Acta Naturae最新文献

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Alterations in the Expression of Proprotein Convertase Genes in Human Esophagus Squamous Cell Carcinomas. 人食管鳞状细胞癌中蛋白转化酶基因表达的改变。
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27437
A A Komissarov, M V Zinovyeva, A V Sass, T V Vinogradova, S I Koshechkin, V V Demkin, I B Zborovskaya, S V Kostrov, I V Demidyuk
{"title":"Alterations in the Expression of Proprotein Convertase Genes in Human Esophagus Squamous Cell Carcinomas.","authors":"A A Komissarov, M V Zinovyeva, A V Sass, T V Vinogradova, S I Koshechkin, V V Demkin, I B Zborovskaya, S V Kostrov, I V Demidyuk","doi":"10.32607/actanaturae.27437","DOIUrl":"https://doi.org/10.32607/actanaturae.27437","url":null,"abstract":"<p><p>Proprotein convertases (PCs) constitute an enzyme family that includes nine highly specific human subtilisin-like serine proteases. It is known that the PCs mRNA levels vary in tumors, and that these proteases are involved in carcinogenesis. Thus, PCs may be considered as potential markers for typing and predicting the course of the disease, as well as potential targets for therapy. We used quantitative real-time PCR to evaluate the expression levels of PC genes in the paired samples of tumor and adjacent normal tissues derived from 19 patients with esophageal squamous cell carcinomas. We observed a significant enrichment of <i>PCSK6</i>, <i>PCSK9</i>, <i>MBTPS1</i>, and <i>FURIN</i> mRNAs in the tumor tissue, which may be indication of the involvement of these PCs in the development and progression of esophageal cancers. Additionally, cluster analysis of PC expression alteration patterns in tumor compared to normal adjacent tissues (esophageal and previously analyzed lung tissue samples) revealed a limited set of scenarios for the changes in PC expression. These scenarios are implemented during malignant transformation of lung and esophagus cells, as well as, probably, the cells of other organs. These findings indicate that PC genes may be important markers of human cancers.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"64-70"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Induction of Chaperone Synthesis in Human Neuronal Cells Blocks Oxidative Stress-Induced Aging. 诱导神经细胞伴侣蛋白合成阻断氧化应激诱导的衰老。
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27531
E A Dutysheva, L S Kuznetcova, I A Utepova, B A Margulis, I V Guzhova, V F Lazarev
{"title":"Induction of Chaperone Synthesis in Human Neuronal Cells Blocks Oxidative Stress-Induced Aging.","authors":"E A Dutysheva, L S Kuznetcova, I A Utepova, B A Margulis, I V Guzhova, V F Lazarev","doi":"10.32607/actanaturae.27531","DOIUrl":"https://doi.org/10.32607/actanaturae.27531","url":null,"abstract":"<p><p>Oxidative stress accompanies many pathologies that are characterized by neuronal degradation leading to a deterioration of the disease. The main causes are the disruption of protein homeostasis and activation of irreversible processes of cell cycle disruption and deterioration of cellular physiology, leading to senescence. In this paper, we propose a new approach to combating senescence caused by oxidative stress. This approach is based on the use of a low-molecular inducer of chaperone synthesis, one of the cell protective systems regulating proteostasis and apoptosis. We present data demonstrating the ability of the pyrrolylazine derivative PQ-29 to induce chaperone accumulation in human neuronal cells and prevent oxidative stress-induced aging.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"29-35"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Galanin Reduces Myocardial Ischemia/Reperfusion Injury in Rats with Streptozotocin Diabetes. 甘丙肽减轻链脲佐菌素糖尿病大鼠心肌缺血/再灌注损伤。
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27506
I M Studneva, L I Serebryakova, O M Veselova, I V Dobrokhotov, M E Palkeeva, D V Avdeev, A S Molokoedov, M V Sidorova, O I Pisarenko
{"title":"Galanin Reduces Myocardial Ischemia/Reperfusion Injury in Rats with Streptozotocin Diabetes.","authors":"I M Studneva, L I Serebryakova, O M Veselova, I V Dobrokhotov, M E Palkeeva, D V Avdeev, A S Molokoedov, M V Sidorova, O I Pisarenko","doi":"10.32607/actanaturae.27506","DOIUrl":"https://doi.org/10.32607/actanaturae.27506","url":null,"abstract":"<p><p>Most clinical studies confirm the negative impact diabetes mellitus (DM) has on the course and outcome of cardiovascular complications caused by a myocardial ischemia-reperfusion injury (IRI). In this regard, the search for new approaches to IRI treatment in diabetic myocardium is of undeniable value. The aim of this work was to study the effect of galanin (G) on the size of myocardial infarct (MI), on mitochondrial functions, and on the energy state