{"title":"Molecular mechanisms of the regulatory action of high-density lipoproteins on the endothelial function.","authors":"O N Poteryaeva, I F Usynin","doi":"10.18097/PBMC20247004206","DOIUrl":"https://doi.org/10.18097/PBMC20247004206","url":null,"abstract":"<p><p>Endothelial dysfunction underlies the pathogenesis of many diseases, primarily cardiovascular diseases. Epidemiological studies have shown an inverse dependence between the plasma level of high-density lipoproteins (HDL) and cardiovascular diseases. The results of experimental studies indicate that the antiatherogenic effect of HDL is associated not only with their participation in the reverse transport of excess cholesterol, but also with their regulatory effect on the functions of cells of various organs and tissues, including endothelial cells. The purpose of this review is to consider recent data on the participation of plasma receptors and related intracellular signaling pathways in the mechanism of protective effect of HDL on endothelial cell functions. Understanding the mechanisms of cell function regulation under the influence of HDL is an important step for the development of new ways of pharmacological correction of impaired endothelial functions and creation of effective endothelial protection drugs.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"206-217"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139211","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}
N V Yunusova, E V Kaigorodova, P A Panfilova, N O Popova, I N Udintseva, I V Kondakova, D A Svarovsky, V E Goldberg
{"title":"Internalization of extracellular vesicles of cancer patients by peripheral blood mononuclear cells during polychemotherapy: connection with neurotoxicity.","authors":"N V Yunusova, E V Kaigorodova, P A Panfilova, N O Popova, I N Udintseva, I V Kondakova, D A Svarovsky, V E Goldberg","doi":"10.18097/PBMC20247004240","DOIUrl":"https://doi.org/10.18097/PBMC20247004240","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), exhibiting their functional activity after internalization by recipient cells, are involved in the pathogenesis of drug-induced polyneuropathy (DIPN), a common complication of antitumor therapy. In this work, the internalization of EVs obtained from colorectal cancer patients undergoing polychemotherapy and its relationship with neurotoxicity were assessed using a model system of mononuclear leukocytes. Circulating EVs were isolated from 8 colorectal cancer patients who received antitumor therapy according to the FOLFOX or XELOX regimens before the start of chemotherapy (point 1) and after 3-4 courses (point 2). Mononuclear leukocytes of a healthy donor served as a cellular model system for EV internalization in vitro. EV internalization was assessed using fluorescence microscopy. It was shown that internalization of EVs obtained from colorectal cancer patients with high neurotoxicity was higher than in the group with low neurotoxicity. The ability of CD11b-positive (CD11b⁺) and CD11b-negative (CD11b⁻) mononuclear leukocytes of a healthy donor to internalize EVs obtained from patients before and after chemotherapy did not reveal significant differences. A direct relationship was found between the relative number of CD11b⁻ cells with internalized EVs and the integral index of neurotoxicity according to the NRS scale at the peak of its manifestation (point 2) (r=0.675, p.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"240-247"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139209","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}
O A Buneeva, I G Kapitsa, L Sh Kazieva, N E Vavilov, V G Zgoda, A E Medvedev
{"title":"The neuroprotective effect of isatin in the rotenone-induced model of parkinonism in rats: the study of delayed effects.","authors":"O A Buneeva, I G Kapitsa, L Sh Kazieva, N E Vavilov, V G Zgoda, A E Medvedev","doi":"10.18097/PBMC20247004231","DOIUrl":"https://doi.org/10.18097/PBMC20247004231","url":null,"abstract":"<p><p>Parkinsonism in rats induced by the pesticide rotenone is one of the most adequate models of Parkinson's disease (PD). Isatin (indole-2,3-dione) is an endogenous regulator found in mammals and humans and exhibiting a wide range of biological activities mediated by numerous isatin-binding proteins, including those associated with neurodegenerative pathology. A course of rotenone administration to rats caused behavioral impairments and changes in the profile and relative content of isatin-binding