Frontiers in Cell and Developmental Biology最新文献

{"title":"Oral microbiota: the overlooked catalyst in cancer initiation and progression.","authors":"Xinlin Wang, Xin He, Bin Zhong","doi":"10.3389/fcell.2024.1479720","DOIUrl":"10.3389/fcell.2024.1479720","url":null,"abstract":"<p><p>The advancement of high-throughput sequencing technology in recent decades has led to a greater understanding of the components of the oral microbiota, providing a solid foundation for extensive research in this field. The oral microbiota plays an important role in an individual's overall health. It has been shown to be significantly correlated with chronic human diseases, including diabetes, rheumatoid arthritis, cardiovascular disease, periodontal disease, and Alzheimer's disease. Furthermore, tumor occurrence and development are closely related to the oral microbiome. Specific bacteria, such as <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>), <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), <i>Streptococcus</i>, <i>Streptomyces</i>, <i>Prevotella</i>, and <i>Fibrophagy</i> gingivalis, play critical roles in cancer development. The oral microbiota has various oncogenic mechanisms, including bacterial inflammation, immunological suppression, tumor growth mediated by bacterial toxins, antiapoptotic activity, and carcinogenic effects. This paper reviews the role of the oral microbiota in the occurrence and progression of cancer and systematically elucidates the molecular mechanisms by which dysbiosis influences tumorigenesis and tumor progression. This information can provide a theoretical basis for exploring cancer treatment strategies and offer new insights for cancer prevention.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1479720"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052181","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":"CD73/adenosine dynamics in treatment-induced pneumonitis: balancing efficacy with risks of adverse events in combined radio-immunotherapies.","authors":"Lena Gockeln, Florian Wirsdörfer, Verena Jendrossek","doi":"10.3389/fcell.2024.1471072","DOIUrl":"10.3389/fcell.2024.1471072","url":null,"abstract":"<p><p>Consolidation with PD-1/PD-L1-based immune checkpoint blockade after concurrent platinum-based chemo-radiotherapy has become the new standard of care for advanced stage III unresectable non-small cell lung cancer (NSCLC) patients. In order to further improve therapy outcomes, innovative combinatorial treatment strategies aim to target additional immunosuppressive barriers in the tumor microenvironment such as the CD73/adenosine pathway. CD73 and adenosine are known as crucial endogenous regulators of lung homeostasis and inflammation, but also contribute to an immunosuppressive tumor microenvironment. Furthermore, the CD73/adenosine pathway can also limit the immune-activating effects of cytotoxic therapies by degrading the pro-inflammatory danger molecule ATP, which is released into the tumor microenvironment and normal lung tissue upon therapy-induced cell damage. Thus, while targeting CD73 may enhance the efficacy of radio-immunotherapies in cancer treatment by mitigating tumor immune escape and improving immune-mediated tumor killing, it also raises concerns about increased immune-related adverse events (irAEs) in the normal tissue. In fact, combined radio-immunotherapies bear an increased risk of irAEs in the lungs, and additional pharmacologic inhibition of CD73 may further enhance the risk of overwhelming or overlapping pulmonary toxicity and thereby limit therapy outcome. This review explores how therapeutic interventions targeting CD73/adenosine dynamics could enhance radiation-induced immune activation in combined radio-immunotherapies, whilst potentially driving irAEs in the lung. We specifically investigate the interactions between radiotherapy and the CD73/adenosine pathway in radiation pneumonitis. Additionally, we compare the incidence of (radiation) pneumonitis reported in relevant trials to determine if there is an increased risk of irAEs in the clinical setting. By understanding these dynamics, we aim to inform future strategies for optimizing radio-immunotherapy regimens, ensuring effective cancer control while preserving pulmonary integrity and patient quality of life.