Russian Journal of Bioorganic Chemistry最新文献

{"title":"Study of the Antiproliferative Activity of a Humanized Antibody to the Cancer-Testis Antigen PRAME","authors":"M. V. Larina,&nbsp;Yu. P. Finashutina,&nbsp;N. A. Kravchuk,&nbsp;V. A. Misyurin,&nbsp;V. N. Novoseletsky,&nbsp;D. S. Balabashin,&nbsp;O. N. Solopova,&nbsp;D. V. Sokolova,&nbsp;V. S. Pokrovsky,&nbsp;D. A. Dolgikh,&nbsp;T. K. Aliev,&nbsp;A. V. Misyurin,&nbsp;M. P. Kirpichnikov","doi":"10.1134/S1068162025603799","DOIUrl":"10.1134/S1068162025603799","url":null,"abstract":"<p><b>Objective:</b> The PRAME antigen (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen expressed in various tumor types, represents an attractive target for targeted cancer therapy. <b>Methods:</b> A humanized antibody (6H8Hu) was developed based on the monoclonal antibody 6H8 specific to the PRAME protein. The antibody was produced in CHO cells. Results and Discussion: The humanized antibody retains the high affinity of the parental mAb to the antigen (1.2 nM), binds to both recombinant and native PRAME protein, inhibits the proliferation of the PRAME-positive human melanoma cell line Mel Ibr, and suppresses tumor nodule growth <i>in vivo</i> to a degree comparable to that of the murine antibody 6H8 and the cytostatic agent melphalan. <b>Conclusions:</b> The humanized antibody 6H8Hu is a promising candidate for targeted therapy against PRAME-positive melanoma, showing potential comparable to murine antibodies and conventional cytotoxic treatments.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2089 - 2099"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coumarins as Emerging Agents in Neurodegenerative Disease Management","authors":"Atyaf Talal Mahmood,&nbsp;Islam Khalid Kamal,&nbsp;Yasser Fakri Mustafa","doi":"10.1134/S1068162025600333","DOIUrl":"10.1134/S1068162025600333","url":null,"abstract":"<p>Neurodegenerative diseases (NDs), including Alzheimer’s, Parkinson’s, and Huntington’s diseases, are debilitating disorders characterized by progressive neuronal loss. These conditions are challenging to treat due to their multifactorial etiology, including genetic, environmental, and oxidative stress-related factors. Recent studies indicate that coumarins (CONs), a class of naturally occurring phytochemicals, may exhibit promising neuroprotective effects against NDs. These compounds demonstrate multiple biological activities, such as neuronal protection, anti-inflammatory effects, and mitigation of oxidative stress, by modulating the underlying molecular pathways. This review summarizes the neuroprotective mechanisms of CONs, with a focus on preclinical studies demonstrating their efficacy in reducing oxidative stress and promoting neuronal survival. Additionally, the review discusses the structural diversity of CONs, highlighting its impact on pharmacokinetics and bioavailability. Moreover, it addresses the modulation of signaling pathways, including MAPK and PI3K/Akt, which contribute to neuroregeneration and neuroprotection. Despite encouraging preclinical evidence, the clinical translation of CON-based therapies faces significant challenges, including poor bioavailability, insufficient clinical trials, and variability in therapeutic responses. Future research should prioritize rigorous clinical studies, interdisciplinary collaboration, and the design of CON derivatives with improved pharmacokinetic properties. Overall, this review underscores the potential of natural compounds such as CONs in developing innovative neurotherapeutic strategies for combating neurodegenerative diseases.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2228 - 2246"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of STK11 Mutation in the LLC1 Mouse Lewis Lung Anedonacrcinoma Line on Sensitivity to Particle Radiotherapy","authors":"E. A. Gantsova,&nbsp;I. V. Arutyunyan,&nbsp;A. G. Soboleva,&nbsp;K. M. Shakirova,&nbsp;E. Yu. Kananykhina,&nbsp;D. V. Balchir,&nbsp;P. A. Vishnyakova,&nbsp;V. O. Saburov,&nbsp;K. B. Gordon,&nbsp;T. Kh. Fathkudinov","doi":"10.1134/S106816202560196X","DOIUrl":"10.1134/S106816202560196X","url":null,"abstract":"<p><b>Objective:</b> Lung adenocarcinoma is a malignant tumor, which is the most common type of non-small cell lung cancer. The low efficiency of standard methods of treatment