Biomeditsinskaia Khimiia[JOURNAL]
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200 papers
Molecular species of glycerophosphoethanolamines in obesity-associated asthma.
Denisenko YK, Omatova UM, Novgorodtseva TP … +1 more , Ermolenko EV
Biomed Khim · 2023 Jun · PMID 37384909 · Publisher ↗
Bronchial asthma (BA) complicated by obesity is a progressive disease phenotype that hardly responds to standard therapy. In this regard, it is important to elucidate cellular and molecular mechanisms of development of t...
Bronchial asthma (BA) complicated by obesity is a progressive disease phenotype that hardly responds to standard therapy. In this regard, it is important to elucidate cellular and molecular mechanisms of development of this comorbid pathology. In recent years, lipidomics has become an active research tool, opening new opportunities not only for understanding cellular processes in health and disease, but also for providing a personalized approach to medicine. The aim of this study was to characterize the lipidome phenotype based on the study of molecular species of glycerophosphatidylethanolamines (GPEs) in blood plasma of patients with BA complicated by obesity. Molecular species of GPEs were studied in blood samples of 11 patients. Identification and quantification of GPEs was carried out using high resolution tandem mass spectrometry. For the first time in this pathology, a change in the lipidome profile of molecular species of diacyl, alkyl-acyl and alkenyl-acyl HPEs of blood plasma was shown. In BA complicated by obesity, acyl groups 18:2 and 20:4 were dominated in the sn2 position of the molecular composition of diacylphosphoethanolamines. Simultaneously with the increase in the level of GPE diacyls with the fatty acids (FA) 20:4, 22:4, and 18:2, there was a decrease in these FAs in alkyl and alkenyl molecular species of GPEs, thus indicating their redistribution between subclasses. The eicosapentaenoic acid (20:5) deficiency at the sn2 position of alkenyl GPEs in patients with BA complicated by obesity indicates a decrease in the substrate for the synthesis of anti-inflammatory mediators. The resulting imbalance in the distribution of GPE subclasses, due to a pronounced increase in the content of diacyl GPE under conditions of the deficiency of molecular species of ether forms, can probably cause chronic inflammation and the development of oxidative stress. The recognized lipidome profile characterized by the modification of the basic composition and the chemical structure of GPE molecular species in BA complicated by obesity indicates their involvement in the pathogenetic mechanisms underlying BA development. The elucidation of particular roles of individual subclasses of glycerophospholipids and their individual members may contribute to the identification of new therapeutic targets and biomarkers of bronchopulmonary pathology.
The study of NF-κB transcription factor activation by Pseudomonas aeruginosa recombinant proteins in eukaryotic cell culture.
Kalinichenko EO, Akhmatova NK, Makarenkova ID … +2 more , Erohova AS, Mikhailova NA
Biomed Khim · 2023 Jun · PMID 37384908 · Publisher ↗
The transcription factor NF-κB is a key factor in the activation of immune responses; it is in turn activated by pattern recognition receptors, such as TLR and NLR receptors. The search for ligands activating innate immu...
The transcription factor NF-κB is a key factor in the activation of immune responses; it is in turn activated by pattern recognition receptors, such as TLR and NLR receptors. The search for ligands activating innate immunity receptors is an important scientific problem due to the possibility of their use as adjuvants and immunomodulators. In this study the effect of recombinant Pseudomonas aeruginosa OprF proteins and a toxoid (a deletion atoxic form of exotoxin A) on the activation of TLR4, TLR9, NOD1, and NOD2 receptors has been investigated. The study was carried out using free and co-adsorbed on Al(OH)₃ P. aeruginosa proteins and eukaryotic cells encoding these receptors and having NF-κB-dependent reporter genes. The enzymes encoded by the reported genes are able to cleave the substrate with the formation of a colored product, the concentration of which indicates the degree of receptor activation. It was found that free and adsorbed forms of the toxoid were able to activate the TLR4 surface receptor for lipopolysaccharide. OprF and the toxoid activated the intracellular NOD1 receptor, but only in the free form. This may be due to the fact that the cell lines used were not able to phagocytize aluminum hydroxide particles with protein adsorbed on them.