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1471072"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052175","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":"Telocytes in inflammatory bowel diseases: contributions to pathology and therapeutic potentials.","authors":"Ronaldo Paolo Panganiban, Christina McAninch, Marina Chulkina, Irina V Pinchuk","doi":"10.3389/fcell.2024.1452258","DOIUrl":"10.3389/fcell.2024.1452258","url":null,"abstract":"<p><p>Telocytes, a novel mesenchymal cell population, are characterized by their distinctive long and slender projections known as telopodes and have garnered significant interest since their formal introduction to the literature in 2010. These cells have been identified in various tissues, including the gastrointestinal (GI) tract, where they are suggested to play important roles in maintaining structural integrity, immune modulation, and barrier function. Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation and fibrosis. While limited information is available on the fate of telocytes in this group of diseases, it has been suggested that loss/plasticity of telocytes can be among the key factors contributing to their pathogenesis. This review focuses on the current understanding of telocytes, their structural features, and their distribution within the GI tract under gut homeostasis and IBD. We also discuss the roles of these cells in immune regulation and intestinal repair. We highlight evidence implicating telocytes in the pathogenesis of IBD and other chronic inflammatory diseases that share similar pathophysiological processes with IBD. Lastly, we discuss the current challenges in gut telocyte biology and the potential therapeutic implications of telocytes in IBD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1452258"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052185","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 dynamics of chemotactic signalling orchestrates dental pulp stem cell fibrosis during aging.","authors":"Tianmeng Sun, Qing Zhong, Xiaoyi Yu, Huanyu Luo, Feilong Ren, Cangwei Liu, Peng Chen, Fabian Flores-Borja, Hongchen Sun, Zhengwen An","doi":"10.3389/fcell.2024.1530644","DOIUrl":"10.3389/fcell.2024.1530644","url":null,"abstract":"<p><p>Aging often triggers dental pulp fibrosis, resulting in clinical repercussions such as increased susceptibility to dental infections, compromised tooth vitality, and reduced responsiveness to dental interventions. Despite its prevalence, the precise molecular mechanisms underlying this condition remains unclear. Leveraging single-cell transcriptome analysis from both our own and publicly available datasets, we identified Ccrl2⁺ macrophages as particularly vulnerable during the early stages of aging. Notably, dental pulp progenitors with high expression of RARRES2, a unique ligand for CCRL2, facilitate the selective recruitment of a specific macrophage population to the stem cell niches. This process culminates in the formation of the ligand-receptor complex that engages CMKLR1, a receptor broadly expressed across macrophage populations. This interaction drives macrophage activation and expansion through the RARRES2/CCRL2/CMKLR1 axis. Through rigorous experimental validation, we demonstrated that macrophage activation and expansion within stem cell niches lead to increased secretion of proinflammatory factors, promoting dental pulp fibrosis during aging. Our findings uncover the intricate molecular dynamics of dental pulp aging, emphasizing immune microenvironment interactions. This study provides a novel perspective on potential therapeutic strategies for age-related pulp diseases by targeting macrophages and modulating the immune microenvironment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1530644"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046019","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":"<i>E3 Siah</i> ubiquitin ligase regulates dichotomous spermatogenesis in <i>Sitotroga cerealella</i>.","authors":"Sakhawat Shah, Chun-Mei Shi, Karam Khamis Elgizawy, Wen-Han Yan, Gang Wu, Xiao-Ping Wang, Feng-Lian Yang","doi":"10.3389/fcell.2024.1507725","DOIUrl":"10.3389/fcell.2024.1507725","url":null,"abstract":"<p><p>Spermatogenesis in Lepidoptera holds significant importance due to its unique process of dichotomous spermatogenesis, yielding eupyrene and apyrene spermatozoa through a complex molecular mechanism. While E3 ubiquitin ligases are known to play vital roles in spermatogenesis across various processes, their functions in dichotomous spermatogenesis remain less known. We utilized the RNAi, biochemical and microscopic procedures to unravel the function of <i>ScE3 Siah</i> in dichotomous spermatogenesis of adult <i>Sitotroga cerealella</i>. In <i>S</i>. <i>cerealella E3</i> ligase <i>Siah</i> predominantly expressed in adult tissues. Knockdown of <i>ScE3 Siah</i> leads to disruptions in testes and sperm morphology, affecting the structure of eupyrene and apyrene sperm bundles and causing defective ultrastructure in eupyrene sperm. This disruption results in a reduction in the number of dichotomous sperms and significantly reduces their motility. Moreover, <i>ScE3 Siah</i> knockdown inhibits the transfer and motility of dichotomous sperm, impacting spermatophore formation in females and ultimately reducing egg production. Understanding the role of <i>ScE3 Siah</i> is not only crucial for comprehending the complex processes involved in dichotomous spermatogenesis and fertilization but also provides an avenue for sustainable pest control management.