Frontiers in Cell and Developmental Biology最新文献

{"title":"An entosis-informed prognostic index for survival stratification and molecular characterization in lung adenocarcinoma.","authors":"Yinqin Liu, Wen Zhao, Shuyi Mu, Silun Liang, Yanping Wen, Shaobin Li, Chengyan Zhan, Yanqi Cheng, Ling Tang, Yuqin Wu, Ziyou Lin, Hong Fang, Yubin Ding","doi":"10.3389/fcell.2026.1943127","DOIUrl":"https://doi.org/10.3389/fcell.2026.1943127","url":null,"abstract":"<p><strong>Background: </strong>Entosis is an actomyosin-dependent cell-in-cell process that may culminate in lysosome-mediated entotic cell death and is implicated in tumor evolution. Its clinical relevance in lung adenocarcinoma (LUAD) remains unclear.</p><p><strong>Methods: </strong>To construct an Entosis-related Prognostic Prediction Index (EPPI), this study integrated TCGA-LUAD transcriptomic, clinical, and somatic mutation data. Three independent GEO cohorts provided external validation. The initial candidate gene set covered components driving cell-in-cell formation and the intracellular degradation of internalized cells. For subgroup comparison, the analytical approach incorporated survival analysis, functional enrichment, tumor microenvironment profiling, mutation analysis, immunotherapy assessment, and drug-sensitivity prediction. Tissue and cellular distributions of the EPPI genes were mapped using spatial transcriptomics and single-cell RNA sequencing. Molecular docking assessed predicted drug-target interactions. Finally, <i>in vitro</i> RAC1 knockdown experiments evaluated the cellular function of a representative EPPI gene.</p><p><strong>Results: </strong>Comprising RND3, RAC1, KRAS, CTNNA1, AURKA, and ACTB, the final EPPI consistently stratified overall survival across all cohorts and showed moderate prognostic discrimination. The high-EPPI group had greater tumor purity and mutational burden, with enhanced cell-cycle, DNA-repair, epithelial-mesenchymal transition, and NF-κB programs, whereas the low-EPPI group showed greater immune and stromal infiltration. TIDE and immunophenoscores also differed between subgroups. Drug-response models predicted greater sensitivity to cisplatin and paclitaxel in the high-EPPI group and to several targeted agents in the low-EPPI group. Molecular docking predicted RAC1-EHT-1864 and AURKA-alisertib interactions. Spatial and single-cell analyses showed heterogeneous EPPI-gene expression, with ACTB and RAC1 broadly distributed and AURKA restricted to selected populations. RAC1 depletion suppressed LUAD-cell proliferation, DNA synthesis, migration, and invasion.</p><p><strong>Conclusion: </strong>The EPPI is an entosis-informed prognostic index for survival stratification in LUAD. Based on this index, patients can be separated into subgroups with distinct proliferative features, genomic alterations, tissue compositions, and predicted drug sensitivities. These findings associate entosis-related molecular features with distinct cellular and clinical characteristics of LUAD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1943127"},"PeriodicalIF":5.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota disturbance disrupts osteonal organization and mechanical competence during postnatal cortical bone maturation in rabbits with local metabolic and transcriptional remodeling.","authors":"Xiaopei Yang, Ziming Geng, Hongji Wang, Gongzi Zhang, Shicheng Luo, Binbin Liu, Yansen Wang, Shuwei Zhang, Lihai Zhang","doi":"10.3389/fcell.2026.1937899","DOIUrl":"https://doi.org/10.3389/fcell.2026.1937899","url":null,"abstract":"<p><strong>Introduction: </strong>Bone strength depends not only on bone mass and mineral density but also on cortical tissue organization and material quality. Osteons are key structural units of cortical bone, yet whether gut microbiota disturbance affects cortical bone maturation at the osteon level remains unclear.</p><p><strong>Methods: </strong>We first characterized cortical canal remodeling and osteonal organization in New Zealand rabbits at 1, 2, and 3 months of age. Antibiotic-induced microbiota disturbance (AIMD) was then applied during this early osteon-forming window, followed by assessments of gut microbiota composition, osteon morphology, cortical bone micro-CT parameters, mechanical performance, femoral metabolomics, and cortical bone transcriptomics.