Biomeditsinskaia Khimiia[JOURNAL]
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200 papers
[Comparative analysis of proteins associated with 26S and 20S proteasomes isolated from rabbit brain and liver].
Buneeva OA, Kopylov AT, Zgoda VG … +5 more , Gnedenko OV, Kaloshina SA, Medvedeva MV, Ivanov AS, Medvedev AE
Biomed Khim · 2022 Jan · PMID 35221293 · Publisher ↗
We have isolated fractions of 26S and 20S proteasomes were from the rabbit liver and the brain. According to mass spectrometric (MS) analysis, the 26S proteasome fractions from these organs contained catalytic and regula...
We have isolated fractions of 26S and 20S proteasomes were from the rabbit liver and the brain. According to mass spectrometric (MS) analysis, the 26S proteasome fractions from these organs contained catalytic and regulatory subunits characteristic of the proteasome core and regulatory subunits. The 20S fractions of brain and liver proteasomes contained only catalytic proteasome subunits. In addition to proteasome subunits, the isolated fractions contained components of the ubiquitin-proteasome system, ubiquitinated proteins, enzymes that play an important role in metabolic processes, cytoskeletal components, signaling, regulatory, and protective proteins, as well as proteins regulating gene expression, cell division, and differentiation. The abundance of a number of proteasome-associated proteins was comparable or exceeded the abundance of intrinsic proteasome components. About a third of the proteins common to all studied fractions (26S and 20S of brain and liver proteasomes) belong to the group of multifunctional proteins. Selective biosensor validation confirmed the affinity binding of proteins (aldolase, phosphoglycerate kinase) identified during MS analysis to the brain 20S proteasome. Comparison of the subproteomes of the 26S and 20S brain proteasomes showed that removal of components of the regulatory (19S) subparticles caused almost two-fold increase in the total number of individual proteins associated with the core part of the proteasome (20S). In the liver, the number of proteins associated with the core part of the proteasome remained basically unchanged after the removal of the components of the regulatory (19S) subparticles. This indicates that in the brain and, possibly, in other organs, proteins of the regulatory (19S) subunit play an important role in the formation of the proteasome interactome.
[Clinical and diagnostic significance of sialic acids determination in biological material].
Volkhina IV, Butolin EG
Biomed Khim · 2022 Jan · PMID 35221292 · Publisher ↗
Sialic acids (SA) are derivatives of neuraminic acid; they are located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role, they either mask recognition sites...
Sialic acids (SA) are derivatives of neuraminic acid; they are located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role, they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be viewed as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme effects on the body and inflammatory processes lead to an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, violation of the membrane integrity and destruction of body cells, and also high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Nevertheless, determining blood SA level and measuring concentration of existing biomarkers can be used to improve diagnostic indicators, to stage and monitor therapeutic response in some types of cancer, when the need for specificity is less than for diagnosis. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, lies in establishing the causes and mechanisms of biochemical changes in the body in certain diseases.
[Predicting the risk of tumor progression in patients with early stages of adenocarcinoma and squamous cell lung carcinoma based on laboratory parameters].
Tahanovich AD, Kauhanka NN, Prohorova VI … +2 more , Murashka DI, Gotko OV
Biomed Khim · 2021 Nov · PMID 34964445 · Publisher ↗
Non-small cell carcinoma (NSCLC) prevails in the structure of the incidence of lung cancer. In patients with I stage NSCLC, only 60-70% overcome the 5-year survival barrier, and at II stage it decreases to 35-40%. The re...
