首页 > 最新文献

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry最新文献

英文 中文
Pregnan X Receptor Functioning under Conditions of Nitrosative Stress 亚硝化应激条件下妊娠X受体的功能
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020020
Y. V. Abalenikhina, E. A. Sudakova, A. A. Seidkulieva, A. V. Shchulkin, E. N. Yakusheva

Abstract

Pregnan X receptor (PXR) is a nuclear receptor that plays an important role in the regulation of the expression enzymes of biotransformation and metabolism. The functioning and possible mechanisms of PXR regulation under conditions of nitrosative stress have not been studied yet and this was the purpose of this study. Nitrosative stress (NS) was modeled in Caco-2 cells, which were incubated in the presence of 1 μM, 10 μM, 50 μM, 100 μM, and 500 μM concentrations of S-nitrosoglutathione (GSNO) for 3 h, 24 h, and 72 h. The amount of PXR was assessed by Western blotting. Incubation of Caco-2 cells with all GSNO concentrations for 3 h led to a decrease in the amount of PXR. Incubation with GSNO (1−50 μM) for 24 h was accompanied by an increase in the amount of PXR, while at a higher concentration (100 μM) this indicator did not significantly differ from the control and at a concentration of 500 μM it was below the control level. Prolonged incubation (for 72 h) enhanced NS and led to a normalization (1 μM GSNO) or a decrease of the PXR level (10−500 μM GSNO). Bityrosine formed during NS induced PXR expression at concentrations of 0.4 mM and 1 mM.

摘要妊娠X受体(pregnan X receptor, PXR)是一种核受体,在生物转化和代谢的表达酶调控中起重要作用。在亚硝化胁迫条件下,PXR调控的功能和可能的机制尚未得到研究,这也是本研究的目的。以Caco-2细胞为模型,分别在1 μM、10 μM、50 μM、100 μM和500 μM浓度的s -亚硝基谷胱甘肽(S-nitrosoglutathione, GSNO)作用下培养3 h、24 h和72 h, Western blotting检测PXR的表达量。Caco-2细胞与所有GSNO浓度孵育3 h后,PXR的含量均有所下降。与GSNO (1 ~ 50 μM)孵育24 h后,PXR的含量有所增加,但在100 μM浓度下,PXR的含量与对照无显著差异,500 μM浓度下PXR的含量低于对照。延长孵育时间(72h)可增强NS,导致PXR水平降低(10 ~ 500 μM GSNO)或正常化(1 μM GSNO)。在0.4 mM和1mm浓度下,NS诱导PXR表达时形成Bityrosine。
{"title":"Pregnan X Receptor Functioning under Conditions of Nitrosative Stress","authors":"Y. V. Abalenikhina,&nbsp;E. A. Sudakova,&nbsp;A. A. Seidkulieva,&nbsp;A. V. Shchulkin,&nbsp;E. N. Yakusheva","doi":"10.1134/S1990750822020020","DOIUrl":"10.1134/S1990750822020020","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Pregnan X receptor (PXR) is a nuclear receptor that plays an important role in the regulation of the expression enzymes of biotransformation and metabolism. The functioning and possible mechanisms of PXR regulation under conditions of nitrosative stress have not been studied yet and this was the purpose of this study. Nitrosative stress (NS) was modeled in Caco-2 cells, which were incubated in the presence of 1 μM, 10 μM, 50 μM, 100 μM, and 500 μM concentrations of S-nitrosoglutathione (GSNO) for 3 h, 24 h, and 72 h. The amount of PXR was assessed by Western blotting. Incubation of Caco-2 cells with all GSNO concentrations for 3 h led to a decrease in the amount of PXR. Incubation with GSNO (1−50 μM) for 24 h was accompanied by an increase in the amount of PXR, while at a higher concentration (100 μM) this indicator did not significantly differ from the control and at a concentration of 500 μM it was below the control level. Prolonged incubation (for 72 h) enhanced NS and led to a normalization (1 μM GSNO) or a decrease of the PXR level (10−500 μM GSNO). Bityrosine formed during NS induced PXR expression at concentrations of 0.4 mM and 1 mM.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"140 - 147"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4698130","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
The Effect of Lipid Derivative of the Anti-Tumor Drug Sarcolysin Embedded in Phospholipid Nanoparticles in the Experiments in Vivo 抗肿瘤药物肌酵素脂质衍生物包埋于磷脂纳米颗粒的体内实验研究
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020093
Yu. A. Tereshkina, T. I. Torkhovskaya, M. A. Sanzhakov, L. V. Kostryukova, Yu. Yu. Khudoklinova, E. G. Tikhonova

In order to improve the therapeutic properties of the antitumor agent sarcolysin, we have previously developed and characterized a dosage form, representing its ester conjugate with decanol embedded in ultra-small phospholipid nanoparticles less than 30 nm (Sarcolysin-NPh). In this study we have compared the effect of this composition with free substance of sarcolysin in vivo. After the intravenous administration to mice, an improvement in the pharmacokinetic parameters of sarcolysin was associated with a higher (by 22%) initial level in the blood and with prolonged circulation. This was also observed in P388 tumor-bearing mice. At the same time, the amount and duration of the presence of sarcolysin in the tumor tissue were significantly higher (more than two times) when compared with the free substance. In mice with three types of tumors (lymphocytic leukemia P388, lymphocytic leukemia L1210, and mammary adenocarcinoma Ca755), a predominant antitumor effect was shown, which manifested itself in a significantly greater inhibition of tumor growth and an increase in the life span of animals. The maximum inhibition of tumor growth during treatment with Sarcolysin-NPh at a dose of 8.4 mg/kg was noted in the case of lymphocytic leukemia L1210 and mouse mammary adenocarcinoma Ca755 (more than 24% and 17% higher, respectively, in comparison with the substance). At a dose of 10 mg/kg, differences in the life expectancy of animals were higher by 25%, 17.4%, and 11% for lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma Ca755, respectively. Sarcolysin-NPh intravenously to rats, demonstrated significantly lower acute toxicity than commercially available free Sarcolysin (Melphalan and Alkeran): the LD50 value for Sarcolysin-NPh was 2–3 times lower than that for free Sarcolysin. This indicates a lower toxicity of Sarcolysin-NPh.