in the area at risk (AAR) in rats with type 1 diabetes mellitus (DM1) subjected to regional myocardial ischemia and reperfusion. Rat G was obtained by solid-phase synthesis using the Fmoc strategy and purified by HPLC. DM1 was induced by streptozotocin administration. Myocardial IRI was modeled by occlusion of the left anterior descending coronary artery and subsequent reperfusion. G at a dose of 1 mg/kg was administered intravenously before reperfusion. G decreased MI size and plasma creatine kinase MB (CK-MB) activity in DM rats by 40 and 28%, respectively. G injection improved mitochondrial respiration in saponin-skinned fibers in the AAR: namely, the maximal ADP-stimulated state 3, respiratory control, and the functional relationship between the mitochondrial CK-MB and oxidative phosphorylation. G provided significantly higher ATP levels, total adenine nucleotide pool, and adenylate energy charge of cardiomyocytes. It also reduced total creatine loss in myocardial AAR in DM rats. The results suggest there is a possibility of therapeutic use of G in myocardial IRI complicated by DM1.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"78-86"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Toxin-Producing Ability of Fusarium Proliferatum Strains Isolated from Grain. 粮食中增殖镰刀菌产毒能力的研究。
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27546
O P Gavrilova, A S Orina, T Yu Gagkaeva, N N Gogina
{"title":"The Toxin-Producing Ability of Fusarium Proliferatum Strains Isolated from Grain.","authors":"O P Gavrilova, A S Orina, T Yu Gagkaeva, N N Gogina","doi":"10.32607/actanaturae.27546","DOIUrl":"https://doi.org/10.32607/actanaturae.27546","url":null,"abstract":"<p><p>The widespread fungus <i>Fusarium proliferatum</i> can infect numerous plant species and produce a range of mycotoxins, the amount of which can vary significantly. Twelve <i>F. proliferatum</i> sensu lato strains isolated from six wheat, four oat, and two maize grain samples were analyzed. The strains were identified through a phylogenetic analysis of nucleotide sequences derived from gene fragments of the translation elongation factor EF-1α, β-tubulin, and RNA polymerase II second subunit. The mating types of the strain were determined by allele-specific PCR. Secondary toxic metabolite production by the strains was quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). All twelve <i>Fusarium</i> strains formed a distinct clade alongside the <i>F. proliferatum</i> reference strains, thereby confirming the taxonomic identification. Only one idiomorph at the MAT locus in each <i>F. proliferatum</i> strain was found, indicative of heterothallic mating. The frequency of the MAT1-1 idiomorph was double that of the MAT1-2 idiomorph. The active biosynthesis of fumonisins B1 (71-6175 mg/kg), B2 (12-2661 mg/kg), and B3 (6-588 mg/kg), significant beauvericin (64-455 mg/kg), and trace amounts of moniliformin (12-6565 μg/kg) were identified across all examined <i>F. proliferatum</i> strains.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"20-28"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pro-inflammatory Cytokines, Ferroptosis, and Cancer. 促炎细胞因子,铁下垂和癌症。
IF 1.5 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27547
A A Vartanian, V S Kosorukov
{"title":"Pro-inflammatory Cytokines, Ferroptosis, and Cancer.","authors":"A A Vartanian, V S Kosorukov","doi":"10.32607/actanaturae.27547","DOIUrl":"10.32607/actanaturae.27547","url":null,"abstract":"<p><p>Ferroptosis, iron-dependent regulated cell death, is induced by the polyunsaturated fatty acid peroxidation of membrane phospholipids and is controlled by glutathione peroxidase 4. In recent years, convincing evidence has emerged, demonstrating a close relationship between chemo-, radio-, immuno-, and targeted therapy resistance and ferroptosis resistance. In this review, we discuss the basic principles of ferroptosis in cancer. Considerable attention is paid to the formation of an immunosuppressive tumor microenvironment. The main focus is centered on the involvement of the excessive, chronic production of pro-inflammatory cytokines in ferroptosis resistance development in tumors.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"4-10"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Parameters of Long-Term Humoral Immunity Induced by a Single Injection of the Sputnik Light Vaccine Among Noninfected Volunteers and Those Infected with SARS-CoV-2. 非感染志愿者和SARS-CoV-2感染者单次注射Sputnik轻型疫苗长期体液免疫参数的研究
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27529
F M Izhaeva, A I Tukhvatulin, A S Dzharullaeva, I V Dolzhikova, O V Zubkova, D V Shcheblyakov, N L Lubenets, E A Smolyarchuk, T G Zubkova, A S Erokhova, I M Cherenkova, K M Bukhtin, O Popova, N M Tukhvatulina, B S Naroditsky, D Y Logunov, A L Gintsburg