proteins in the brain. In this study, we have investigated the delayed neuroprotective effect of isatin (5 days after completion of the course of rotenone administration) on behavioral reactions and the relative content of isatin-binding proteins in the brain of rats with rotenone-induced experimental parkinsonism. Although during this period the rats retained locomotor dysfunction, the proteomic analysis data (profile of isatin-binding proteins in the brain and changes in their relative content) differed from the results obtained immediately after completion of the course of rotenone administration. Moreover, all isatin-binding proteins with altered relative content changed during this period are associated to varying degrees with neurodegeneration (many with Parkinson's and Alzheimer's diseases).</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"231-239"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139212","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}
{"title":"Apoptotic endonuclease EndoG induces alternative splicing of Caspase-2.","authors":"D D Zhdanov, Yu A Gladilina, A N Shisparenok","doi":"10.18097/PBMC20247004218","DOIUrl":"10.18097/PBMC20247004218","url":null,"abstract":"<p><p>Caspase-2 (Casp-2) is an enzyme that regulates the development of apoptosis upon alternative splicing of its mRNA. The long form of Casp-2 (Casp-2L) promotes apoptosis while the short form (Casp-2S) has decreased enzymatic activity and inhibits the development of apoptotic processes. However, very little is known about the mechanism of Casp-2 alternative splicing. Several endonucleases are known to participate in this process. The aim of this study was to determine the role of EndoG in regulation of Casp-2 alternative splicing. Strong correlation between expression levels of EndoG and Casp-2 splice-variants was found in CD4⁺ and CD8⁺ human T lymphocytes. Such correlation increased after incubation of these cells with etoposide. Increased expression of Casp-2S was determined during EndoG over-expression in CD4⁺ T-cells, after EndoG treatment of cell cytoplasm and nuclei and after nuclei incubation with EndoG digested cell RNA. Casp-2 alternative splicing was induced by a 60-mer RNA oligonucleotide in naked nuclei and in cells after transfection. The identified long non-coding RNA of 1016 nucleotides is the precursor of the 60-mer RNA oligonucleotide. Based on the results the following mechanism has been proposed. Casp-2 pre-mRNA is transcribed from the coding DNA strand while long non-coding RNA is transcribed from the template strand of the Casp-2 gene. EndoG digests long non-coding RNA and produces the 60-mer RNA oligonucleotide complementary to the Casp-2 pre-mRNA exon 9 and intron 9 junction place. Interaction of the 60-mer RNA oligonucleotide and Casp-2 pre-mRNA causes alternative splicing.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"218-230"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139207","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}
O A Buneeva, V I Fedchenko, S A Kaloshina, M G Zavyalova, V G Zgoda, A E Medvedev
{"title":"Proteomic profiling of renal tissue of normo- and hypertensive rats with the renalase peptide RP220 as an affinity ligand.","authors":"O A Buneeva, V I Fedchenko, S A Kaloshina, M G Zavyalova, V G Zgoda, A E Medvedev","doi":"10.18097/PBMC20247003145","DOIUrl":"10.18097/PBMC20247003145","url":null,"abstract":"<p><p>Renalase (RNLS) is a recently discovered protein that plays an important role in the regulation of blood pressure by acting inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase that oxidizes isomeric forms of β-NAD(P)H. Extracellular renalase lacking its N-terminal peptide and cofactor FAD exerts various protective effects via non-catalytic mechanisms. Certain experimental evidence exists in the literature that the RP220 peptide (a 20-mer peptide corresponding to the amino acid sequence RNLS 220-239) reproduces a number of non-catalytic effects of this protein, acting on receptor proteins of the plasma membrane. The possibility of interaction of this peptide with intracellular proteins has not been studied. Taking into consideration the known role of RNLS as a possible antihypertensive factor, the aim of this study was to perform proteomic profiling of the kidneys of normotensive and hypertensive rats using RP220 as an affinity ligand. Proteomic (semi-quantitative) identification revealed changes in the relative content of about 200 individual proteins in the kidneys of hypertensive rats bound to the affinity sorbent as compared to the kidneys of normotensive animals. Increased binding of SHR renal proteins to RP220 over the normotensive control was found for proteins involved in the development of cardiovascular pathology. Decreased binding of the kidney proteins from hypertensive animals to RP220 was noted for components of the ubiquitin-proteasome system, ribosomes, and cytoskeleton.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 3","pages":"145-155"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465934","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}