Implication of integrin α5β1 in senescence of SK-Mel-147 human melanoma cells.
Kozlova NI, Morozevich GE, Gevorkian NM … +2 more , Kurbatov LK, Berman AE
Biomed Khim · 2023 Jun · PMID 37384907 · Publisher ↗
Downregulation of α5β1 integrin in the SK-Mel-147 human melanoma culture model sharply inhibits the phenotypic manifestations of tumor progression: cell proliferation and clonal activity. This was accompanied by a 2-3-fo...
Downregulation of α5β1 integrin in the SK-Mel-147 human melanoma culture model sharply inhibits the phenotypic manifestations of tumor progression: cell proliferation and clonal activity. This was accompanied by a 2-3-fold increase in the content of SA-β-Gal positive cells thus indicating an increase in the cellular senescence phenotype. These changes were accompanied by a significant increase in the activity of p53 and p21 tumor suppressors and components of the PI3K/Akt/mTOR/p70 signaling pathway. Pharmacological inhibition of mTORC1 reduced the content of SA-β-Gal positive cells in the population of α5β1-deficient SK-Mel-147 cells. A similar effect was observed with pharmacological and genetic inhibition of the activity of Akt1, one of the three Akt protein kinase isoenzymes; suppression of other Akt isozymes did not affect melanoma cell senescence. The results presented in this work and previously obtained indicate that α5β1 shares with other integrins of the β1 family the function of cell protection from senescence. This function is realized via regulation of the PI3K/Akt1/mTOR signaling pathway, in which Akt1 exhibits a non-canonical activity.
β-Like DNA polymerases and prospects for their use as targets in chemotherapy of tumors.
Davydov VV, Bukhvostov AA, Kuznetsov DA
Biomed Khim · 2023 Jun · PMID 37384906 · Publisher ↗
DNA polymerases β are enzymes that perform repair of damaged DNA. In the cells of malignant tumors, there is a change in the production and properties of these enzymes, which is accompanied by altered viability of tumor...
DNA polymerases β are enzymes that perform repair of damaged DNA. In the cells of malignant tumors, there is a change in the production and properties of these enzymes, which is accompanied by altered viability of tumor cells. Analysis of the publications available in Russian and international databases (Pubmed, Elsevier) on the structure and properties of DNA polymerases β and their role in cell growth and proliferation, published over the past 20 years, has shown overexpression of genes encoding β-like DNA polymerases in many types of malignant tumors cells. This explains the maintenance of their viability and proliferative activity. Targeted inhibition of β-like DNA polymerases is accompanied by antiproliferative and antitumor effects. Stable paramagnetic isotopes of magnesium (25Mg2+) or other divalent metals (43Ca2+ and 67Zn2+) with uncompensated nuclear spin isotopes, as well as short single-stranded polydeoxyribonucleotides, can be used as promising antitumor pharmacophores.
RETRACTION NOTICE.
Biomed Khim · 2023 Mar · PMID 37134213 · Publisher ↗
The authors retracted this paper (Yu.A. Gladilina, A.N. Shishparenok, D.D. Zhdanov (2023) "Approaches for improving L-asparaginase expression in heterologous systems", Biomeditsinskaya Khimiya, 2023, 69(1), 19-38. DOI: 1...
The authors retracted this paper (Yu.A. Gladilina, A.N. Shishparenok, D.D. Zhdanov (2023) "Approaches for improving L-asparaginase expression in heterologous systems", Biomeditsinskaya Khimiya, 2023, 69(1), 19-38. DOI: 10.18097/PBMC20236901019) from the first issue the journal Biomeditsinskaya Khimiya (2023). Their decision is explained by identification of errors and inconsistences in the interpretation and citation of literature data recognized after the publication, which question correctness of important points considered in the review.