</p><p><strong>Results: </strong>AIMD reduced gut microbial diversity and altered microbial community structure. At 3 months of age, AIMD-treated rabbits showed impaired osteonal organization, including a reduced proportion of secondary osteons and altered osteon morphology. These osteon-level changes were accompanied by decreased maximum load and stiffness, whereas conventional micro-CT parameters of cortical geometry and mineral density remained unchanged. Multi-omics analyses further revealed local metabolic and transcriptional remodeling involving lipid-related metabolites, bone matrix regulation, osteocyte communication, and metabolic enzyme programs.</p><p><strong>Discussion: </strong>These findings suggest that early gut microbiota disturbance impairs osteon-level cortical bone maturation and reduces mechanical competence. Osteonal organization may therefore represent a sensitive layer of cortical bone quality affected by gut microbiota disturbance during postnatal skeletal development.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1937899"},"PeriodicalIF":5.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on an elderly low-vision field-aid system based on augmented reality.","authors":"Xi Chen, Xu Jing, Tinglong Liu, Pin Ju, Yige Zhang, Raymond Liu, Wenlong Liu, Like Xie, Xiaofeng Hao","doi":"10.3389/fcell.2026.1892801","DOIUrl":"10.3389/fcell.2026.1892801","url":null,"abstract":"<p><strong>Introduction: </strong>The global population is aging rapidly. Low vision among the elderly has become increasingly common. This condition seriously affects their quality of life. This study aims to develop a low-vision field-aid system for the elderly. The system is based on augmented reality (AR). It is designed to address visual field deficiency in this population.</p><p><strong>Methods: </strong>The proposed system integrates several key technologies. These include clinical field diagnosis assistance. Other components are AR-based field expansion, precise field detection, personalized field compensation, and intelligent environmental perception. The research encompasses system design, implementation of core technologies, experimental verification, and performance evaluation.</p><p><strong>Results: </strong>Experimental verification and performance evaluation were conducted. The results demonstrate that the system effectively expands the visual field. It also enhances environmental perception. Moreover, it improves mobility safety for elderly low-vision users. The system achieves personalized field compensation. This is based on individual field defect maps. It also shows stable performance under various environmental conditions.</p><p><strong>Conclusion: </strong>This AR-based field-aid system provides an innovative technical solution. It is designed for elderly low-vision rehabilitation. The system has the potential to significantly improve visual function. It can also enhance daily living safety.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1892801"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of luteolin in treating chronic heart failure by regulating HIF-1 signaling pathway-mediated mitochondrial damage to inhibit cardiomyocyte apoptosis.","authors":"Weiqi Shi, Zhide Zhu, Junshen Lu, Meiling Tang, Yan Pang, Zhilin Peng, Jie Lu, Puwei Huang, Shanyun Zou, Jiaji Wu, Yarou Tu, Chunmei Fan, Yuyun Gan, Lihui Hu, Qi Lin, Liuqin Qin, Rusheng Shi, Fei Zhong, Yuxuan Shen, Jianqi Lu","doi":"10.3389/fcell.2026.1977166","DOIUrl":"10.3389/fcell.2026.1977166","url":null,"abstract":"<p><strong>Background: </strong>Chronic heart failure (CHF) is a systemic cardiovascular disease characterized by an extremely poor prognosis. Luteolin demonstrates promising therapeutic potential in the prevention and management of CHF. This study aims to explore the mechanism by which luteolin ameliorates CHF through mitigating mitochondrial damage and inhibiting cardiomyocyte apoptosis, using bioinformatics analysis combined with <i>in vitro</i> and <i>in vivo</i> experiments.</p><p><strong>Methods: </strong>Network pharmacology was employed to identify functional targets of luteolin, as well as target genes associated with CHF and mitochondrial damage. The overlapping targets from the three datasets were obtained to construct a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, followed by molecular docking, were then conducted. Bioinformatic approaches were utilized to screen potential signature genes from the PPI network to build a clinical prediction model. Single-cell transcriptomics (scRNA-seq) was performed to characterize the expression profiles of these signature genes in cardiomyocyte subpopulations. Lastly, the results were comprehensively validated by <i>in vitro</i> and <i>in vivo</i> experiments.