Biomeditsinskaia Khimiia[JOURNAL]
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200 papers
Personalization of a computational systems biology model of blood platelet calcium signaling.
Balabin FA, Korobkina JDD, Galkina SV … +2 more , Panteleev MA, Sveshnikova AN
Biomed Khim · 2024 Dec · PMID 39718102 · Publisher ↗
Anuclear blood cells, platelets, are the basis for the formation of blood clots in human vessels. While antiplatelet therapy is most often used after ischemic events, there is a need for its personalization due to the li...
Anuclear blood cells, platelets, are the basis for the formation of blood clots in human vessels. While antiplatelet therapy is most often used after ischemic events, there is a need for its personalization due to the limited effectiveness and risks of bleeding. Previously, we developed a series of computational models to describe intracellular platelet signaling and a set of experimental methods to characterize the platelets of a given patient. To build a personalized model of platelet signaling, we also conducted research on platelet proteomics. The aim of this study was to personalize the central module of intracellular platelet signaling responsible for the formation of calcium oscillations in response to activation. The model consists of 26 ordinary differential equations. To personalize the model, proteomics data were used and unknown model parameters were selected based on experimental data on the shape and frequency of calcium oscillations in single platelets. As a result of the study, it has been shown that the key personalized parameters of the platelet oscillatory response are the degree of asymmetry of a single calcium spike and the maximum frequency of oscillations. Based on the listed experimentally determined parameters and proteomics data, an algorithm for personalization of the model has been proposed. Here we considered three healthy pediatric donors of different ages. Based on the models, personal curves of platelet calcium response to activation were obtained. The analysis of the models has shown that while there is a large heterogeneity of individual indicators of intracellular signaling, such as the activity of calcium pumps (SERCA) and inositoltriphosphate (IP₃) receptors (IP₃R), these indicators compensate each other in each donors. This observation is confirmed by the analysis of proteomics data from 15 healthy patients: this analysis demonstrates a correlation between the total amount of SERCA and IP₃R. Thus, several new features of human platelet calcium signaling are shown and an algorithm for personalizing its model is proposed.
Chronobiotics: classifications of existing circadian clock modulators, future perspectives.
Solovev IA, Golubev DA
Biomed Khim · 2024 Dec · PMID 39718101 · Publisher ↗
The review summarizes recent achievements and future prospects in the use of chronobiotics for regulating circadian rhythms regulation. Special attention is paid to the mechanisms' action, their classification, and the i...
The review summarizes recent achievements and future prospects in the use of chronobiotics for regulating circadian rhythms regulation. Special attention is paid to the mechanisms' action, their classification, and the impact of chemical interventions on the biological clock. Chronobiotics defined as a diverse group of compounds capable of restoring disrupted circadian functions, addressing challenges such as irregular work schedules, artificial light exposure or ageing. The review categorizes these compounds by their pharmacological effects, molecular targets, and chemical structures, underlining their ability to enhance or inhibit key circadian components like CLOCK, BMAL1, PER, and CRY. A particular focus is placed on the therapeutic applications of chronobiotics, including their potential for treating sleep disorders, metabolic issues, and age-related rhythm disturbances, underscoring their wide-ranging applicability in health care. Chronobiotic compounds have promising roles in maintaining physiological rhythms, supporting healthy aging, and enhancing personalised health care. Given their diverse therapeutic potential, chronobiotics are positioned as a significant avenue for further clinical application, marking them as a crucial area of ongoing research and innovation.
The human proteome size as a technological development function.
Sarygina EV, Kozlova AS, Ponomarenko EA … +1 more , Ilgisonis EV
Biomed Khim · 2024 Sep · PMID 39324201 · Publisher ↗
Changes in information on the number of human proteoforms, post-translational modification (PTM) events, alternative splicing (AS), single-amino acid polymorphisms (SAP) associated with protein-coding genes in the neXtPr...
Changes in information on the number of human proteoforms, post-translational modification (PTM) events, alternative splicing (AS), single-amino acid polymorphisms (SAP) associated with protein-coding genes in the neXtProt database have been retrospectively analyzed. In 2016, our group proposed three mathematical models for predicting the number of different proteins (proteoforms) in the human proteome. Eight years later, we compared the original data of the information resources and their contribution to the prediction results, correlating the differences with new approaches to experimental and bioinformatic analysis of protein modifications. The aim of this work is to update information on the status of records in the databases of identified proteoforms since 2016, as well as to identify trends in changes in the quantities of these records. According to various information models, modern experimental methods may identify from 5 to 125 million different proteoforms: the proteins formed due to alternative splicing, the implementation of single nucleotide polymorphisms at the proteomic level, and post-translational modifications in various combinations. This result reflects an increase in the size of the human proteome by 20 or more times over the past 8 years.