Oxygen-binding properties of blood in insulin resistance with different asprosin content.
Zinchuk VV, Al-Jebur JSO, Glutkina NV
Biomed Khim · 2023 Apr · PMID 37132495 · Publisher ↗
The oxygen-binding properties of blood were studied in male patients with insulin resistance (IR) with different levels of asprosin. The content of asprosin, parameters of blood oxygen transport function, as well as gas...
The oxygen-binding properties of blood were studied in male patients with insulin resistance (IR) with different levels of asprosin. The content of asprosin, parameters of blood oxygen transport function, as well as gas transmitters, nitrogen monoxide and hydrogen sulfide, were determined in the venous blood plasma. In the studied IR patients with increased blood asprosin content, impaired blood oxygenation was noted; IR patients with normal body weight had increased hemoglobin affinity for oxygen, while in IR patients with overweight and the 1st degree obesity, this parameter decreased. The detected increase in the concentration of nitrogen monoxide and the decrease in hydrogen sulfide may be important for the oxygen-binding properties of the blood and the development of metabolic imbalance.
Significance of salivary poly (ADP-ribose)-polymerase in the assessment of age-dependent pathological processes in the oral cavity.
Bazarnyi VV, Kopenkin MA, Polushina LG … +3 more , Maximova AY, Sementsova EA, Mandra YV
Biomed Khim · 2023 Apr · PMID 37132494 · Publisher ↗
Age-related changes in the oral cavity are accompanied by the development of age-related pathology, such as chronic periodontitis (CP). Although apoptosis plays a certain role in its pathogenesis, this fact, however, has...
Age-related changes in the oral cavity are accompanied by the development of age-related pathology, such as chronic periodontitis (CP). Although apoptosis plays a certain role in its pathogenesis, this fact, however, has not been evaluated clinically, and the diagnostic information content of biomarkers of apoptosis and aging has not been determined. The aim of the study was to evaluate the content of cleaved poly-(ADP-ribose)-polymerase (cPARP) and caspase-3 (Casp3) in mixed saliva of elderly patients with age-related dental diseases and in mature patients with mild to moderate CP. The study included 69 people. The control group included 22 healthy young volunteers aged 18 to 44 years. The main group included 22 elderly patients aged 60 to 74 years. They were divided into subgroups according to clinical manifestations: occlusion (comparison group), periodontal, and dystrophic syndromes. Additionally, a group of 25 patients of mature age from 45 to 59 years old with mild to moderate CP was analyzed. The content of salivary Casp3 in patients with occlusion syndrome was lower than in healthy young people (p=0.014). In patients with the periodontal syndrome, the content of cPARP was higher than in the comparison group (p=0.031). The group with dystrophic syndrome had the highest level of Casp3 in comparison with the control group and the comparison group (p=0.012, p=0.004, respectively). There were no statistically significant differences between patients of different age groups with mild to moderate CP. Evaluation of the correlation between cPARP and Casp3 levels revealed a direct relationship in the group of elderly patients and in patients with mild CP (r=0.69, r=0.81, respectively). We assessed the effect of Casp3 levels on changes in the cPARP levels by means of a simple linear regression analysis. The cPARP level correlated with the content of Casp3 (r²=0.555). According to the results of the ROC analysis, it was found that using the cPARP indicator it would be possible to distinguish between groups of elderly patients with periodontal and occlusion syndromes (AUC=0.71), while using Casp3 it would be possible to distinguish patients with the occlusion syndrome and the control group (AUC=0.78). Since the level of Casp3 in young people is significantly higher than in the elderly patients, its decrease can be considered as a potential salivary biomarker of aging. The level of studied cPARP in the elderly has clinical value in periodontal syndrome and low age dependence.
The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats.