</p><p><strong>Results: </strong>In total, 329 overlapping targets of luteolin, mitochondrial damage and CHF were obtained; 122 core targets with above-average degree values were mainly enriched in the HIF-1 pathway. Six signature genes (HIF1A, NOS2, BNIP3, BNIP3L, PDK1, and BBC3; collectively termed the L-M-C gene set) were identified through 113 machine-learning combinations. The six-gene clinical model demonstrated favorable predictive performance. scRNA-seq demonstrated progressive upregulation of L-M-C genes during the transition from normal to injured cardiomyocytes in CHF. <i>In vitro</i>, luteolin markedly downregulated L-M-C genes (<i>P</i> < 0.05) and attenuated doxorubicin-induced cardiomyocyte injury. <i>In vivo</i>, in CHF rats, luteolin reduced myocardial L-M-C gene expression (<i>P</i> < 0.05), ameliorated myocardial lesions, and suppressed fibrosis and cardiomyocyte apoptosis.</p><p><strong>Conclusion: </strong>Luteolin exerts therapeutic effects against CHF by inhibiting the HIF-1 signaling pathway and downregulating the expression of target genes such as NOS2 and BNIP3. This regulatory action attenuates myocardial mitochondrial damage and fibrosis, thereby ameliorating the pathological structural remodeling of the myocardium.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1977166"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stage-specific transcriptional atlas of goose satellite cells uncovers sex-biased molecular dynamics associated with embryonic skeletal muscle development.","authors":"Cui Wang, Kai Shi, Yi Liu, Yongping Yang, Guitao Jiang, Chuang Li, Shufang Chen, Huiying Wang, Daqian He","doi":"10.3389/fcell.2026.1957937","DOIUrl":"10.3389/fcell.2026.1957937","url":null,"abstract":"<p><strong>Introduction: </strong>Sexual dimorphism in avian skeletal muscle is established during embryogenesis, but the stage-resolved transcriptional programs governing this process in geese remain largely unexplored.</p><p><strong>Methods: </strong>To construct a stage-specific transcriptional atlas of muscle satellite cells (SMSCs), we performed histological examination and RNA sequencing of PAX7⁺ SMSCs isolated from male and female Zhedong White goose embryos across four developmental stages (E13, E15, E18, and E23). Quantitative PCR was used to validate selected differentially expressed genes (DEGs).</p><p><strong>Results: </strong>Although myofiber morphology exhibited no overt sexual divergence, immunofluorescence revealed distinct sex- and stage-dependent dynamics, with male embryos displaying a higher PAX7⁺ cell abundance at E18 and females at E23. Transcriptomic profiling identified 357, 261, 312, and 672 DEGs at E13, E15, E18, and E23, respectively, uncovering a progressively intensifying sexual bias. At E13, female-biased DEGs were enriched for positional identity genes (HOXC9/C11, HOXD12/13) and pro-proliferative factors (GDF7, FGF16), whereas male-biased DEGs included adhesion molecules (IGSF10/11). At E15, females upregulated genes linked to myofiber maturation (ACTA1, MYH7B) and lipid metabolism (PLIN1, ADIPOQ), while males showed enrichment in extracellular matrix remodeling (MMP7, COL17A1) and immune-related pathways. At E18, females enhanced neuroendocrine signaling (ADCYAP1, AGTR2), whereas males upregulated contractile apparatus components (RYR1, CASQ1) and testis-associated transcripts (BRDT, DHH). By E23, females exhibited signatures of metabolic and neuromuscular optimization, whereas males showed enrichment in extracellular matrix genes (COL11A2, COL9A1/2) and masculinization-associated factors (YBX2, GGN). Temporal pathway analysis demonstrated a progression from immune/chemokine processes at E13, through cytoskeletal organization at E15 and supramolecular fiber components at E18, to DNA metabolism coupled with chemokine signaling at E23. Protein-protein interaction network analysis pinpointed stage-specific hub genes: EGFR (E13), ACTA1/ADIPOQ (E15), RAC2 (E18), and GNG10 (E23). Quantitative PCR validated eight selected DEGs.</p><p><strong>Discussion: </strong>Collectively, this transcriptional atlas delineates sex-biased molecular dynamics that operate within the Zhedong White goose SMSC pool in the absence of conspicuous histological differences, and provides a foundational gene resource for prioritizing mechanistic investigations into sexually dimorphic muscle development, focusing specifically on the embryonic leg muscles.