Frontiers in bioscience (Landmark edition)最新文献

{"title":"Study of the Role of E2F1 and TMEM132A in Prostate Cancer Development.","authors":"Ying Wang, Haifeng Hu, Huilin Liu, Dandan Zhou, Yinghui Zhang, Lu Li, Chunxin Huang","doi":"10.31083/j.fbl2910360","DOIUrl":"https://doi.org/10.31083/j.fbl2910360","url":null,"abstract":"<p><strong>Objective: </strong>Identify transcription factors and target genes associated with prostate cancer, offering new therapy approaches.</p><p><strong>Methods: </strong>Gene Set Enrichment Analysis (GSEA) investigates early 2 factor (E2F) transcription factor family roles in prostate cancer using the TCGA database. Survival analysis examined E2F factors and patient survival connections. Dataset analysis identified E2F1-involved key genes. Quantitative Real-time PCR (qPCR), which combines ultrasound-guided methods to collect clinical samples from prostate cancer patients, was utilized to determine the expression levels of <i>E2F1</i> and its target genes in patient samples and cancer cells. The effect of <i>E2F1</i> and its target gene expression alterations on prostate cell proliferation was examined utilizing the cell counting kit-8 (CCK8) technique. Double fluorescence enzyme experiment verified E2F1-target gene connections.</p><p><strong>Results: </strong>E2F family genes induce prostate cancer and show correlated co-expression. <i>E2F1</i>, <i>E2F2</i>, <i>E2F3</i>, <i>E2F5</i>, and <i>E2F7</i> were considerably over-expressed in prostate cancer tissues. While <i>E2F4</i> and <i>E2F6</i> were notably underexpressed, there was no statistically important change in the <i>E2F8</i> expression between prostate cancer and surrounding tissues. High expression of <i>E2F</i> genes is associated with lower patient survival. The transmemrane protein 132 (<i>TMEM132A</i>) was identified as a key gene for <i>E2F1</i> action and is associated with poor prognosis in patients. The essential gene for <i>E2F1</i> function, <i>TMEM132A</i>, was discovered. According to the qPCR results, <i>E2F1</i> and <i>TMEM132A</i> are considerably expressed in cancer cells and patient samples. Interfering with its expression significantly inhibited the proliferation ability of cancer cells. The double luciferase experiment showed that <i>E2F1</i> regulates the expression level in phase by binding directly to the <i>TMEM132A</i> promoter.</p><p><strong>Conclusions: </strong>The E2F transcription factor family induces prostate cancer and correlates with poor prognosis. <i>E2F1</i> directly regulates <i>TMEM132A</i> by binding its promoter and controlling the degree of protein expression, thereby affecting cancer cell growth.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"360"},"PeriodicalIF":3.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549253","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":"Role of Denitrification in Selenite Reduction by <i>Azospirillum brasilense</i> with the Formation of Selenium Nanoparticles.","authors":"Anna V Tugarova, Polina V Mamchenkova, Anastasiya A Vladimirova, Lilia P Petrova, Andrei V Shelud'ko, Alexander A Kamnev","doi":"10.31083/j.fbl2910361","DOIUrl":"https://doi.org/10.31083/j.fbl2910361","url":null,"abstract":"<p><strong>Background: </strong>Many bacteria are capable of reducing selenium oxyanions, primarily selenite (SeO₃^2-), in most cases forming selenium(0) nanostructures. The mechanisms of these transformations may vary for different bacterial species and have so far not yet been clarified in detail. Bacteria of the genus <i>Azospirillum</i>, including ubiquitous phytostimulating rhizobacteria, are widely studied and have potential for agricultural biotechnology and bioremediation of excessively seleniferous soils, as they are able to reduce selenite ions.</p><p><strong>Methods: </strong>Cultures of <i>A.brasilense</i> Sp7 and its derivatives (mutant strains) were grown on the modified liquid malate salt medium in the presence or absence of selenite. The following methods were used: spectrophotometric monitoring of bacterial growth; inhibition of glutathione (GSH) synthesis in bacteria by L-buthionine-sulfoximine (BSO); optical selenite and nitrite reduction assays; transmission electron microscopy of cells grown with and without BSO and/or selenite.