Frontiers in Cell and Developmental Biology最新文献

{"title":"Understanding the impact of ER stress on lung physiology.","authors":"Zhiling Fu, Wei Wang, Yuan Gao","doi":"10.3389/fcell.2024.1466997","DOIUrl":"10.3389/fcell.2024.1466997","url":null,"abstract":"<p><p>Human lungs consist of a distinctive array of cell types, which are subjected to persistent challenges from chemical, mechanical, biological, immunological, and xenobiotic stress throughout life. The disruption of endoplasmic reticulum (ER) homeostatic function, triggered by various factors, can induce ER stress. To overcome the elevated ER stress, an adaptive mechanism known as the unfolded protein response (UPR) is activated in cells. However, persistent ER stress and maladaptive UPR can lead to defects in proteostasis at the cellular level and are typical features of the lung aging. The aging lung and associated lung diseases exhibit signs of ER stress-related disruption in cellular homeostasis. Dysfunction resulting from ER stress and maladaptive UPR can compromise various cellular and molecular processes associated with aging. Hence, comprehending the mechanisms of ER stress and UPR components implicated in aging and associated lung diseases could enable to develop appropriate therapeutic strategies for the vulnerable population.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1466997"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914152","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":"PCAT19: the role in cancer pathogenesis and beyond.","authors":"Haijun Hu, Hongliang Luo, Ziqing Deng","doi":"10.3389/fcell.2024.1435717","DOIUrl":"10.3389/fcell.2024.1435717","url":null,"abstract":"<p><p>PCAT19, a long non-coding RNA, has attracted considerable attention due to its diverse roles in various malignancies. This work compiles current research on PCAT19's involvement in cancer pathogenesis and progression. Abnormal expression of PCAT19 has been observed in various cancers, and its correlation with clinical features and prognosis positions it as a promising prognostic biomarker. Additionally, its ability to effectively differentiate between tumor and normal tissues suggests significant diagnostic value. PCAT19 exhibits a dual nature, functioning either as an oncogene or a tumor suppressor, depending on the cancer type. It is implicated in a range of tumor-related activities, including cell proliferation, apoptosis, invasion, migration, metabolism, as well as tumor growth and metastasis. PCAT19 acts as a competing endogenous RNA (ceRNA) or interacts with proteins to regulate critical cancer-related pathways, such as MELK signaling, p53 signaling, and cell cycle pathways. Furthermore, emerging evidence suggests that PCAT19 plays a role in the modulation of neuropathic pain, adding complexity to its functional repertoire. By exploring the molecular mechanisms and pathways associated with PCAT19, we aim to provide a comprehensive understanding of its multifaceted roles in human health and disease, highlighting its potential as a therapeutic target for cancer and pain management.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1435717"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914148","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":"Differentiation ability of hematopoietic stem cells and mesenchymal stem cells isolated from human peripheral blood.","authors":"Echambadi Loganathan Samundeshwari, Surekha Kattaru, Sireesha Kodavala, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma","doi":"10.3389/fcell.2024.1450543","DOIUrl":"10.3389/fcell.2024.1450543","url":null,"abstract":"<p><p>Human hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are the major stem cells of the bone marrow and are usually isolated from the peripheral blood. In the present study, we isolated these stem cells by an apheresis method from a donor who was administered granulocyte colony-stimulating factor (G-CSF). <i>In vitro</i> propagation of these stem cells showed a plastic-adherence property expressing CD73 and CD105 surface markers, which is a characteristic feature of MSCs. HSCs are non-adherent cells growing as a suspension culture, expressing CD150, CD133, CD34, and CD45 on their surface, which regulate the quiescence nature, and they derive energy from anaerobic glycolysis. The HSCs grow slowly compared to MSCs, are more viable, and survive for long periods under <i>in vitro</i> conditions, which are due to the expression of telomerase, BCL2, and Notch1 genes. The poor viability of MSCs in the culture due to the prominent expression of apoptotic genes BAX, caspase-3, and caspase-9 leads to rapid apoptosis. This was evident even in cells (astrocytes, osteocytes, and beta cells of the islets of Langerhans) differentiated from HSCs and MSCs, thus highlighting the importance of HSCs, the naive stem cells, in regeneration of tissues.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1450543"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914141","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":"Ferroptosis and its role in osteoarthritis: mechanisms, biomarkers, and therapeutic perspectives.","authors":"Shanyu Lu, Zhenyu Liu, Meiling Qi, Yingchao Wang, Le Chang, Xiaolong Bai, Yingguang Jiao, Xinyao Chen, Junping Zhen","doi":"10.3389/fcell.2024.1510390","DOIUrl":"10.3389/fcell.2024.1510390","url":null,"abstract":"<p><p>Osteoarthritis (OA) is one of the leading causes of disability worldwide, characterized by a complex pathological process involving cartilage degradation, synovial inflammation, and subchondral bone remodeling. In recent years, ferroptosis, a form of programmed cell death driven by iron-dependent lipid peroxidation, has been recognized as playing a critical role in the onset and progression of OA. Investigating the molecular mechanisms of ferroptosis and its involvement in OA may offer novel strategies for diagnosing and treating this disease. This review first outlines the core mechanisms of ferroptosis, with a particular focus on the roles of critical molecules such as Glutathione Peroxidase 4 (GPX4), Transferrin Receptor 1 (TfR1), and Nuclear Receptor Coactivator 4 (NCOA4). Subsequently, this study examines the specific impacts of ferroptosis on the pathophysiology of OA. Building on this, the potential of ferroptosis-related biomarkers for OA diagnosis and treatment is highlighted, along with proposed therapeutic strategies targeting ferroptosis regulation. This review aims to deepen the understanding of ferroptosis mechanisms and advance the clinical application of regulatory therapies for OA.