Frontiers in bioscience (Landmark edition)最新文献

{"title":"Protective Role of <i>Cynara cardunculus</i> L. var. <i>altilis</i> Against Oxidative Stress and Corneal Dysfunction in High Glucose-Damaged Human Corneal Epithelial Cells.","authors":"Carmelina Daniela Anfuso, Caterina Ledda, Alessia Cosentino, Aleksandra Agafonova, Chiara Prinzi, Sara Lombardo, Gaetano Pandino, Maria Scuto, Gabriella Lupo, Angela Trovato Salinaro","doi":"10.31083/FBL43138","DOIUrl":"https://doi.org/10.31083/FBL43138","url":null,"abstract":"<p><strong>Background: </strong>The global increase in diabetes mellitus has been accompanied by a significant rise in related complications. Diabetic patients frequently experience ocular surface disorders and multiple studies have demonstrated that the diabetic corneal epithelium is characterized by increased cellular fragility and compromised barrier integrity. It has been demonstrated that the processes of oxidative stress and inflammation are pivotal in causing ocular tissue damage in diabetic patients. Numerous studies have explored the protective effects of various antioxidants, especially those sourced from plants. <i>Cynara cardunculus</i> L. var. <i>altilis</i> (DC.), a species widely integrated into the Mediterranean diet and commonly known as cultivated cardoon (CC), is particularly rich in bioactive phenolic compounds, recognized for their antioxidant effects.</p><p><strong>Methods: </strong>The current work focuses on assessing the effect of CC leaf extracts on high glucose-treated human corneal epithelial cells (HCEpiCs). HCEpiCs were cultured for 24 h in a medium supplemented with glucose up to a concentration of 25 mM. Mannitol treatment was included to distinguish whether the observed effects were due to glucose metabolism or solely osmotic stress. To evaluate the effect of CC extracts, corneal cells were pre-incubated with the CC extract 10-20 μg/mL for 24 h before high glucose (HG) treatment. Cell viability, transepithelial electrical resistance, wound healing assay and reactive oxygen species (ROS) measurements were performed after HG treatment. To evaluate the levels of oxidative stress, the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), along with glutathione (GSH) levels were assayed. The mitogen-activated protein kinase ERK1/2/cytosolic phospholipases A₂ (cPLA₂)/cyclooxygenase-2 (COX-2) signaling pathway, triggering the inflammatory process, was evaluated by western blot analyses.</p><p><strong>Results: </strong>Our findings indicate that CC extract (i) improved viability, reducing oxidative stress by lowering ROS production and enhancing SOD, CAT activities and GSH content in human corneal epithelial cells exposed to high glucose concentrations; (ii) maintained a high TEER and promoted corneal epithelial wound healing; and (iii) induced down-regulation of the ERK 1/2/cPLA₂/COX-2 signaling pathway involved in the inflammatory process and ROS production.</p><p><strong>Conclusions: </strong>CC leaf extract could improve human corneal epithelial cell function suggesting its potential as a preventive agent against the development of chronic diabetic complications.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"43138"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016764","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":"Biomembranal Myristoyl-Phosphatidylcholine as a Potential Target of the Cell Injury Activity of Vitamin D Decomposition Products in Eukaryotic Cells.","authors":"Hirofumi Shimomura, Kiyofumi Wanibuchi, Kouich Hosoda, Avarzed Amgalanbaatar, Mitsuru Shoji, Shunji Hayashi","doi":"10.31083/FBL45142","DOIUrl":"https://doi.org/10.31083/FBL45142","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D decomposition products target a myristic acid sidechain of the predominant glycerophospholipid constructed in the biomembranes of <i>Helicobacter pylori,</i> causing gastric cancer in humans, and disrupt the membrane structure, followed by bacteriolysis. No earlier studies, however, elucidate whether vitamin D decomposition products interact with the glycerophospholipids that construct the eukaryotic biomembranes and confer whatever cell disorders.</p><p><strong>Methods: </strong>A gastric cancer cell line, MKN45, and a non-cancer cell line, Vero, were used in this study. Cell injury activities of vitamin D decomposition products (VDP1 and VD2-1) and a VDP1 derivative (VD3-7) were examined by the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Identification of a glycerophospholipid was performed by ¹H-nuclear magnetic resonance (NMR). Fatty acid composition and glycerophospholipid molecular species were analyzed by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), respectively. Structure collapse-induction activity of VDP1, VD2-1 and VD3-7 to glycerophospholipid vesicles was examined using the pigment-containing lamellar vesicles.