为了提高抗肿瘤药物肌酵素的治疗性能,我们之前已经开发并表征了一种剂型,将其与decanol的酯偶联物嵌入在小于30 nm的超小磷脂纳米颗粒中(肌酵素- nph)。在本研究中,我们比较了该组合物与肌溶素游离物质在体内的作用。静脉给药小鼠后,肌溶素的药代动力学参数的改善与血液中初始水平升高(22%)和循环时间延长有关。在P388荷瘤小鼠中也观察到这一点。同时,与游离物质相比,肌溶素在肿瘤组织中存在的量和持续时间明显高于游离物质(两倍以上)。在患有三种类型肿瘤(淋巴细胞白血病P388、淋巴细胞白血病L1210和乳腺腺癌Ca755)的小鼠中,显示出明显的抗肿瘤作用,表现为对肿瘤生长的显著抑制和动物寿命的延长。在淋巴细胞白血病L1210和小鼠乳腺腺癌Ca755中,8.4 mg/kg剂量的肌酵素- nph对肿瘤生长的抑制作用最大(分别比该物质高24%和17%)。在10 mg/kg剂量下,淋巴细胞白血病P388、淋巴细胞白血病L1210和腺癌Ca755的动物预期寿命差异分别高出25%、17.4%和11%。大鼠静脉注射肌酵素- nph的急性毒性明显低于市售的游离肌酵素(Melphalan和Alkeran):肌酵素- nph的LD50值比游离肌酵素低2-3倍。这表明肌酵素- nph的毒性较低。
{"title":"The Effect of Lipid Derivative of the Anti-Tumor Drug Sarcolysin Embedded in Phospholipid Nanoparticles in the Experiments in Vivo","authors":"Yu. A. Tereshkina,&nbsp;T. I. Torkhovskaya,&nbsp;M. A. Sanzhakov,&nbsp;L. V. Kostryukova,&nbsp;Yu. Yu. Khudoklinova,&nbsp;E. G. Tikhonova","doi":"10.1134/S1990750822020093","DOIUrl":"10.1134/S1990750822020093","url":null,"abstract":"<p>In order to improve the therapeutic properties of the antitumor agent sarcolysin, we have previously developed and characterized a dosage form, representing its ester conjugate with decanol embedded in ultra-small phospholipid nanoparticles less than 30 nm (Sarcolysin-NPh). In this study we have compared the effect of this composition with free substance of sarcolysin in vivo. After the intravenous administration to mice, an improvement in the pharmacokinetic parameters of sarcolysin was associated with a higher (by 22%) initial level in the blood and with prolonged circulation. This was also observed in P388 tumor-bearing mice. At the same time, the amount and duration of the presence of sarcolysin in the tumor tissue were significantly higher (more than two times) when compared with the free substance. In mice with three types of tumors (lymphocytic leukemia P388, lymphocytic leukemia L1210, and mammary adenocarcinoma Ca755), a predominant antitumor effect was shown, which manifested itself in a significantly greater inhibition of tumor growth and an increase in the life span of animals. The maximum inhibition of tumor growth during treatment with Sarcolysin-NPh at a dose of 8.4 mg/kg was noted in the case of lymphocytic leukemia L1210 and mouse mammary adenocarcinoma Ca755 (more than 24% and 17% higher, respectively, in comparison with the substance). At a dose of 10 mg/kg, differences in the life expectancy of animals were higher by 25%, 17.4%, and 11% for lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma Ca755, respectively. Sarcolysin-NPh intravenously to rats, demonstrated significantly lower acute toxicity than commercially available free Sarcolysin (Melphalan and Alkeran): the LD<sub>50</sub> value for Sarcolysin-NPh was 2–3 times lower than that for free Sarcolysin. This indicates a lower toxicity of Sarcolysin-NPh.</p>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"125 - 133"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4693724","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
Prenatal Exposure to Alcohol Alters TLR4 Mediated Signaling in the Prefrontal Cortex in Rats 产前酒精暴露改变大鼠前额皮质TLR4介导的信号传导
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020032
M. I. Airapetov, S. O. Eresko, E. R. Bychkov, A. A. Lebedev, P. D. Shabanov

Abstract

Prenatal alcohol exposure (PAE) can lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in the development of defects in the nervous system caused by PAE. However, how PAE affects the TLR4 response in the brain remains unclear. Using the model of semi-forced alcoholization of pregnant rats, we have investigated TLR4-mediated signaling on the 30th day of postnatal development in their offspring. Rats exposed to PAE showed a higher expression of proinflammatory cytokines in the prefrontal cortex, but TLR4-mediated signaling in response to lipopolysaccharide (LPS) was weakened. These data suggest that PAE can lead to neuroinflammation and suppression of the TLR4-mediated response to LPS in the prefrontal cortex of young rats. Since innate immunity plays an important role in brain development, PAE-induced suppression of the TLR4-mediated response may be one of the mechanisms for the development of CNS pathology.