of lung adenocarcinoma with mutation of the <i>Stk11</i> tumor suppressor gene is a serious problem in clinical practice. The search for and improvement of new therapeutic approaches to this disease remains an urgent task of modern biomedicine. The aim of the work was to create an <i>in vitro</i> model of lung cancer based on the LLC1 cell line with knockout of the <i>Stk11</i> gene to assess the sensitivity of mutant cells to various types of radiation therapy, including irradiation with photons, protons and neutrons. <b>Methods:</b> The main methods used were CRISPR/Cas9 genome editing technologies to obtain mutant clones, laser cell sorting, PCR analysis to confirm the deletion, as well as an assessment of the viability, proliferation (metabolic tests, <i>Mki67</i> marker expression), apoptosis induction (annexin V-PI method), and <i>Pten</i> gene expression after cell irradiation with a dose of 2 Gy. <b>Results and Discussion:</b> As a result, heterozygous mutant lines LLC1-STK11-Mut were obtained. Cell irradiation revealed that in Stk11 mutant cells, radio-induced growth stimulation persisted longer than in wild-type cells, and a significant increase in the proportion of late apoptotic and necrotic cells was observed. At the same time, <i>Mki67</i> expression temporarily decreased after irradiation, but quickly recovered in mutant cells, which indicates their higher radioresistance. Unlike wild-type cells, the expression level of the <i>Pten</i> gene in mutant cells did not change significantly after irradiation. <b>Conclusions:</b> The <i>Stk11</i> mutation contributes to the formation of radioresistance in tumor cells by triggering various adaptation mechanisms. The obtained <i>in vitro</i> model can be used for the further study of radioresistance and development of new approaches to the therapy of tumors with the <i>Stk11</i> mutation.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1970 - 1981"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLS Peptide Improves the Efficiency of pDNA Delivery into Eukaryotic Cells Mediated by Cationic Liposomes","authors":"E. V. Shmendel,&nbsp;O. V. Markov,&nbsp;M. A. Zenkova,&nbsp;M. A. Maslov","doi":"10.1134/S1068162025602010","DOIUrl":"10.1134/S1068162025602010","url":null,"abstract":"<p><b>Objective:</b> The main limitation of DNA use in the therapy of genetic and acquired diseases is the development of its effective delivery systems. The aim of this work is to evaluate the effect of the NLS peptide (CKRPAATKKAGQAKKKK) on the efficiency of pDNA delivery by conventional and multifunctional cationic liposomes into eukaryotic cells. <b>Methods:</b> The effect of the NLS peptide on the efficiency of pDNA binding in the presence and absence of cationic liposomes was studied using gel electrophoresis and dynamic laser light scattering. Complexes of cationic liposomes were formed with pDNA in the presence or absence of the NLS peptide at different component ratios (N/P). The transfection efficiency of the complexes in HEK 293 and KB-3-1 cells was studied using flow cytometry. <b>Results and Discussion:</b> In the case of using NLS for targeted delivery of pDNA (at low N/P ratios) into KB-3-1 cells, the most optimal systems are multifunctional cationic liposomes F2P2 containing 2 mol % folate and 2 mol % PEG-lipid Р800. At higher N/P ratios in the case of accumulation of liposome complexes with pDNA/NLS, the most optimal systems were conventional cationic liposomes L for HEK 293 cells and PEGylated liposomes P4 containing 4% PEG-lipid P800 for KB-3-1 cells. <b>Conclusions:</b> The obtained data can be used to solve the problem of efficient delivery of pDNA into eukaryotic cells and increase the efficiency of protein expression by 1.5–2 times.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2014 - 2021"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antibacterial Activity, Acute Toxicity, and Antibacterial Mechanism of 2,6-Dimethyl-4-aminophenol Hydrochloride","authors":"Kezhuang Wang,&nbsp;Chuanjin Wang,&nbsp;Chengguo Sun","doi":"10.1134/S1068162024606499","DOIUrl":"10.1134/S1068162024606499","url":null,"abstract":"<p><b>Objective:</b> The problem of bacterial resistance has attracted increasing attention, and the development of novel antibacterial agents is paramount in addressing this challenge. 