Frontiers in bioscience (Landmark edition)最新文献

{"title":"Targeting the <i>AURKB</i>-<i>MAD2L2</i> Axis Disrupts the DNA Damage Response and Glycolysis to Inhibit Colorectal Cancer Progression.","authors":"Shengjie Li, Jiayou Ye, Kaifeng Yang, Chengfan Xu, Zhixiang Qin, Yiyang Xue, Lanjian Yu, Tianyu Zhou, Ziming Yin, Bin Sun, Jun Xu","doi":"10.31083/FBL26532","DOIUrl":"https://doi.org/10.31083/FBL26532","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated metabolic pathways, including glycolysis and a compromised DNA damage response (DDR), are linked to the progression of colorectal cancer (CRC). The mitotic arrest deficient-like 2 (<i>MAD2L2</i>) and aurora kinase B (<i>AURKB</i>) genes play roles in cell cycle regulation and the DDR, making them potential targets for CRC therapy.</p><p><strong>Methods: </strong>Differential expression analysis was performed using The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) and GSE47074 datasets. A predictive model was established, and gene expression levels were further analyzed. The Gene Expression Profiling Interaction Analysis database and co-immunoprecipitation experiments assessed the correlation between AURKB and MAD2L2. Knockdown experiments in CRC cell lines further investigated the role of <i>AURKB</i>, followed by analyses of cell behavior, oxidative stress, glycolysis, DDR, and interaction with <i>MAD2L2</i>.</p><p><strong>Results: </strong>The risk model identified six prognostic genes (BUB1 mitotic checkpoint serine/threonine kinase B (<i>BUB1B</i>), <i>AURKB</i>, aurora kinase A (<i>AURKA</i>), exonuclease 1 (<i>EXO1</i>), topoisomerase II alpha (<i>TOP2A</i>), cyclin A2 (<i>CCNA2</i>)) associated with CRC, which were significantly expressed in tumor samples from the TCGA-COAD and GSE47074 datasets. <i>In vitro</i> assays confirmed that <i>AURKB</i> knockdown inhibited CRC cell behavior, induced G1 cell cycle arrest, and increased oxidative stress and apoptosis. <i>AURKB</i> knockdown also impaired glycolysis, reducing lactate production, glucose uptake, and ATP levels. Overexpression of <i>MAD2L2</i> partially reversed these effects, restored glycolytic activity, and mitigated the cell cycle arrest and DDR caused by <i>AURKB</i> knockdown.</p><p><strong>Conclusion: </strong><i>AURKB</i> regulates CRC progression by modulating glycolysis and DDR pathways. Targeting the <i>AURKB</i>-<i>MAD2L2</i> axis offers a promising therapeutic strategy for disrupting fundamental metabolic and DNA repair mechanisms in CRC.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"26532"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525424","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":"Polarized Tissue-Derived Macrophages Display Enhanced M2d Phenotype after Prolonged Stimulation with Adenosine A_2A Receptor Agonist in the Presence of LPS.","authors":"Julia Barilo, Mariane Ratsimor, Agnes Chan, Hannah Hembruff, Sam Basta","doi":"10.31083/FBL27638","DOIUrl":"https://doi.org/10.31083/FBL27638","url":null,"abstract":"<p><strong>Background: </strong>Macrophages (Mφ) are innate immune cells known for their different activation phenotypes, classically described as falling within two broad categories, M1 and M2. The latter were originally described as alternatively activated M2 cells to differentiate them from classically activated M1 cells. M2 cells were later classified into M2a (interleukin (IL)-4), M2b (immune complex), M2c (IL-10) and M2d (5-(N-ethylcarboxamido) adenosine (NECA) + lipopolysaccharide (LPS)) based on their inducing stimuli. Considering the established role of M2d/tumour-associated macrophage (TAM) cells within cancer initiation and proliferation, expanding on the knowledge of M2d characteristics can provide fundamental information for Mφ targeted immunotherapy. The precise characterization of M2d cells derived from tissues has not been described in detail.</p><p><strong>Methods: </strong>Our study focused on spleen-derived macrophages (SpM), which were also compared to bone marrow-derived macrophages (BMDMs).</p><p><strong>Results: </strong>By investigating different conditions for M2d-specific stimulation and employing various assays including functional tests, we show how Mφ M2d (NECA + LPS) polarization can be affected by prolonged culture conditions to induce a phenotype that was clearly different from M2a cells.