</p><p><strong>Results: </strong>MKN45 cells exhibited higher susceptibility to the cell injury activity of VDP1 and VD2-1 than Vero cells. In the analysis of biomembrane lipids, the glycerophospholipid phosphatidylcholine (PC) molecular species turned out to conspicuously differ between MKN45 cells and Vero cells. Contents of myristoyl-PC were higher in MKN45 cells than in Vero cells, while contents of oleoyl-PC were higher in Vero cells than in MKN45 cells. Meanwhile, the contents of palmitoyl- and palmitoleoyl-PC were almost equal between these cells. We next examined the structure collapse-induction activity of VDP1, VD2-1 and VD3-7 on the lamellar vesicles prepared with dimyristoyl-PC, dipalmitoyl-PC and dioleoyl-PC. The vitamin D decomposition products and a VDP1 derivative induced the structural collapse of dimyristoyl- and dipalmitoyl-PC lamellar vesicles but almost no structural collapse of dioleoyl-PC lamellar vesicles. These results suggest that the contents of myristoyl-PC in biomembranes are associated with the susceptibility of eukaryotic cells to the cell injury activity of VDP1, VD2-1 and VD3-7. In addition, no VD3-7 affected the viability of Vero cells and selectively decreased the viability of MKN45 cells.</p><p><strong>Conclusions: </strong>In the future, we will expect to be capable of developing novel antitumor agents targeting the myristic acid sidechain of biomembranal PC using a vitamin D decomposition product as the fundamental structure.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"45142"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016803","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":"Extended Insights Into Advancing Multi-Omics and Prognostic Methods for Cancer Prognosis Forecasting.","authors":"Jindong Xie, Junjie Xu, Zhi Tian, Jian Liang, Hailin Tang","doi":"10.31083/FBL44091","DOIUrl":"10.31083/FBL44091","url":null,"abstract":"<p><p>Zhang <i>et al</i>.'s recent article utilizes comprehensive single-cell data to identify differences in tumor cell populations, highlighting the <i>CKS1B</i>+ malignant cell subcluster as a potential target for immunotherapy. It develops a prognostic and immunotherapeutic signature (PIS) based on this subcluster, demonstrating good performance in predicting lung adenocarcinoma (LUAD) prognosis. The study also validates the role of <i>PSMB7</i> in LUAD progression. However, there are areas for improvement. There is a lack of clarity regarding the relationship between the <i>CKS1B</i>+ malignant cell subcluster and the PIS, particularly in terms of why <i>PSMB7</i> was selected for functional studies. The sequencing data are retrospectively obtained from public databases and lack prospective clinical validation. It is suggested to collect LUAD patient tissues for RT-qPCR and RNA-seq analysis and seek external multi-center validations. Additionally, integrating emerging multi-omics methods is recommended to further validate the findings. Despite these limitations, the study represents progress in understanding LUAD and treatment strategies, and continuous evaluation and refinement of multi-omics and machine learning methods are expected for future research and clinical practice.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"44091"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016723","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":"Dendritic Cells Induce Clec5a-mediated Immune Modulation in MPTP-induced Parkinson's Disease Mouse Model.","authors":"So-Yeon Choi, Ji-Hee Nam, Min-Seon Song, Jun-Ho Lee, Kyung-Eun Noh, Ji-Soo Oh, Nam-Chul Jung, Jie-Young Song, Dae-Seog Lim","doi":"10.31083/FBL39570","DOIUrl":"https://doi.org/10.31083/FBL39570","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is characterized by a progressive decline in dopaminergic neurons within the substantia nigra (SN). Although its underlying cause has yet to be fully elucidated, accumulating evidence suggests that neuroinflammation contributes substantially to disease development. Treatment strategies targeting neuroinflammation could improve PD outcomes. Monocyte-derived tolerogenic dendritic cells (tolDCs) modulate immune responses and induce regulatory T cells (Tregs) during various inflammatory diseases. However, the mechanisms underlying tolDC-mediated immunoregulation in PD remain unclear.</p><p><strong>Methods: </strong>We investigated the immune modulatory role of tolDCs by analyzing gene expression patterns and identified that the C-type lectin domain family 5 member A (Clec5a) was highly induced in tolDCs. To assess its function, we generated Clec5a-knockdown tolDCs and measured cytokine production, including interleukin (IL)-10 and IL-6, forkhead box protein P3 (Foxp3)⁺ Treg induction, and nuclear factor kappa B (NF-κB) signaling activity. Furthermore, we evaluated the therapeutic effects of Clec5a-expressing dendritic cells (DCs) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Dopaminergic neuron survival, α-synuclein (α-syn) accumulation, neuroinflammatory markers, and locomotor behavior were analyzed following DC administration.