2,6-Dimethyl-4-aminophenol hydrochloride (DMAPH) is a known compound with several reported applications, but no antibacterial effects have been described to date. The objective of this study was to investigate the antibacterial activity of DMAPH, examine its mechanism of action against <i>S. aureus</i>, and evaluate its oral acute toxicity in mice to assess its potential as an antibacterial agent. <b>Methods:</b> The antibacterial activity of DMAPH was evaluated against six bacterial species. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The effects of DMAPH on cell membrane and cell wall permeability of <i>S. aureus</i> were examined through the leakage of intracellular components (nucleic acids, proteins, potassium ions, and alkaline phosphatase). Oral acute toxicity was assessed in mice, and the LD₅₀ value was calculated. <b>Results and Discussion:</b> DMAPH exhibited significant antibacterial activity, with the strongest inhibition observed against <i>S. aureus</i> and <i>S. epidermidis</i>. MIC and MBC values were 4.88 and 9.76 μg/mL, respectively. DMAPH disrupted the cell membrane and wall integrity of <i>S. aureus</i>, leading to leakage of cellular components and bacterial death. The oral acute toxicity test in mice yielded an LD₅₀ value of 1052 mg/kg (95% confidence interval: 972–1139 mg/kg), indicating low toxicity. These findings suggest that DMAPH is a promising antibacterial agent with a membrane-targeting mechanism. <b>Conclusions:</b> DMAPH demonstrates notable antibacterial activity and low acute toxicity, supporting its potential as a candidate for antibacterial drug development. However, current data are insufficient to confirm its <i>in vivo</i> efficacy, and further studies are required to validate its therapeutic potential.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2142 - 2151"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Antidiabetic Screening of Chalcone-Based N-Acetyl Pyrazoles","authors":"N. Iqbal,&nbsp;W. Rehman,&nbsp;O-U-R Abid,&nbsp;L. Rasheed,&nbsp;H. Sarfaraz,&nbsp;Y. Khan,&nbsp;A. F. AlAsmari,&nbsp;F. Alasmari,&nbsp;M. Khan","doi":"10.1134/S1068162025600084","DOIUrl":"10.1134/S1068162025600084","url":null,"abstract":"<p><b>Objective:</b> To synthesize chalcone-based <i>N</i>-acetyl pyrazoles and evaluate their antidiabetic activity. <b>Methods:</b> A total of 19 pyrazole analogues based on the chalcone scaffold were synthesized <i>via</i> reflux and screened for α-glucosidase inhibitory activity using acarbose as a positive control (IC₅₀ = 12.50 ± 0.20 μM). <b>Results and Discussion:</b> The compounds generally exhibited excellent inhibitory activity, with some exceptions. Compounds (<b>10</b>), (<b>13</b>), (<b>14</b>), (<b>17</b>), and (<b>18</b>) were the most potent compared to standard acarbose. The inhibitory potentials of selected analogues were as follows: (<b>2j</b>) 10.66 ± 0.88 μM; (<b>2m</b>) 9.81 ± 0.66 μM; (<b>2n</b>) 4.12 ± 0.12 μM; (<b>2q</b>) 6.22 ± 0.90 μM; (<b>2r</b>) 3.60 ± 0.98 μM. The remaining 14 analogues showed moderate to satisfactory activity. <b>Conclusions:</b> Structure–activity relationship (SAR) analysis indicated that the presence of electron-donating and electron-withdrawing groups, particularly at the <i>ortho</i> and <i>para</i> positions of the phenyl ring, enhanced inhibitory activity. Structural confirmation was carried out using various spectroscopic techniques, including ¹H, ¹³C NMR, and HR-EI-MS.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2205 - 2216"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, In Vitro and In Vivo Antifungal Activities of Novel Coumarin–Tryptophan Conjugates","authors":"Neha Tiwari,&nbsp;Ankita Kumari,&nbsp;Saurabh Sharma,&nbsp;Vaishali Raghuvanshi,&nbsp;Gunjan Uttam,&nbsp;Vineeta Singh,&nbsp;Karuna Singh,&nbsp;Diksha Katiyar","doi":"10.1134/S1068162024607407","DOIUrl":"10.1134/S1068162024607407","url":null,"abstract":"<p><b>Objective:</b> Persistent fungal infections, especially those caused by <i>Candida</i> spp., pose a serious health risk to humans. Treatment of these infections is highly challenging due to the spread of resistance to first-line antifungal drugs. Therefore, the identification and development of novel antifungal agents are in great demand. In this study, a series