Kustova MV, Prokofiev II, Perfilova VN … +6 more , Muzyko EA, Zavadskaya VE, Varlamova SV, Kucheryavenko AS, Tyurenkov IN, Vasilyeva OS
Biomed Khim · 2023 Apr · PMID 37132493 · Publisher ↗
The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synt...
The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells. This led to an increase in myocardial contractility. The studied compounds, glufimet and mefargin, caused a statistically significant increase in the rates of myocardial contraction and relaxation, left ventricular pressure, and also reduced NO production. This was accompanied by a decrease in the intensity of LPO processes and an increase in the respiratory control ratio (RCR), reflecting the coupling between respiration and phosphorylation processes during activation of the respiratory chain complexes I and II. The decrease in NO concentration during selective blockade of iNOS and administration of the studied substances was less pronounced than without blockade of the enzyme. This suggests the putative effect of new derivatives of neuroactive amino acids on the NO system.
The effect of phytoprotectors on the functioning of liver NAD⁺- and NADP⁺-maliс enzymes in rats with alloxan diabetes.
Eprintsev AT, Selivanova NV
Biomed Khim · 2023 Apr · PMID 37132492 · Publisher ↗
The development of experimental alloxan diabetes in rats was accompanied by the increase the activity of liver NAD⁺- and NADP⁺-dependent malic enzymes (ME; NAD⁺-ME, EC 1.1.1.39 and NADP⁺-ME, 1.1.1.40) associated with an...
The development of experimental alloxan diabetes in rats was accompanied by the increase the activity of liver NAD⁺- and NADP⁺-dependent malic enzymes (ME; NAD⁺-ME, EC 1.1.1.39 and NADP⁺-ME, 1.1.1.40) associated with an increase in the rate of transcription of genes encoding these enzymes. Oral administration of aqueous extracts of Jerusalem artichoke and olive to diabetic rats caused a noticeable decrease in blood glucose, a decrease in the rate of transcription of the studied genes; and a decrease in ME activity towards normal values. Thus, extracts of Jerusalem artichoke and olive can be used as additives to the standard therapy of diabetes mellitus.
Enalaprilat as a new means of preventing the development of retinopathy of prematurity.
Katargina LA, Chesnokova NB, Pavlenko TA … +3 more , Beznos OV, Osipova NA, Panova AY
Biomed Khim · 2023 Apr · PMID 37132491 · Publisher ↗
In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina wer...
In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina were investigated. The study was performed on 136 newborn Wistar rat pups divided into 2 groups: group A - experimental (animals with ROP, n=64) and group B - control (n=72). Each group was further divided into 2 subgroups: A0 and B0 (n=32 and n=36, respectively) - animals that did not receive injections of enalaprilat, and A1 and B1 (n=32 and n=36, respectively) - animals treated with daily intraperitoneal (i.p.) injections of enalaprilat (0.6 mg/kg of body weight). This treatment started on day 2 and lasted either to day 7 or to day 14 in accordance with the therapeutic scheme. Animals were taken out of the experiment on day 7 and day 14. In samples of the vitreous body and retina, the content of ACE and AT-II was determined by enzyme immunoassay. On day 7 in subgroups A1 and B1 the levels of ACE and AT-II in the vitreous did not differ, while on day 14 were lower than in subgroups A0 and B0, respectively. Changes in the parameters studied in the retina were somewhat different from those found in the vitreous body. On the seventh day, the level of ACE in the retina of animals of subgroup B1 did not differ significantly from subgroup B0, and in subgroup A1 it was increased compared to subgroup A0. On day 14, its significant decrease was noted in subgroups A1 and B1 as compared with subgroups A0 and B0. At the same time, the level of AT-II in the retina of rat pups of subgroup B1 was lower than in subgroup B0, both on day 7 and day 14. On day 7, the concentration of AT-II, as well as the concentration of ACE, increased in subgroup A1 as compared to subgroup A0. On day 14, this parameter in subgroup A1 was significantly lower as compared to subgroup A0, but significantly higher than in subgroup B1. It should be noted that i.p. injections of enalaprilat, increased a death rate of animals of both groups. The use of enalaprilat, starting from the preclinical period of the ROP development, led to a decrease in the activity of the renin-angiotensin system (RAS) in ROP animals at the onset of retinopathy in the experimental model used. This opens up prospects for considering enalaprilat as a means of preventing the development of this pathology; however, the recognized high toxicity of the drug requires further studies and correction of the timing of its administration and dosage in order to achieve a balance of efficacy and safety of use in order to prevent the development of ROP in children.