Proteome of plasma extracellular vesicles as a source of colorectal cancer biomarkers.
Soloveva NA, Novikova SE, Farafonova TE … +3 more , Tikhonova OV, Zgoda VG, Archakov AI
Biomed Khim · 2024 Sep · PMID 39324200 · Publisher ↗
The search for minimally invasive methods for diagnostics of colorectal cancer (CRC) is the most important task for early diagnostics of the disease and subsequent successful treatment. Human plasma represents the main t...
The search for minimally invasive methods for diagnostics of colorectal cancer (CRC) is the most important task for early diagnostics of the disease and subsequent successful treatment. Human plasma represents the main type of biological material used in the clinical practice; however, the complex dynamic range of substances circulating in it complicates determination of CRC protein markers by the mass spectrometric (MS) method. Studying the proteome of extracellular vesicles (EVs) isolated from human plasma represents an attractive approach for the discovery of tissue-secreted CRC markers. We performed shotgun mass spectrometry analysis of EV samples obtained from plasma of CRC patients and healthy volunteers. This MS analysis resulted in identification of 370 proteins (which were registered by at least two peptides). Stable isotope-free relative quantitation identified 55 proteins with altered abundance in EV samples obtained from plasma samples of CRC patients as compared to healthy controls. Among the EV proteins isolated from blood plasma we found components involved in cell adhesion and the VEGFA-VEGFR2 signaling pathway (TLN1, HSPA8, VCL, MYH9, and others), as well as proteins expressed predominantly by gastrointestinal tissues (polymeric immunoglobulin receptor, PIGR). The data obtained using the shotgun proteomic profiling may be added to the panel for targeted MS analysis of EV-associated protein markers, previously developed using CRC cell models.
Registration of activity of a single molecule of horseradish peroxidase using a detector based on a solid-state nanopore.
Ivanov YD, Ableev AN, Vinogradova AV … +11 more , Nevedrova ED, Shumov ID, Ziborov VS, Kozlov AF, Ivanova IA, Vaulin NV, Lebedev DV, Bukatin AS, Mukhin IS, Ponomarenko EA, Archakov AI
Biomed Khim · 2024 Sep · PMID 39324199 · Publisher ↗
This work demonstrates the use of a solid-state nanopore detector to monitor the activity of a single molecule of a model enzyme, horseradish peroxidase (HRP). This detector includes a measuring cell, which is divided in...
This work demonstrates the use of a solid-state nanopore detector to monitor the activity of a single molecule of a model enzyme, horseradish peroxidase (HRP). This detector includes a measuring cell, which is divided into cis- and trans- chambers by a silicon nitride chip (SiN structure) with a nanopore of 5 nm in diameter. To entrap a single HRP molecule into the nanopore, an electrode had been placed into the cis-chamber; HRP solution was added into this chamber after application of a negative voltage. The reaction of the HRP substrate, 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), oxidation by the enzyme molecule was performed in the presence of hydrogen peroxide. During this reaction, the functioning of a single HRP molecule, entrapped in the nanopore, was monitored by recording the time dependence of the ion current flowing through the nanopore. The approach proposed in our work is applicable for further studies of functioning of various enzymes at the level of single molecules, and this is an important step in the development of single-molecule enzymology.
Detection of low-copy proteins in proteomic studies: issues and solutions.
Archakov AI, Vavilov NE, Zgoda VG
Biomed Khim · 2024 Sep · PMID 39324198 · Publisher ↗
Detection of low-copy proteins in complex biological samples is one of the most important issues of modern proteomics. The main reason for inefficient detection of low protein concentrations is the insufficient sensitivi...
Detection of low-copy proteins in complex biological samples is one of the most important issues of modern proteomics. The main reason for inefficient detection of low protein concentrations is the insufficient sensitivity of mass spectrometric detectors and the high dynamic range of protein concentrations. In this study we have investigated the possibilities and limitations of a targeted mass spectrometric analysis using the reconstructed system of standard proteins UPS1 (Universal Proteomic Standard 1) as an example. The study has shown that the sensitivity of the method is affected by the concentration of target proteins of the UPS1 system, as well as by a high level of biological noise modelled by proteins of whole E. coli cell lysate. The limitations of the method have been overcome by concentrating and pre-fractionating the sample peptides in a reversed phase chromatographic system under alkaline elution conditions. Proteomic analysis of the biological sample (proteins of the human hepatocellular carcinoma cell line HepG2 encoded by genes of human chromosome 18) showed an increase in the sensitivity of the method as compared to the standard targeted mass spectrometric analysis. This culminated in registration of 94 proteins encoded by genes located on human chromosome18.