Non-small cell carcinoma (NSCLC) prevails in the structure of the incidence of lung cancer. In patients with I stage NSCLC, only 60-70% overcome the 5-year survival barrier, and at II stage it decreases to 35-40%. The reason for such a high mortality rate is almost always a relapse of the disease. The main histological forms of NSCLC - adenocarcinoma (AC) and squamous cell carcinoma (SCLC) - differ in the course, protocols and effectiveness of the treatment. Comparative survival data for AK and PCLC are controversial, and reliable biomarkers for determining the risk of tumor progression are lacking. In thus study 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 AC and SCLC to determine the risk of disease progression. We retrospectively analyzed the duration of the relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II of adenocarcinoma, G1-3 and 434 with early stages of SCLC, G1-3). In 81 patients with AC and 36 - with SCLC (stages I-II, G1-3) the level of CYFRA 21-1 and SCC by electrochemiluminescent method, chemokines CXCL5, CXCL8, TPA, pyruvate kinase M2, HIF-1α and hyaluronic acid by enzyme immunoassay, receptors CXCR1, CXCR2, CD44v6 by flow cytometry were determined. 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. In the case of the one-year survival rate of patients with AC was higher than with SCLC. In patients with AC and a high risk of tumor recurrence, compared with a low one, the level of CYFRA 21-1, the mean intensity of fluorescence (MFI) of the CXCR1 receptor in granulocytes, and the relative content of the CXCR2 receptor in lymphocytes were higher. In the case of rapid progression of SCLC in patients, the relative content of the CXCR2 receptor in lymphocytes, the proportion of monocytes equipped with the CD44v6 receptor, and the SCC level were higher than with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC - 0,512, for SCLC - 0,409, sensitivity - 91,9% and 90,0%, specificity - 90,0% and 87,5%, respectively), allow to predict the probability of tumor recurrence.
[Prenatal exposure to alcohol alters TLR4 signaling in the prefrontal cortex in rats].
Airapetov MI, Eresko SO, Bychkov ER … +2 more , Lebedev AA, Shabanov PD
Biomed Khim · 2021 Nov · PMID 34964444 · Publisher ↗
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 nerv...
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 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.
[The effect of lipid derivative of anti-tumor drug sarcolysin embedded in phospholipid nanoparticles in the experiments in vivo].
Tereshkina YA, Torkhovskaya TI, Sanzhakov MA … +3 more , Kostryukova LV, Khudoklinova YY, Tikhonova EG
Biomed Khim · 2021 Nov · PMID 34964443 · Publisher ↗
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 nan...
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 in size ("Sarcolysin-NP"). The effect of the resulting composition was investigated in vivo in comparison with the free substance of sarcolysin. The composition intravenous administration to mice showed an improvement in the pharmacokinetic parameters of sarcolysin associated with its initial higher (by 22%) level in the blood and prolonged circulation, which was also observed in mice with P388 tumor. In mice with three types of tumors - lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma of the mammary gland Ca755 - administration of two doses of sarcolysin over a period of 7 days showed its predominant antitumor effect. The maximum tumor growth inhibition was noted for lymphocytic leukemia L1210 and adenocarcinoma of the mouse mammary gland Ca755 (at a dose of Sarcolysin-NP - 8,4 mg/kg), which was higher in comparison with free substance by more than 24% and 17%, respectively. Differences in the life span of the treated animals were revealed significantly at a dose of 10 mg/kg and amounted to 25% and 17,4% for lymphocytic leukemia P388 and L1210, respectively, and 11% for adenocarcinoma Ca755. In an experiment on rats, acute toxicity of Sarcolysin-NP administered intravenously showed that an average LD50 value 2-3 times exceeded a similar parameter for commercial preparations of free sarcolysin (Melphalan and Alkeran), which indicates its lower toxicity.
[Effect of methylene blue and its metabolite - azure I - on bioenergetic parameters of intact mice brain mitochondria].
Gureev AP, Samoylova NA, Potanina DV … +1 more , Popov VN
Biomed Khim · 2021 Nov · PMID 34964442 · Publisher ↗
Methylene blue is a phenothiazine dye that is widely used in medicine and clinical trials for the treatment of Alzheimer's disease. One of the factors of the unique therapeutic effect of methylene blue is its redox prope...
Methylene blue is a phenothiazine dye that is widely used in medicine and clinical trials for the 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 the mitochondria and transfer it 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. We have shown that azure I, unlike methylene blue, 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, the 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. As a consequence, 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 drug, but not as a substance with a potentially powerful antidepressant effect.
[The bioinformatic identification of proteins with varying levels of post-translational modifications in experimental ischemic stroke in mice].
Skvortsov VS, Ivanova YO, Voronina AI
Biomed Khim · 2021 Nov · PMID 34964441 · Publisher ↗
The experimental data obtained by Simats A. et al. (Molecular and Cellular Proteomics, 2020, 19(12), 1921-1936) was analysed using a bioinformatic approach. Original experimental results available in the ProteomeXchange...
The experimental data obtained by Simats A. et al. (Molecular and Cellular Proteomics, 2020, 19(12), 1921-1936) was analysed using a bioinformatic approach. Original experimental results available in the ProteomeXchange database were obtained using a comprehensive multidomain 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 likely change in precisely PTM levels was shown for 27 proteins, which include dynamin, glycogen phosphorylase and 70 kDa heat shock protein.