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1507725"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046016","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":"Rab10-associated tubulation as an early marker for biogenesis of the assembly compartment in cytomegalovirus-infected cells.","authors":"Hana Mahmutefendić Lučin, Igor Štimac, Marina Marcelić, Matej Skočaj, Berislav Lisnić, Alen Omerović, Ivona Viduka, Barbara Radić, Ljerka Karleuša, Gordana Blagojević Zagorac, Martina Deželjin, Antonija Jurak Begonja, Pero Lučin","doi":"10.3389/fcell.2024.1517236","DOIUrl":"10.3389/fcell.2024.1517236","url":null,"abstract":"<p><strong>Introduction: </strong>Cytomegalovirus (CMV) infection reorganizes early endosomes (EE), recycling endosome (RE), and trans-Golgi network (TGN) and expands their intermediates into a large perinuclear structure that forms the inner part of the cytoplasmic assembly complex (AC). The reorganization begins and results with the basic configuration (known as pre-AC) in the early (E) phase of infection, but the sequence of developmental steps is not yet well understood. One of the first signs of the establishment of the inner pre-AC, which can be observed by immunofluorescence, is the accumulation of Rab10. This study aims to investigate whether Rab10-positive domain (Rab10-PD) is expanded during the E phase of infection.</p><p><strong>Methods: </strong>We performed long-term live imaging of EGFP-Rab10 with epifluorescence imaging-enhanced digital holotomographic microscopy (DHTM), confocal imaging of known Rab10 interactors and identification of important Rab10 interactors with the proximity-dependent biotin identification assay (BioID). The accumulation of Rab10-PD was analyzed after knock-down of EHBP1 and Rabin8, two proteins that facilitate Rab10 recruitment to membranes, and after blocking of PI(4,5)P2 by PI(4,5)P2-binding protein domains.</p><p><strong>Results: </strong>Our study shows the gradual expansion of Rab10-PD in the inner pre-AC, the association of Rab10 with EHBP1 and MICAL-L1, and the dependence of Rab10-PD expansion on EHBP1 and PI(4,5)P2 but not Rabin8, indicating the expansion of EE-derived tubular recycling endosome-like membranes in the pre-AC. Silencing of Rab10 and EHBP1 suggests that Rab10-PD expansion is not required for the establishment of the inner pre-AC nor for the expansion of downstream tubular domains.</p><p><strong>Conclusion: </strong>The present work characterizes one of the earliest sequences in the establishment of pre-AC and suggests that subsets of EE-derived tubular membranes may serve as the earliest biomarkers in pre-AC biogenesis. Our study also indicates that the pre-AC biogenesis is complex and likely involves multiple parallel processes, of which Rab10-PD expansion is one. Our experiments, particularly our silencing experiments, show that Rab10 and EHBP-1 do not play a significant role in the later stages of inner pre-AC biogenesis or in the expansion of downstream tubular domains. A more comprehensive understanding of the tubular domain expansion remains to be established.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1517236"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046021","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":"HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.","authors":"Shruti Ghai, Rejina Shrestha, Kuo-Hui Su","doi":"10.3389/fcell.2024.1500880","DOIUrl":"10.3389/fcell.2024.1500880","url":null,"abstract":"<p><p>Heat Shock Factor 1 (HSF1) is a major transcriptional factor regulating the heat shock response and has become a potential target for overcoming cancer chemoresistance. This review comprehensively examines HSF1's role in chemoresistance and its potential as a therapeutic target in cancer. We explore the complex, intricate mechanism that regulates the activation of HSF1, HSF1's function in promoting resistance to chemotherapy, and the strategies used to manipulate HSF1 for therapeutic benefit. In addition, we discuss