</p><p><strong>Conclusion: </strong>This work offers new insights into the properties of primary M2d Mφ following extended stimulation with LPS and NECA.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"27638"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525396","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":"Uncovering Sex-Related Differences in Skin Macrophage Polarization During Wound Healing in Diabetic Mice.","authors":"Coco X Huang, Elisha Siwan, Callum J Baker, Zhuoran Wei, Diana Shinko, Helen M McGuire, Stephen M Twigg, Danqing Min","doi":"10.31083/FBL27113","DOIUrl":"https://doi.org/10.31083/FBL27113","url":null,"abstract":"<p><strong>Background: </strong>Chronic wounds, such as diabetes-related foot ulcers, arise from delayed wound healing and create significant health and economic burdens. Macrophages regulate healing by shifting between pro- and anti-inflammatory phenotypes, known as macrophage polarization. Sex and diabetes can impair wound healing, but their influence on macrophage phenotype in skin tissue during wound healing remains unclear, which was investigated in this study using a novel two-sex diabetic mouse model.</p><p><strong>Methods: </strong>Diabetes was induced in male and female C57BL/6J mice using low-dose streptozotocin injections and high-fat diet feeding, with chow-fed mice as controls. After 18 weeks, each mouse received four circular full-thickness dorsal skin wounds. The macrophage phenotypes in wounded skin tissues at Day 0 and Day 10 post-wounding were analyzed using mass cytometry with manual gating and automated computational clustering.</p><p><strong>Results: </strong>Male diabetic mice exhibited more severe hyperglycemia and insulin resistance compared to females. Although diabetic mice did not display delayed wound healing, male mice had a greater proportion of total macrophages than females, especially a higher proportion of pro-inflammatory matrix metalloproteinase-9 (MMP-9)+ macrophages and a lower proportion of anti-inflammatory adiponectin receptor 1 (AdipoR1)+ macrophages in male diabetic mice compared to females, indicating an imbalanced polarization towards a pro-inflammatory phenotype that could result in poorer wound healing. Interestingly, computational clustering identified a new pro-inflammatory, pro-healing phenotype (Ly6C+AdipoR1+CD163-CD206-) more abundant in females than males, suggesting this phenotype may play a role in the transition from the inflammatory to the proliferative stage of wound healing.</p><p><strong>Conclusions: </strong>This study demonstrated a significant sex-based difference in macrophage populations, with male diabetic mice showing a pro-inflammatory bias that may impair wound healing, while a unique pro-inflammatory, pro-healing macrophage population more abundant in females could facilitate recovery. Further research is needed to investigate the role of these newly identified phenotypes in regulating impaired wound healing.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"27113"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525449","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":"Bacteria- and Phage-Derived Proteins in Phage Infection.","authors":"Olga I Guliy, Stella S Evstigneeva","doi":"10.31083/FBL24478","DOIUrl":"https://doi.org/10.31083/FBL24478","url":null,"abstract":"<p><p>Phages have exerted severe evolutionary pressure on prokaryotes over billions of years, resulting in major rearrangements. Without every enzyme involved in the phage-bacterium interaction being examined; bacteriophages cannot be used in practical applications. Numerous studies conducted in the past few years have uncovered a huge variety of bacterial antiphage defense systems; nevertheless, the mechanisms of most of these systems are not fully understood. Understanding the interactions between bacteriophage and bacterial proteins is important for efficient host cell infection. Phage proteins involved in these bacteriophage-host interactions often arise immediately after infection. Here, we review the main groups of phage enzymes involved in the first stage of viral infection and responsible for the degradation of the bacterial membrane. These include polysaccharide depolymerases (endosialidases, endorhamnosidases, alginate lyases, and hyaluronate lyases), and peptidoglycan hydrolases (ectolysins and endolysins). Host target proteins are inhibited, activated, or functionally redirected by the phage protein. These interactions determine the phage infection of bacteria. Proteins of interest are holins, endolysins, and spanins, which are responsible for the release of progeny during the phage lytic cycle. This review describes the main bacterial and phage enzymes involved in phage infection and analyzes the therapeutic potential of bacteriophage-derived proteins.