Frontiers in Cell and Developmental Biology最新文献

{"title":"Harnessing the interaction between redox signaling and senescence to restrain tumor drug resistance.","authors":"Hao Wu, Yang Yu, Xiangning He, Yanju Gong, Jianqing Huang, Peijie Wu","doi":"10.3389/fcell.2025.1639772","DOIUrl":"https://doi.org/10.3389/fcell.2025.1639772","url":null,"abstract":"<p><p>The persistent challenge of tumor drug resistance remains a critical issue in medical practice, particularly during anti-neoplastic therapies, where the plasticity of the tumor microenvironment (TME) significantly complicates clinical treatment. Cellular senescence, an irreversible and permanent arrest of the cell cycle, has been implicated in various vital physiological and pathological processes. However, increasing evidence suggests that senescent cells arising in the tumor microenvironment have emerged as key contributors to tumor drug resistance, primarily through a highly active secretome termed the senescence-associated secretory phenotype (SASP), which includes growth factors, chemokines, cytokines, and stromal metalloproteinases. These SASP secretions significantly reshape the TME, enabling cancer cells to evade immune destruction. Interestingly, redox signaling networks are deeply intertwined with the cellular senescence process, influencing tumor progression and therapeutic outcomes. These studies highlight the complexity and heterogeneity of cellular senescence and redox signaling in diverse cancers. Notably, characterizing the heterogeneity of senescent cell populations in the context of drug resistance could facilitate the identification of key signaling nodes. Therefore, a thorough comprehension of the adaptive interactions between redox signaling and senescence across various tumor stages and cell subsets may reveal novel therapeutic targets. In this review, we will interpret the role of redox signaling in driving senescence and its regulation of SASP secretion in TME. Additionally, we will provide insights into existing and emerging clinical interventions that harness redox modulation to improve therapeutic efficacy while minimizing adverse effects. Together, co-targeting tumor cells and senescent counterparts in the tumor microenvironment may provide the potential to achieve enhanced therapeutic benefits and restrain tumor relapse in future clinical oncology.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1639772"},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697999","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":"The pathogenesis and therapeutic strategies of heat stroke-induced endothelial injury.","authors":"Shaokang Wang, Xiaoting Zhang, Yongqi Zhang, Nannan Wu, Lulong Bo, Meitang Wang","doi":"10.3389/fcell.2025.1569346","DOIUrl":"https://doi.org/10.3389/fcell.2025.1569346","url":null,"abstract":"<p><p>Heat stroke is a severe and life-threatening condition characterized by elevated core body temperature and central nervous system dysfunction, often accompanied by multi-organ damage. The incidence and mortality of heat stroke are increasing due to global warming and more frequent heatwaves. This review aims to summarize the recent progress in understanding the pathogenesis of heat stroke-induced endothelial injury and explore potential therapeutic strategies. The vascular endothelium plays a crucial role in maintaining vascular homeostasis, and its dysfunction is a key factor in the development of heat stroke complications. The pathogenesis of heat stroke-induced endothelial injury involves multiple mechanisms, including degradation of the endothelial glycocalyx, impaired vascular tone regulation, disruption of intercellular junctional proteins, and activation of regulated cell death pathways. Biomarkers such as syndecan-1, endothelin-1, and von Willebrand factor are associated with endothelial injury and can predict disease severity and outcomes. Potential interventions include early fluid resuscitation, heat acclimation, and targeted therapies to inhibit specific cell death pathways or protect the endothelial glycocalyx. Further research is needed to elucidate the detailed mechanisms and develop targeted therapeutic interventions to reduce the morbidity and mortality of heat stroke.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1569346"},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698037","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":"Comprehensive fragmentation of cell-free repetitive DNA for enhanced cancer detection in plasma.","authors":"Mingguang Zhang, Shuohui Dong, Wei Rao, Shiwen Mei, Gang Hu, Ling Liu, Zhen Wang, Jianqiang Tang","doi":"10.3389/fcell.2025.1630231","DOIUrl":"https://doi.org/10.3389/fcell.2025.1630231","url":null,"abstract":"<p><strong>Background: </strong>Repetitive elements account for a large proportion of the human genome and undergo alterations during early tumorigenesis. However, the exclusive fragmentation pattern of DNA-derived cell-free repetitive elements (cfREs) remains unclear.