</p><p><strong>Results: </strong>In a set of separate comparative studies of nitrite and selenite reduction by the wild-type strain <i>A.brasilense</i> Sp7 and its three specially selected derivatives (mutant strains) with different rates of nitrite reduction, a direct correlation was found between their nitrite and selenite reduction rates for all the strains used in the study. Moreover, for BSO it has been shown that its presence does not block selenite reduction in <i>A.brasilense</i> Sp7.</p><p><strong>Conclusions: </strong>Evidence has been presented for the first time for bacteria of the genus <i>Azospirillum</i> that the denitrification pathway known to be inherent in these bacteria, including nitrite reductase, is likely to be involved in selenite reduction. The results using BSO also imply that detoxification of selenite through the GSH redox system (which is commonly considered as the primary mechanism of selenite reduction in many bacteria) does not play a significant role in <i>A.brasilense</i>. The acquired knowledge on the mechanisms underlying biogenic transformations of inorganic selenium in <i>A.brasilense</i> is a step forward both in understanding the biogeochemical selenium cycle and to a variety of potential nano- and biotechnological applications.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"361"},"PeriodicalIF":3.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549251","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":"Roles of Chemokine Axes in Breast Cancer.","authors":"Deok-Soo Son, Samuel E Adunyah","doi":"10.31083/j.fbl2910358","DOIUrl":"https://doi.org/10.31083/j.fbl2910358","url":null,"abstract":"<p><p>Chemokines bind to specific chemokine receptors, known as cell surface G protein-coupled receptors, constructing chemokine axes which lead to cell migration and invasion in developmental stage, pathophysiological process, and immune reactions. The chemokine axes in the tumor microenvironment are involved in tumor growth, angiogenesis, cancer stem-like cell properties, metastasis, and chemoresistance, modifying tumor immune contexture and cancer progression. Clinical features, including tumor state, grade, lymph node metastasis, and cancer subtypes, are related to the specific chemokine axes, which play a significant role in immune contexture and cell to cell interaction in the tumor microenvironment, followed by altered cancer prognosis and overall survival. The present review summarizes the role of chemokine axes in breast cancer, based on data obtained from cell line and animal models and human tumor samples. This review provides information that understand the important roles of each chemokine axis in breast cancer, probably offering a clue of adjuvant therapeutic options to improve the quality of life and survival for patients with breast cancer.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"358"},"PeriodicalIF":3.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549252","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":"FBW7-Mediated Degradation of CHD3 Suppresses Hepatocellular Carcinoma Metastasis and Stemness to Enhance Oxaliplatin Sensitivity.","authors":"Shijie Li, Tingting Fan, Changjun Wu","doi":"10.31083/j.fbl2910357","DOIUrl":"https://doi.org/10.31083/j.fbl2910357","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitination plays a key role in various cancers, and F-box and WD repeat domain containing 7 (FBW7) is a tumor suppressor that targets several cancer-causing proteins for ubiquitination. This paper set out to pinpoint the role of FBW7 in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The target proteins of FBW7 and the expression of hromodomain helicase DNA binding protein 3 (<i>CHD3</i>) were analyzed in liver HCC (LIHC) samples using the BioSignal Data website. The effects of CHD3 and FBW7 on HCC cell viability, migration, invasion and stemness were investigated through cell counting kit (CCK)-8, wound healing, transwell and sphere formation assays. Detection on CHD3 and FBW7 expressions as well as their relationship was performed employing quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunoprecipitation, ubiquitination and western blot analyses.