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1957937"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRNA regulatory ecosystem states shape tissue and circulating small-RNA landscapes in gastric cancer.","authors":"Jie Liu, Yangyang Chen, Jiaqing Hu, Xujin Wei, Xiaoling Zheng","doi":"10.3389/fcell.2026.1960697","DOIUrl":"10.3389/fcell.2026.1960697","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is a heterogeneous disease shaped by the co-evolution of malignant epithelial programs, stromal remodeling, and immune contexture. Transfer RNA (tRNA) regulation sits at a strategic junction in this biology: it governs translational capacity and selectivity while generating tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs)-a family of regulatory small RNAs detectable in both tissue and blood.</p><p><strong>Objective: </strong>We asked whether the coordinated machinery responsible for tRNA transcription, maturation, modification, charging, and cleavage defines biologically meaningful gastric cancer ecosystem states, and whether a corresponding circulating small-RNA phenotype can be detected across independent cohorts of chronic atrophic gastritis (CAG), early gastric cancer (EGC), and gastric cancer (GC).</p><p><strong>Methods: </strong>We integrated transcriptomic, genomic, proteomic, and tissue small-RNA data across complementary gastric cancer series and localized the program in single-cell expression maps. The clinical arm comprised independent serum samples from CAG, EGC, and GC participants.</p><p><strong>Results: </strong>A 70-gene tRNA-regulatory program resolved three ecosystem states (TRES-1, TRES-2, and TRES-3). TRES-3 exhibited high tRNA-regulatory activity coupled with proliferative and DNA-repair protein expression, whereas TRES-1 was enriched for receptor-signaling and cell-cycle-restraint proteins. These states also differed in copy-number alterations and non-synonymous variant burden at the program level. Direct tissue small-RNA profiling revealed a marked expansion of tRF output and repertoire breadth in TRES-2 and TRES-3, with state-specific tRF classes, parent-tRNA modules, and exact sequences. A shared set of 446 exact tRF sequences connected the tissue and serum catalogues. In an independent gastric cancer series, the three-state architecture aligned with ACRG molecular subtypes, RNA cargo selection, extracellular vesicle release, and stress-response programs. Single-cell mapping placed tRNA-regulatory activity across epithelial, stromal, and immune compartments. In our serum cohort, the 14-30-nt fraction declined from 47.4% in CAG to 37.8% in EGC and 33.6% in GC, while the 31-40-nt fraction rose from 52.6% to 62.2% and 66.4% (absolute Spearman rho = 0.791; BH-adjusted P = 0.0112; exact-permutation P = 0.0214).</p><p><strong>Conclusion: </strong>tRNA regulation defines gastric cancer ecosystem states with distinct genomic, proteomic, and tissue small-RNA correlates. In our serum cohort, the reciprocal shift in circulating tRF/tiRNA length composition-a decline in the 14-30-nt fraction and a rise in the 31-40-nt fraction-parallels the transition from CAG to EGC to GC. These findings establish a testable molecular framework for paired tissue-serum validation and position circulating tRF/tiRNA architecture as a candidate readout of gastric cancer ecosystem biology.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1960697"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALYREF regulates glycolysis and promotes the progression of endometrial cancer through m⁵C modification of PKM2 mRNA.","authors":"Yun Feng, Xueyin Li","doi":"10.3389/fcell.2026.1831562","DOIUrl":"10.3389/fcell.2026.1831562","url":null,"abstract":"<p><p>Endometrial cancer (EC) is one of the most common gynecologic malignancies, and effective treatment options for advanced or recurrent cases remain limited. Here, we investigated the biological function and molecular mechanism of the RNA-binding protein ALYREF in EC. Bioinformatics analysis of public datasets revealed that ALYREF is significantly upregulated in EC tissues, and high ALYREF expression is associated with poor overall survival in the Kaplan-Meier Plotter cohort. Clinical validation using paired EC tissues confirmed ALYREF upregulation at protein level, and high ALYREF expression was associated with aggressive clinicopathological features. Functional assays revealed that ALYREF promotes EC cell proliferation, migration, and invasion <i>in vitro</i> and enhances tumor growth and metastasis <i>in vivo</i>. Mechanistically, ALYREF increases the stability of PKM2 mRNA, which we demonstrate to be m⁵C-modified in EC, leading to elevated PKM2 protein expression, enhanced glycolytic metabolism and tumor progression. Rescue experiments confirmed that