</p><p><strong>Methods: </strong>This study enrolled 32 healthy volunteers and 112 patients with five types of cancer. A novel repetitive fragmentomics approach was proposed to profile cfREs using low-pass whole genome sequencing (WGS). Five innovative repetitive fragmentomic features were designed: fragment ratio, fragment length, fragment distribution, fragment complexity, and fragment expansion. A machine learning-based multimodal model was developed using these features.</p><p><strong>Results: </strong>The multimodal model achieved high prediction performance for early tumor detection, even at ultra-low sequencing depths (0.1×, AUC = 0.9824). Alu and short tandem repeat (STR) were identified as the primary cfREs after filtering out low-efficiency subfamilies. Characterization of cfREs within tumor-specific regulatory regions enabled accurate tissue-of-origin (TOO) prediction (0.1×, accuracy = 0.8286) and identified aberrantly transcribed tumor driver genes.</p><p><strong>Conclusion: </strong>This study highlights the abundance of repetitive DNA in plasma. The innovative fragmentomics approach provides a sensitive, robust, and cost-effective method for early tumor detection and localization.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1630231"},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697997","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":"Integrative multi-omics analysis and experimental validation identify molecular subtypes, prognostic signature, and CA9 as a therapeutic target in oral squamous cell carcinoma.","authors":"Yun Zhao, Jing Yang, Yamei Jiang, Jingbiao Wu","doi":"10.3389/fcell.2025.1629683","DOIUrl":"https://doi.org/10.3389/fcell.2025.1629683","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is a challenging malignancy with poor prognosis despite therapeutic advancements. This study seeks to derive a precise molecular subtyping and prognostic model for personalized treatment strategies.</p><p><strong>Methods: </strong>Multi-omics data from TCGA cohort was analyzed using consensus clustering algorithms for subtype classification. Based on the classification, a multi-omics cancer subtyping signature (MSCC) model was constructed using machine learning methods. The model's clinical utility was assessed by evaluating immune features and immunotherapy response. Potential therapeutic agents were identified through drug sensitivity analysis.</p><p><strong>Results: </strong>Three distinct OSCC subtypes with unique genetic and immunological profiles were identified. The MSCC model, developed using the StepCox [both]+plsRcox algorithm, demonstrated superior prognostic performance compared to existing models. High MSCC scores correlated with poor prognosis, reduced immune cell infiltration, and decreased likelihood of benefiting from immune checkpoint inhibitor therapy. Docetaxel and paclitaxel emerged as potential therapeutic candidates. <i>In vitro</i> experiments validated CA9 as a promising therapeutic target, with its knockdown significantly inhibiting OSCC cell proliferation and migration.</p><p><strong>Conclusion: </strong>This multi-omics analysis unveiled subtype-specific differences in OSCC and established an MSCC model for predicting prognosis and treatment response. These findings provide a foundation for early diagnosis, molecular subtyping, and personalized treatment strategies in OSCC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1629683"},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698000","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":"The role of lipophagy in liver cancer: mechanisms and targeted therapeutic interventions.","authors":"Peiyu Han, Han Wang, Yuyu Chen, Yuqiu Ge, Huiting Xu, Hongbo Ren, Yiteng Meng","doi":"10.3389/fcell.2025.1562542","DOIUrl":"10.3389/fcell.2025.1562542","url":null,"abstract":"<p><p>Liver cancer, the advanced stage of various chronic liver diseases, has garnered attention due to its high incidence and insidious progression. Lipid droplets (LDs), unique lipid storage organelles in hepatocytes, play a pivotal role in lipid metabolism. Lipophagy, a selective autophagy process initially identified in hepatocytes, regulates lipid homeostasis by selectively degrading LDs. This process offers a novel therapeutic avenue for addressing lipid metabolism disorders in liver cancer. This review highlights the regulatory role of lipophagy in liver cancer progression and its therapeutic potential. It elaborates on the molecular mechanisms underlying lipophagy-mediated LDs degradation and discusses the dual regulatory role of lipophagy in liver cancer. While lipophagy can suppress liver cancer development, under specific conditions, it may promote cancer cell proliferation, inhibit apoptosis, facilitate invasion and metastasis, and contribute to treatment resistance. Consequently, strategies targeting lipophagy for liver cancer prevention and therapy hold significant promise. These include interventions through traditional Chinese and Western medicine, as well as lifestyle modifications. This review evaluates current research, hotspots, and controversies in the field, aiming to provide innovative therapeutic strategies for liver cancer associated with abnormal lipid metabolism.