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1510390"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914143","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":"FTO in health and disease.","authors":"Daniel Benak, Anezka Sevcikova, Kristyna Holzerova, Marketa Hlavackova","doi":"10.3389/fcell.2024.1500394","DOIUrl":"10.3389/fcell.2024.1500394","url":null,"abstract":"<p><p>Fat mass and obesity-associated (FTO) protein, a key enzyme integral to the dynamic regulation of epitranscriptomic modifications in RNAs, significantly influences crucial RNA lifecycle processes, including splicing, export, decay, and translation. The role of FTO in altering the epitranscriptome manifests across a spectrum of physiological and pathological conditions. This review aims to consolidate current understanding regarding the implications of FTO in health and disease, with a special emphasis on its involvement in obesity and non-communicable diseases associated with obesity, such as diabetes, cardiovascular disease, and cancer. It also summarizes the established molecules with FTO-inhibiting activity. Given the extensive impact of FTO on both physiology and pathophysiology, this overview provides illustrative insights into its roles, rather than an exhaustive account. A proper understanding of FTO function in human diseases could lead to new treatment approaches, potentially unlocking novel avenues for addressing both metabolic disorders and malignancies. The evolving insights into FTO's regulatory mechanisms hold great promise for future advancements in disease treatment and prevention.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1500394"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914145","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":"Insights and therapeutic advances in pancreatic cancer: the role of electron microscopy in decoding the tumor microenvironment.","authors":"Hong Dai, Xingxuan Chen, Jiawen Yang, Rodrigo Azevedo Loiola, Aiping Lu, Kenneth C P Cheung","doi":"10.3389/fcell.2024.1460544","DOIUrl":"10.3389/fcell.2024.1460544","url":null,"abstract":"<p><p>Pancreatic cancer is one of the most lethal cancers, with a 5-year overall survival rate of less than 10%. Despite the development of novel therapies in recent decades, current chemotherapeutic strategies offer limited clinical benefits due to the high heterogeneity and desmoplastic tumor microenvironment (TME) of pancreatic cancer as well as inefficient drug penetration. Antibody- and nucleic acid-based targeting therapies have emerged as strong contenders in pancreatic cancer drug discovery. Numerous studies have shown that these strategies can significantly enhance drug accumulation in tumors while reducing systemic toxicity. Additionally, electron microscopy (EM) has been a critical tool for high-resolution analysis of the TME, providing insights into the ultrastructural changes associated with pancreatic cancer progression and treatment responses. This review traces the current and technological advances in EM, particularly the development of ultramicrotomy and improvements in sample preparation that have facilitated the detailed visualization of cellular and extracellular components of the TME. This review highlights the contribution of EM in assessing the efficacy of therapeutic agents, from revealing apoptotic changes to characterizing the effects of novel compounds like ionophore antibiotic gramicidin A on cellular ultrastructures. Moreover, the review delves into the potential of EM in studying the interactions between the tumor microbiome and cancer cell migration, as well as in aiding the development of targeted therapies like antibody-drug conjugates (ADCs) and aptamer-drug conjugates (ApDCs).</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1460544"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914146","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":"Transcriptomics as a predictor of biopharmaceutically favourable glycan profiles.","authors":"Ben West, Pavlos Kotidis, Alena Istrate, Daniele Perna, Gary Finka, A Jamie Wood, Daniel Ungar","doi":"10.3389/fcell.2024.1504381","DOIUrl":"10.3389/fcell.2024.1504381","url":null,"abstract":"<p><p><i>N</i>-glycosylation plays a crucial role in defining the pharmacological properties and efficacy of therapeutic proteins, commonly referred to as biologics. The inherent complexity and lack of a templated process in glycosylation leads to a wide variation in glycan structures, posing significant challenges in achieving consistent glycan profiles on biologics. This study leverages omics technologies to predict which cell lines are likely to yield optimal glycosylation profiles, based on the existing knowledge of the functional impact of specific glycan structures on the pharmacokinetics, immunogenicity, and stability of therapeutic antibodies. The study highlights that bulk RNA-sequencing data holds