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"24478"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525320","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":"Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson's Disease Models.","authors":"Hongquan Wang, Shuang Wu, Qiang Li, Huiyan Sun, Yumin Wang","doi":"10.31083/FBL26679","DOIUrl":"https://doi.org/10.31083/FBL26679","url":null,"abstract":"<p><strong>Background: </strong>Salsolinol (SAL) is a dopamine metabolite and endogenous neurotoxin that exerts neurotoxicity to dopaminergic neurons and is involved in the genesis of Parkinson's disease (PD). However, the machinery underlying SAL-induced neurotoxicity in PD is still being elucidated.</p><p><strong>Methods: </strong>In the present study, we first used RNA-seq and KEGG analysis to examine differentially expressed genes in SAL-challenged SH-SY5Y cells. PD animal models were established and treated with acteoside. Cell viability assays, lipid peroxidation assessments (malondialdehyde [MDA] and 4-Hydroxynonenal [4-HNE]), immunoblot, and transmission electron microscopy were used to confirm acteoside-mediated inhibition of ferroptosis and its neuroprotective effect on dopaminergic (DA) neurons.</p><p><strong>Results: </strong>We found that ferroptosis-related pathway was enriched by SAL. SAL inducing ferroptosis through upregulating long-chain acyl-CoA synthetase family member 4 (ACSL4) in SH-SY5Y cells, which neurotoxic effect was reversed by ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO). Acteoside, a phenylethanoid glycoside of plant origin with a neuroprotective effect, attenuates SAL-induced neurotoxicity by inhibiting ferroptosis in <i>in vitro</i> and <i>in vivo</i> PD models through downregulating ACSL4.</p><p><strong>Conclusions: </strong>The present study revealed a novel molecular mechanism underlying SAL-induced neurotoxicity via induction of ferroptosis in PD, and uncovered a new pharmacological effect against PD through inhibiting ferroptosis. This study highlights SAL-induced neurotoxicity via ferroptosis as a potential therapeutic target in PD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"26679"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525421","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":"METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells.","authors":"Hongjun Liu, Shasha Tan, Zhenyu Zhao, Xiaoping Tang, Zhou Li, Jian Qi","doi":"10.31083/FBL25718","DOIUrl":"https://doi.org/10.31083/FBL25718","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are aggressive brain tumors known for their poor prognosis and resistance to standard treatment options. Ferroptosis is an iron-dependent form of regulated cell death that has emerged as a promising target for cancer treatment. This study examined how the methyltransferase-like 3/YTH domain family protein 1 (<i>METTL3/YTHDF1</i>) axis influences ferroptosis and glioma progression by stabilizing mitochondrial carrier homolog 2 (<i>MTCH2</i>) messenger RNA (mRNA).</p><p><strong>Methods: </strong><i>MTCH2</i> expression in glioma tissues and cell lines was evaluated through quantitative real-time polymerase chain reaction (PCR) and western blot analyses. To assess the effects of <i>MTCH2</i> knockdown and overexpression on glioma cell functions, we performed a series of functional assays, including cell viability, colony formation, and measurements of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA) levels. Additionally, we conducted RNA immunoprecipitation (RIP) and RNA stability assays to explore the underlying mechanisms governing the interaction between <i>METTL3</i>, <i>YTHDF1</i>, and the stability of <i>MTCH2</i> mRNA.