产前酒精暴露(PAE)可导致中枢神经系统(CNS)发育障碍和智力低下。toll样受体(TLR) 4在PAE引起的神经系统缺陷的发生发展中起重要作用。然而,PAE如何影响大脑中的TLR4反应仍不清楚。利用妊娠大鼠半强迫酒精化模型,我们研究了tlr4在其后代出生后发育第30天介导的信号通路。暴露于PAE的大鼠前额皮质中促炎细胞因子的表达较高,但tlr4介导的脂多糖(LPS)应答信号被削弱。这些数据表明,PAE可导致神经炎症和抑制tlr4介导的幼年大鼠前额皮质对LPS的反应。由于先天免疫在脑发育中起着重要作用,pae诱导的tlr4介导的应答抑制可能是中枢神经系统病理发展的机制之一。
{"title":"Prenatal Exposure to Alcohol Alters TLR4 Mediated Signaling in the Prefrontal Cortex in Rats","authors":"M. I. Airapetov,&nbsp;S. O. Eresko,&nbsp;E. R. Bychkov,&nbsp;A. A. Lebedev,&nbsp;P. D. Shabanov","doi":"10.1134/S1990750822020032","DOIUrl":"10.1134/S1990750822020032","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Prenatal alcohol exposure (PAE) can lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in the development of defects in the nervous system caused by PAE. However, how PAE affects the TLR4 response in the brain remains unclear. Using the model of semi-forced alcoholization of pregnant rats, we have investigated TLR4-mediated signaling on the 30th day of postnatal development in their offspring. Rats exposed to PAE showed a higher expression of proinflammatory cytokines in the prefrontal cortex, but TLR4-mediated signaling in response to lipopolysaccharide (LPS) was weakened. These data suggest that PAE can lead to neuroinflammation and suppression of the TLR4-mediated response to LPS in the prefrontal cortex of young rats. Since innate immunity plays an important role in brain development, PAE-induced suppression of the TLR4-mediated response may be one of the mechanisms for the development of CNS pathology.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"134 - 139"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4695430","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
The Effect of Methylene Blue and Its Metabolite—Azure I—on Bioenergetic Parameters of Intact Mouse Brain Mitochondria 亚甲基蓝及其代谢物蔚蓝i对完整小鼠脑线粒体生物能量参数的影响
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020044
A. P. Gureev, N. A. Samoylova, D. V. Potanina, V. N. Popov

Abstract

Methylene blue, a phenothiazine dye, that is widely used in medicine and is under clinical trials as an agent for treatment of Alzheimer’s disease. One of the factors of the unique therapeutic effect of methylene blue is its redox properties, allowing implementation of alternative electron transport: the dye accepts electrons from reducing equivalents in mitochondria and transfer them to other components of the respiratory chain or molecular oxygen. Azure I, an N-dimethylated metabolite of methylene blue, is potentially a more effective compound than methylene blue, but its ability for alternative electron transport has not been studied yet. We have shown that in contrast to methylene blue, azure I is unable to restore the membrane potential in isolated mouse brain mitochondria, inhibited by rotenone and, therefore, is unable to perform bypass of the respiratory chain complex I. Moreover, addition of azure I does not affect the rate of mitochondrial respiration in contrast to methylene blue, which increases the rate of non-phosphorylation respiration. At the same time, both dyes stimulate an increase in H2O2 production. Thus, only methylene blue is capable of alternative electron transport, while azure I does not produce complex I bypass. This limits its therapeutic application only as a mitochondrial-targeted agent, but does not question its antidepressant effects.

亚甲基蓝是一种吩噻嗪类染料,广泛应用于医学,目前正在临床试验中作为治疗阿尔茨海默病的药物。亚甲基蓝独特的治疗效果的因素之一是它的氧化还原特性,允许实现替代电子传输:染料接受线粒体中还原等量物的电子,并将其转移到呼吸链或分子氧的其他组成部分。亚甲基蓝的n -二甲基化代谢物Azure I可能是一种比亚甲基蓝更有效的化合物,但其替代电子传递的能力尚未得到研究。我们已经证明,与亚甲基蓝相比,天青I无法恢复分离小鼠脑线粒体的膜电位,受到鱼藤酮的抑制,因此无法进行呼吸链复合体I的旁路。此外,与亚甲基蓝相比,天青I的加入不会影响线粒体呼吸速率,而亚甲基蓝则会增加非磷酸化呼吸速率。同时,两种染料都刺激H2O2的产生。因此,只有亚甲基蓝能够替代电子传递,而天蓝I不产生络合物I旁路。这限制了其仅作为线粒体靶向药物的治疗应用,但不质疑其抗抑郁作用。
{"title":"The Effect of Methylene Blue and Its Metabolite—Azure I—on Bioenergetic Parameters of Intact Mouse Brain Mitochondria","authors":"A. P. Gureev,&nbsp;N. A. Samoylova,&nbsp;D. V. Potanina,&nbsp;V. N. Popov","doi":"10.1134/S1990750822020044","DOIUrl":"10.1134/S1990750822020044","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Methylene blue, a phenothiazine dye, that is widely used in medicine and is under clinical trials as an agent for treatment of Alzheimer’s disease. One of the factors of the unique therapeutic effect of methylene blue is its redox properties, allowing implementation of alternative electron transport: the dye accepts electrons from reducing equivalents in mitochondria and transfer them to other components of the respiratory chain or molecular oxygen. Azure I, an <i>N</i>-dimethylated metabolite of methylene blue, is potentially a more effective compound than methylene blue, but its ability for alternative electron transport has not been studied yet. We have shown that in contrast to methylene blue, azure I is unable to restore the membrane potential in isolated mouse brain mitochondria, inhibited by rotenone and, therefore, is unable to perform bypass of the respiratory chain complex I. Moreover, addition of azure I does not affect the rate of mitochondrial respiration in contrast to methylene blue, which increases the rate of non-phosphorylation respiration. At the same time, both dyes stimulate an increase in H<sub>2</sub>O<sub>2</sub> production. Thus, only methylene blue is capable of alternative electron transport, while azure I does not produce complex I bypass. This limits its therapeutic application only as a mitochondrial-targeted agent, but does not question its antidepressant effects.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"148 - 153"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1990750822020044.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4695431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Bioinformatic Identification of Proteins with Varying Levels of Post-Translational Modifications in Experimental Ischemic Stroke in Mice 小鼠实验性缺血性卒中中不同水平翻译后修饰蛋白的生物信息学鉴定
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S199075082202007X
V. S. Skvortsov, Ya. O. Ivanova, A. I. Voronina