of coumarin–tryptophan conjugates were synthesized and their antifungal activities evaluated. <b>Methods:</b> <i>In vitro</i> antifungal activities of compounds (<b>IVa–IVe</b>) were determined by the minimum inhibitory concentration (MIC) method. The <i>in vivo</i> activity of the most active compound, (<b>IVe</b>), was assessed using a murine model of dermal candidiasis. Docking studies were performed using the AutoDock 4.0 software package. <b>Results and Discussion:</b> Several compounds exhibited broad-spectrum activity against the tested strains, with favorable MIC values in the range of 6.25–25 µg/mL. Compound (<b>IVe</b>) showed significant antifungal activity with an MIC of 6.25 µg/mL against <i>A. flavus</i> and <i>C. albicans</i>. In the murine dermal candidiasis model, (<b>IVe</b>) reduced the fungal burden in nearly all vital organs of the experimental animals and demonstrated therapeutic healing effects on ulcers induced by <i>C. albicans</i> infection. Molecular docking results indicated that these compounds have potential as antifungal agents. Evaluation of drug-like properties of compounds (<b>IVa–IVe</b>) using the SwissADME web tool revealed that these molecules possess favorable druggability profiles. <b>Conclusions:</b> Compound (<b>IVe</b>), having shown excellent antifungal activity, can be considered a promising antifungal agent for further investigation.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2170 - 2184"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Bacterial Expression System for Producing 15N/13C-Labeled Neuroglobin and Cytochrome C","authors":"M. A. Semenova,&nbsp;O. M. Smirnova,&nbsp;V. V. Britikov,&nbsp;E. V. Britikova,&nbsp;A. P. Khodnenko,&nbsp;Y. V. Bershatskii,&nbsp;A. A. Ignatova,&nbsp;E. V. Bocharov,&nbsp;M. P. Kirpichnikov,&nbsp;D. A. Dolgikh,&nbsp;R. V. Chertkova","doi":"10.1134/S1068162025602083","DOIUrl":"10.1134/S1068162025602083","url":null,"abstract":"<p><b>Objective:</b> Neuroglobin and cytochrome <i>c</i> are hemoproteins whose interaction is suggested to play an important role in preventing apoptotic cell death of neurons. Therefore, studying the molecular mechanism of neuroglobin-cytochrome <i>c</i> complex formation is of significant interest. Given their small hydrodynamic size and high water solubility, these hemoproteins are well-suited for NMR spectroscopy studies, provided they are isotopically labeled with ¹³C and ¹⁵N. The aim of this work was to develop a highly efficient system for the production of ¹⁵N/¹³C-labeled human neuroglobin and cytochrome <i>c</i>. <b>Methods:</b> The corresponding producer strains were constructed, and optimal cultivation conditions were selected, including incubation temperature and duration, medium composition, and the concentration of the expression inducer. The purified ¹⁵N-labeled hemoproteins were analyzed using UV-Vis, circular dichroism (CD), and ¹H-¹⁵N HSQC NMR spectroscopy. <b>Results and Discussion:</b> Far- and near-UV CD spectroscopy analysis results indicated that the secondary structure composition of ¹⁵N-neuroglobin is consistent with the theoretical prediction, and the heme orientation within the molecules is predominantly canonical. According to the 2D ¹H-¹⁵N HSQC NMR spectra of human neuroglobin and cytochrome <i>c</i>, the proteins are folded into their native conformation, characterized by a predominantly α-helical structure. <b>Conclusions:</b> An effective system for producing isotopically labeled human neuroglobin and cytochrome <i>c</i> has been developed. This system enables the preparation of high-purity ¹⁵N/¹³C-labeled proteins suitable for structure and dynamics studies using modern high-resolution NMR spectroscopy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2077 - 2088"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Finger Viper Toxins: cDNA Cloning and Expression in E. coli Using a Chimeric (Hybrid) Construction with a SUMO Fusion Partner Protein","authors":"D. A. Sukhov,&nbsp;L. O. Ojomoko,&nbsp;I. V. Shelukhina,&nbsp;M. V. Vladykina,&nbsp;V. Yu. Kost,&nbsp;R. Kh. Ziganshin,&nbsp;O. V. Geraskina,&nbsp;S. V. Balandin,&nbsp;T. V. Ovchinnikova,&nbsp;V. I. Tsetlin,&nbsp;Yu. N. Utkin","doi":"10.1134/S1068162025602526","DOIUrl":"10.1134/S1068162025602526","url":null,"abstract":"<p><b>Objective:</b> Three-finger