</p><p><strong>Results: </strong>The prediction of Ubibrowser revealed CHD3 as a target protein of FBW7. The data of starBase exhibited a higher expression level of <i>CHD3</i> in LIHC samples relative to normal samples. <i>CHD3</i> was upregulated in HCC cells. <i>CHD3</i> knockdown inhibited HCC cell proliferation, migration, invasion, stemness and oxaliplatin sensitivity. FBW7 targeted CHD3 for ubiquitination. <i>FBW7</i> overexpression restrained HCC cell migration, invasion and stemness, and attenuated the effects of overexpressed <i>CHD3</i> on promoting migration, invasion, stemness and oxaliplatin resistance in HCC cells.</p><p><strong>Conclusion: </strong>FBW7 overexpression suppresses HCC cell metastasis, stemness and oxaliplatin resistance via targeting CHD3 for ubiquitylation and degradation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"357"},"PeriodicalIF":3.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549327","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":"Neuroprotective Potential of Ethoxzolamide Targeting Oxidative Stress and Inflammation in Experimental Models of Intracerebral Hemorrhage.","authors":"Yongxia Li, Gang Shen, Jiarui Du, Wei Dai, Zuopeng Su","doi":"10.31083/j.fbl2910356","DOIUrl":"https://doi.org/10.31083/j.fbl2910356","url":null,"abstract":"<p><strong>Background: </strong>As antioxidant and anti-inflammatory agents, carbonic anhydrase inhibitors can exert potentially useful therapeutic effects following central nervous system trauma, including intracerebral hemorrhage (ICH). However, the therapeutic efficacy of ethoxyzolamide (ETZ) as a novel carbonic anhydrase inhibitor for ICH has not yet been determined.</p><p><strong>Methods: </strong>An autologous blood injection method was used to establish ICH models, which were then used to establish the effects of intraperitoneal injection of ETZ on ICH. Neuronal damage, apoptotic protein expression, oxidative and inflammatory factor content, microglia marker Iba-1 positivity, hepatic and renal pathological changes, and serum concentrations of hepatic and renal function indices were assessed by Nissl staining, western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, hematoxylin and eosin (HE) staining, and automatic biochemical analysis in brain tissues.</p><p><strong>Results: </strong>The ICH group showed massive hemorrhagic foci; significant increases in brain water content, modified mouse neurological deficit scoring (mNSS) score, pro-apoptotic protein expression, oxidative factors, pro-inflammatory factors, and Iba-1 positivity; and significant reductions in Nissl body size, anti-apoptotic protein expression, and antioxidant factors, all of which were reversed by ETZ in a dose-dependent manner. ETZ has a good biosafety profile with no significant burden on the human liver or kidneys. The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was mildly activated in ICH mice, and was further increased after ETZ injection. Molecular docking experiments revealed that ETZ could dock onto the Nrf2-binding domain of keap1.</p><p><strong>Conclusions: </strong>ETZ, as a novel carbonic anhydrase inhibitor, further activated the Keap1/Nrf2 pathway by docking with the Nrf2-binding domain of keap1, thereby exerting antioxidant, anti-inflammatory, anti-apoptotic, and cerebral neuroprotective effects in ICH mice.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"356"},"PeriodicalIF":3.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549336","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":"Reply to Comment on Ou Y, <i>et al</i>. \"UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma\". Frontiers in Bioscience-Landmark. 2024; 29: 144.","authors":"Yuhong Ou, Hongtao Luo, Qiuning Zhang, Tianqi Du, Ruifeng Liu, Dandan Wang, Junru Chen, Meng Dong, Yuhang Wang, Zhen Yang, Xiaohu Wang","doi":"10.31083/j.fbl2910354","DOIUrl":"https://doi.org/10.31083/j.fbl2910354","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"354"},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549249","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":"RGS Proteins in Sympathetic Nervous System Regulation: Focus on Adrenal RGS4.","authors":"Anastasios Lymperopoulos, Renee A Stoicovy","doi":"10.31083/j.fbl2910355","DOIUrl":"https://doi.org/10.31083/j.fbl2910355","url":null,"abstract":"<p><p>The sympathetic nervous system (SNS) consists largely of two different types of components: neurons that release the neurotransmitter norepinephrine (NE, noradrenaline) to modulate homeostasis of the innevrvated effector organ or tissue and adrenal chromaffin cells, which synthesize and secrete the hormone epinephrine (Epi, adrenaline) and some NE into the blood circulation to act at distant organs and tissues that are not directly innervated by the SNS. Like almost every physiological process in the human body, G protein-coupled receptors (GPCRs) tightly modulate both NE release from sympathetic neuronal terminals and catecholamine (CA) secretion from the adrenal medulla. Regulator of G protein Signaling (RGS) proteins, acting as guanosine triphosphatase (GTPase)-activating proteins (GAPs) for the Gα subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins), play a central role in silencing G protein signaling from a plethora of GPCRs. Certain RGS proteins and, in particular, RGS4, have been implicated in regulation of SNS activity and of adrenal chromaffin cell CA secretion. More specifically, recent studies have implicated RGS4 in regulation of NE release from cardiac sympathetic neurons by means of terminating free fatty acid receptor (FFAR)-3 calcium signaling and in regulation of NE and Epi secretion from the adrenal medulla by means of terminating cholinergic calcium signaling in adrenal chromaffin cells. Thus, in this review, we provide an overview of the current literature on the involvement of RGS proteins, with a particular focus on RGS4, in these two processes, i.e., NE release from sympathetic nerve terminals & CA secretion from adrenal chromaffin cells. We also highlight the therapeutic potential of RGS4 pharmacological manipulation for diseases characterized by sympathetic dysfunction or SNS hyperactivity, such as heart failure and hypertension.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"355"},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549250","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":"Cox Regression in Glioma Prognosis Analysis: Challenges with the Proportional Hazards Assumption and Coping Strategies. Comment on Ou Y, <i>et al</i>. \"<i>UBA2</i> as a Prognostic Biomarker and Potential Therapeutic Target in Glioma\". Frontiers in Bioscience-Landmark. 2024; 29: 144.","authors":"Jihao Xue, Ligang Chen","doi":"10.31083/j.fbl2910353","DOIUrl":"https://doi.org/10.31083/j.fbl2910353","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"353"},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549320","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":"<i>SLC30A2</i>-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway.","authors":"Fan Li, Xiaohong Zhang, Li Feng, Xingxing Zhang","doi":"10.31083/j.fbl2910351","DOIUrl":"https://doi.org/10.31083/j.fbl2910351","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a significant global health burden with limited treatment options. The purpose of this study was to investigate the role of <i>SLC30A2</i>, a zinc transporter, in GC development and its capacity as a target for therapy.</p><p><strong>Methods: </strong>A comprehensive analysis of GC datasets (GSE54129 and stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA)) was conducted using bioinformatics tools to examine differential gene expression, focusing on <i>SLC30A2</i>. Functional assays, including Cell counting kit-8 (CCK-8) and transwell assays, were carried out on GC cell lines to determine the impact of <i>SLC30A2</i> knockdown on cell behavior. Flow cytometry was utilized to quantitatively observe cell apoptosis and cell cycle progression. The impact of zinc sulfate (ZnSO₄) on GC cells was evaluated by detecting apoptosis markers, Wnt/β-catenin signaling pathway activity, and oxidative stress biomarkers, focusing on the regulatory effect of <i>SLC30A2</i> overexpression.</p><p><strong>Results: </strong>Our analysis revealed significant upregulation of <i>SLC30A2</i> in GC samples compared to normal samples, and high <i>SLC30A2</i> expression was linked to poor prognosis. <i>SLC30A2</i> knockdown repressed proliferation, invasion, and migration of GC cells, induced apoptosis, as well as arrested the cell cycle. Additionally, ZnSO₄ treatment induced cytotoxicity and oxidative stress in GC cells, while <i>SLC30A2</i> overexpression rescued ZnSO₄-induced, migration, invasion, and proliferation. Moreover, ZnSO4 had been shown to bolster apoptosis and trigger the Wnt/β-catenin signaling pathway, effects which were mitigated by the overexpression of <i>SLC30A2</i>.