Abstract

The experimental data obtained by Simats, A. et al. (Molecular and Cellular Proteomics, 2020, vol. 19, no. 12, pp. 1921–1936) were analyzed using a bioinformatic aproach. Original experimental results available in the ProteomeXchange database were obtained using a comprehensive multiomics approach to identify potential blood biomarkers in ischemic stroke in mice. The identification of peptides with post-translational modification (PTM) was performed by us using the raw data (accession code PXD016538). Only phosphorylation and deamination were considered as PTMs. Different combinations of data sets (ischemic tissue with intact tissue, ischemic tissue with control taken from mice after sham surgery, etc.) were compared both in terms of the ratio of abundance for the modified peptide to the unmodified variant and in terms of absolute values of abundance. The most probable change in the PTM levels was shown for 27 proteins, which included dynamin, glycogen phosphorylase and 70 kDa heat shock protein.

摘要:Simats, A. et al. (Molecular and Cellular Proteomics, 2020, vol. 19, no. 5)获得的实验数据。12, pp. 1921-1936)使用生物信息学方法进行分析。ProteomeXchange数据库中的原始实验结果是使用综合多组学方法鉴定小鼠缺血性中风中潜在的血液生物标志物获得的。我们使用原始数据(登录码PXD016538)进行翻译后修饰肽的鉴定。只有磷酸化和脱氨作用被认为是PTMs。不同的数据集组合(缺血组织与完整组织、缺血组织与假手术后小鼠的对照等)在修饰肽与未修饰变体的丰度比率以及丰度绝对值方面进行了比较。27种蛋白的PTM水平最有可能发生变化,其中包括动力蛋白、糖原磷酸化酶和70 kDa热休克蛋白。
{"title":"The Bioinformatic Identification of Proteins with Varying Levels of Post-Translational Modifications in Experimental Ischemic Stroke in Mice","authors":"V. S. Skvortsov,&nbsp;Ya. O. Ivanova,&nbsp;A. I. Voronina","doi":"10.1134/S199075082202007X","DOIUrl":"10.1134/S199075082202007X","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>The experimental data obtained by Simats, A. et al. (<i>Molecular and Cellular Proteomics</i>, 2020, vol. 19, no. 12, pp. 1921–1936) were analyzed using a bioinformatic aproach. Original experimental results available in the ProteomeXchange database were obtained using a comprehensive multiomics approach to identify potential blood biomarkers in ischemic stroke in mice. The identification of peptides with post-translational modification (PTM) was performed by us using the raw data (accession code PXD016538). Only phosphorylation and deamination were considered as PTMs. Different combinations of data sets (ischemic tissue with intact tissue, ischemic tissue with control taken from mice after sham surgery, etc.) were compared both in terms of the ratio of abundance for the modified peptide to the unmodified variant and in terms of absolute values of abundance. The most probable change in the PTM levels was shown for 27 proteins, which included dynamin, glycogen phosphorylase and 70 kDa heat shock protein.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"113 - 124"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4698129","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: 1
Determination of the Risk of Tumor Progression in Patients with Early Stages of Adenocarcinoma and Squamous Cell Lung Carcinoma Based on Laboratory Parameters 基于实验室参数测定早期腺癌和鳞状细胞肺癌患者肿瘤进展风险
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020081
A. D. Tahanovich, N. N. Kauhanka, V. I. Prohorova, D. I. Murashka, O. V. Gotko

Abstract

Non-small cell lung cancer (NSCLC) dominates in the morbidity of lung cancer. In stage I, only 60–70% patients overcome the 5-year survival barrier, and in stage II 5-year survival rate is declining to 35–40%. The reason for such a high mortality is relapse of the disease. The main histological forms of NSCLC are adenocarcinoma (AС) and squamous cell carcinoma (SCC). They differ in course, protocols and effectiveness of treatment. Comparative survival data for AC and SCC are controversial, and reliable biomarkers for determining the risk of tumor progression still have not been found. In order to determine the risk of disease progression we have investigated the possibility of using laboratory parameters characterizing the level of some blood proteins involved in carcinogenesis in patients with early stages of AС and SCC. We retrospectively analyzed the duration of relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II AC, G1-3 and 434 with early stages of SCC, G1-3). In 81 AC patients and 36 SCC patients (stages I−II, G1-3) we determined the level of CYFRA 21-1 and SCC, TPA, chemokines CXCL5, CXCL8, pyruvate kinase M2, HIF-1α, hyaluronic acid and receptors CXCR1, CXCR2, CD44v6. Using the Kaplan−Meier graphical analysis, groups of low (stage I G1-2 + stage II G1) and high (stage I G3 + stage II G2-3) risk of tumor progression were identified. The one-year survival rate of AС patients was higher than in SCC patients. AС patients with high risk of tumor recurrence had higher levels of CYFRA 21-1, the mean intensity of fluorescence (MFI) of CXCR1 receptor in granulocytes, and the relative content of CXCR2 receptor in lymphocytes than patients with low risk. In the case of rapid disease progression in SCC patients, the relative content of CXCR2 receptor in lymphocytes, the proportion of monocytes supplied with CD44v6 receptor, and SCC level were higher than in patients with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC—0.512, for SCC—0.409, sensitivity—91.9% and 90.0%, specificity—90.0% and 87.5%, respectively), allow to predict the probability of tumor recurrence.