</p><p><strong>Results: </strong><i>MTCH2</i> was significantly upregulated in glioma tissues and cell lines. Silencing of <i>MTCH2</i> resulted in decreased glioma cell proliferation and induced ferroptosis, as evidenced by increased lipid peroxidation and ROS accumulation. Conversely, overexpression of <i>MTCH2</i> enhanced glioma cell survival and reduced ferroptosis. <i>METTL3</i>-mediated N6-methyladenosine (m6A) modification enhanced <i>MTCH2</i> mRNA stability by enabling YTHDF1 to bind and protect the modified mRNA from degradation.</p><p><strong>Conclusion: </strong>The <i>METTL3/YTHDF1/MTCH2</i> axis plays a critical role in glioma progression by inhibiting ferroptosis and promoting tumor cell survival. Targeting this pathway may provide a new and effective treatment strategy for glioma patients.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"25718"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525332","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":"Hypertrophic Cardiomyopathy: Genes and Mechanisms.","authors":"Jinli Chen, Yang Xing, Jie Sun, Yongming Liu, Zekun Lang, Lei Zhang, Jinggang Yang","doi":"10.31083/FBL25714","DOIUrl":"https://doi.org/10.31083/FBL25714","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is a hereditary disease of the myocardium characterized by asymmetric hypertrophy (mainly the left ventricle) not caused by pressure or volume load. Most cases of HCM are caused by genetic mutations, particularly in the gene encoding cardiac myosin, such as <i>MYH7</i>, <i>TNNT2</i>, and <i>MYBPC3</i>. These mutations are usually inherited autosomal dominantly. Approximately 30-60% of HCM patients have a family history of similar cases among their immediate relatives. This underscores the significance of genetic factors in the development of HCM. Therefore, we summarized the gene mutation mechanisms associated with the onset of HCM and potential treatment directions. We aim to improve patient outcomes by increasing doctors' awareness of genetic counseling, early diagnosis, and identification of asymptomatic patients. Additionally, we offer valuable insights for future research directions, as well as for early diagnosis and intervention.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"25714"},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525169","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":"Current Topics in Dental Follicle Cell Research.","authors":"Christian Morsczeck","doi":"10.31083/FBL25327","DOIUrl":"https://doi.org/10.31083/FBL25327","url":null,"abstract":"<p><p>Dental follicle cells (DFCs) are dental stem cells that can only be obtained from tooth germs or after extraction of unerupted wisdom teeth. For many years, DFCs have been studied in basic research and preclinical studies in regenerative dentistry, as they are involved in both the development of the periodontium and tooth eruption. Since the first isolation, the number of studies with DFCs has increased. This article summarizes the most important articles of the last five years to provide an overview of current research topics. The focus was on basic research and preclinical research. Basic research includes articles on tooth development and tooth eruption, as well as research into molecular mechanisms during osteogenic differentiation. In addition, articles on preclinical research with DFCs focused on regenerative therapies and immunotherapies are also discussed. These new studies show that DFCs have improved our understanding of periodontal development and regeneration. DFC research is important for the regenerative dentistry of the future; however, preclinical studies indicate that significant progress is still needed before DFCs can be integrated into routine clinical practice.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"25327"},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525360","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":"Proteomic Screening of Early Reperfusion in Acute Ischemic Heart and Insights into Mitochondrial-Associated Cell Damage: Role of RIP3.","authors":"Andrea Marciníková, Csaba Horváth, Izabela Jarabicová, Petra Majerová, Dominika Olešová, M Saadeh Suleiman, Adriana Adameová","doi":"10.31083/FBL27119","DOIUrl":"https://doi.org/10.31083/FBL27119","url":null,"abstract":"<p><strong>Background: </strong>Regulated forms of necrosis-like cell death (e.g., necroptosis) have been shown to contribute to cardiac ischemia/reperfusion (I/R) injury. However, pro-inflammatory necroptosis is unlikely to be involved during early reperfusion and little is known about the associated molecular changes. Thus, this study aimed to provide an in-depth protein screening with a particular focus on pro-pyroptotic and mitochondrial damage-related pathways.