{"title":"The Parameters of Long-Term Humoral Immunity Induced by a Single Injection of the Sputnik Light Vaccine Among Noninfected Volunteers and Those Infected with SARS-CoV-2.","authors":"F M Izhaeva, A I Tukhvatulin, A S Dzharullaeva, I V Dolzhikova, O V Zubkova, D V Shcheblyakov, N L Lubenets, E A Smolyarchuk, T G Zubkova, A S Erokhova, I M Cherenkova, K M Bukhtin, O Popova, N M Tukhvatulina, B S Naroditsky, D Y Logunov, A L Gintsburg","doi":"10.32607/actanaturae.27529","DOIUrl":"https://doi.org/10.32607/actanaturae.27529","url":null,"abstract":"<p><p>Although the immunogenicity of clinically approved COVID-19 vaccines remains under intensive investigation, little is still known about the parameters of long-term immune responses. In this paper, we present for the first time the parameters of humoral immunity studied in the phase 1-2 open-label clinical trial of the Sputnik Light vaccine, with a special focus on late follow-up time points (90 and 180 days). For the most accurate assessment of the parameters of humoral post-vaccination immunity (titer and avidity index of antigen-specific antibodies against the RBD domain of SARS-CoV-2), we conducted an additional analysis that allowed us to triage volunteers with immunity formed only in response to vaccination, as well as those with hybrid immunity (infected with SARS-CoV-2 before and after vaccination). The findings indicate that single-shot vaccination with the Sputnik Light vaccine induces a durable (seroconversion 73% on day 180) and mature humoral immunity. Natural immunization as a result of the SARS-CoV-2 infection leads to significant changes in the studied parameters of post-vaccination immunity.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"52-63"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunoregulatory Enzymes. 免疫调节酶。
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27549
S V Kupriyanov, K M Kirilenko, D N Starkov
{"title":"Immunoregulatory Enzymes.","authors":"S V Kupriyanov, K M Kirilenko, D N Starkov","doi":"10.32607/actanaturae.27549","DOIUrl":"https://doi.org/10.32607/actanaturae.27549","url":null,"abstract":"<p><p>Immunoregulatory enzymes, which function both as biological catalysts and regulatory elements, play a crucial role in controlling immune responses. Dysfunction of these proteins can contribute to various pathological conditions, such as the suppression of antitumor immunity or impairment of anti-infectious immune responses. This review discusses the most extensively studied immunoregulatory enzymes, including indoleamine 2,3-dioxygenase 1, arginase 1, inducible nitric oxide synthase, glyceraldehyde-3-phosphate dehydrogenase, and ectonucleoside triphosphate diphosphohydrolase 1. Their classification is provided, along with an analysis of the distinctive characteristics inherent to this group of enzymes. Additionally, new directions for the medical application of immunoregulatory enzymes are explored.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"11-19"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of HBV Replication by a Fully Humanized Neutralizing Antibody In Vivo and In Vitro. 一种完全人源化中和抗体在体内和体外抑制HBV复制。
IF 1.5 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27457
Zhipeng Zhang, Yanqin Ma, Yan He, Dong Wang, Huaien Song, Kun Yue, Xiaomei Zhang
{"title":"Inhibition of HBV Replication by a Fully Humanized Neutralizing Antibody In Vivo and In Vitro.","authors":"Zhipeng Zhang, Yanqin Ma, Yan He, Dong Wang, Huaien Song, Kun Yue, Xiaomei Zhang","doi":"10.32607/actanaturae.27457","DOIUrl":"10.32607/actanaturae.27457","url":null,"abstract":"<p><p>Neutralizing antibodies are capable of specifically binding to the HBsAg virus, thereby preventing HBV infection and subsequently reducing viral antigen load in both the liver and systemic circulation. This has significant implications for restoring the postnatal immune function. By utilizing the phage antibody library technology, we successfully screened a fully humanized neutralizing antibody targeting the hepatitis B surface antigen. The antiviral activity was assessed in primary human hepatocytes (PHHs) by determining the EC<sub>50</sub> values for HBeAg and HBsAg biomarkers in HBV types B, C, and D; no cytotoxicity was observed within the tested concentration range. Furthermore, HT-102 exhibited no ADCC effect but displayed a weak CDC effect along with a dose-dependent response. We established an AAV/HBV mouse model and observed significant dose-dependent reduction in HBsAg and HBV DNA levels for both the medium-dose and highdose groups. The immunohistochemical staining data showed dose-dependent reduction in HBsAg expression in the liver, with high-dose group exhibiting minimal positive expression. Finally, a mild immune response was induced, while reducing the burden of antigen-antibody complexes circulating within the system. Consequently, strain on the patient's immune system was alleviated by effectively slowing down CD8<sup>+</sup>T lymphocyte depletion, and functional cure was ultimately achieved as intended.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"97-105"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rhodobacter capsulatus PG Lipopolysaccharide As a Potential Blocker of Toll-like Receptor 2 and 4 Activation. 荚膜红杆菌PG脂多糖作为toll样受体2和4激活的潜在阻断剂。
