Frontiers in Cell and Developmental Biology最新文献

{"title":"Editorial: Immunoregulation by adenosine signaling in infection and inflammation.","authors":"Xiangsheng Huang, Weidong Zhao, Tingting Mills, Lei Shi, Xiaoyi Yuan","doi":"10.3389/fcell.2025.1586379","DOIUrl":"10.3389/fcell.2025.1586379","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1586379"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779470","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":"Exploring the role of gut microbiota in colorectal liver metastasis through the gut-liver axis.","authors":"Qiu-Luo Liu, Huijie Zhou, Ziqiang Wang, Yan Chen","doi":"10.3389/fcell.2025.1563184","DOIUrl":"10.3389/fcell.2025.1563184","url":null,"abstract":"<p><p>Colorectal liver metastasis (CRLM) represents a major therapeutic challenge in colorectal cancer (CRC), with complex interactions between the gut microbiota and the liver tumor microenvironment (TME) playing a crucial role in disease progression via the gut-liver axis. The gut barrier serves as a gatekeeper, regulating microbial translocation, which influences liver colonization and metastasis. Through the gut-liver axis, the microbiota actively shapes the TME, where specific microbial species and their metabolites exert dual roles in immune modulation. The immunologically \"cold\" nature of the liver, combined with the influence of the gut microbiota on liver immunity, complicates effective immunotherapy. However, microbiota-targeted interventions present promising strategies to enhance immunotherapy outcomes by modulating the gut-liver axis. Overall, this review highlights the emerging evidence on the role of the gut microbiota in CRLM and provides insights into the molecular mechanisms driving the dynamic interactions within the gut-liver axis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1563184"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779421","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 effect of Polybrominated diphenyl ethers at the fetal blood-brain-barrier: evaluation using a microphysiological system.","authors":"Sourabh Sharma, Manuel Vidal, Souvik Paul, Arum Han, Ramkumar Menon, Lauren S Richardson","doi":"10.3389/fcell.2025.1543710","DOIUrl":"10.3389/fcell.2025.1543710","url":null,"abstract":"<p><strong>Background: </strong>Glutamate dysregulation leading to neuronal excitotoxicity and neuroinflammation are associated with neurological disorders, specifically autism spectrum disorders (ASD) in preterm neonates. The lack of physiologically relevant <i>in vitro</i> models has limited mechanistic understanding of glutamate dysregulation and neuroinflammation during pregnancy. This study evaluated the effect of environmental pollutant and flame retardant, Polybrominated Diphenyl Ethers (PBDE) 99 and 47, on cell viability, glutamate dysregulation, and neuroinflammation using a microphysiologic system (MPS) of human fetal blood-brain-barrier organ on a chip (FB-OOC).</p><p><strong>Methods: </strong>The FB-OOC is composed of 3-cell culture chambers, connected by microchannels, containing 1) human brain microvessel endothelial cells (HBMEC), 2) human vascular pericytes (HBVP), and 3) a triculture of neurons, astrocytes, and microglia in a 5:2:1 ratio, respectively. To assess the effect of toxicants on glutamate dysregulation and neuroinflammation, control (standard media) endothelial cells were exposed to PBDE 99 and 47 (150 ng/mL). To mimic the passage of PBDE through the placenta, endothelial cells in FB-OOC were exposed to conditioned PDBE media (1:1) derived from a placenta-OOC. In parallel, triculture cells were directly treated in a 96-well plate. Dextran propagation over 72 h confirmed FB barrier function. The activation status of microglia was determined using immunocytochemistry for CD11 b and Iba1, respectively. Cell morphology (microscopy), cell cytotoxicity (Lactate Dehydrogenase and glutamate assays), and cytokines (multiplex assay) were measured.</p><p><strong>Results: </strong>Physiologic FB-OOCs were characterized by 1) viable cell cultures expressing standard cell morphologies and cell-specific markers, 2) barrier formation confirmed by decreased dextran propagation over 72 h, and 3) baseline glutamate and pro-inflammatory cytokine production. On-chip PBDE and placenta-derived metabolites of PBDE treatment in the endothelial chamber induced cell cytotoxicity and significant upregulation of glutamate in the triculture but did not induce neuroinflammation nor microglia activation compared to the controls. Conversely, 2D triculture experiments showed direct PBDE treatment-induced significant neuroinflammation (TNF-α, GM-CSF, IL-8) compared to PBDE placenta-derived metabolites or controls.