</p><p><strong>Conclusion: </strong>Our results implied that <i>SLC30A2</i> was essential for GC progression by modulating zinc homeostasis and cellular processes. Targeting <i>SLC30A2</i> or zinc signaling may represent a potential therapeutic approach for GC treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"351"},"PeriodicalIF":3.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549311","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":"Dose-Response Effect of Various Concentrations of Cl-Containing Water-Soluble Derivatives of C₆₀ Fullerenes on a Selective Regulation of Gene Expression in Human Embryonic Lung Fibroblasts (HELF).","authors":"Svetlana V Kostyuk, Elena M Malinovskaya, Pavel E Umriukhin, Elena N Mikheeva, Elizaveta S Ershova, Ekaterina A Savinova, Larisa V Kameneva, Pavel A Troshin, Olga A Kraevaya, Ivan V Rodionov, Svetlana E Kostyuk, Tatyana A Salimova, Sergey I Kutsev, Natalia N Veiko","doi":"10.31083/j.fbl2910352","DOIUrl":"https://doi.org/10.31083/j.fbl2910352","url":null,"abstract":"<p><strong>Background: </strong>The new synthesized water-soluble derivatives of C₆₀ fullerenes are of a great interest to researchers since they can potentially be promising materials for drug delivery, bioimaging, biosonding, and tissue engineering. Surface functionalization of fullerene derivatives changes their chemical and physical characteristics, increasing their solubility and suitability for different biological systems applications, however, any changes in functionalized fullerenes can modulate their cytotoxicity and antioxidant properties. The toxic or protective effect of fullerene derivatives on cells is realized through the activation or inhibition of genes and proteins of key signaling pathways in cells responsible for regulation of cellular reactive oxygen species (ROS) level, proliferation, and apoptosis.</p><p><strong>Methods: </strong>The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to assess cells viability. Flow cytometry analyses was applied to measure proteins levels in human embryonic lung fibroblasts (HELF) cells. HELF is a standard, stable and well described human cell line that can be passaged many times. Quantitation of ROS was assessed using H2DCFH-DA. Fluorescence images were obtained using microscopy. Expression of <i>BCL2</i>, <i>CCND1</i>, <i>CDKN2A</i>, <i>BRCA1</i>, <i>BAX</i>, <i>NFKB1</i>, <i>NOX4</i>, <i>NRF2</i>, <i>TBP</i> (reference gene) was analyzed using real-time Polymerase chain reaction (PCR).</p><p><strong>Results: </strong>We found that high and low concentrations of fullerene C₆₀ derivatives with the five residues of potassium salt of 6-(3-phenylpropanamido)hexanoic (F1) or 6-(2-(thiophen-2-yl)acetamido)hexanoic (F2) acid and a chlorine atom attached directly to the cage cause diametrically opposite activation of genes and proteins of key signaling pathways regulating the level of oxidative stress and apoptosis in HELF. High concentrations of F1 and F2 have a genotoxic effect, causing NADPH oxidase 4 (NOX4) expression activation in 24-72 hours (2-4 fold increase), ROS synthesis induction (increase by 30-40%), DNA damage and breaks (2-2.5 fold 8-oxodG level increases), and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (by 40-80%) against the background of reduced NF-E2-related factor 2 (NRF2) expression (by 20-45%). Low concentrations of F1 and F2 produced a cytoprotective effect: in 24-72 hours they reduce the oxidative DNA damage (by 20-40%), decrease the number of double-strand DNA breaks (by 20-30%), increase the level of anti-apoptotic proteins and enhance the antioxidant response activating the NRF2 expression (NRF2 gene expression increases 1.5-2.3 fold, phosphorylated form of the NRF2 protein increases 2-3 fold).</p><p><strong>Conclusions: </strong>Obtained results show that in low doses studied fullrens may serve as perspective DNA protectors against the damaging genotoxic factors.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"352"},"PeriodicalIF":3.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549323","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}