A V Sinitskaya, E A Velikanova, E A Senokosova, M Yu Sinitsky, M V Khutornaya, M A Asanov, A O Poddubnyak, A V Ponasenko
{"title":"The cytokine response of human coronary artery endothelial cells treated with doxorubicin: results of an in vitro experiment.","authors":"A V Sinitskaya, E A Velikanova, E A Senokosova, M Yu Sinitsky, M V Khutornaya, M A Asanov, A O Poddubnyak, A V Ponasenko","doi":"10.18097/PBMC20247003156","DOIUrl":"https://doi.org/10.18097/PBMC20247003156","url":null,"abstract":"<p><p>The cytokine profile of primary coronary artery endothelial cells cultivated in the presence of doxorubicin (2 μg/ml and 6 μg/ml) was evaluated using enzyme-linked immunosorbent assay and qPCR. Cultivation of cells in the presence of these concentrations of doxorubicin for 24 h, upregulated expression of the following genes: IL6 (by 2.30 and 2.66 times, respectively), IL1B (by 1.25 and 3.44 times), and CXCL8 (by 6.47 times and 6.42 times), MIF (2.34 and 2.28 times), CCL2 (4.22 and 3.98 times). Under these conditions the following genes were downregulated: IL10, IL1R2, TNF. Cultivation of cells in the presence of doxorubicin (2 μg/ml and 6 μg/ml) for 24 h also increased the secretion of IL-6.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 3","pages":"156-160"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465935","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}
{"title":"Dynamics in cortisol levels in Danio rerio fish under the influence of a synthetic analog of kisspeptin 1.","authors":"A A Nuzhnova, M I Kostina, A A Blazhenko","doi":"10.18097/PBMC20247003176","DOIUrl":"10.18097/PBMC20247003176","url":null,"abstract":"<p><p>The effect of a synthetic analog of kisspeptin 1, a peptide involved in the regulation of the hypothalamicpituitary- gonadal (HPG) stress axis, on the cortisol level of Danio rerio fish was investigated. Kisspeptin 1 was administered at doses of 2 μg/kg and 8 μg/kg followed by resting for 1 h and 4 h. We found that kisspeptin at doses of 2 μg/kg and 8 μg/kg increased cortisol levels, with a significant spike in cortisol levels at 1 h post-injection.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 3","pages":"176-179"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465931","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}
{"title":"Novel spiro[indoline-3,2'thiazolo[5,4-e]pyrimido[1,2-a] pyrimidine] derivatives as possible anti-dermatophytic and anti-candidiasis agent.","authors":"G Sharma, R Sharma","doi":"10.18097/PBMC20247003180","DOIUrl":"https://doi.org/10.18097/PBMC20247003180","url":null,"abstract":"<p><p>A novel series of 5'-benzylidene-3'-phenylspiro[indoline-3,2'-thiazolidine]-2,4'(1H)-diones 6a-d and spiro[indoline-3,2'-thiazolo[5,4-e]pyrimido[1,2-a]pyrimidin]-2(1H)-one 9a-d derivatives have been synthesized. All the newly synthesized compounds were evaluated for antifungal and anti-candidiasis activity by using Disc Diffusion and Modified Microdilution methods. The antimicrobial experiments have shown that the synthesized compounds demonstrated broad-spectrum antifungal activity in vitro. Among them, compounds 9a-9d had stronger antifungal activity against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans; compounds 6a-d also showed significant antifungal activity against selected fungal strains as compared to ketoconazole, the reference antifungal drug. The evaluation of antifungal activity against drug-resistant fungal variants showed that the designed compounds had significant antifungal activity against the tested variants. The combination of compounds (6a-d) and (9a-d) exhibited that the synthesized compounds had synergistic effects or additive effects. These results demonstrated that the synthesized compounds were putative chitin synthase inhibitors exhibiting broad spectrum antifungal activities. The present results indicate that novel spiro pyrimidine derivatives can be used as an active pharmaceutical ingredient for novel drug candidate for treatment of dermatophytosis and other fungal agents.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 3","pages":"180-186"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465933","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}