Clinical metabolomics: current state and prospects in Russia.
Lokhov PG, Balashova EE, Trifonova OP … +12 more , Maslov DL, Lokhov AP, Ponomarenko EA, Lisitsa AV, Ugrumov MV, Stilidi IS, Kushlinskii NE, Nikityuk DB, Tutelyan VA, Shestakova MV, Dedov II, Archakov AI
Biomed Khim · 2024 Sep · PMID 39324197 · Publisher ↗
Using analytical technologies it is possible now to measure the entire diversity of molecules even in a small amount of biological samples. Metabolomic technologies simultaneously analyze thousands of low-molecular subst...
Using analytical technologies it is possible now to measure the entire diversity of molecules even in a small amount of biological samples. Metabolomic technologies simultaneously analyze thousands of low-molecular substances in a single drop of blood. Such analytical performance opens new possibilities for clinical laboratory diagnostics, still relying on the measurement of only a limited number of clinically significant substances. However, there are objective difficulties hampering introduction of metabolomics into clinical practice. The Institute of Biomedical Chemistry (IBMC), consolidating the efforts of leading scientific and medical organizations, has achieved success in this area by developing a clinical blood metabogram (CBM). CBM opens opportunities to obtain overview on the state of the body with the detailed individual metabolic characteristics of the patient. A number of scientific studies have shown that the CBM is an effective tool for monitoring the state of the body, and based on the CBM patterns (signatures), it is possible to diagnose and monitor the treatment of many diseases. Today, the CBM creation determines the current state and prospects of clinical metabolomics in Russia. This article, dedicated to the 80th anniversary of IBMC, is a review of these achievements focused on a discussion of their implementation in clinical practice.
In silico and in cellulo approaches for functional annotation of human protein splice variants.
Kiseleva OI, Arzumanian VA, Kurbatov IY … +1 more , Poverennaya EV
Biomed Khim · 2024 Sep · PMID 39324196 · Publisher ↗
The elegance of pre-mRNA splicing mechanisms continues to interest scientists even after over a half century, since the discovery of the fact that coding regions in genes are interrupted by non-coding sequences. The vast...
The elegance of pre-mRNA splicing mechanisms continues to interest scientists even after over a half century, since the discovery of the fact that coding regions in genes are interrupted by non-coding sequences. The vast majority of human genes have several mRNA variants, coding structurally and functionally different protein isoforms in a tissue-specific manner and with a linkage to specific developmental stages of the organism. Alteration of splicing patterns shifts the balance of functionally distinct proteins in living systems, distorts normal molecular pathways, and may trigger the onset and progression of various pathologies. Over the past two decades, numerous studies have been conducted in various life sciences disciplines to deepen our understanding of splicing mechanisms and the extent of their impact on the functioning of living systems. This review aims to summarize experimental and computational approaches used to elucidate the functions of splice variants of a single gene based on our experience accumulated in the laboratory of interactomics of proteoforms at the Institute of Biomedical Chemistry (IBMC) and best global practices.
Nanowire-based biosensors for solving biomedical problems.
Goldaeva KV, Pleshakova TO, Ivanov YD
Biomed Khim · 2024 Sep · PMID 39324195 · Publisher ↗
The review considers modern achievements and prospects of using nanowire biosensors, principles of their operation, methods of fabrication, and the influence of the Debye effect, which plays a key role in improving the b...
The review considers modern achievements and prospects of using nanowire biosensors, principles of their operation, methods of fabrication, and the influence of the Debye effect, which plays a key role in improving the biosensor characteristics. Special attention is paid to the practical application of such biosensors for the detection of a variety of biomolecules, demonstrating their capabilities and potential in the detection of a wide range of biomarkers of various diseases. Nanowire biosensors also show excellent results in such areas as early disease diagnostics, patient health monitoring, and personalized medicine due to their high sensitivity and specificity. Taking into consideration their high efficiency and diverse applications, nanowire-based biosensors demonstrate significant promise for commercialization and widespread application in medicine and related fields, making them an important area for future research and development.