toxins (TFTs) form one of the most abundant families of toxins in snake venoms. TFTs are characteristic of most elapid venoms, but have almost never been found in viper venoms. The aim of this work was to obtain viper TFTs, the mRNAs of which are present in the viper venom glands, and to study their properties. <b>Methods:</b> PCR was used to amplify cDNA encoding TFTs from viper venom glands. The TFTs were then heterologously expressed in <b><i>E. coli</i></b> as plant SUMO fusion proteins, purified by affinity chromatography, and cleaved using the plant protease BdSENP1, followed by final chromatographic purification. <b>Results and Discussion:</b> Using the venom glands of the vipers <i>Vipera nikolskii</i> and <i>V. berus</i>, 21 cDNA clones encoding this group of toxins were obtained. The amino acid sequences of nine TFTs were deduced from their corresponding cDNA sequences. All viper TFTs belong to the group of nonconventional toxins, and their sequences contain 9 cysteine residues. The TFT encoded by one of the transcripts was obtained. Analysis of its biological activity showed that this toxin is a weak antagonist of neuronal nicotinic acetylcholine receptors of the α7 and α3β2 subtypes. Using a SUMO fusion protein approach, an attempt was made to obtain the TFT Aze-2 of the viper <i>Azemiops feae</i>, which was identified in minimal quantities in the venom of this snake. However, this method failed to yield a toxin matching the exact mass of Aze-2. <b>Conclusions:</b> As a result of the work, the amino acid sequences of 9 viper TFTs were established, one of which was obtained by gene expression in <i>E. coli</i> cells and showed the ability to interact with neuronal nicotinic acetylcholine receptors of the α7 and α3β2 subtypes.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2064 - 2076"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome Analysis of Zyxin Cytoskeletal Protein Levels: Influence on Metabolism and Signaling Pathways in a Model of Xenopus laevis Embryos","authors":"E. A. Parshina,&nbsp;A.G. Zaraisky,&nbsp;N.Y. Martynova","doi":"10.1134/S1068162025601983","DOIUrl":"10.1134/S1068162025601983","url":null,"abstract":"<p><b>Objective:</b> Zyxin is a cytoskeletal protein that plays a crucial role in the assembly and restoration of actin filaments. Research conducted in our laboratory utilizing a <i>Xenopus laevis</i> embryo model has demonstrated that zyxin is significantly involved in gene expression regulation and cell differentiation processes. In recent years, we have acquired compelling data suggesting the capacity of this mechanosensitive protein to participate in mechanisms that link morphogenetic movements to the expression of genes responsible for axial structure formation and stem cell maintenance during embryogenesis. In this article, we present the latest findings from our investigation into genes, signaling pathways, and biological processes regulated in conjunction with zyxin activity. <b>Methods:</b> High-throughput mRNA sequencing was performed on RNA pools from <i>X. laevis</i> embryonic cells at the neurula stage. This analysis included samples with normal zyxin function, as well as those with increased or suppressed zyxin function induced by morpholino oligomers (MO). <b>Results and Discussion:</b> Bioinformatics analysis enabled identification of zyxin-dependent signaling pathways and biological processes essential for embryogenesis from a comprehensive gene dataset. Our results indicate that zyxin expression suppression leads to alterations in expression profiles of genes involved in more than 16 distinct signaling cascades and impacts 27 biological processes. The most pronounced effects were observed in processes associated with morphogenesis and gene expression regulation. <b>Conclusions:</b> These findings hold significant fundamental implications. Investigating zyxinʼs role in transducing mechanical stimuli to gene expression machinery is vital for understanding coordination between biomechanics and differentiation during embryogenesis. Furthermore, this research may facilitate utilization of zyxin as a potential diagnostic marker for various diseases.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1990 - 1999"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}