PKM2 is an important downstream effector of ALYREF-mediated oncogenic activity. Collectively, this study identifies the ALYREF-PKM2 axis as an important regulator linking RNA methylation and glucose metabolism in EC, suggesting that this axis may be a potential therapeutic target for EC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1831562"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism of dynamic regulation of the proNGF/NGF ratio in controlling hair follicle cycle transition in liaoning cashmere goats.","authors":"Bing Luo, Di Han, Meng Sun, Jianwei Wei, Mingqian Li, Shuai Chang, Zhiguo Quan, Ying Wang, Chunqiang Wang, Wei Ma","doi":"10.3389/fcell.2026.1940416","DOIUrl":"10.3389/fcell.2026.1940416","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Nerve growth factor (NGF) and its precursor proNGF exert opposing biological functions in cell proliferation and apoptosis through distinct receptor systems-TrkA versus p75NTR/Sortilin. This study aimed to investigate whether dynamic changes in the relative ratio of proNGF to NGF regulate hair follicle cycle transition in Liaoning cashmere goats (Capra hircus) via the dynamic balance of the TrkA/p75NTR signaling axis, and to elucidate the underlying molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Skin samples from Liaoning cashmere goats were collected during the telogen (March), anagen (September), and catagen (January) phases. Histological structures of hair follicles were examined via hematoxylin and eosin (H&E) staining. The mRNA and protein expression levels of NGF, proNGF, TrkA, p75NTR, and Sortilin across distinct hair follicle cycle stages were assessed using quantitative real-time PCR (qRT-PCR) and Western blotting. &lt;i&gt;In vitro&lt;/i&gt;, rat hair follicle stem cells (rHFSCs) and human dermal papilla cells (hDPCs) were employed as cellular models and subjected to 11 different treatment conditions, including NGF alone, proNGF alone, combined treatments with varying proNGF/NGF ratios, and intervention with the TrkA inhibitor K252a. Cell proliferation and apoptosis were evaluated via CCK-8 assay and flow cytometry. Differential ratio groups (control, high-ratio, and low-ratio groups) were selected for transcriptomic sequencing to analyze differentially expressed genes (DEGs) and their enriched signaling pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;H&E staining revealed the highest secondary hair follicle activity during the anagen phase. qRT-PCR and Western blot analyses showed that NGF and TrkA expression levels were significantly elevated in anagen (P &lt; 0.05), whereas proNGF, p75NTR, and Sortilin exhibited significantly increased expression in catagen (P &lt; 0.05). The proNGF/NGF protein expression ratio was lowest in anagen (0.56), highest in catagen (1.89), and intermediate in telogen (1.56). CCK-8 assay results indicated that NGF treatment alone significantly promoted the proliferation of both rHFSCs and hDPCs (P &lt; 0.05), an effect that was completely abrogated by K252a; proNGF treatment alone exerted no significant effect on proliferation. At proNGF/NGF ratios of 1.56 and 1.89, cell proliferation rates were significantly lower than those in the NGF-alone group (P &lt; 0.05), whereas at a ratio of 0.56, the proliferation rate showed no significant difference from the NGF-alone group but was significantly higher than that of the control group. Flow cytometry confirmed that proNGF treatment alone and high proNGF/NGF ratios (1.56 and 1.89) significantly induced apoptosis. Transcriptomic sequencing revealed that, in the high-ratio group (proNGF/NGF = 1.89) compared with the low-ratio group (0.56), DEGs were significantly enriched in pathways related to \"regulation of apoptotic process\" and \"steroid hormone biosynthe","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1940416"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylglyoxal hampers the angiogenic capacity of human retinal endothelial cells modifying cell transcriptome with the contribution of NRSF/REST.","authors":"Marianna Aprile, Cecilia Nigro, Caterina Perfetto, Alessia Leone, Simona Cataldi, Antonella Nicolò, Mariagiovanna Tramontano, Antonella Desiderio, Francesco Beguinot, Valerio Costa, Claudia Miele, Alfredo Ciccodicola","doi":"10.3389/fcell.2026.1762167","DOIUrl":"10.3389/fcell.2026.1762167","url":null,"abstract":"<p><strong>Background: </strong>The functional impairment of retinal microvascular cells is an early and central event in diabetic retinopathy (DR). Methylglyoxal (MGO), the most reactive precursor of advanced glycation end products (AGEs), has been implicated in vascular injury and neuro-retinal dysfunction. Its direct effects on retinal endothelial cells and underlying molecular mechanisms remain poorly understood.