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1562542"},"PeriodicalIF":4.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689709","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":"Epidermal lamellar bodies, essential organelles for the skin barrier.","authors":"Corinne Leprince, Michel Simon","doi":"10.3389/fcell.2025.1597884","DOIUrl":"10.3389/fcell.2025.1597884","url":null,"abstract":"<p><p>Skin lamellar bodies are members of the Lysosome-Related-Organelle (LRO) family, characterized by specific features related to the skin's primary function, i.e., protecting the body from external assaults while minimizing dehydration. In the uppermost living cell layers of the epidermis, the vesicles and tubulovesicular network that make up the « lamellar body system » as identified by electron microscopists, play a crucial role in maintaining the skin barrier. As a secretory compartment, lamellar bodies carry a variety of compounds that, when released in the extracellular space or exposed at the membrane, contribute to the unique hydrophobic structure of the upper epidermis (lipids and lipid metabolism enzymes), regulate desquamation (proteases and inhibitors) and provide anti-microbial defense. The molecular machinery involved in the biogenesis and trafficking of skin lamellar bodies is only beginning to be deciphered, including the Rab11A GTPase, the Myosin5B molecular motor, and the CHEVI complex. This later one is constituted of the Vps33B and VIPAR tethering molecules, whose mutations lead to the ARC and ARKID syndromes. Further studies are needed to identify the key molecules regulating the various stages of LB biogenesis, maturation and exocytosis. It is likely that some of these molecules will be shared with other members of the LRO family. These studies will further enhance our understanding of the relationships between lamellar body trafficking and skin barrier dysfunction.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1597884"},"PeriodicalIF":4.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689708","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":"The vascular endothelium as decision maker in lung injury.","authors":"Diana Klein","doi":"10.3389/fcell.2025.1564627","DOIUrl":"10.3389/fcell.2025.1564627","url":null,"abstract":"<p><p>The vascular endothelium is the largest organ in the human body, capable of performing a wide range of cellular signaling and synthetic functions. It is also subjected to considerable mechanical stress due to the shear forces generated by blood flow, which amounts to approximately 10,000 L per day. The endothelial layer plays a crucial role in regulating vascular tone locally and controlling the extravasation of certain blood components. Additionally, it is integral to the coagulation process. The endothelium serves as the entry point for immune cells, which migrate from the bloodstream to surrounding tissues by passing through the endothelial layer. This underscores the importance of proper endothelial function for the health of the body's tissues and organs. When the endothelium fails to perform these functions adequately, leading to endothelial dysfunction, pathological conditions are more likely to develop. Notably, acute lung injury and its severe form, acute respiratory distress syndrome (ARDS), are often associated with endothelial dysfunction. ARDS refers to pulmonary edema with increased vascular permeability resulting from various pulmonary or systemic insults. In most cases, an exaggerated inflammatory and pro-thrombotic response to the initial insult causes disruption of the alveolar-capillary membrane and leakage of vascular fluid. This review emphasizes the central role of the vascular endothelium in acute conditions and seeks to clarify the concepts and interplay between endothelial activation, dysfunction, and damage.