非小细胞肺癌(NSCLC)在肺癌发病率中占主导地位。在I期,只有60-70%的患者克服了5年生存障碍,而在II期,5年生存率下降到35-40%。死亡率如此之高的原因是疾病的复发。非小细胞肺癌的主要组织学形式是腺癌(AС)和鳞状细胞癌(SCC)。它们在疗程、方案和治疗效果上有所不同。AC和SCC的比较生存数据存在争议,确定肿瘤进展风险的可靠生物标志物仍未发现。为了确定疾病进展的风险,我们研究了在早期AС和SCC患者中使用实验室参数表征一些参与癌变的血液蛋白水平的可能性。我们回顾性分析了1250例患者手术治疗后一年的无复发时间(816例为ⅰ期和ⅱ期AC, G1-3, 434例为早期SCC, G1-3)。在81例AC患者和36例SCC患者(I - II期,G1-3期)中,我们检测了CYFRA 21-1和SCC、TPA、趋化因子CXCL5、CXCL8、丙酮酸激酶M2、HIF-1α、透明质酸和受体CXCR1、CXCR2、CD44v6的水平。通过Kaplan - Meier图形分析,将肿瘤进展风险分为低(I期G1-2 + II期G1)和高(I期G3 + II期G2-3)两组。AС患者的1年生存率高于SCC患者。AС肿瘤复发高危患者的CYFRA 21-1水平、粒细胞中CXCR1受体的平均荧光强度(MFI)、淋巴细胞中CXCR2受体的相对含量均高于低危患者。在SCC快速进展患者中,淋巴细胞中CXCR2受体的相对含量、CD44v6受体供血的单核细胞比例以及SCC水平均高于进展缓慢患者。回归方程,包括上述参数的组合(AC-0.512的阈值,SCC-0.409的阈值,敏感性分别为91.9%和90.0%,特异性分别为90.0%和87.5%),可以预测肿瘤复发的概率。
{"title":"Determination of the Risk of Tumor Progression in Patients with Early Stages of Adenocarcinoma and Squamous Cell Lung Carcinoma Based on Laboratory Parameters","authors":"A. D. Tahanovich,&nbsp;N. N. Kauhanka,&nbsp;V. I. Prohorova,&nbsp;D. I. Murashka,&nbsp;O. V. Gotko","doi":"10.1134/S1990750822020081","DOIUrl":"10.1134/S1990750822020081","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Non-small cell lung cancer (NSCLC) dominates in the morbidity of lung cancer. In stage I, only 60–70% patients overcome the 5-year survival barrier, and in stage II 5-year survival rate is declining to 35–40%. The reason for such a high mortality is relapse of the disease. The main histological forms of NSCLC are adenocarcinoma (AС) and squamous cell carcinoma (SCC). They differ in course, protocols and effectiveness of treatment. Comparative survival data for AC and SCC are controversial, and reliable biomarkers for determining the risk of tumor progression still have not been found. In order to determine the risk of disease progression we have investigated the possibility of using laboratory parameters characterizing the level of some blood proteins involved in carcinogenesis in patients with early stages of AС and SCC. We retrospectively analyzed the duration of relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II AC, G1-3 and 434 with early stages of SCC, G1-3). In 81 AC patients and 36 SCC patients (stages I−II, G1-3) we determined the level of CYFRA 21-1 and SCC, TPA, chemokines CXCL5, CXCL8, pyruvate kinase M2, HIF-1α, hyaluronic acid and receptors CXCR1, CXCR2, CD44v6. Using the Kaplan−Meier graphical analysis, groups of low (stage I G1-2 + stage II G1) and high (stage I G3 + stage II G2-3) risk of tumor progression were identified. The one-year survival rate of AС patients was higher than in SCC patients. AС patients with high risk of tumor recurrence had higher levels of CYFRA 21-1, the mean intensity of fluorescence (MFI) of CXCR1 receptor in granulocytes, and the relative content of CXCR2 receptor in lymphocytes than patients with low risk. In the case of rapid disease progression in SCC patients, the relative content of CXCR2 receptor in lymphocytes, the proportion of monocytes supplied with CD44v6 receptor, and SCC level were higher than in patients with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC—0.512, for SCC—0.409, sensitivity—91.9% and 90.0%, specificity—90.0% and 87.5%, respectively), allow to predict the probability of tumor recurrence.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"154 - 163"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4696699","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
Production and Internalization of Extracellular Vesicles in Norm and under Conditions of Hyperglycemia and Insulin Resistance 正常及高血糖和胰岛素抵抗条件下细胞外囊泡的产生和内化
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-05-17 DOI: 10.1134/S199075082202010X
N. V. Yunusova, E. E. Dandarova, D. A. Svarovsky, N. S. Denisov, D. N. Kostromitsky, M. R. Patysheva, O. V. Cheremisina, L. V. Spirina

Abstract

Extracellular vesicles (EVs) are spherical functionally important structures of cell membrane origin ranging in size from 40 nm to 5000 nm. They are involved in the horizontal transfer of mainly proteins and microRNAs. The mechanisms of EV internalization include clathrin-dependent endocytosis, caveolin-dependent endocytosis, raft-mediated endocytosis, and macropinocytosis. Type 2 diabetes mellitus (T2DM) is a common group of metabolic disorders in adults; the incidence and prevalence of T2DM increase in parallel with the obesity epidemic. Since adipose tissue plays a key role in the development of insulin resistance, EVs secreted by adipose tissue may be considered as an information transmitter in this process. EVs of the adipocyte origin are predominantly captured up by tissue macrophages, adipocytes themselves, hepatocytes, and skeletal muscles. The EV uptake promotes M1 polarization of macrophages, a decrease in glucose uptake by hepatocytes and myocytes due to the transfer of functionally active microRNAs influencing carbohydrate and lipid metabolism. Patients with T2DM and impaired glucose tolerance, have a significantly higher level of CD235a-positive (erythrocyte) EVs and a trend to the increase in CD68-positive (leukocyte) and CD62p-positive (platelet/endothelial cells) EVs. The levels of CD31+/CD146-positive EVs (endothelial cells) were comparable between diabetic and euglycemic patients. EVs from diabetic patients were preferentially internalized by monocytes (predominantly classical and transitional, and to a lesser extent nonclassical monocyte fractions) and B cells as compared to euglycemic patients. Internalization of EVs from patients with T2DM by monocytes led to a decrease in their apoptosis, changes in differentiation, and suppression of monocyte reactions controlling oxidative stress. Thus, insulin resistance increases the secretion of EVs, which are preferentially internalized by monocytes and alter their function. EVs are considered as sources of promising clinical markers of insulin resistance, complications of diabetes mellitus (endothelial dysfunction, retinopathy, nephropathy, neuropathy), and EV markers can also be used to monitor the effectiveness of therapy for these complications.