</p><p><strong>Methods: </strong>Langendorff-perfused rat hearts were subjected to 30-minute global ischemia followed by 10-minute reperfusion. Liquid chromatography coupled with mass spectrometry (LC-MS/MS) and immunoblotting techniques were used to study the complex cardiac proteome. In addition, calcium-induced mitochondrial swelling and lactate dehydrogenase (LDH) release were examined to assess mitochondrial stress and necrosis phenotype, respectively.</p><p><strong>Results: </strong>Approximately 160 proteins linked to cell death signaling, cellular metabolism, and post-translational modifications were significantly differentially expressed in I/R hearts compared to controls. Conventional proteins of pyroptosis, either of canonical or non-canonical signaling, were not affected during the short reperfusion. Notably, this type of I/R was associated with increased expression of p25 cleaved form of poly [ADP-ribose] polymerase 1 (PARP1 p25) and mature apoptosis-inducing factor (AIF), alongside nitrosative stress and mitochondrial swelling. Conversely, a receptor-interacting protein kinase 3 (RIP3) inhibitor (GSK'872, 250 nM) reversed mitochondrial swelling and plasma membrane rupture and mitigated the increase in the expression of PARP1 p25 and AIF.</p><p><strong>Conclusions: </strong>This study shows for the first time that necrosis-like injury during early I/R of the isolated heart is associated with mitochondrial events, rather than pro-inflammatory pyroptotic cell death. Furthermore, the inhibition of RIP3 mitigates this injury independent of targeting pro-inflammatory signaling.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"27119"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525399","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":"Copy Number Variations of Human Ribosomal Genes in Health and Disease: Role and Causes.","authors":"Natalia N Veiko, Elizaveta S Ershova, Elena I Kondratyeva, Lev N Porokhovnik, Rena A Zinchenko, Yuliya L Melyanovskaya, Stanislav A Krasovskiy, Tatiana P Vasilyeva, George P Kostyuk, Natalia V Zakharova, Svetlana V Kostyuk","doi":"10.31083/FBL25765","DOIUrl":"https://doi.org/10.31083/FBL25765","url":null,"abstract":"<p><strong>Background: </strong>A number of association studies have linked ribosomal DNA gene copy number (rDNA CN) to aging and pathology. Data from these studies are contradictory and depend on the quantitative method.</p><p><strong>Methods: </strong>The hybridization technique was used for rDNA quantification in human cells. We determined the rDNA CN from healthy controls (HCs) and patients with schizophrenia (SZ) or cystic fibrosis (CF) (total number of subjects N = 1124). For the first time, rDNA CN was quantified in 105 long livers (90-101 years old). In addition, we conducted a joint analysis of the data obtained in this work and previously published by our group (total, N = 3264).</p><p><strong>Results: </strong>We found increased rDNA CN in the SZ group (534 ± 108, N = 1489) and CF group (567 ± 100, N = 322) and reduced rDNA CN in patients with mild cognitive impairment (330 ± 60, N = 93) compared with the HC group (422 ± 104, N = 1360). For the SZ, CF, and HC groups, there was a decreased range of rDNA CN variation in older age subgroups compared to child subgroups. For 311 patients with SZ or CF, rDNA CN was determined two or three times, with an interval of months to several years. Only 1.2% of patients demonstrated a decrease in rDNA CN over time. We did not find significant rDNA CN variation in eight different organs of the same patient or in cells of the same fibroblast population.</p><p><strong>Conclusions: </strong>The results suggest that rDNA CN is a relatively stable quantitative genetic trait statistically associated with some diseases, which however, can change in rare cases under conditions of chronic oxidative stress. We believe that age- and disease-related differences between the groups in mean rDNA CN and its variance are caused by the biased elimination of carriers of marginal (predominantly low) rDNA CN values.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"25765"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525322","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}