</p><p><strong>Methods: </strong>Human retinal endothelial cells (hRECs) were exposed to MGO and the effect of sublethal doses on the proangiogenic function was evaluated by migration, tube formation and pericyte recruitment assays. MGO derived AGEs were evaluated by western blot. Transcriptome and miRNome profiling were performed to identify gene expression and microRNA perturbations. Integrative <i>in silico</i> analyses combining RNA-Seq with ENCODE ChIP-Seq datasets were used to identify transcriptional regulators responsible for MGO-induced gene deregulation. Transcriptomic profiles were compared with independent human DR datasets, and <i>REST</i> was silenced by siRNAs followed by analyses of proangiogenic function.</p><p><strong>Results: </strong>The exposure of hRECs to MGO for 72 h is sufficient to increase protein glycation adducts, impair the migration, tube-formation and the recruitment of pericytes. Transcriptome and miRNome analyses highlight that MGO induces extensive transcriptional perturbations, related to gene expression regulation, cell cycle, cell death and vasculature development. Among the identified transcriptional regulators, Neuron-Restrictive Silencer Factor/RE1-Silencing Transcription Factor (NRSF/REST) emerges as a candidate mediator, with binding sites enriched in 56% of deregulated genes. NRSF/REST expression markedly increases after 24 h of MGO treatment, suggesting it is an early event of the exposure to MGO. Protein-protein interaction network analysis prioritized NRSF/REST as a central node linking key MGO-responsive pathways. Accordingly, NRSF/REST knockdown is associated with the reduction of <i>TP53</i> and <i>FOSL2</i>, which are induced by MGO and display NRSF binding sites and known migration-related functions. Importantly, <i>REST</i> silencing significantly attenuates MGO-induced defects in endothelial migration, tube formation and pericyte recruitment, supporting its contribution to both transcriptional and functional endothelial alterations induced by MGO in hRECs.</p><p><strong>Conclusion: </strong>These findings demonstrate that MGO exposure disrupts endothelial function and transcriptional homeostasis in hRECs, identifying NRSF/REST as a contributor to MGO-induced endothelial dysfunction and supporting further investigations of the MGO/NRSF-REST axis as a potential therapeutic target for DR.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1762167"},"PeriodicalIF":5.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing cellular provenance in the cancer extracellular matrix.","authors":"Mingtao Ma, Yihan Huang, Enni Tang, Yueying Zhang, Xixi Yang, Lin Huang, Hu Ma","doi":"10.3389/fcell.2026.1984128","DOIUrl":"10.3389/fcell.2026.1984128","url":null,"abstract":"<p><p>Composition, architecture, and mechanics are central descriptors of the tumor extracellular matrix (ECM), but they do not identify the cells that synthesized and deposited it. Cellular provenance should therefore be distinguished from production context, deposition context, post-secretory history, and final matrix state. The central causal question is whether producer identity or state creates a persistent functional difference after abundance, proteoform, location, processing, assembly, and receptor environment are accounted for. Current evidence remains compatible with three explanations. The producer-mediated determinant model invokes source-linked proteoforms, co-secretomes, deposition patterns, or assembly routes. The provenance-associated model treats producer identity as a marker of abundance, timing, location, or cell state. The provenance-independent model predicts functional equivalence once molecular and matrix states are matched. Studies of collagen I, tenascin C, and fibronectin reveal three recurring patterns: producer-linked proteoform differences, stage-dependent source replacement, and source redundancy or assembly dependence. Protein-level source attribution and source-specific necessity are increasingly feasible, but abundance- and location-matched reciprocal source exchange remains uncommon. Cellular provenance should therefore be treated as a falsifiable variable whose functional significance is traced to a measurable molecular, spatial, mechanical, or assembly mediator.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1984128"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}