摘要/ abstract摘要:细胞外囊泡(EVs)是起源于细胞膜的具有重要功能的球形结构,大小在40 ~ 5000nm之间。它们主要参与蛋白质和microrna的水平转移。EV内化的机制包括网格蛋白依赖的内吞作用、小窝蛋白依赖的内吞作用、筏子介导的内吞作用和巨噬细胞作用。2型糖尿病(T2DM)是一种常见的成人代谢性疾病;2型糖尿病的发病率和流行率与肥胖流行同步增加。由于脂肪组织在胰岛素抵抗的发展中起着关键作用,脂肪组织分泌的EVs可能被认为是这一过程中的信息传递者。脂肪细胞来源的EVs主要被组织巨噬细胞、脂肪细胞本身、肝细胞和骨骼肌捕获。EV摄取促进巨噬细胞的M1极化,肝细胞和肌细胞由于影响碳水化合物和脂质代谢的功能活性microrna的转移而减少葡萄糖摄取。伴有糖耐量受损的T2DM患者,cd235a阳性(红细胞)EVs水平明显升高,cd68阳性(白细胞)和cd62p阳性(血小板/内皮细胞)EVs有升高的趋势。CD31+/ cd146阳性EVs(内皮细胞)水平在糖尿病患者和正常血糖患者之间具有可比性。与血糖正常的患者相比,糖尿病患者的ev更倾向于被单核细胞(主要是经典和过渡性单核细胞,以及较小程度的非经典单核细胞)和B细胞内化。T2DM患者EVs被单核细胞内化导致其凋亡减少,分化改变,单核细胞控制氧化应激的反应受到抑制。因此,胰岛素抵抗增加了ev的分泌,这些ev被单核细胞优先内化并改变了它们的功能。EVs被认为是胰岛素抵抗、糖尿病并发症(内皮功能障碍、视网膜病变、肾病、神经病变)的有希望的临床标志物的来源,EVs标志物也可用于监测治疗这些并发症的有效性。
{"title":"Production and Internalization of Extracellular Vesicles in Norm and under Conditions of Hyperglycemia and Insulin Resistance","authors":"N. V. Yunusova,&nbsp;E. E. Dandarova,&nbsp;D. A. Svarovsky,&nbsp;N. S. Denisov,&nbsp;D. N. Kostromitsky,&nbsp;M. R. Patysheva,&nbsp;O. V. Cheremisina,&nbsp;L. V. Spirina","doi":"10.1134/S199075082202010X","DOIUrl":"10.1134/S199075082202010X","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Extracellular vesicles (EVs) are spherical functionally important structures of cell membrane origin ranging in size from 40 nm to 5000 nm. They are involved in the horizontal transfer of mainly proteins and microRNAs. The mechanisms of EV internalization include clathrin-dependent endocytosis, caveolin-dependent endocytosis, raft-mediated endocytosis, and macropinocytosis. Type 2 diabetes mellitus (T2DM) is a common group of metabolic disorders in adults; the incidence and prevalence of T2DM increase in parallel with the obesity epidemic. Since adipose tissue plays a key role in the development of insulin resistance, EVs secreted by adipose tissue may be considered as an information transmitter in this process. EVs of the adipocyte origin are predominantly captured up by tissue macrophages, adipocytes themselves, hepatocytes, and skeletal muscles. The EV uptake promotes M1 polarization of macrophages, a decrease in glucose uptake by hepatocytes and myocytes due to the transfer of functionally active microRNAs influencing carbohydrate and lipid metabolism. Patients with T2DM and impaired glucose tolerance, have a significantly higher level of CD235a-positive (erythrocyte) EVs and a trend to the increase in CD68-positive (leukocyte) and CD62p-positive (platelet/endothelial cells) EVs. The levels of CD31+/CD146-positive EVs (endothelial cells) were comparable between diabetic and euglycemic patients. EVs from diabetic patients were preferentially internalized by monocytes (predominantly classical and transitional, and to a lesser extent nonclassical monocyte fractions) and B cells as compared to euglycemic patients. Internalization of EVs from patients with T2DM by monocytes led to a decrease in their apoptosis, changes in differentiation, and suppression of monocyte reactions controlling oxidative stress. Thus, insulin resistance increases the secretion of EVs, which are preferentially internalized by monocytes and alter their function. EVs are considered as sources of promising clinical markers of insulin resistance, complications of diabetes mellitus (endothelial dysfunction, retinopathy, nephropathy, neuropathy), and EV markers can also be used to monitor the effectiveness of therapy for these complications.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 2","pages":"104 - 112"},"PeriodicalIF":0.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4697679","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: 1
Integral Tests of the Hemostasis System in Assessing the Efficiency of Acetylsalicylic Acid in Patients with Ischemic Heart Disease 评估乙酰水杨酸对缺血性心脏病患者止血系统的整体试验
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-02-14 DOI: 10.1134/S199075082201005X
O. S. Melnichnikova, I. A. Nazarova, O. V. Sirotkina, A. V. Panov, I. T. Abesadze, M. Z. Alugishvili, N. L. Lokhovinina, T. V. Vavilova