[Production and internalization of extracellular vesicules in normal and under conditions of hyperglycemia and insulin resistance].
Yunusova NV, Dandarova EE, Svarovsky DA … +5 more , Denisov NS, Kostromitsky DN, Patysheva MR, Cheremisina OV, Spirina LV
Biomed Khim · 2021 Nov · PMID 34964440 · Publisher ↗
Extracellular vesicles (EVs) are spherical structures of cell membrane origin, ranging in the size from 40 nm to 5000 nm. They are involved in the horizontal transfer of many proteins and microRNAs. The mechanisms EV int...
Extracellular vesicles (EVs) are spherical structures of cell membrane origin, ranging in the size from 40 nm to 5000 nm. They are involved in the horizontal transfer of many proteins and microRNAs. The mechanisms 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 increase in parallel with the obesity epidemic. Since adipose tissue plays a crucial role in the development of insulin resistance, EVs secreted by adipose tissue can be a kind of information transmitter in this process. EVs of adipocytic origin are predominantly absorbed by tissue macrophages, adipocytes themselves, hepatocytes, and skeletal muscles. This contributes to the M1 polarization of macrophages, a decrease in glucose uptake by hepatocytes and myocytes due to the transfer of functionally active microRNAs by these EVs, which affect carbohydrate and lipid metabolism. Patients with T2DM and impaired glucose tolerance have significantly higher levels of CD235a-positive (erythrocyte) EVs, as well as a tendency to increase CD68-positive (leukocyte) and CD62p-positive (platelets/endothelial cells) EVs. The levels of CD31+/CD146-positive BB (endothelial cells) were comparable between diabetic and euglycemic patients. EVs from diabetic patients were preferably internalized by monocytes (mainly classical and intermediate monocyte fractions and to a lesser extent by non-classical monocyte fractions) and B cells compared to euglycemic patients. Internalization of EVs from patients with T2DM by monocytes leads to decreased apoptosis, changes in differentiation, and suppression of reactions controlling oxidative stress in monocytes. Thus, insulin resistance increases secretion of EVs, which are preferentially internalized by monocytes and influence their function. EVs are considered as sources of promising clinical markers of insulin resistance, complications of diabetes mellitus (endothelial dysfunction, retinopathy, nephropathy, neuropathy), and markers of EVs can also be used to monitor the effectiveness of therapy for these complications.
[Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis].
Gureeva TA, Timoshenko OS, Kugaevskaya EV … +1 more , Solovyova NI
Biomed Khim · 2021 Nov · PMID 34964439 · Publisher ↗
Cysteine cathepsins (Cts) also known as thiol proteinases belong to the superfamily of cysteine proteinases (EC 3.4.22). Cts are known as lysosomal proteases responsible for the intracellular proteins degradation. All Ct...
Cysteine cathepsins (Cts) also known as thiol proteinases belong to the superfamily of cysteine proteinases (EC 3.4.22). Cts are known as lysosomal proteases responsible for the intracellular proteins degradation. All Cts are synthesized as zymogens, activation of which occurs autocatalytically. Their activity is regulated by endogenous inhibitors. Cts can be secreted into the extracellular environment, which is of particular importance in tumor progression. Extracellular Cts not only hydrolyze extracellular matrix (ECM) proteins, but also contribute to ECM remodeling, processing and/or release of cell adhesion molecules, growth factors, cytokines and chemokines. In cancer, the expression and activity of Cts sharply increase both in cell lysosomes and in the intercellular space, which correlates with neoplastic transformation, invasion, metastasis and leads to further tumor progression. It has been shown that Cts expression depends on the cells type, therefore, their role in the tumor development differs depending on their cellular origin. The mechanism of Cts action in cancer is not limited only by their proteolytic action. The Cts influence on signal transduction pathways associated with cancer development, including the pathway involving growth factors, which is mediated through receptors tyrosine kinases (RTK) and various signaling mitogen-activated protein kinases (MAPK), has been proven. In addition, Cts are able to promote the epithelial-mesenchymal transition (EMT) by activating signal transduction pathways such as Wnt, Notch, and the pathway involving TGF-β. So, Ctc perform specific both destructive and regulatory functions, carrying out proteolysis, both inside and outside the cell.