Features of oxidative stress in alcoholism.
Prokopieva VD, Vetlugina TP
Biomed Khim · 2023 Apr · PMID 37132490 · Publisher ↗
The review considers molecular mechanisms underlying formation and development of oxidative stress (OS) in patients with alcohol dependence. The major attention is paid to the effects of ethanol and its metabolite acetal...
The review considers molecular mechanisms underlying formation and development of oxidative stress (OS) in patients with alcohol dependence. The major attention is paid to the effects of ethanol and its metabolite acetaldehyde associated with additional sources of generation of reactive oxygen species (ROS) in response to exogenous ethanol. The own results of studies of the in vitro effect of ethanol and acetaldehyde on the concentration of peripheral OS markers - products of oxidative modification of proteins (protein carbonyls), lipids (lipid peroxidation products), DNA (8-hydroxy-2-deoxyguanosine, 8-OHdG) in blood plasma are presented. The changes in these parameters and the activity of antioxidant enzymes (SOD, catalase) in patients with alcohol dependence were analyzed. Own and literature data indicate that at a certain stage of the disease OS can play a protective rather than pathogenic role in the body.
[Quantitative assessment of breast cancer resistance protein during pregnancy in rabbits].
Popova NM, Slepnev AA, Abalenikhina YV … +3 more , Shchulkin AV, Rokunov ED, Yakusheva EN
Biomed Khim · 2023 Feb · PMID 36857429 · Publisher ↗
Breast cancer resistance protein (BCRP,ABCG2) is an efflux transporter protein that transports various substrates from the cell to the extracellular space or organ cavities. The aim of this study was a complex assessment...
Breast cancer resistance protein (BCRP,ABCG2) is an efflux transporter protein that transports various substrates from the cell to the extracellular space or organ cavities. The aim of this study was a complex assessment of the amount of BCRP during pregnancy in rabbits. The amount of BCRP in samples of the rabbit jejunum, liver, kidney, cerebral cortex, and placenta was determined by enzyme immunoassay, and in human hepatocellular carcinoma (HepG2) cells by the Western blot. To study the mechanisms involved in control of the dynamic BCRP levels during pregnancy, serum concentrations of sex hormones were investigated by radioimmunoassay and relative amounts of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in these organs were evaluated using the Western blot method. The putative role of CAR and PXR in regulation of the BCRP level by progesterone was evaluated in vitro experiments on HepG2 cells. It was found that amount of BCRP in the jejunum of pregnant rabbits was higher than in the placenta, liver, kidneys, and cerebral cortex. An increase in the amount of BCRP in the liver of rabbits was noted on the 21st day of pregnancy and a tendency to the increase was also detected on the 28th day; in the kidney and cerebral cortex increased BCRP levels were detected on the 28th day and 14th day of pregnancy, respectively, as compared with non-pregnant females. In vitro experiments with HepG2 cells have shown that the increase in the BCRP level is determined by the activating effect of progesterone on PXR.
[Effect of erastin and G3139 on rat liver mitochondria in chronic alcoholic intoxication].
Baburina YL, Zvyagina AI, Odinokova IV … +1 more , Krestinina OV
Biomed Khim · 2023 Feb · PMID 36857428 · Publisher ↗
The effect of modulators of VDAC channels - G3139 and erastin on the mitochondrial permeability transition pore (mPTP) functioning and changes in the content of proteins involved in regulation of mPTP (VDAC, CNPase, and...