I V Kirsanova, A V Kolesnikov, A V Shchulkin, Yu V Abalenikhina, P D Erokhina, E N Yakusheva
{"title":"The effect of lactoferin on the free radical and cytokine status of cornea in the experimental thermal burn.","authors":"I V Kirsanova, A V Kolesnikov, A V Shchulkin, Yu V Abalenikhina, P D Erokhina, E N Yakusheva","doi":"10.18097/PBMC20247003168","DOIUrl":"https://doi.org/10.18097/PBMC20247003168","url":null,"abstract":"<p><p>The free radical and cytokine statuses of the cornea during its thermal burn and the possibility of its correction by lactoferrin have been studied in Soviet Chinchilla rabbits. The development of a corneal thermal burn was accompanied by the development of oxidative stress (increased levels of TBA-reactive substances and carbonyl derivatives of proteins, decreased activity of SOD and GPx enzymes) and a pronounced inflammatory reaction with increased levels of TNF-1α, IL-10, TGF-1β. The use of lactoferrin had a pronounced therapeutic effect, which was manifested by accelerated healing, prevention of the development of complications (corneal perforations), a decrease in the severity of oxidative stress, an increase in the concentrations of TNF-1α (in the early stages), IL-10 (in the later stages), TGF-1β (throughout the experiment). At the same time, by the end of regeneration more severe corneal opacification was recognized compared to the control group. This may be associated with an increased level of anti-inflammatory cytokines, especially TGF-1β.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 3","pages":"168-175"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465936","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}
I M Studneva, O M Veselova, I V Dobrokhotov, L I Serebryakova, M E Palkeeva, D V Avdeev, A S Molokoedov, M V Sidorova, O I Pisarenko
{"title":"The structural analogue of apelin-12 prevents energy disorders in the heart in experimental type 1 diabetes mellitus.","authors":"I M Studneva, O M Veselova, I V Dobrokhotov, L I Serebryakova, M E Palkeeva, D V Avdeev, A S Molokoedov, M V Sidorova, O I Pisarenko","doi":"10.18097/PBMC20247003135","DOIUrl":"https://doi.org/10.18097/PBMC20247003135","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is the most severe form of diabetes, which is characterized by absolute insulin deficiency induced by the destruction of pancreatic beta cells. The aim of this study was to evaluate the effect of a structural analogue of apelin-12 ((NαMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, metilin) on hyperglycemia, mitochondrial (MCh) respiration in permeabilized cardiac left ventricular (LV) fibers, the myocardial energy state, and cardiomyocyte membranes damage in a model of streptozotocin (STZ) diabetes in rats. Metilin was prepared by solid-phase synthesis using the Fmoc strategy and purified using HPLC. Four groups of animals were used: initial state (IS); control (C), diabetic control (D) and diabetic animals additionally treated with metilin (DM). The following parameters have been studied: blood glucose, MCh respiration in LV fibers, the content of cardiac ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr), the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in blood plasma. Administration of metilin to STZ-treated rats decreased blood glucose, increased state 3 oxygen consumption, the respiratory control ratio in MCh of permeabilized LV fibers, and increased the functional coupling of mitochondrial CK (mt-CK) to oxidative phosphorylation compared with these parameters in group D. In STZ-treated animals metilin administration caused an increase in the PCr content and prevention of the loss of total creatine (ΣCr=PCr+Cr) in the diabetic hearts, as well as restoration of the PCr/ATP ratio in the myocardium and a decrease in the activity of CK-MB and LDH in plasma to initial values. Thus, metilin prevented energy disorders disturbances in cardiomyocytes of animals with experimental T1DM.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 3","pages":"135-144"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465937","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}