[Impairments in metabolism of amino acids - precursors of gasotransmitters - in the premature birth].
Mikhelson AA, Pogorelova TN, Gunko VO … +2 more , Nikashina AA, Palieva NV
Biomed Khim · 2021 Sep · PMID 34730558 · Publisher ↗
The content of amino acids - sources of gasotransmitters and the activity of enzymes of their metabolism have been studied in the placenta and amniotic fluid in full-term and complicated by preterm birth (PB). Determinat...
The content of amino acids - sources of gasotransmitters and the activity of enzymes of their metabolism have been studied in the placenta and amniotic fluid in full-term and complicated by preterm birth (PB). Determination of amino acids was carried out using an automatic analyzer; specific spectrophotometric methods were used to assess the activity of enzymes. The development of PB is accompanied by changes in the amino acid level already in the second trimester of pregnancy. Correlation of differently directions was found between the level of amino acids and the activity of the corresponding enzymes. The imbalance of amino acids in the fetoplacental system in PB is accompanied by a change in the production of their low molecular weight derivatives gas transmitters (NO, CO, H2S), which play an important role in the regulation of numerous metabolic processes.
[Diagnostic efficiency of determining CXCR1, CXCR2 and hyaluronic acid blood level in non-small cell lung cancer patients].
Murashka DI, Tahanovich AD, Kauhanka MM … +2 more , Prokhorova VI, Gotko OV
Biomed Khim · 2021 Sep · PMID 34730557 · Publisher ↗
In the structure of lung cancer incidence most cases belong to non-small cell lung cancer (NSCLC) which is subdivided into two histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). A five-year sur...
In the structure of lung cancer incidence most cases belong to non-small cell lung cancer (NSCLC) which is subdivided into two histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). A five-year survival rate of patients with stage I NSCLC is two times higher than in patients with stage II and more than five times higher than in stages III-IV. Currently, there are no informative blood biomarkers to diagnose early stages of NSCLC. The aim of the study was to evaluate complex determination of hyaluronic acid (HA), CXCR2 and CXCR1 levels blood of patients with AC and SCC. Blood samples from of 107 patients with SCC, 90 patients with AC, and 40 healthy people were used in this study. Concentration of HA in blood serum was determined by enzyme linked immunoassay. The level of CXCR2 and CXCR1 was determined by flow cytometry. Diagnostic parameters were determined by constructing mathematical models in the form of regression equations using the method of stepwise inclusion of predictors and subsequent ROC-analysis. Results of the study indicate that MFI CXCR1 in granulocytes, proportion of lymphocytes containing CXCR2 and concentration of HA in blood serum in stage I AC and SCC are significantly higher than in healthy people. The level of these parameter significantly increases at stage II of the disease compared to stage I and demonstrates further growth at its later stages. Based on the obtained results, regression equations were created: (i) including MFI CXCR1 in granulocytes, proportion of lymphocytes supplied with CXCR2 and HA concentration in the serum to detect stages I-II SCC (diagnostic sensitivity - 95.7%, specificity - 93.7%, threshold value - 0.59) and stages III-IV SCC (diagnostic sensitivity - 93.1%, specificity - 93.3%, threshold value - 0.64); (ii) including the proportion of lymphocytes supplied with CXCR2 MFI CXCR1 in granulocytes and CYFRA 21-1 blood level, which allows the detection of I-II stages of AC (sensitivity - 91.3%, specificity - 94.7%, threshold value - 0.61); (iii) including the proportion of lymphocytes supplied with CXCR2 and CYFRA 21-1 blood level, which allows the detection of AC stages III-IV (sensitivity - 94.6%, specificity - 91.3%, threshold value - 0.15); (iv) including the proportion of lymphocytes supplied with CXCR2 and HA level in the serum to differentiate stage II SCC from stage I (sensitivity - 94.4%, specificity - 87.5%, threshold value - 0.44) and II stage AC from stage I (sensitivity - 88.5%, specificity - 91.2%, threshold value - 0.46).
[Integral tests of the hemostasis system in assessing the efficiency of acetylsalicylic acid in patients with ischemic heart disease].
Melnichnikova OS, Nazarova IA, Sirotkina OV … +5 more , Panov AV, Abesadze IT, Alugishvili MZ, Lokhovinina NL, Vavilova TV
Biomed Khim · 2021 Sep · PMID 34730556 · Publisher ↗
Despite the fact that acetylsalicylic acid (ASA) is the "gold" standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothr...