The effect of modulators of VDAC channels - G3139 and erastin on the mitochondrial permeability transition pore (mPTP) functioning and changes in the content of proteins involved in regulation of mPTP (VDAC, CNPase, and TSPO) has been investigated in liver mitochondria of rats with chronic alcohol intoxication. It was shown that the mitochondria of rats treated with ethanol were more sensitive to mPTP induction. Moreover, ethanol induced changes in the expression of mPTP regulator proteins. G3139 and erastin were also able to influence the studied mitochondrial parameters, and they increased their effect in the liver mitochondria of rats treated with ethanol, as compared to the mitochondria of control rats. We hypothesize that the results of this study may help to elucidate the mechanisms of chronic action of ethanol on mitochondria and contribute to the development of new therapeutic strategies for treating the consequences of ethanol-related diseases.
[Pharmacological importance of novel spiro derivatives against human pathogenic fungi].
Sharma G, Sharma R, Saxena R … +2 more , Rajni E, Prakash Mamoria V
Biomed Khim · 2023 Feb · PMID 36857427 · Publisher ↗
Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. In the present study, antifungal activity of earlier synthesized spiro-1,4-dihydropyridi...
Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. In the present study, antifungal activity of earlier synthesized spiro-1,4-dihydropyridines (1,4-DHPs) was investigated. The antifungal activity of spiro-1,4-DHPs compounds were screened against Aspergillus flavus, A. fumigatus, and Candida albicans by using Disc Diffusion and Modified Microdilution method. Among six spiro-1,4-DHPs compounds tested all of them showed stronger antifungal activity possibly through inhibiting the synthesis of chitin in cell wall against A. flavus, A. fumigatus, and C. albicans as compared to fluconazole, a standard antifungal drug. The combination of compounds showed that the synthesized compounds had synergistic, additive effects as compared to currently used drugs as an antifungal agent. These results indicated that these designed compounds were potential chitin synthase inhibitors and had excellent antimycotic activity for the treatment of fungal infections.
[Characteristics of behavioral reactions and the profile of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism].
Kapitsa IG, Kazieva LS, Vavilov NE … +4 more , Zgoda VG, Kopylov AT, Medvedev AE, Buneeva OA
Biomed Khim · 2023 Feb · PMID 36857426 · Publisher ↗
The neurotoxins rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (МPTP) are used for modeling Parkinson's disease in animals (PD). They induce the mitochondrial respiratory chain dysfunction, which leads to the...
The neurotoxins rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (МPTP) are used for modeling Parkinson's disease in animals (PD). They induce the mitochondrial respiratory chain dysfunction, which leads to the dopaminergic (DA) neuron degeneration. The advantage of the rotenone model consists in ability of rotenone to cause neurodegeneration showing symptoms and molecular biological characteristics similar to those of PD. Isatin (indoldione-2,3) is an endogenous regulator found in tissues and biological fluids of humans and animals. It exhibits a broad range of biological activity mediated by numerous isatin-binding proteins. In this work we have investigated behavioral reactions and profiles of brain isatin-binding proteins of rats with Parkinson's syndrome (PS) in comparison with the corresponding parameters of MPTP-induced Parkinsonism in mice. Systemic injection of rotenone caused severe PS comparable with the effect of MPTP injection. It was accompanied by significant body weight loss, death, oligokinesia, muscular rigidity, and postural instability of animals. In spite of the same pathogenic basis of PS caused by rotenone and MPTP, the molecular mechanisms of their action differ. In the case of rotenone-induced PS, the pool of isatin-binding proteins common of the control rats and the rats with PS (146) significantly exceeded the pool of the common proteins of control mice and mice with PS induced by MPTP, whether right after neurotoxin injection (27), or (all the more) in a week after the MPTP injection (14). The comparison of isatin-binding proteins specific of the animals with MPTP-induced PS and with the rotenone-induced PS (as compared with the control animals) revealed total absence of proteins common of these two models of PD. It is to be noted that both neurotoxins particularly affected the proteins participating in the signal transmission and enzyme activity regulation. The changes of the profile of isatin-binding proteins in response to the injection of rotenone suggest that the neuroprotector isatin could also influence positively in the case of the rotenone model of PD.
