Frontiers in Cell and Developmental Biology最新文献

{"title":"Cell-based high-content approach for SARS-CoV-2 neutralization identifies unique monoclonal antibodies and PI3K pathway inhibitors.","authors":"Carly R Cabel, Briana A Guzman, Elaheh Alizadeh, Shuaizhi Li, Cameron Holberg, Chonlarat Wichaidit, Darren A Cusanovich, Andrew L Paek, Gregory R J Thatcher, Koenraad Van Doorslaer, Rachel S Nargi, Rachel E Sutton, Naveenchandra Suryadevara, James E Crowe, Robert H Carnahan, Samuel K Campos, Curtis A Thorne","doi":"10.3389/fcell.2025.1538934","DOIUrl":"10.3389/fcell.2025.1538934","url":null,"abstract":"<p><p>The sudden rise of the SARS-CoV-2 virus and the delay in development of effective therapeutics for mitigation made evident a need for ways to screen compounds that can block infection and prevent further pathogenesis and spread. However, identifying effective drugs that are efficacious against viral infection and replication with minimal toxicity for the patient can be difficult. Monoclonal antibodies were shown to be effective, but as the SARS-CoV-2 mutated, these antibodies became ineffective. Small-molecule antivirals were identified using pseudovirus constructs to recapitulate infection in nonhuman cells, such as Vero E6 cells. However, the impact was limited due to poor translation of these compounds in the clinical setting. This is partly due to the lack of similarity of screening platforms to the <i>in vivo</i> physiology of the patient and partly because drugs effective <i>in vitro</i> showed dose-limiting toxicities. In this study, we performed two high-throughput screens in human lung adenocarcinoma cells with authentic SARS-CoV-2 virus to identify both monoclonal antibodies that neutralize the virus and clinically useful kinase inhibitors to block the virus and prioritize minimal host toxicity. Using high-content imaging combined with single-cell and multidimensional analysis, we identified antibodies and kinase inhibitors that reduce viral infection without affecting the host. Our screening technique uncovered novel antibodies and overlooked kinase inhibitors (i.e., PIK3i, mTORi, and multiple RTKi) that could be effective against the SARS-CoV-2 virus. Further characterization of these molecules will streamline the repurposing of compounds for the treatment of future pandemics and uncover novel mechanisms viruses use to hijack and infect host cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1538934"},"PeriodicalIF":4.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247300","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":"Unraveling the deadly dance: endothelial cells and neutrophils in sepsis-induced acute lung injury/acute respiratory distress syndrome.","authors":"Xiujuan Xu, Qi Zhang, Zheng Lv, Chuji Cheng, Junjing Zha, Huaqing Shu, Hairong Xiao, Shangwen Pan","doi":"10.3389/fcell.2025.1551138","DOIUrl":"10.3389/fcell.2025.1551138","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe complications with high morbidity and mortality rates, characterized primarily by diffuse alveolar damage, endothelial dysfunction, and local inflammatory responses. Neutrophils and endothelial cells (ECs) play crucial roles in the pathogenesis and progression of these diseases. Neutrophils are important regulators of inflammation, while endothelial dysfunction exacerbates vascular permeability and the inflammatory cascade. The interaction between neutrophils and ECs is vital for the development of ALI/ARDS induced by sepsis, driving the pathological processes of inflammation and tissue damage. Despite advancements in treatment strategies such as protective mechanical ventilation and fluid management, effective methods for rapid lung tissue recovery or significant improvement in outcomes remain lacking. Therefore, we comprehensively summarize the current literature to gain deeper insights into the roles of neutrophils, ECs, and their interactions in sepsis-induced ALI/ARDS, hoping to provide critical insights into the mechanisms underlying sepsis-related ALI/ARDS and potential pathways for developing new therapeutic approaches.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1551138"},"PeriodicalIF":4.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233627","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":"Corrigendum: A novel variant in <i>CLCN7</i> regulates the coupling of angiogenesis and osteogenesis.","authors":"Hui Peng, Hong-Bo He, Ting Wen","doi":"10.3389/fcell.2025.1616778","DOIUrl":"https://doi.org/10.3389/fcell.2025.1616778","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fcell.2020.599826.].</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1616778"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224936","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":"Synchrotron radiation FTIR microspectroscopy enables measuring dynamic cell identity patterning during human 3D differentiation.","authors":"Tanja Dučić, Francisco Rodriguez-Yañez, Elena Gonzalez-Muñoz","doi":"10.3389/fcell.2025.1569187","DOIUrl":"10.3389/fcell.2025.1569187","url":null,"abstract":"<p><p>Human cell fate specification, particularly in neural development, is difficult to study due to limited access to embryonic tissues and differences from animal models. Human induced pluripotent stem cells (hiPSCs) and 3D organoid models enable the study of early human neural development, surpassing limitations of 2D cultures by incorporating crucial cell-cell and cell-matrix interactions. In this study, we used synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy to examine biomolecular profiles of 3D-differentiated organoids, specifically embryoid bodies (EBs) and neural spheroids (NS), derived from hiPSCs. SR-FTIR allowed us to analyze these organoids' cellular identity at a biomolecular