Despite the fact that acetylsalicylic acid (ASA) is the "gold" standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed in platelet-rich plasma (PRP) using integral tests of the hemostasis study: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT). The study involved 34 patients with stable CAD (11 women, 23 men) and people (15 women, 18 men) in the control group. As a result of assessing the activity of thrombus formation using the T-TAS system, a significant decrease in the area under the curve (AUC10) was found in the group with CAD patients compared with the control (135.6 [88.0-222.3] and 260.5 [217.3-301.9], respectively, p.
[PCR analysis of the expression of chromosome 18 genes in human liver tissue: interindividual variability].
Timoshenko OS, Khmeleva SA, Poverennaya EV … +8 more , Kiseleva YY, Kurbatov LK, Radko SP, Buromski IV, Markin SS, Lisitsa AV, Archakov AI, Ponomarenko EA
Biomed Khim · 2021 Sep · PMID 34730555 · Publisher ↗
Using human chromosome 18 (Ch18) genes as an example, a PCR analysis of the interindividual variability of gene expression in liver tissue was performed. Although the quantitative profiles of the Ch18 transcriptome, expr...
Using human chromosome 18 (Ch18) genes as an example, a PCR analysis of the interindividual variability of gene expression in liver tissue was performed. Although the quantitative profiles of the Ch18 transcriptome, expressed in the number of cDNA copies per single cell, showed a high degree of correlation between donors (Pearson correlation coefficients ranged from 0.963 to 0.966), the expression of the significant number of genes (from 13% to 19%, depending on the method of experimental data normalization) varied by more than 4-fold when comparing donors pairwise. At the same time, the proportion of differentially expressed genes increased with a decrease in the level of their expression. It is shown that the higher quantitative variability of low-abundance transcripts is mainly not technical, but biological. Bioinformatic analysis of the interindividual variability of the differential expression of chromosome 18 genes in human liver tissue did not reveal any statistically significant groups of genes related to certain biological processes that indicated a rather transient nature of the interindividual variability of their expression, probably reflecting the response of cells of an individual to specific external stimuli.
[Increase in the level of orexin receptor 1 (OX1R) mRNA in the brain structures of rats prone to impulsivity in behavior].
Sekste EA, Lebedev AA, Bychkov ER … +4 more , Airapetov MI, Gramota KE, Thyssen IY, Shabanov PD
Biomed Khim · 2021 Sep · PMID 34730554 · Publisher ↗
Orexin and its receptors 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 an...
Orexin and its receptors 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 work was to study 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 expression of the OX1R gene was higher in the hypothalamus by 122% and in the hippocampus by 149% in rats that preferred 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. In the prefrontal cortex, on the contrary, no significant changes were observed in the level of OX1R mRNA. The level of OX2R mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data indicate involvement of OX1R in the hypothalamus and hippocampus in mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.
[Influence of pantogam and atomoxetine on attention stability and distribution of dopamine D2 and GABAB receptors in the attention deficit mouse model].
Kovalev GI, Sukhorukova NA, Vasileva EV … +2 more , Kondrakhin EA, Salimov RM
Biomed Khim · 2021 Sep · PMID 34730553 · Publisher ↗
The closed enriched cross maze test was employed as a new experimental model of the attention deficit disorder (ADD) for evaluation of the behavioral and neurochemical effects of the nootropic drug pantogam (100 mg/kg, i...
The closed enriched cross maze test was employed as a new experimental model of the attention deficit disorder (ADD) for evaluation of the behavioral and neurochemical effects of the nootropic drug pantogam (100 mg/kg, intraperitoneally) and atomoxetine hydrochloride (3 mg/kg, intraperitoneally) administered subchronically to CD-1 outbred mice. Two subpopulations of rodents differed spontaneously in attention to enriched compartments (ED-Low and ED-High), were estimated on the basis of time spent by the mice in the empty or enriched compartments. The ED-Low and ED-High mice insignificantly differed in parameters associated with anxiety, exploratory efficacy and motor activity. Subchronic administration of both drugs in selected doses produced corrective effect on animal behavior seen as a selective increase in the ED-ratio values in the ED-Low subpopulation. Differences in the distribution of dopamine D2 and GABAB receptors (Bmax) between placebo-treated ED-Low and ED-High mice were found in the prefrontal cortex using the radioligand binding method. The neuroreceptor effects of atomoxetine were seen in prefrontal cortex of ED-Low mice as decrease in the Bmax values of D2 receptors by 14%. Pantogam in the prefrontal cortex of ED-Low subpopulation showed a decrease in the Bmax values of D2 receptors by 22% and an increase for GABAB receptors by 44%. Therefore, subchronic administration of pantogam had a positive corrective effect on the behavior parameters and the density of the studied receptor subtypes in animals with severe attention deficit.