predictive power for glycosylation outcomes in of monoclonal antibodies (mAbs). For instance, Alg5 is identified to be predictive, before beginning a mAb production run, of mAbs bearing higher levels of Man5. This is inferred to increase glycosylation site occupancy on endogenous proteins, thereby intensifying competition for glycosylation enzymes in the Golgi and indirectly influencing mAb glycan processing. Additionally, the elevation of the UDP-Gal transporter in cell lines expressing mAbs with a single galactose residue is also observed intranscriptomic data prior to beginning a production run. These findings suggest that early-stage transcriptomics can aid in the streamlined development of cell lines by enabling pre-emptive adjustments to enhance glycosylation. The study also underscores that while transcriptomic data can predict certain glycosylation trends, more crucial factors affecting glycan profiles, such as enzyme localization within the Golgi apparatus and endogenous competition for glycosylation machinery, are not captured within the transcriptomic data. These findings suggest that while transcriptomics provides valuable insights, enzyme localization and intracellular dynamics are critical determinants of glycosylation outcomes. Our study starts to address the relevant mechanisms essential for improving cell line development strategies and achieving consistent glycosylation in biologics production.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1504381"},"PeriodicalIF":4.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914150","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":"Flow-cytometry reveals mitochondrial DNA accumulation in <i>Saccharomyces cerevisiae</i> cells during cell cycle arrest.","authors":"Elena Yu Potapenko, Nataliia D Kashko, Dmitry A Knorre","doi":"10.3389/fcell.2024.1497652","DOIUrl":"10.3389/fcell.2024.1497652","url":null,"abstract":"<p><p>Mitochondria are semi-autonomous organelles containing their own DNA (mtDNA), which is replicated independently of nuclear DNA (nDNA). While cell cycle arrest halts nDNA replication, mtDNA replication continues. In <i>Saccharomyces cerevisiae</i>, flow cytometry enables semi-quantitative estimation of mtDNA levels by measuring the difference in signals between cells lacking mtDNA and those containing mtDNA. In this study, we used flow cytometry to investigate mtDNA accumulation in yeast cells under G1 and G2 phase cell cycle arrest conditions utilising thermosensitive mutants <i>cdc4-3</i> and <i>cdc15-2</i>. In line with the previous studies, cell cycle arrest induced a several-fold accumulation of mtDNA in both mutants. The total DNA levels in arrested cells correlated with cell forward scattering, suggesting a relationship between individual cell mtDNA quantity and size. In cell cycle-arrested cells, we observed no correlation between cell size and intercellular mtDNA copy number variability. This implies that as cell size increases during arrest, the mtDNA content remains within a specific limited range for each size class. This observation suggests that mtDNA quantity control mechanisms can function in cell cycle-arrested cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1497652"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906614","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":"Advancements in pseudouridine modifying enzyme and cancer.","authors":"Kaijie Liu, Shujun Zhang, Yafeng Liu, Xinjun Hu, Xinyu Gu","doi":"10.3389/fcell.2024.1465546","DOIUrl":"10.3389/fcell.2024.1465546","url":null,"abstract":"<p><p>Pseudouridine (Ψ) is a post-transcriptional modifier of RNA, often referred to as the 'fifth nucleotide' owing to its regulatory role in various biological functions as well as because of its significant involvement in the pathogenesis of human cancer. In recent years, research has revealed various Ψ modifications in different RNA types, including messenger RNA, transfer RNA, ribosomal RNA, small nuclear RNA, and long noncoding RNA. Pseudouridylation can significantly alter RNA structure and thermodynamic stability, as the Ψ-adenine (A) base pair is more stable than the typical uridine (U)-A base pair is due to its structural similarity to adenine. Studies have linked Ψ expression to the development and progression of several digestive system cancers, such as liver cancer and colorectal cancer, and nondigestive system cancers, such as breast cancer, non-small cell lung cancer, prostate cancer, glioblastoma, ovarian cancer, oral squamous cell carcinoma, and pituitary cancer. The present review briefly outlines the chemical structure, synthesis, and regulatory mechanisms of Ψ. This review summarizes the effects of pseudouridylation on various substrates of RNA and briefly discusses methods for detecting Ψ. Last, it focuses on how RNA pseudouridylation influences different cancers, emphasizing the search for novel approaches to cancer diagnosis, treatment, and prognosis through Ψ modification.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1465546"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906611","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":"Retraction: Designing of SiO₂ mesoporous nanoparticles loaded with mometasone furoate for potential nasal drug delivery: <i>Ex vivo</i> evaluation and determination of pro-inflammatory interferon and interleukin mRNA expression.","authors":"","doi":"10.3389/fcell.2024.1540228","DOIUrl":"https://doi.org/10.3389/fcell.2024.1540228","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fcell.2022.1026477.].</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1540228"},"PeriodicalIF":4.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902691","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}