[Correction of serum prooncogenic cytokines and metastases by 5-hydroxypyrimidine derivatives and doxorubicin after removal of a primary tumor node in mice with the Lewis lung epidermoid carcinoma].
Kovalenko LP, Korzhova KV, Nikitin SV … +2 more , Ivanova EA, Zhurikov RV
Biomed Khim · 2023 Feb · PMID 36857425 · Publisher ↗
The effect of a single injection of doxorubicin, 8-day administration of two 5-hydroxypyrimidine derivatives, SNK-411 (2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5-...
The effect of a single injection of doxorubicin, 8-day administration of two 5-hydroxypyrimidine derivatives, SNK-411 (2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine), on metastases, lifespan and serum cytokines has been investigated in С57ВL/6 mice after removal of a primary tumor node of Lewis lung carcinoma (LLC). LLC cells (1×106) were injected in the footpad of right hind feet of mice in control and experimental groups; after 14 days of tumor development the hind feet with the tumor were amputated at the ankle level. One hour before the amputation mice received a single injection of doxorubicin (4 mg/kg) and 8-day therapy with the 5-hydroxypyrimidine derivatives started. SNK-578 monotherapy was performed at a dose of 10 mg/kg administered intraperitoneally (i.p.). SNK-411 was administered per os at a dose of 25 mg/kg. In the case of combined therapy mice also received a single injection of doxorubicin (4 mg/kg; i.p.). The metastasis inhibition index in mice-treated with SNK-411 and SNK-578 were 53.3% as compared with control mice (with removed tumor). The mice-treated with SNK-411, doxorubicin, and the combination SNK-578 + doxorubicin had lifespan increased by 60.2%, 53.9%, and 42.9%, respectively. A single injection of doxorubicin, the course administration of the 5-hydroxypyrimidine derivative alone and in combination with single injection of doxorubicin completely decreased serum levels of the prooncogenic Th2-cytokines IL-4, and IL-6 and significantly decreased the level of the Th2-cytokine IL-5. Administration of doxorubicin, SNK-411 and SNK-578 did not influence serum concentration of Th1-cytokine interferon gamma (IFN-γ). These data confirm our previous findings that administration of the compounds studied decreased concentrations of prooncogenic IL-4 and IL-6 in tumor-bearing mice with LLC and had no effect on concentrations of the Th1-cytokine IFN-γ.
[Approaches for improving L-asparaginase expression in heterologous systems].
Gladilina YA, Shishparenok AN, Zhdanov DD
Biomed Khim · 2023 Feb · PMID 36857424 · Publisher ↗
L-asparaginase (EC 3.5.1.1) is one of the most demanded enzymes used in the pharmaceutical industry as a drug and in the food industry to prevent the formation of toxic acrylamide. Researchers aimed to improve specific a...
L-asparaginase (EC 3.5.1.1) is one of the most demanded enzymes used in the pharmaceutical industry as a drug and in the food industry to prevent the formation of toxic acrylamide. Researchers aimed to improve specific activity and reduce side effects to create safer and more potent enzyme products. However, protein modifications and heterologous expression remain problematic in the production of asparaginases from different species. Heterologous expression in optimized producer strains is rationally organized; therefore, modified and heterologous protein expression is enhanced, which is the main strategy in the production of asparaginase. This strategy solves several problems: incorrect protein folding, metabolic load on the producer strain and codon misreading, which affects translation and final protein domains, leading to a decrease in catalytic activity. The main approaches developed to improve the heterologous expression of L-asparaginases are considered in this paper.