level, offering a holistic view that complements specific cell markers. Our findings reveal distinct biomolecular identities in 3D organoids, with differences in DNA structure, lipid saturation, phospholipid composition, and protein conformations. This approach highlights that cellular identity is shaped by more than gene expression alone; it involves unique biomolecular compositions that can be detected even in complex, multicellular environments. By demonstrating the role of molecular configuration in cell differentiation, our findings suggest that differentiation processes extend beyond genetics, involving interdependent biochemical signals. This study demonstrates the unique efficacy SR-FTIR in analyzing human-specific 3D models for investigating complex multicellular differentiation mechanisms, offering new avenues for understanding the biochemical basis of human development and disease.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1569187"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224938","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":"Based on TransRes-Pix2Pix network to generate the OBL image during SMILE surgery.","authors":"Zeyu Zhu, Peifen Lin, Lingling Zhong, Qing Wang, Jingjing Xu, Kang Yu, Zheliang Guo, Yicheng Xu, Taorong Qiu, Yifeng Yu","doi":"10.3389/fcell.2025.1598475","DOIUrl":"10.3389/fcell.2025.1598475","url":null,"abstract":"<p><strong>Aim: </strong>Generative adversarial networks (GANs) were employed to predict the morphology of OBL before femtosecond laser scanning during SMILE.</p><p><strong>Methods: </strong>A retrospective cross-sectional analysis was conducted on 4,442 eyes from 2,265 patients who underwent SMILE surgery at the Ophthalmic Center of the Second Affiliated Hospital of Nanchang University between June 2021 and August 2022. Surgical videos, preoperative panoramic corneal images, and intraoperative OBL images were collected. The dataset was randomly split into a training set of 3,998 images and a test set of 444 images for model development and evaluation, respectively. Structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) were used to quantitatively assess OBL image quality. The accuracy of intraoperative OBL image predictions was also compared across different models.</p><p><strong>Results: </strong>Seven GAN models were developed. Among them, the model incorporating a residual structure and Transformer module within the Pix2pix framework exhibited the best predictive performance. This model's intraoperative OBL morphology prediction demonstrated high consistency with actual images (SSIM = 0.67, PSNR = 26.02). The prediction accuracy of Trans-Pix2Pix (SSIM = 0.66, PSNR = 25.76), Res-Pix2Pix (SSIM = 0.65, PSNR = 23.08), and Pix2Pix (SSIM = 0.64, PSNR = 22.97), Pix2PixHD (SSIM = 0.63, PSNR = 23.46), DCGAN (SSIM = 0.58, PSNR = 20.46) was slightly lower, while the CycleGAN model (SSIM = 0.51, PSNR = 18.30) showed the least favorable results.</p><p><strong>Conclusion: </strong>The GAN model developed for predicting intraoperative OBL morphology based on preoperative panoramic corneal images demonstrates effective predictive capabilities and offers valuable insights for ophthalmologists in surgical planning.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1598475"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224935","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 potent neuroepithelium-promoting activity of Otx2 during gastrulation, as demonstrated by its exogenous epiblast-wide expression in chicken embryos.","authors":"Naoya Takami, Kagayaki Kato, Koya Yoshihi, Akihito Kawamura, Hideaki Iida, Hisato Kondoh","doi":"10.3389/fcell.2025.1599287","DOIUrl":"10.3389/fcell.2025.1599287","url":null,"abstract":"<p><p>Although Otx2 has been a topic of research for over 3 decades, the role of Otx2 expressed in the brain-forming anterior epiblast during gastrulation has not been clarified. We focused on epiblast regions where Otx2 expression is absent or downregulated, namely, the posterior epiblast and tissue belts along the bending of the neural plate. The developmental events that occurred after filling these gaps with exogenous Otx2 provided information about the roles of Otx2 during gastrulation. The following pleiotropic effects were observed: (1) development of an open and flat midbrain and hindbrain, which occurred by unzippering the previously closed neural tube; (2) precocious neural tube development at the cervical level, which resulted in thick and unclosed neural tissue; (3) absence of the sinus rhomboidalis, where neuromesodermal progenitor (NMP) stem cells multiply to provide a cell source for the trunk posterior extension; and (4) inhibition of somite development. To elucidate the principles underlying these developmental abnormalities, the cellular events were analyzed using live imaging of epiblast cells, the cell states were characterized via transcriptome analysis, and the spatial organization of transcription factor expression was determined by immunohistology. Common Otx2 activities that accounted for these pleiotropic effects were identified: (1) significant promotion of neuroepithelium development, which overrides the bipotential nature of NMPs, resulting in the loss of paraxial mesoderm precursors and multiplying NMP stem cell populations, and (2) the development of bending-refractory neural tissues. Owing to these Otx2 functions, Otx2-expressing anterior epiblast cells develop into vast amounts of brain tissue in advance of trunk neurogenesis, which occurs on a much smaller scale. We did not observe that exogenous Otx2 expression affected CNS regional specification during gastrulation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1599287"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224939","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":"\"Proteinjury\": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.","authors":"Vladimir F Lazarev, Bashar A Alhasan, Irina V Guzhova, Boris A Margulis","doi":"10.3389/fcell.2025.1593122","DOIUrl":"10.3389/fcell.2025.1593122","url":null,"abstract":"<p><p>Cerebrospinal fluid (CSF) is a vital body fluid that supports the normal physiological functions of the brain and spinal cord. However, pathological conditions associated with injuries and neurodegenerative diseases lead to the accumulation of peptides, proteins, and their oligomers or aggregated forms in the CSF. In such cases, the CSF serves as a carrier and distributor of these pathogenic structures, facilitating secondary damage through the cytotoxic effects of protein aggregates. To describe this phenomenon, we introduce the term \"proteinjury.