</p><p><strong>Conclusion: </strong>This study established an FB model that recreated intercellular interactions. We report PBDE-induced glutamate dysregulation, often associated with the development of ASD, independent of neuroinflammation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1543710"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718442","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":"Perspectives on the α5 nicotinic acetylcholine receptor in lung cancer progression.","authors":"Jiaying Cai, Jingting Wang, Zengping Wang, Jing Wang, Yanfei Jia, Xiaoli Ma","doi":"10.3389/fcell.2025.1489958","DOIUrl":"10.3389/fcell.2025.1489958","url":null,"abstract":"<p><p>Nicotinic acetylcholine receptors (nAChRs) are widely expressed in a variety of cell types and are involved in multiple physiological regulatory mechanisms in cells, tissues and systems. Increasing evidence suggests that the α5 nicotinic acetylcholine receptor (α5-nAChR), encoded by the CHRNA5 gene, is one of a key mediator involved in lung cancer development and immune responses. Several studies have shown that it is a regulator that stimulates processes via various signaling pathways, including STAT3 in lung cancer. In addition, α5-nAChR has a profound effect on lung immune response through multiple immune-related factor pathways. In this review, we focus on the perspectives on α5-nAChR in lung cancer progression, which indicates that targeting α5-nAChR could provide novel anticancer and immune therapy strategies for lung cancer.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1489958"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718412","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: DNA replication barriers and the origins of cancer.","authors":"Michalis Fragkos","doi":"10.3389/fcell.2025.1585382","DOIUrl":"https://doi.org/10.3389/fcell.2025.1585382","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1585382"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718405","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":"Sodium butyrate and sodium propionate inhibit breast cancer cell migration and invasion through regulation of epithelial-to-mesenchymal transition and suppression of MEK/ERK signaling pathway.","authors":"Dania Mahmoud Kharazi, Louna Karam, Charbel El Boustany, José-Noel Ibrahim","doi":"10.3389/fcell.2025.1535563","DOIUrl":"10.3389/fcell.2025.1535563","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the roles played by NaB and NaP in breast carcinogenesis by elucidating their potential anti-metastatic effects in the context of tumor migration, invasion, and EMT regulation in two distinct breast cancer cell lines, MCF-7 and MDA-MB-231.</p><p><strong>Methods: </strong>The cytotoxic effect of both compounds on 3D spheroid formation was evaluated using a hanging drop assay. The anti-migratory and anti-invasive potentials of NaB and NaP were investigated through transwell migration and invasion assays. Moreover, their role in regulating epithelial-to-mesenchymal transition (EMT) was examined by assessing E-cadherin, vimentin, and β-catenin mRNA and protein expression levels through RT-qPCR and Western blot or flow cytometry. β-Catenin localization upon treatment was further visualized via immunofluorescence. Protein expression of MEK, p-MEK, ERK, and p-ERK was analyzed by Western blot.</p><p><strong>Results: </strong>Our results revealed a dose- and time-dependent impairment of spheroid formation in both cell lines, with NaB exerting a more potent effect than NaP. Both SCFAs were able to significantly inhibit migration and invasion of MDA-MB-231 cells following 24 h of treatment. Moreover, treatment with NaB or NaP altered the mRNA and protein profile of EMT-associated markers and abrogated the nuclear translocation of β-catenin. Finally, ERK and MEK phosphorylation was reduced in MDA-MB-231 and MCF-7 cells upon treatment with NaB, and less prominently with NaP.</p><p><strong>Conclusion: </strong>Our study highlights the promising therapeutic potential of NaB and NaP, providing insight into their inhibitory effects on 3D formation, migration, and invasion through EMT regulation and deactivation of MEK/ERK signaling in breast cancer.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1535563"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718440","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":"Regulation of HSC development and function by Lin28b.","authors":"Grant Cox, Michihiro Kobayashi, Brian D Rudd, Momoko Yoshimoto","doi":"10.3389/fcell.2025.1555877","DOIUrl":"10.3389/fcell.2025.1555877","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) provide all kinds of blood cells for life while maintaining self-renewal ability. During development, HSCs are first produced in the mouse embryo around embryonic day (E) 11. At this time, only one or two transplantable HSCs can be detected per embryo. Then, HSCs migrate to the fetal liver, where the number of HSCs rapidly increases, showing enhanced self-renewal ability. After birth, a transition occurs from the rapidly proliferating fetal HSCs to the more slowly dividing adult HSCs, which ends by 3-4 weeks of age. It is known that fetal HSCs express distinct surface markers and transcriptomes and produce a variety of distinct immune cells that are not made by adult HSCs. Accumulating evidence indicates that the ontogeny of the hematopoietic system is driven by a highly conserved and developmentally regulated RNA binding protein known as <i>Lin28b</i>. <i>Lin28b</i> is predominantly expressed in the fetal hematopoietic stem and progenitor cells (HSPCs) and regulates the developmental switch from fetal to adult HSCs. In this review, we will provide an overview of how <i>Lin28b</i> regulates the expansion and differentiation of HSCs in early life. These insights can be taken into consideration when developing <i>ex vivo</i> HSC expansion utilizing such physiological characteristics of HSCs.