[Functioning of pregnan X receptor under conditions of nitrosative stress].
Abalenikhina YV, Sudakova EA, Seidkulieva AA … +2 more , Shchulkin AV, Yakusheva EN
Biomed Khim · 2021 Sep · PMID 34730552 · Publisher ↗
Pregnan X receptor (PXR) is a nuclear receptor that plays an important role in the regulation of the expression of biotransformation and metabolic enzymes. The functioning and possible mechanisms of PXR regulation under...
Pregnan X receptor (PXR) is a nuclear receptor that plays an important role in the regulation of the expression of biotransformation and metabolic enzymes. The functioning and possible mechanisms of PXR regulation under conditions of nitrosative stress have not been studied, which served as the purpose of this study. The work was performed on Caco-2 cells. Nitrosative stress (NS) was modeled using S-nitrosoglutathione (GSNO) at concentrations of 1 μM, 10 μM, 50 μM, 100 μM, and 500 μM and incubation during of 3 h, 24 h, and 72 h. The amount of PXR was assessed byWestern blotting. Incubation of Caco-2 cells with all concentrations GSNO 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 concentration of 100 μM this indicator did not significantly differ from the control, at a concentration of 500 μM it was lower. Prolonged incubation (72 h) enhanced NS and led to a normalization (1 μM GSNO) or a decrease of the PXR level (10-500 μM GSNO). The induction of PXR by GSNO was mediated by the effect of the nitrosative stress product bityrosine on the transcription factor. It was shown that bityrosine at concentrations of 0,4 mM and 1 mM increased the amount of PXR.
[Atmospheric reactive oxygen species and some aspects of the antiviral protection of the respiratory epithelium].
Salmin VV, Morgun AV, Olovyannikova RY … +4 more , Kutyakov VA, Lychkovskaya EV, Brusina EB, Salmina AB
Biomed Khim · 2021 Sep · PMID 34730551 · Publisher ↗
The review focuses on molecular and biochemical mechanisms of nonspecific protection of respiratory epithelium. The authors provide a comprehensive analysis of up-to-date data on the activity of the lactoperoxidase syste...
The review focuses on molecular and biochemical mechanisms of nonspecific protection of respiratory epithelium. The authors provide a comprehensive analysis of up-to-date data on the activity of the lactoperoxidase system expressed on the surface of the respiratory epithelium which provides the generation of hypothiocyanate and hypoiodite in the presence of locally produced or inhaled hydrogen peroxide. Molecular mechanisms of production of active compounds with antiviral and antibacterial effects, expression profiles of enzymes, transporters and ion channels involved in the generation of hypothiocyanite and hypoiodate in the mucous membrane of the respiratory system in physiological and pathological conditions (inflammation) are discussed. In the context of antibacterial and antiviral defense special attention is paid to recent data confirming the effects of atmospheric air composition on the efficiency of hypothiocyanite and hypoiodate synthesis in the respiratory epithelium. The causes and outcomes of lactoperoxidase system impairment due to the action of atmospheric factors are discussed in the context of controlling the sensitivity of the epithelium to the action of bacterial agents and viruses. Restoration of the lactoperoxidase system activity can be achieved by application of pharmacological agents aimed to compensate for the lack of halides in tissues, and by the control of chemical composition of the inhaled air.
[A pilot study of cytokine profile in cerebrospinal fluid of children with acute lymphocytic leukemia and neurotoxic side effects of chemotherapy].
Bazarnyi VV, Kovtun OP, Koryakina OV … +2 more , Polushina LG, Maksimova AY
Biomed Khim · 2021 Jul · PMID 34414897 · Publisher ↗
In some cases standard chemotherapy of acute lymphocytic leukemia (ALL) leads to neurotoxicity; its mechanisms, methods of prognosis, and prevention are being actively studied. The aim of this study was to assess the cyt...