</p><p><strong>Results: </strong>Clec5a-knockdown tolDCs exhibited reduced immunomodulatory function and IL-10 levels but enhanced IL-6 levels. In addition, these cells induced fewer Foxp3⁺ Tregs and showed significantly enhanced NF-κB signaling activity. In the MPTP-induced PD model, administration of Clec5a-expressing DCs ameliorated dopaminergic neuron loss and α-syn accumulation. Furthermore, Clec5a-expressing DCs reduced the number of CD45^highCD11b⁺CD86⁺ macrophages in the brain, reduced brain inflammatory cytokine expression, and improved locomotor activity.</p><p><strong>Conclusions: </strong>These findings suggest that Clec5a plays a critical role in the immunomodulatory function of tolDCs. The administration of Clec5a-expressing DCs effectively reduced neuroinflammation and protected dopaminergic neurons in an MPTP-induced PD model. Therefore, Clec5a-expressing tolDCs may demonstrate therapeutic potential by managing PD symptoms by suppressing inflammatory responses associated with neurodegeneration.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"39570"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016777","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":"CysB in the Multiverse of Functions: Regulatory Roles in Cysteine Biosynthesis and Beyond.","authors":"Erin N LeBoeuf, Anne Grove","doi":"10.31083/FBL36563","DOIUrl":"https://doi.org/10.31083/FBL36563","url":null,"abstract":"<p><p>CysB is a member of the large bacterial LysR-type transcriptional regulator (LTTR) protein family. Like the majority of LTTRs, CysB functions as a homotetramer in which each subunit has an N-terminal winged-helix-turn-helix (wHTH) DNA-binding domain connected to an effector-binding domain by a helical hinge region. CysB is best known for its role in regulating the expression of genes associated with sulfur uptake and biosynthesis of cysteine in Gram-negative species such as <i>Escherichia coli</i> and <i>Salmonella enterica</i>. Activation of CysB target genes generally requires the effector N-acetyl-L-serine, which derives from an intermediate in the cysteine biosynthetic pathway. Here, we outline the established roles of CysB in controlling the cysteine regulon, complemented with an interpretation of DNA binding modes inspired by the recently published structure of full-length CysB that is consistent with the 'sliding dimer' model proposed for many LTTRs. Notably, CysB orthologs have been described for which N-acetyl-L-serine does not appear to be required as an effector, and CysB regulons frequently include genes that are not directly related to sulfur assimilation and cysteine biosynthesis. Examples include <i>hslJ</i>, which encodes a predicted membrane protein involved in novobiocin resistance in <i>E. coli</i>, and <i>pqsR</i>, encoding a transcriptional regulator involved in <i>Pseudomonas</i> Quinolone Signal production and virulence in <i>Pseudomonas aeruginosa</i>. These data suggest that CysB orthologs have diverged to ensure optimal function and incorporation in distinct gene regulatory networks.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"36563"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016800","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":"Changes in Pre- and Post-Treatment Gut Microbiota and Metabolites in Neonates With Hyperbilirubinemia.","authors":"Liyi Mo, Yanwen Luo, Yan Liu, Qinqin Chen, Minxiu Ye, Dongzi Lin, Cheng Xu","doi":"10.31083/FBL42716","DOIUrl":"https://doi.org/10.31083/FBL42716","url":null,"abstract":"<p><strong>Background: </strong>Neonatal jaundice affects up to 60% of newborns, with pathological cases frequently associated with impaired bilirubin metabolism and gut microbiota dysbiosis. Although evidence implicates gut microbiota in bilirubin metabolism, the precise mechanisms remain incompletely characterized. This study investigated treatment-associated changes in gut microbiota composition, fecal metabolites, and liver function in neonates with hyperbilirubinemia.</p><p><strong>Methods: </strong>A total of forty-two neonates diagnosed with hyperbilirubinemia were recruited. Fecal samples were collected pre- and post-treatment. Gut microbiota composition was analyzed via 16S rRNA gene sequencing, while fecal metabolites were profiled using untargeted metabolomics. Liver function parameters, including serum bilirubin levels, were measured. Statistical analyses encompassed alpha/beta diversity assessments, Spearman correlation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.</p><p><strong>Results: </strong>Post-treatment gut microbial diversity decreased significantly, marked by increased abundance of <i>Streptococcus thermophilus</i> and <i>Rothia</i> and reduced levels of <i>Pseudomonas</i> and <i>Staphylococcus</i>. Key altered metabolites included 9,11-methane-epoxy PGF1α, prostaglandin E2 isopropyl ester, and 7-methylthioheptyl glucosinolate. Notably, <i>Streptococcus thermophilus</i> abundance inversely correlated with 7-methylthioheptyl glucosinolate but positively correlated with 9,11-methane-epoxy PGF1α and prostaglandin E2 isopropyl ester. Total bilirubin levels decreased significantly post-treatment, alongside improvements in other liver function markers.