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1555877"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718436","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":"Action and therapeutic targets of folliculin interacting protein 1: a novel signaling mechanism in redox regulation.","authors":"Qingzhi Ran, Aoshuang Li, Bo Yao, Chunrong Xiang, Chunyi Qu, Yongkang Zhang, Xuanhui He, Hengwen Chen","doi":"10.3389/fcell.2025.1523489","DOIUrl":"10.3389/fcell.2025.1523489","url":null,"abstract":"<p><p>Rapid activation of adenosine monophosphate-activated protein kinase (AMPK) induces phosphorylation of mitochondrial-associated proteins, a process by which phosphate groups are added to regulate mitochondrial function, thereby modulating mitochondrial energy metabolism, triggering an acute metabolic response, and sustaining metabolic adaptation through transcriptional regulation. AMPK directly phosphorylates folliculin interacting protein 1 (FNIP1), leading to the nuclear translocation of transcription factor EB (TFEB) in response to mitochondrial functions. While mitochondrial function is tightly linked to finely-tuned energy-sensing mobility, FNIP1 plays critical roles in glucose transport and sensing, mitochondrial autophagy, cellular stress response, and muscle fiber contraction. Consequently, FNIP1 emerges as a promising novel target for addressing aberrant mitochondrial energy metabolism. Recent evidence indicates that FNIP1 is implicated in mitochondrial biology through various pathways, including AMPK, mTOR, and ubiquitination, which regulate mitochondrial autophagy, oxidative stress responses, and skeletal muscle contraction. Nonetheless, there is a dearth of literature discussing the physiological mechanism of action of FNIP1 as a novel therapeutic target. This review outlines how FNIP1 regulates metabolic-related signaling pathways and enzyme activities, such as modulating mitochondrial energy metabolism, catalytic activity of metabolic enzymes, and the homeostasis of metabolic products, thereby controlling cellular function and fate in different contexts. Our focus will be on elucidating how these metabolite-mediated signaling pathways regulate physiological processes and inflammatory diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1523489"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718420","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":"Cerebrospinal fluid-contacting neurons: a promising source for adult neural stem cell transplantation in spinal cord injury treatment.","authors":"Zhangrong Luo, Zeyu Shangguan, Liang Cao, Yi Zhang, Qizhe Li, Xuexing Shi, Jiangquan Fu, Chunqing Wang, Xiaowei Dou, Wei Tan, Qing Li","doi":"10.3389/fcell.2025.1549194","DOIUrl":"10.3389/fcell.2025.1549194","url":null,"abstract":"<p><p>Transplantation of adult neural stem cells (NSCs) is regarded as one of the most promising approaches for treating spinal cord injury (SCI). However, securing a sufficient and reliable source of adult NSCs remains one of the primary challenges in applying this method for SCI treatment. Cerebrospinal fluid-contacting neurons (CSF-cNs) act as adult NSCs and can be substantially expanded <i>in vitro</i> while maintaining their NSC characteristics even after 60 passages. When CSF-cNs are transplanted into the injury sites of SCI mice, they demonstrate high survival rates along with the ability to proliferate and differentiate into neurons, astrocytes, and oligodendrocytes. Additionally, significant improvements in motor function have been observed in SCI mice following the transplantation of CSF-cNs. These results suggest that CSF-cNs may represent a promising source of adult NSCs for transplantation therapy in SCI.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1549194"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718425","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":"Functions of <i>Drosophila</i> Toll/NF-κB signaling in imaginal tissue homeostasis and cancer.","authors":"Fabienne Brutscher, Konrad Basler","doi":"10.3389/fcell.2025.1559753","DOIUrl":"10.3389/fcell.2025.1559753","url":null,"abstract":"<p><p>The Toll/NF-κB pathway plays a central role in patterning the <i>Drosophila</i> embryo and in orchestrating the innate immune response against microbial infections. Both discoveries were associated with a Nobel Prize award and led to the recognition of the Toll-like receptor pathway in mammals, which has significant implications for diseases. Recent discoveries have revealed that the Toll/NF-κB pathway also maintains epithelial homeostasis of imaginal tissues during development: local Toll/NF-κB signaling activity monitors internal cellular fitness, and precancerous mutant cells can trigger systemic Toll/NF-κB pathway activation. However, this signaling can be exploited in diseases like cancer, in which Toll/NF-κB signaling is often co-opted or subverted. Various models have been proposed to explain how Toll/NF-κB signaling contributes to different types of cancer. Here we provide an overview of the functions of Toll/NF-κB signaling in imaginal tissue homeostasis with a focus on their misuse in pathological contexts, particularly their significance for tumor formation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1559753"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718407","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}