Despite the fact that acetylsalicylic acid (ASA) is the “gold” standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), some patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed using integral hemostasis tests: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT) in platelet-rich plasma (PRP). The study involved 34 patients with stable CAD (11 women, 23 men) and 33 people (15 women, 18 men) in the control group. Evaluation of the activity of thrombus formation by means of the T-TAS system revealed a significant decrease in the area under the curve (AUC10) in the group of CAD patients as compared with the control (135.6 [88.0–222.3] and 260.5 [217.3–301.9], p < 0.05). The TGT analysis in PRP has shown that in CAD patients, there was a decrease in the peak concentration of thrombin (PTh) and the rate of thrombin (VI) formation (100.5 [78.3–127.7] and 125.7 [118.7–161.5], nmol; 7.2 [4.7–11.1] and 14.9 [11.6–18.1], nmol/min, p < 0.01, respectively), and an increase in time parameters of the test. The number of patients with high platelet reactivity detected by T-TAS was higher than those detected by TGT (38.2% (n = 13) and 20.8% (n = 7), respectively). In the group of CAD patients correlation analysis revealed a relationship between an increase in VI with an increase in AUC10 according to T-TAS data (r = 0.37; p = 0.03). Thus, the study, T-TAS and TGT in PRP have shown their effectiveness in assessing the antithrombotic properties of ASA in CAD patients.

尽管乙酰水杨酸(ASA)是预防冠心病(CAD)患者心血管并发症的“金”标准,但部分患者仍存在动脉粥样硬化血栓形成的风险。在本研究中,ASA在冠心病患者中的抗血栓作用通过综合止血试验进行评估:T-TAS系统(总血栓形成分析系统)和富血小板血浆(PRP)凝血酶生成试验(TGT)。该研究纳入了34例稳定型CAD患者(11名女性,23名男性)和对照组33人(15名女性,18名男性)。通过T-TAS系统评估血栓形成活性显示,与对照组相比,CAD患者的曲线下面积(AUC10)显著降低(135.6[88.0-222.3]和260.5 [217.3-301.9],p <0.05)。PRP中的TGT分析显示,CAD患者凝血酶(PTh)峰值浓度和凝血酶(VI)形成率降低(100.5[78.3-127.7]和125.7 [118.7-161.5],nmol;7.2(4.7 - -11.1)和14.9 (11.6 - -18.1),nmol / min, p & lt;,分别为0.01),试验时间参数增加。T-TAS检测出高血小板反应性的患者数量高于TGT检测出高血小板反应性的患者数量(分别为38.2% (n = 13)和20.8% (n = 7))。在CAD患者组中,相关分析显示,根据T-TAS数据,VI升高与AUC10升高之间存在相关性(r = 0.37;P = 0.03)。因此,该研究表明,PRP中的T-TAS和TGT在评估冠心病患者ASA抗血栓特性方面具有有效性。
{"title":"Integral Tests of the Hemostasis System in Assessing the Efficiency of Acetylsalicylic Acid in Patients with Ischemic Heart Disease","authors":"O. S. Melnichnikova,&nbsp;I. A. Nazarova,&nbsp;O. V. Sirotkina,&nbsp;A. V. Panov,&nbsp;I. T. Abesadze,&nbsp;M. Z. Alugishvili,&nbsp;N. L. Lokhovinina,&nbsp;T. V. Vavilova","doi":"10.1134/S199075082201005X","DOIUrl":"10.1134/S199075082201005X","url":null,"abstract":"<p>Despite the fact that acetylsalicylic acid (ASA) is the “gold” standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), some patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed using integral hemostasis tests: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT) in platelet-rich plasma (PRP). The study involved 34 patients with stable CAD (11 women, 23 men) and 33 people (15 women, 18 men) in the control group. Evaluation of the activity of thrombus formation by means of the T-TAS system revealed a significant decrease in the area under the curve (AUC10) in the group of CAD patients as compared with the control (135.6 [88.0–222.3] and 260.5 [217.3–301.9], <i>p</i> &lt; 0.05). The TGT analysis in PRP has shown that in CAD patients, there was a decrease in the peak concentration of thrombin (PTh) and the rate of thrombin (VI) formation (100.5 [78.3–127.7] and 125.7 [118.7–161.5], nmol; 7.2 [4.7–11.1] and 14.9 [11.6–18.1], nmol/min, <i>p</i> &lt; 0.01, respectively), and an increase in time parameters of the test. The number of patients with high platelet reactivity detected by T-TAS was higher than those detected by TGT (38.2% (<i>n</i> = 13) and 20.8% (<i>n</i> = 7), respectively). In the group of CAD patients correlation analysis revealed a relationship between an increase in VI with an increase in AUC10 according to T-TAS data (<i>r</i> = 0.37; <i>p</i> = 0.03). Thus, the study, T-TAS and TGT in PRP have shown their effectiveness in assessing the antithrombotic properties of ASA in CAD patients.</p>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 1","pages":"60 - 65"},"PeriodicalIF":0.6,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4863059","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
Increase in the Level of Orexin Receptor 1 (OX1R) mRNA in the Brain Structures of Rats Prone to Impulsivity in Behavior 行为冲动大鼠脑结构中食欲素受体1 (OX1R) mRNA水平升高
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-02-14 DOI: 10.1134/S1990750822010085
E. A. Sekste, A. A. Lebedev, E. R. Bychkov, M. I. Airapetov, K. E. Gramota, I. Yu. Tissen, P. D. Shabanov

Abstract

Orexin and its receptors (OXR) are involved in the mechanisms of pathological craving for alcohol and psychoactive drugs. The orexin system is also involved in the mechanisms of non-chemical forms of addiction: binge eating and gambling. The aim of this study was to investigate the level of orexin receptor mRNA in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior in a model for studying the elements of gambling addiction (a variant of the Iowa Gambling Task test). Brain structures were isolated on the 22nd day of the experiment. The OX1R gene expression was higher in the hypothalamus by 122% and in the hippocampus—by 149% in rats preferring to receive a high reward, but with a low probability as compared with a group of animals that preferred a low level of reinforcement, but with a 100% probability. On the contrary, no significant changes were observed in the level of OX1R mRNA in the prefrontal cortex. The level of OX2R mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data obtained suggest involvement of OX1R in the hypothalamus and hippocampus in the mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.