emerging research implicating HSF1's roles in autophagy, apoptosis, DNA damage repair, drug efflux, and thus chemoresistance. This article highlights the significance of HSF1 in cancer chemoresistance and its potential as a target for enhancing cancer treatment efficacy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1500880"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028504","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: Fertilization and early embryogenesis: from research to clinical practice.","authors":"Martin Anger, Katerina Komrskova, Ahmed Z Balboula, Paolo Rinaudo, Jason G Knott","doi":"10.3389/fcell.2024.1547205","DOIUrl":"https://doi.org/10.3389/fcell.2024.1547205","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1547205"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028480","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":"Formononetin promotes porcine oocytes maturation and improves embryonic development by reducing oxidative stress.","authors":"Na Wang, Han Yang, Yelei Chen, Hekun Wang, Chaorui Wang, Jianglin Fan, Yajie Chen, Yinghua Li, Maobi Zhu","doi":"10.3389/fcell.2024.1520429","DOIUrl":"10.3389/fcell.2024.1520429","url":null,"abstract":"<p><p>Increasing evidence has demonstrated that oxidative stress impairs oocyte maturation and embryonic development. Conventionally, antioxidants have been applied <i>in vitro</i> systems to improve oocyte maturation and blastocyst rates. Formononetin (FMN) is a flavonoid that has been shown to have various pharmacological effects, including antioxidants. In this study, we delved into the impact of FMN, acting as an antioxidant, on the <i>in vitro</i> development of oocytes and blastocysts within the culture system. FMN supplementation at 0.5 μM enhanced the rate of first polar body extrusion and blastocyst formation post parthenogenetic activation. It also increased mitochondrial function and ATP levels, reduced intracellular reactive oxygen species, and elevated intracellular GSH levels in both oocytes and embryos. Moreover, FMN significantly decreased autophagy and apoptosis levels in blastocyst cells, potentially via regulation of the Nrf2/Keap1 pathway. This is the first study to report that FMN supplementation benefits the <i>in vitro</i> culture of oocytes and early embryo development, potentially by regulating oxidative stress, mitochondrial function, and autophagy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1520429"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028498","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":"Organoids and spheroids: advanced <i>in vitro</i> models for liver cancer research.","authors":"Mirella Pastore, Alessia Giachi, Elena Spínola-Lasso, Fabio Marra, Chiara Raggi","doi":"10.3389/fcell.2024.1536854","DOIUrl":"10.3389/fcell.2024.1536854","url":null,"abstract":"<p><p>Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional <i>in vivo</i> animal models have played a vital role in liver cancer research, ethical concerns and the demand for more human-relevant systems have driven the development of advanced <i>in vitro</i> models. Spheroids and organoids have emerged as powerful tools due to their ability to replicate tumor microenvironment and facilitate preclinical drug development. Spheroids are simpler 3D culture models that partially recreate tumor structure and cell interactions. They can be used for drug penetration studies and high-throughput screening. Organoids derived from stem cells or patient tissues that accurately emulate the complexity and functionality of liver tissue. They can be generated from pluripotent and adult stem cells, as well as from liver tumor specimens, providing personalized models for studying tumor behavior and drug responses. Liver organoids retain the genetic variability of the original tumor and offer a robust platform for high-throughput drug screening and personalized treatment strategies. However, both organoids and spheroids have limitations, such as the absence of functional vasculature and immune components, which are essential for tumor growth and therapeutic responses. The field of preclinical modeling is evolving, with ongoing efforts to develop more predictive and personalized models that reflect the complexities of human liver cancer. By integrating these advanced <i>in vitro</i> tools, researchers can gain deeper insights into liver cancer biology and accelerate the development of novel treatments.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1536854"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028429","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}