</p><p><strong>Conclusions: </strong>This study demonstrates significant treatment-associated shifts in gut microbiota and metabolites in hyperbilirubinemic neonates, suggesting microbial dysbiosis may contribute to altered bilirubin metabolism. These findings highlight the potential of early microbiome-targeted interventions for managing neonatal jaundice and identify candidate therapeutic targets and biomarkers.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"42716"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016738","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":"Immune Characteristics of eQTL and Gene Risk Model and the Inhibitory Effect of DCTD and RRAS on Ferroptosis in Glioblastoma.","authors":"Lulin Zhang, Wei Chen, Weibin Huang, Haoling Cheng","doi":"10.31083/FBL42844","DOIUrl":"https://doi.org/10.31083/FBL42844","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an extremely aggressive brain tumor, marked by restricted therapeutic possibilities and a generally unfavorable prognosis. GBM's complexity and heterogeneity necessitate comprehensive genetic and immunological profiling to enhance therapeutic strategies.</p><p><strong>Methods: </strong>The study integrated The Cancer Genome Atlas (TCGA) and Integrative Epidemiology Unit Open Genome-Wide Association Studies (IEU OpenGWAS) data to identify genetic factors influencing GBM using expression quantitative trait loci (eQTL) and genome-wide association studies (GWAS). Mendelian randomization (MR) analysis revealed 250 GBM-associated genes. A GBM risk prediction model was built using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression. The research examined immune infiltration, drug response, and mutation profiles to characterize GBM molecular features. Functional enrichment and <i>in vitro</i> experiments validated key findings.</p><p><strong>Results: </strong>The analysis uncovered significant genetic associations with GBM, emphasizing key genes such as follistatin-like 1 (<i>FSTL1</i>), FXYD domain-containing ion transport regulator 5 (<i>FXYD5</i>), Ras-related protein (<i>RRAS</i>), and ring finger protein 216 pseudogene 1 (<i>RNF216P1</i>). The risk model effectively categorized patients into low-risk and high-risk groups, showing significantly worse survival outcomes in the high-risk group. Immune profiling revealed differential infiltration of cancer-associated fibroblasts (CAFs), macrophages, and T cells, which correlated with the expression levels of the genes that were identified. Patients at high risk showed increased sensitivity to chemotherapeutic drugs such as dasatinib and lapatinib, while those at low risk were more responsive to elesclomol and lisitinib. Notably, key genes such as DCMP Deaminase (<i>DCTD</i>) and <i>RRAS</i> were found to regulate ferroptosis, underscoring their potential as therapeutic targets for GBM treatment.</p><p><strong>Conclusion: </strong>This study deepens the understanding of GBM by pinpointing critical genetic markers and elucidating their influence on the tumor immune microenvironment (TME) as well as treatment response. The risk model developed in this study holds promise for enhancing prognostic accuracy and facilitating the personalization of GBM therapy.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"42844"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016717","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":"Increased Ribosome Biogenesis and Increased Oxidative Stress in Blood Leukocytes of Patients With Catatonic Schizophrenia Compared With Paranoid Schizophrenia.","authors":"Elisaveta S Ershova, Natalia N Veiko, Oksana N Agafonova, Andrey V Martynov, Roman V Veiko, Lev N Porokhovnik, Tatyana A Salimova, Georgy P Kostyuk, Natalia V Zakharova, Svetlana V Kostyuk","doi":"10.31083/FBL39426","DOIUrl":"https://doi.org/10.31083/FBL39426","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia (SZ) is associated with chronic oxidative stress in the patient's body. Previous studies revealed an increased copy number of genes for 47S pre-ribosomal RNA (pre-rRNA) in SZ patients. In this study, levels of oxidative stress and factors involved in the adaptive response to chronic stress (rDNA transcription) were, for the first time, compared in blood cells of patients with catatonic SZ(C) and paranoid SZ(P), chronic forms of schizophrenia, as well as healthy controls (HC).</p><p><strong>Methods: </strong>Ribosomal DNA (rDNA) and telomere repeat (TR) were quantified in leukocyte DNA using non-radioactive quantitative hybridization. Fragments of 5' external transcribed spacer (5' ETS) and 18S rRNA were assayed in leukocyte RNA using quantitative reverse transcription PCR (RT-qPCR). Proteins γ-histone H2AX (γH2AX), NADPH-oxidase 4 (NOX4), nuclear factor erythroid 2-related factor 2 (NRF2), BCL2-like protein 4 (BAX), BCL2, and oxidation marker 8-oxo-2'-deoxyguanosine (8-oxodG) were quantified in blood lymphocytes using flow cytometry.