hypotension, directly in the walls of blood vessels.

摘要 通过吸入动物和人体内的气态氮氧化物缺乏降压作用的原因已经查明。由于在给动物(大鼠)静脉注射低分子质量硫醇溶液的同时吸入 NO 完全消除了这一缺陷,因此得出结论:气态 NO 经肺进入血液循环的大循环圈后,由于单电子氧化作用而转化为亚硝基锍阳离子(NO+),这种阳离子无法对动物和人类产生血管扩张作用,因而也就无法产生降血压作用。NO+ 与低分子质量硫醇结合后会转化为 S-亚硝基硫醇,然后以具有降压活性的中性 NO 分子的形式释放出这种亚硝基物质。在这些实验中,没有检测到在实验动物的血液和器官组织中与含硫醇配体形成二亚硝基铁络合物,而这种络合物可能会导致降血压效应。在肺部发现的吸入 NO 的降压作用可能是由于 NO 穿透血管外壁,随后直接在血管壁上激活了鸟苷酸环化酶(血管舒张和降压的诱导剂)。
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引用次数: 0
Biosensor Systems: Determination of Optimal Time Parameters of Olfactory Stimulation 生物传感器系统:确定嗅觉刺激的最佳时间参数
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-18 DOI: 10.1134/S000635092306012X
A. E. Matukhno, M. V. Petrushan, L. V. Lysenko, V. N. Kiroy

Biosensor analysis methods are being actively improved and are becoming increasingly important in the fields of safety, medicine, in particular, cancer monitoring, environmental quality control, etc. In this paper, we considered the development of a biosensor system based on the technology of using the olfactory bulb (OB) of macrosmatic animals with optical methods of imaging odorant-specific patterns of glomerular activity. The difficulties of automatic detection of odor-triggered patterns during repetitive stimulation are due to adaptation processes manifested in a reversible change in the sensitivity of the neural structures of the olfactory analyzer. The optimal duration of stimuli and interstimular intervals has been experimentally found; this made it possible to stabilize the glomerular response during repeated stimulation and visualize patterns of glomerular activity with constant accuracy. The results we obtained expand the existing tools used for the development of biosensor systems.

摘要 生物传感器分析方法正在得到积极改进,并在安全、医学(特别是癌症监测)、环境质量控制等领域变得越来越重要。在本文中,我们考虑开发一种生物传感器系统,其技术基础是利用大型动物的嗅球(OB)和光学方法对肾小球活动的气味特异性模式进行成像。在重复刺激过程中自动检测气味触发模式的困难在于适应过程,表现为嗅觉分析器神经结构敏感性的可逆变化。我们通过实验找到了最佳的刺激持续时间和刺激间歇时间;这使得在重复刺激过程中稳定肾小球反应和持续准确地观察肾小球活动模式成为可能。我们取得的成果拓展了用于开发生物传感器系统的现有工具。
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引用次数: 0
Comparative Analysis of the Degree of Hydrolysis of Biopolymers in Hyaline Cartilage Homogenates in the Presence of Proteolytic Enzymes 蛋白水解酶作用下透明软骨匀浆中生物聚合物水解程度的比较分析
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-18 DOI: 10.1134/S0006350923060143
T. I. Nikolaeva, D. A. Barsuk, M. V. Molchanov, D. A. Prokhorov, V. I. Emelyanenko, P. V. Shekhovtsov

The study of the degree of hydrolysis depending on the action of various proteolytic enzymes is one of the tasks in the development of nutraceuticals from connective tissues for biomedicine. Hydrolysis of biopolymers in hyaline cartilage homogenates from the trachea of cattle and pigs was carried out under the action of the enzymes pancreatin, chymopsin, papain, and the proteolytic drug karipazim containing papain. It has been shown that karipazim produced by MedFlorina acted more effectively than karipazim produced by Vifitech, and the degree of collagen hydrolysis was maximal at 60°C and a concentration of karipazim of 10%. A more complete hydrolysis of proteoglycans was observed in the homogenates of hyaline cartilage of cattle, since glucose, the final product of glycosaminoglycan hydrolysis, was identified on NMR spectra.

摘要 研究水解程度取决于各种蛋白水解酶的作用,这是开发结缔组织营养保健品用于生物医学的任务之一。在胰蛋白酶、糜蛋白酶、木瓜蛋白酶和含有木瓜蛋白酶的蛋白水解药物卡里巴嗪的作用下,对牛和猪气管透明软骨匀浆中的生物聚合物进行了水解。结果表明,MedFlorina 公司生产的卡里巴嗪比 Vifitech 公司生产的卡里巴嗪更有效,在温度为 60°C 和卡里巴嗪浓度为 10%时,胶原蛋白的水解程度最大。在牛的透明软骨匀浆中观察到蛋白多糖水解得更彻底,因为在核磁共振光谱中发现了糖胺聚糖水解的最终产物葡萄糖。
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引用次数: 0
The Physicochemical Properties and Composition of Liposome Lipids from Lecithin Depending on the Conditions of Their Formation 卵磷脂脂质体的理化性质和组成取决于其形成条件
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-18 DOI: 10.1134/S0006350923060179
L. N. Shishkina, D. V. Paramonov, M. A. Klimovich, M. V. Kozlov

The influence of the composition and physicochemical properties of lecithin lipids, the duration of exposure to ultrasound, and centrifugation on the composition and physicochemical properties of liposomes formed from lecithin has been studied. It has been revealed that the intensity of lipid peroxidation has an inverse correlation with the phospholipid level in the total lipid composition of lecithin and a direct correlation with the relative content of cardiolipin in the composition of lecithin phospholipids. It has been shown that the duration of ultrasound exposure and centrifugation causes changes in the composition and properties of the liposome lipids. Decreases in the pH of the medium and the intensity of lipid peroxidation of liposomes were observed under centrifugation. It was revealed that the changes in the ability of the liposome lipids to oxidation depending on the duration of ultrasound exposure and centrifugation are due to the relative changes in the sum percentage of the acidic minor fractions in the composition of their phospholipids.

摘要 研究了卵磷脂脂质的组成和理化性质、暴露于超声波的时间以及离心对卵磷脂形成的脂质体的组成和理化性质的影响。研究发现,脂质过氧化的强度与卵磷脂总脂质成分中磷脂的含量成反比,与卵磷脂磷脂成分中心磷脂的相对含量成正比。研究表明,超声暴露和离心的持续时间会导致脂质体脂质的组成和性质发生变化。在离心过程中,观察到培养基的 pH 值下降,脂质体的脂质过氧化强度降低。研究表明,脂质体脂质氧化能力的变化取决于超声暴露和离心的持续时间,这是由于其磷脂组成中酸性次要组分的总百分比发生了相对变化。
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引用次数: 0
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