Biosensing platforms for DNA diagnostics based on CRISPR/Cas nucleases: towards the detection of nucleic acids at the level of single molecules in non-laboratory settings.
Khmeleva SA, Ptitsyn KG, Kurbatov LK … +4 more , Timoshenko OS, Suprun EV, Radko SP, Lisitsa AV
Biomed Khim · 2024 Sep · PMID 39324194 · Publisher ↗
The use of CRISPR/Cas nucleases for the development of DNA diagnostic systems in out-of-laboratory conditions (point-of-need testing, PONT) has demonstrated rapid growth in the last few years, starting with the appearanc...
The use of CRISPR/Cas nucleases for the development of DNA diagnostic systems in out-of-laboratory conditions (point-of-need testing, PONT) has demonstrated rapid growth in the last few years, starting with the appearance in 2017-2018 of the first diagnostic platforms known as DETECTR and SHERLOCK. The platforms are based on a combination of methods of nucleic acid isothermal amplification with selective CRISPR/Cas detection of target amplicons. This significantly improves the sensitivity and specificity of PONT, making them comparable with or even superior to the sensitivity and specificity of polymerase chain reaction, considered as the "gold standard" of DNA diagnostics. The review considers modern approaches to the coupling of CRISPR/Cas detection using Cas9, Cas12a, Cas12b, Cas13a, Cas14, and Cas3 nucleases to various methods of nucleic acid isothermal amplification, with an emphasis on works in which sensitivity at the level of single molecules (attomolar and subattomolar concentrations of the target) is achieved. The properties of CRISPR/Cas nucleases used for targeted DNA diagnostics and the features of methods of nucleic acid isothermal amplification are briefly considered in the context of the development of diagnostic biosensing platforms. Special attention is paid to the most promising directions for the development of DNA diagnostics using CRISPR/Cas nuclease.
AFM-fishing technology for protein detection in solutions.
Pleshakova TO, Ershova MO, Valueva AA … +3 more , Ivanova IA, Ivanov YD, Archakov AI
Biomed Khim · 2024 Sep · PMID 39324193 · Publisher ↗
The review considers the possibility of using atomic force microscopy (AFM) as a basic method for protein detection in solutions with low protein concentrations. The demand for new bioanalytical approaches is determined...
The review considers the possibility of using atomic force microscopy (AFM) as a basic method for protein detection in solutions with low protein concentrations. The demand for new bioanalytical approaches is determined by the problem of insufficient sensitivity of systems used in routine practice for protein detection. Special attention is paid to demonstration of the use in bioanalysis of a combination of AFM and fishing methods as an approach of concentrating biomolecules from a large volume of the analyzed solution on a small surface area.
Fundamentals of protein chemistry at the Institute of Biomedical Chemistry.
Kolesnichenko AV, Pleshakova TO
Biomed Khim · 2024 Sep · PMID 39324192 · Publisher ↗
Eighty years ago, the Institute of Biomedical Chemistry (IBMC) initially known as the Institute of Biological and Medical Chemistry of the Academy of Sciences of the USSR was founded. During the first decades significant...
Eighty years ago, the Institute of Biomedical Chemistry (IBMC) initially known as the Institute of Biological and Medical Chemistry of the Academy of Sciences of the USSR was founded. During the first decades significant studies were performed; they not only contributed to a deeper understanding of biochemical processes in the living organisms, but also laid the foundation for further development of these fields. The main directions of IBMC were focused on studies of structures of enzymes (primarily various proteases), their substrates and inhibitors, the role of enzymes of carbohydrate metabolism in the development of pathologies, study of the mechanisms of hydrolytic and oxidative-hydrolytic transformation of organic compounds, studies of connective tissue proteins, including collagens, study of amino acid metabolism. It is difficult to find papers from that period in current online literature databases, so this review will help to understand the value of studies performed at IBMC during the first 40 years after its organization, as well as their impact on modern research.
Bioinformatic identification of proteins with altered PTM levels in a mouse line established to study the mechanisms of the development of fibromuscular dysplasia.
Voronina AI, Miroshnichenko YV, Skvortsov VS
Biomed Khim · 2024 Aug · PMID 39239899 · Publisher ↗
Data from a mass spectrometry experiment of a mouse line developed to study the mechanisms of fibromuscular dysplasia and deposited by d'Escamard et al. in ProteomeXchange (PXD051750) have been analyzed. Identification o...