[Antibody proteomics].
Kazieva LS, Farafonova TE, Zgoda VG
Biomed Khim · 2023 Feb · PMID 36857423 · Publisher ↗
Antibodies represent an essential component of humoral immunity; therefore their study is important for molecular biology and medicine. The unique property of antibodies to specifically recognize and bind a certain molec...
Antibodies represent an essential component of humoral immunity; therefore their study is important for molecular biology and medicine. The unique property of antibodies to specifically recognize and bind a certain molecular target (an antigen) determines their widespread application in treatment and diagnostics of diseases, as well as in laboratory and biotechnological practices. High specificity and affinity of antibodies is determined by the presence of primary structure variable regions, which are not encoded in the human genome and are unique for each antibody-producing B cell clone. Hence, there is little or no information about amino acid sequences of the variable regions in the databases. This differs identification of antibody primary structure from most of the proteomic studies because it requires either B cell genome sequencing or de novo amino acid sequencing of the antibody. The present review demonstrates some examples of proteomic and proteogenomic approaches and the methodological arsenal that proteomics can offer for studying antibodies, in particular, for identification of primary structure, evaluation of posttranslational modifications and application of bioinformatics tools for their decoding.
[Lymphocytes enzymatic status and peripheral blood neutrophils oxygen-dependent metabolism in patients with renal cancer].
Zukov RA, Slepov EV, Kurtasova LM … +1 more , Inzhevatkin EV
Biomed Khim · 2022 Dec · PMID 36573413 · Publisher ↗
The immune system, one of the most important homeostatic organism systems, is actively involved in the protection against malignant tumors. The earliest sighs of immune homeostasis disorders should be invetigated at the...
The immune system, one of the most important homeostatic organism systems, is actively involved in the protection against malignant tumors. The earliest sighs of immune homeostasis disorders should be invetigated at the cellular level, because of cell functional manifestations depend on the state of intracellular metabolic reactions. The study of lymphocyte NAD(P)-dependent dehydrogenases activity and peripheral blood neutrophils oxygen-dependent metabolism in patients with renal cellular carcinoma (RCC) showed a decrease in the intensity of ribose-5-phosphate and NADH-dependent synthetic processes, inhibition of terminal reactions of glycolysis. Altered activities of the studied enzymes favor an increase in outflow of intermediates of the Krebs cycle on the reaction of amino acid metabolism in peripheral blood lymphocytes. Radical nephrectomy was accompanied by increased activity of glycolysis. The basal level chemiluminescent of peripheral neutrophils of RCC patients response was higher both before and after operations. Stimulation of neutrophils by opsonized zymosan in vitro leads to increase in oxidative metabolism activity, most in 14 days after surgery period. Before and 30 days after surgery, adaptive metabolic capabilities of neutrophilic granulocytes decreased.
[The prediction of SARS-CoV-2 main protease inhibition with filtering by position of ligand].
Ivanova YO, Voronina AI, Skvortsov VS
Biomed Khim · 2022 Dec · PMID 36573412 · Publisher ↗
The paper analyzes a set of equations that adequately predict the IC50 value for SARS-CoV-2 main protease inhibitors. The training set was obtained using filtering by criteria independent of prediction of target value. I...
The paper analyzes a set of equations that adequately predict the IC50 value for SARS-CoV-2 main protease inhibitors. The training set was obtained using filtering by criteria independent of prediction of target value. It included 76 compounds, and the test set included nine compounds. We used the values of energy contributions obtained in the calculation of the change of the free energy of complex by MMGBSA method and a number of characteristics of the physical and chemical properties of the inhibitors as independent variables. It is sufficient to use only seven independent variables without loss of prediction quality (Q² = 0.79; R²prediction = 0.89). The maximum error in this case does not exceed 0.92 lg(IC50) units with a full range of observed values from 1.26 to 4.95.
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