In some cases standard chemotherapy of acute lymphocytic leukemia (ALL) leads to neurotoxicity; its mechanisms, methods of prognosis, and prevention are being actively studied. The aim of this study was to assess the cytokine profile in cerebrospinal fluid (CSF) of children with ALL and neurotoxic side effects of chemotherapy. This prospective study included 24 children with ALL aged from 3 to 17 years. Patients were further subdivided into ALL patients with (main group) and without neurological complications (comparison group). The level of cytokines in CSF was measured by Xmap technology (Luminex) using Invitrogen test systems (eBioscience) and the Luminex 200 system. The comparative analysis of the cytokine profile in the group of children with chemotherapy-induced neurotoxic complications revealed elevated levels of chemokine CXCL12 (SDF-1α) and stem cell factor (SCF). Increased level of these cytokines in CSF was characterized by a relatively risk for development of toxic peripheral neuropathy.
[The study of mRNA expression profiles of main cell function regulator genes in unchanged colonic mucosa from healthy donors].
Zakharenko MV, Bozhenko VK, Kiseleva YY … +10 more , Dzhikiya EL, Stanoevich US, Kulinich TM, Melnikova NV, Senchukova AL, Urakova AB, Grunin IB, Goncharov SV, Bliznyukov OP, Solodkiy VA
Biomed Khim · 2021 Jul · PMID 34414896 · Publisher ↗
A comparative analysis of molecular genetic phenotypes of mucous membrane cells in five anatomical regions of the colon in a group of healthy donors was conducted by comparing mRNA expression profiles of 62 genes involve...
A comparative analysis of molecular genetic phenotypes of mucous membrane cells in five anatomical regions of the colon in a group of healthy donors was conducted by comparing mRNA expression profiles of 62 genes involved in the regulation of vital cellular function. We used 181 biopsy samples of morphologically unchanged colonic mucosa, obtained from the colon (ascending, transverse-colon, descending, sigmoid) and rectum sections during prophylactic colonoscopy of 58 donors with no colon pathology. The mRNA levels for 62 genes involved in the regulation of apoptosis, proliferation, transcription, differentiation, cell-cell adhesion, and immune response were assessed by RT-PCR. Statistically significant differences were found for the molecular phenotypes of five sections of the colon. The results of the study can serve as a basis for creating a reference database (values of expression profiles), developing methods of differential diagnostics and screening of various pathologies of the colon.
[Oxytocin receptor expression is associated with estrogen receptor status in breast tumors].
Kalinina TS, Kononchuk VV, Sidorov SV … +3 more , Obukhova DA, Abdullin GR, Gulyaeva LF
Biomed Khim · 2021 Jul · PMID 34414895 · Publisher ↗
The oxytocin receptor (OXTR) plays an important role in childbirth, breastfeeding, and social interactions. There is emerging evidence that OXTR is associated with the breast cancer (BC) initiation and progression. Howev...
The oxytocin receptor (OXTR) plays an important role in childbirth, breastfeeding, and social interactions. There is emerging evidence that OXTR is associated with the breast cancer (BC) initiation and progression. However, the mechanisms leading to a change in its expression, the diagnostic or prognostic value of the receptor in BC are currently poorly understood. Here, we have evaluated the relative level of OXTR expression in BC samples (n=107), and also investigated the effect of estradiol on its expression in MCF-7 and MDA-MB-231 cells. The level of OXTR expression was significantly lower in breast tumor tissue than in normal tissue obtained from the same patient. The expression of OXTR was dependent on the status and expression of the estrogen receptor (ER): the level of OXTR mRNA was significantly lower in ER-negative BC samples compared to ER-positive BC samples. Moreover, OXTR expression was also lower in samples from patients with luminal subtype with a low value of ER expression (0-5 score according to the IHC assay, Allred scoring) compared with samples with high ER expression (6-8 score). In luminal BC, OXTR expression was associated with the HER2 expression level: the OXTR mRNA level was higher in tumors with a HER2 IHC score of 1+ as compared to cases with the HER2 expression score of 2+, 3+. We also showed that estradiol increased the level of OXTR mRNA in MCF-7 cells, but not in ER-negative MDA-MB-231 cells. These data indicate that changes in OXTR expression in BC tissues can be caused by increased ER expression. We found no association between OXTR and T or N stages and progesterone receptor expression.
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