</p><p><strong>Results: </strong>SZ(C) cells exhibited higher levels of the oxidative stress markers than SZ(P) and HC cells. The rDNA copy numbers in SZ(C) genomes negatively correlated with the amounts of the oxidative stress markers levels. Thus, genomes of blood cells isolated from catatonic patients harbor more copies of ribosomal genes than those from paranoid schizophrenia patients, correlating with higher levels of rRNA in catatonic patients.</p><p><strong>Conclusions: </strong>The upregulated ribosome biogenesis appears to be required for adaptive response to the elevated levels of oxidative stress in catatonic compared to paranoid patients.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"39426"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016733","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":"The Role of Extracellular Histones in Disease Progression: A Potential Therapeutic Target for Disease Modulation.","authors":"Danmei Zhang, Yukun Wang, Jin Guo, Xiaoya Zhang, Zuojiong Gong","doi":"10.31083/FBL27428","DOIUrl":"https://doi.org/10.31083/FBL27428","url":null,"abstract":"<p><p>Histones were once thought to be exclusive to the nucleus, but were recently discovered in the extracellular space, where they play important roles in disease pathogenesis. In addition to their traditional functions in chromatin organization and gene regulation, extracellular histones also serve as damage-associated molecular patterns (DAMPs), drive inflammation and immune responses, and are responsible for the progression of diseases such as sepsis, autoimmune diseases, and inflammatory diseases. To effectively target extracellular histones and improve disease progression, this review begins with the release and pathogenic mechanisms of histones and explains the main pathogenic mechanisms of extracellular histones in many diseases. In addition, common antagonistic methods for targeting extracellular histones are summarized, and the mechanisms that need to be further studied at this stage are discussed, providing new directions for the future development of effective and safe histone-targeting drugs.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"27428"},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016743","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":"MED10 as a Novel Oncogenic Driver in HCC: Promoting Cell Cycle Progression and Proliferation Through RAF1 Activation.","authors":"Junhao Liu, Yongxue Lv, Kejun Liu, Zhengquan Li, Bendong Chen, Yang Bu","doi":"10.31083/FBL39944","DOIUrl":"10.31083/FBL39944","url":null,"abstract":"<p><strong>Background: </strong>Mediator complex subunit 10 (MED10) serves as a critical regulator of eukaryotic gene expression by facilitating RNA polymerase II activity. Our investigation aims to characterize MED10's functional contributions and underlying molecular pathways in hepatocellular carcinoma (HCC) development.</p><p><strong>Methods: </strong>MED10 expression patterns in HCC and their correlation with clinicopathological parameters and patient outcomes were examined using bioinformatics databases and immunohistochemistry. Subsequently, we systematically investigated the biological functions of MED10 in the malignant progression of HCC through comprehensive <i>in vitro</i> experiments, including assessments of cell migration (transwell and wound healing assays), proliferative capacity (cell counting kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays), and cell cycle progression (flow cytometry analysis). Furthermore, we elucidated the underlying molecular mechanisms using real-time quantitative PCR (RT-qPCR), western blotting, immunofluorescence staining, and public database analyses. Furthermore, an <i>in vivo</i> subcutaneous xenograft model was employed to validate MED10's impact on tumor growth.</p><p><strong>Results: </strong>The results revealed a marked increase in MED10 expression levels within HCC tissues, showing a strong association with unfavorable clinical outcomes. Mechanistically, MED10 induced the epithelial-mesenchymal transition (EMT) and enhanced HCC cell migration. Moreover, MED10 overexpression drives HCC cell cycle progression and proliferation by activating rapidly accelerated fibrosarcoma 1 (RAF1), a process potentially mediated through the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)/cellular myelocytomatosis oncogene (c-Myc) signaling axis.</p><p><strong>Conclusion: </strong>MED10 promotes HCC cell migration and EMT but, more importantly, also drives cell cycle progression and proliferation via RAF1 activation, and is related to the MEK/ERK/c-Myc axis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"39944"},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016808","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}