Data from a mass spectrometry experiment of a mouse line developed to study the mechanisms of fibromuscular dysplasia and deposited by d'Escamard et al. in ProteomeXchange (PXD051750) have been analyzed. Identification of peptides with post-translational modifications (PTMs) was repeated using more stringent conditions than in the original work. The following modifications were considered during analysis of changes in the PTM levels in experimental and control groups of mice: acetylation of lysine residue and N-terminal protein peptide, ubiquitination of lysine residue, phosphorylation of serine, threonine and tyrosine residues, and deamination of asparagine and glutamine residues. The multistage analysis resulted in selection of 23 proteins with PTMs for which different levels of modification between experimental and control groups could be assumed. These included six proteins with N-terminal protein acetylation, which were particularly interesting: P80318 (T-complex protein 1 subunit gamma), P43274 (Histone H1.4), P97823 (Acyl-protein thioesterase 1), P63242 (Eukaryotic translation initiation factor 5A-1), Q3UMT1 (Protein phosphatase 1 regulatory subunit 12C), Q9D8Y0 (EF-hand domain-containing protein D2). Thus, repeated bioinformatic analysis of the data deposited in the specialized databases resulted in detection of changes in the level of N-terminal acetylation of proteins that might be functionally significant in the mechanisms underlying the development of fibromuscular dysplasia.
Internalization of extracellular vesicles of cancer patients by peripheral blood mononuclear cells during polychemotherapy: connection with neurotoxicity.
Yunusova NV, Kaigorodova EV, Panfilova PA … +5 more , Popova NO, Udintseva IN, Kondakova IV, Svarovsky DA, Goldberg VE
Biomed Khim · 2024 Aug · PMID 39239898 · Publisher ↗
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 ther...
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.
The neuroprotective effect of isatin in the rotenone-induced model of parkinonism in rats: the study of delayed effects.
Buneeva OA, Kapitsa IG, Kazieva LS … +3 more , Vavilov NE, Zgoda VG, Medvedev AE
Biomed Khim · 2024 Aug · PMID 39239897 · Publisher ↗
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 wid...
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).
Apoptotic endonuclease EndoG induces alternative splicing of Caspase-2.
Zhdanov DD, Gladilina YA, Shisparenok AN
Biomed Khim · 2024 Aug · PMID 39239896 · Publisher ↗
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 enzymat...
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.
Molecular mechanisms of the regulatory action of high-density lipoproteins on the endothelial function.
Poteryaeva ON, Usynin IF
Biomed Khim · 2024 Aug · PMID 39239895 · Publisher ↗
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)...
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.
MicroRNAs as promising diagnostic and prognostic markers for the human genitourinary cancer.
Kugaevskaya EV, Timoshenko OS, Gureeva TA … +2 more , Radko SP, Lisitsa AV
Biomed Khim · 2024 Aug · PMID 39239894 · Publisher ↗
Genitourinary cancer (GUC) represents more than one fifth of all human cancers. This makes the development of approaches to its early diagnosis an important task of modern biomedicine. Circulating microRNAs, short (17-25...
Genitourinary cancer (GUC) represents more than one fifth of all human cancers. This makes the development of approaches to its early diagnosis an important task of modern biomedicine. Circulating microRNAs, short (17-25 nucleotides) non-coding RNA molecules found in human biological fluids and performing a regulatory role in the cell, are considered as promising diagnostic and prognostic biomarkers of cancers, including GUC. In this review we have considered the current state of research aimed at assessing microRNAs as biomarkers of such human GUC types as malignant tumors of the bladder, kidney, prostate, testicles, ovaries, and cervix. A special attention has been paid to studies devoted to the identification of microRNAs in urine as a surrogate "liquid biopsy" that may provide the simplest and cheapest approach to mass non-invasive screening of human GUC. The use of microRNA panels instead of single types of microRNA generally leads to higher sensitivity and specificity of the developed diagnostic tests. However, to date, work on the microRNAs assessment as biomarkers of human GUC is still of a research nature, and the further introduction of diagnostic tests based on microRNAs into practice requires successful clinical trials.
Novel spiro[indoline-3,2'thiazolo[5,4-e]pyrimido[1,2-a] pyrimidine] derivatives as possible anti-dermatophytic and anti-candidiasis agent.
Sharma G, Sharma R
Biomed Khim · 2024 Jun · PMID 38940208 · Publisher ↗
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...
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.
Dynamics in cortisol levels in Danio rerio fish under the influence of a synthetic analog of kisspeptin 1.
Nuzhnova AA, Kostina MI, Blazhenko AA
Biomed Khim · 2024 Jun · PMID 38940207 · Publisher ↗
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...
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.
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