\" To date, accumulating experimental evidence has identified key protein complexes that contribute to proteinjury, particularly in the context of neurodegenerative diseases, traumatic brain injuries, ischemic strokes and others commonly associated with cell death and the appearance of formerly cytoplasmic proteins in the extracellular milieu. This review explores the mechanisms underlying the formation of pathogenic protein complexes in CSF, the diagnostic potential of CSF protein biomarkers, and the prospects for rehabilitation therapies aimed at preventing secondary damage mediated by pathogenic protein structures in CSF. Based on the findings discussed in this review, we conclude that proteinjury represents a universal and critical mechanism in the progression of various neurodegenerative disorders, and a deeper understanding of this phenomenon may provide new insights for the development of targeted interventions to improve clinical outcomes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1593122"},"PeriodicalIF":4.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215430","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 orobasal organ (of Ackerknecht) is present in prenatal mice.","authors":"Sven Schumann, Jan R Munk, Michael J Schmeisser, Moritz Staeber","doi":"10.3389/fcell.2025.1590311","DOIUrl":"10.3389/fcell.2025.1590311","url":null,"abstract":"<p><strong>Background: </strong>In 1912, the veterinary anatomist Eberhard Ackerknecht described morphologically highly variable epithelial invaginations behind the medial mandibular incisors. This orobasal organ (of Ackerknecht) is present in different mammalian species including humans, but its presence in mice was under debate in literature. While the function of the orobasal organ is still unknown, it might play a role in the development of cysts of the oral floor.</p><p><strong>Methods: </strong>H&E-stained histological serial slides of the developing oral floor of C57BL/6J mice embryos were investigated (n = 40).</p><p><strong>Results: </strong>The orobasal organ was present in mice and developed between prenatal days E15 and E17 (prevalence in E15 embryos: 0%, prevalence in E17 embryos: 90.5%). The organ was present both in male and female embryos. In E17, the organ had an average size of 68.75 (±41.1) μm x 58.75 (±8.5) μm x 345 (±28.3) μm (length x depth x width).</p><p><strong>Discussion: </strong>While the existence of an orobasal organ was already shown for pre- and postnatal rats, there was only one publication dealing with the orobasal organ in mice. In this study, adult mice were investigated and no orobasal organ was found. Here, we demonstrate the existence of an orobasal organ in mice, at least in embryos. The presence of the orobasal organ in a common model organism will help to investigate its pre- and postnatal development, as well as possible physiological functions of this structure.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1590311"},"PeriodicalIF":4.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215442","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":"Architecture and molecular machinery of skeletal myofibers: a systematic review of the structure-function relationships.","authors":"Jing Zhao, Xu Du, Wei Fang, Hongxia Zhu, Binglin Yue","doi":"10.3389/fcell.2025.1602607","DOIUrl":"10.3389/fcell.2025.1602607","url":null,"abstract":"<p><p>The skeletal muscle, one of the largest tissues in mammals, plays a crucial role in maintaining body movement and energy metabolism. Dysfunction or damage to the skeletal muscle can lead to various muscle diseases, such as muscular dystrophy, myasthenia, and others. The myofiber presents the fundamental structural unit of the skeletal muscle, and research on its structure and biological function is of great significance. Here, we review the latest progress in the structural and functional aspects of the myofiber, focusing on myofibril, the sarcoplasmic reticulum, mitochondria, and the cytoskeleton. The basic properties and dynamic interactions of a large number of muscle proteins have been described in detail, including the scaffold construction of core protein components and the fine-tuning of secondary protein components with functional redundancy. This overview provides new insights into skeletal muscle pathophysiology.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1602607"},"PeriodicalIF":4.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215431","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":"Generalized arteriomegaly as a precursor to multifocal aneurysmal disease: implications for early intervention.","authors":"Zhaohua Cai, Ben He","doi":"10.3389/fcell.2025.1592225","DOIUrl":"10.3389/fcell.2025.1592225","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1592225"},"PeriodicalIF":4.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215441","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}