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27555
S V Zubova, Ya V Radzyukevich, N I Kosyakova, I R Prokhorenko
{"title":"Rhodobacter capsulatus PG Lipopolysaccharide As a Potential Blocker of Toll-like Receptor 2 and 4 Activation.","authors":"S V Zubova, Ya V Radzyukevich, N I Kosyakova, I R Prokhorenko","doi":"10.32607/actanaturae.27555","DOIUrl":"https://doi.org/10.32607/actanaturae.27555","url":null,"abstract":"<p><p>TLR2 and TLR4 play a key role in the development of an inflammation in response to a bacterial infection. We studied the effect of <i>Rhodobacter capsulatus</i> PG lipopolysaccharide (LPS) on proinflammatory cytokine synthesis activation by the TLR2 and TLR4 agonists <i>E. coli</i> LPS, <i>Streptococcus pyogenes</i> lipoteichoic acid (LTA), and Pam3CSK4 (a synthetic bacterial lipopeptide) in human whole blood cells. <i>Rhodobacter capsulatus</i> PG LPS was shown to exhibit antagonistic properties against the studied TLR4 and TLR2 agonists, blocking the synthesis of the cytokines TNF-α, IL-6, and IL-8. Possible mechanisms behind the suppressing effect of <i>Rhodobacter capsulatus</i> PG LPS are proposed. <i>Rhodobacter capsulatus</i> PG LPS can serve as a prototype for drugs against both gram-negative and gram-positive bacteria.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"106-109"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of the ERK1/2 Molecular Pathways and Its Relation to the Pathogenicity of Human Malignant Tumors. ERK1/2分子通路的激活及其与人类恶性肿瘤致病性的关系
IF 2 4区 生物学
Acta Naturae Pub Date : 2025-01-01 DOI: 10.32607/actanaturae.27497
A G Emelyanova, M A Zolotovskaia, E V Poddubskaya, A A Modestov, V S Prassolov, D V Kuzmin, A A Buzdin
{"title":"Activation of the ERK1/2 Molecular Pathways and Its Relation to the Pathogenicity of Human Malignant Tumors.","authors":"A G Emelyanova, M A Zolotovskaia, E V Poddubskaya, A A Modestov, V S Prassolov, D V Kuzmin, A A Buzdin","doi":"10.32607/actanaturae.27497","DOIUrl":"https://doi.org/10.32607/actanaturae.27497","url":null,"abstract":"<p><p>Mitogen-activated protein kinases, ERK1/2 (MAPK3/1), play a key role in the regulation of cell growth, differentiation, and apoptosis. We have previously presented evidence proving that activation of the ERK1/2 axis in cancer cells following the administration of therapeutics leads to the overexpression of growth factor receptors and drug resistance. Recently, we have proposed a new bioinformatic technique that enables direct construction of interactome network-based molecular pathways for gene products of interest, as well as quantitation of their activation levels using high-throughput gene expression data. In this study, we, for the first time, algorithmically constructed ERK1/2 molecular pathways and investigated how their activation levels (PALs) affect survival and responsiveness to targeted drugs at the pan-cancer level based on transcriptomic data. We examined a total of 11 287 human tumor profiles from 31 types of cancer, drawn from 53 of our previously published and other literature datasets, looking at patient survival and clinical response to 29 chemo- and targeted therapy regimens. We found that activation of the ERK1/2 pathways has different prognostic significance depending on cancer type. In glioblastoma, sarcoma, lung, kidney, bladder, gastric, colon, and several other cancer types, ERK pathway activation was associated with worse survival. In contrast, the same phenomenon was associated with a better chance of survival in HER2+, luminal A and luminal B breast cancer, and uterine corpus cancer. These trends were consistent with treatment response analysis. At the same time, we found significantly worse associations with the expression levels of individual <i>MAPK1</i> and <i>MAPK3</i> genes: hence, ERK1/2 pathway activation levels can be considered putative biomarkers for predicting clinical outcomes and selecting new personalized treatment strategies, such as the use of MAPK inhibitors.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"36-51"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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