食欲素及其受体(OXR)参与了对酒精和精神药物的病理性渴求机制。食欲素系统也与非化学形式的成瘾机制有关:暴饮暴食和赌博。本研究的目的是在研究赌博成瘾因素的模型(爱荷华赌博任务测试的一种变体)中,研究易冲动行为的大鼠下丘脑、海马和前额叶皮层中食欲素受体mRNA的水平。实验第22天分离脑结构。OX1R基因在下丘脑和海马体的表达分别高出122%和149%,前者倾向于获得高奖励,但获得高奖励的概率较低,而另一组偏好低水平强化的动物则有100%的概率获得高奖励。相反,前额叶皮层OX1R mRNA水平未见明显变化。易冲动行为大鼠下丘脑、海马和前额叶皮层的OX2R mRNA水平变化不显著。这些数据表明,下丘脑和海马的OX1R参与了冲动行为的调节机制,以及正强化在其强度和概率变化方面的意义选择。
{"title":"Increase in the Level of Orexin Receptor 1 (OX1R) mRNA in the Brain Structures of Rats Prone to Impulsivity in Behavior","authors":"E. A. Sekste,&nbsp;A. A. Lebedev,&nbsp;E. R. Bychkov,&nbsp;M. I. Airapetov,&nbsp;K. E. Gramota,&nbsp;I. Yu. Tissen,&nbsp;P. D. Shabanov","doi":"10.1134/S1990750822010085","DOIUrl":"10.1134/S1990750822010085","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Orexin and its receptors (OXR) are involved in the mechanisms of pathological craving for alcohol and psychoactive drugs. The orexin system is also involved in the mechanisms of non-chemical forms of addiction: binge eating and gambling. The aim of this study was to investigate the level of orexin receptor mRNA in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior in a model for studying the elements of gambling addiction (a variant of the Iowa Gambling Task test). Brain structures were isolated on the 22nd day of the experiment. The <i>OX1R</i> gene expression was higher in the hypothalamus by 122% and in the hippocampus—by 149% in rats preferring to receive a high reward, but with a low probability as compared with a group of animals that preferred a low level of reinforcement, but with a 100% probability. On the contrary, no significant changes were observed in the level of <i>OX1R</i> mRNA in the prefrontal cortex. The level of <i>OX2R</i> mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data obtained suggest involvement of <i>OX1R</i> in the hypothalamus and hippocampus in the mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 1","pages":"38 - 44"},"PeriodicalIF":0.6,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4863073","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: 1
Impairments in Metabolism of Amino Acids—Precursors of Gasotransmitters—in the Premature Birth 早产儿中气体递质前体氨基酸代谢的损伤
IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-02-14 DOI: 10.1134/S1990750822010061
A. A. Mikhelson, T. N. Pogorelova, V. O. Gunko, A. A. Nikashina, N. V. Palieva

Abstract

The content of amino acids, the sources of gasotransmitters and activities of enzymes involved in their metabolism have been studied in the placenta and amniotic fluid in full-term and complicated by preterm birth. Determination of amino acids was performed using an automatic analyzer and enzyme activities were assayed by means of specific spectrophotometric methods. The development of preterm birth was accompanied by notable changes in metabolism amino acids already in the second trimester of pregnancy. Differently directed correlations were found between the level of amino acids and the activity of the corresponding enzymes. The imbalance of amino acids in the fetoplacental system in preterm birth was accompanied by changes in the production of their low molecular weight derivatives—gasotransmitters (NO, CO, H2S), playing an important role in the regulation of numerous metabolic processes.

摘要:本文研究了足月及早产儿胎盘和羊水中氨基酸含量、气递质来源及其代谢酶的活性。用自动分析仪测定氨基酸,用专用分光光度法测定酶活性。早产的发生伴随着妊娠中期代谢氨基酸的显著变化。氨基酸水平与相应酶的活性之间存在不同方向的相关性。早产儿胎儿胎盘系统中氨基酸的失衡伴随着其低分子量衍生物气体递质(NO, CO, H2S)产生的变化,在许多代谢过程的调节中起着重要作用。
{"title":"Impairments in Metabolism of Amino Acids—Precursors of Gasotransmitters—in the Premature Birth","authors":"A. A. Mikhelson,&nbsp;T. N. Pogorelova,&nbsp;V. O. Gunko,&nbsp;A. A. Nikashina,&nbsp;N. V. Palieva","doi":"10.1134/S1990750822010061","DOIUrl":"10.1134/S1990750822010061","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>The content of amino acids, the sources of gasotransmitters and activities of enzymes involved in their metabolism have been studied in the placenta and amniotic fluid in full-term and complicated by preterm birth. Determination of amino acids was performed using an automatic analyzer and enzyme activities were assayed by means of specific spectrophotometric methods. The development of preterm birth was accompanied by notable changes in metabolism amino acids already in the second trimester of pregnancy. Differently directed correlations were found between the level of amino acids and the activity of the corresponding enzymes. The imbalance of amino acids in the fetoplacental system in preterm birth was accompanied by changes in the production of their low molecular weight derivatives—gasotransmitters (NO, CO, H<sub>2</sub>S), playing an important role in the regulation of numerous metabolic processes.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 1","pages":"54 - 59"},"PeriodicalIF":0.6,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4567147","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: 2
期刊
Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1