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1564627"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682337","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":"Wnt-dependent mechanism of the apical constriction of roof plate cells in developing mouse spinal cord.","authors":"Takuma Shinozuka, Tadashi Okubo, Noriaki Sasai, Shinji Takada","doi":"10.3389/fcell.2025.1571770","DOIUrl":"10.3389/fcell.2025.1571770","url":null,"abstract":"<p><p>Apical constriction of epithelial cells usually occurs in a local portion of epithelial sheet, which results in bending of epithelial tissues. However, it is uncertain whether diffusible signal molecules, like Wnt, regulate such locally restricted events. Here, we show that Wnt ligands are required for apical constriction of Wnt1-expressing roof plate (RP) cells during development of the neural tube. Analysis of <i>Wntless</i> conditional knock-out (cKO) embryos, in which Wnt secretion from Wnt1-expressing roof plate cells is impaired, revealed that RP-derived Wnt ligands are required for phosphorylation of myosin light chain (MLC) and apical constriction of RP cells. Loss- or gain-of-function analysis of β-catenin reveals that this apical constriction is regulated in a β-catenin-dependent manner. Consistent with the timing of apical constriction, Wnt ligands accumulate on the apical side of RP cells. In embryos with Wnt1-expressing RP-specific defects in synthesis of heparan sulfate proteoglycan, apical accumulation of Wnt ligands and apical constriction are impaired. Therefore, we propose that specific accumulation of Wnt ligands on RP cells drives apical constriction of these cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1571770"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682249","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":"Editorial: Advancements in hematopoietic stem cell proliferation and self-renewal maintenance.","authors":"Pawan Kumar Raghav, Gurudutta Gangenahalli, Takahiko Hara","doi":"10.3389/fcell.2025.1607145","DOIUrl":"10.3389/fcell.2025.1607145","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1607145"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682335","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":"Water temperature modulates multidimensional plastic responses to water flow during the ontogeny of a neotropical fish (<i>Astyanax lacustris</i>, characiformes).","authors":"Leandro Lofeu, Bianca Bonini-Campos, Tiana Kohlsdorf","doi":"10.3389/fcell.2025.1531162","DOIUrl":"10.3389/fcell.2025.1531162","url":null,"abstract":"<p><strong>Introduction: </strong>Plastic phenotypes result from multidimensional developmental systems responding to distinct yet simultaneous environmental signals, which may differently affect the magnitude and directions of plastic responses.Concomitant environmental signals during development may result in dominant, synergistic, or even antagonistic phenotypic effects, so that a given condition may amplify or minimize plastic responses to other environmental stimuli. Knowledge on how external information shapes complex plastic phenotypes is essential to predict potential evolutionary trajectories driven by developmental plasticity.</p><p><strong>Methods: </strong>Here, we manipulate water temperature to evaluate its effects on the well-described phenotypic accommodation of fish growth in the presence of water flow, using the neotropical species <i>Astyanax lacustris</i>. We include larval and juvenile ontogenetic stages to examine the interaction between these two environmental signals in plastic responses related to body size and shape, skeleton ossification and gene expression, using <i>bmp4</i> as a proxy for ossification pathways.</p><p><strong>Results and discussion: </strong>Our results demonstrate that water temperature plays a crucial role determining the expression of plastic variation at all dimensions, and effects of water flow were restricted to specific thermal regimes. Combination of high temperature and water flow has a major effect on body shape and unveils unique phenotypic patterns, supporting the prediction that high temperatures can amplify plastic responses to external signals. Specifically, fish raised in the presence of water flow at warmer environments grew faster and ossified earlier, and this condition increased <i>bmp4</i> expression levels especially at later developmental stages. Such plastic phenotypes likely involve a functional relationship with swimming performance in running-water environments. Our findings highlight the importance of studying developmental plasticity in complex environments using a multidimensional approach, especially considering increments in water temperatures due to accelerated climate changes that likely impact the fish developmental potential to mitigate environmental changes through plastic responses.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1531162"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682338","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}