Giuseppe Murdaca, Francesca Paladin, Sebastiano Gangemi
{"title":"Potential Genetic Approach to Specific Primary Immunodeficiencies: Which Perspectives?","authors":"Giuseppe Murdaca, Francesca Paladin, Sebastiano Gangemi","doi":"10.31083/FBL36795","DOIUrl":"https://doi.org/10.31083/FBL36795","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36795"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revisiting the Role of Platelet-Activating Factor in COVID-19-Induced Cardiovascular Complications.","authors":"Smaragdi Antonopoulou","doi":"10.31083/FBL36981","DOIUrl":"https://doi.org/10.31083/FBL36981","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36981"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna F Sheptulina, Ekaterina O Liusina, Olga A Zlobovskaya, Anton R Kiselev, Oxana M Drapkina
{"title":"Possible Role of Platelets in the Development and Progression of Non-Alcoholic Fatty Liver Disease.","authors":"Anna F Sheptulina, Ekaterina O Liusina, Olga A Zlobovskaya, Anton R Kiselev, Oxana M Drapkina","doi":"10.31083/FBL26748","DOIUrl":"10.31083/FBL26748","url":null,"abstract":"<p><p>To date, an increasing body of evidence supports the potential role of activated platelets in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This is likely due to their ability to secrete biologically active substances that regulate liver regeneration processes, ensure hemostasis, and participate in the immune response. Additionally, several studies have demonstrated the efficacy of antiplatelet agents in reducing inflammation, the severity of liver fibrosis, and the progression of fibrosis in non-alcoholic steatohepatitis (NASH). Since NAFLD is not an independent indication for antiplatelet therapy, the primary evidence regarding their efficacy in NAFLD has been derived from studies using animal models of NAFLD or in patients with concomitant cardiovascular diseases. This narrative review will discuss the main functions of platelets, their unique interactions with liver cells, and the outcomes of these interactions, as well as the results of studies evaluating the efficacy and safety of antiplatelet therapy in patients with NAFLD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26748"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NO Pain! No Cancer? The Crosstalk Between Nociception, ROS, and Cancer Development.","authors":"Tzu-Yin Chen, Tohru Yoshioka, Wen-Li Hsu","doi":"10.31083/FBL31328","DOIUrl":"10.31083/FBL31328","url":null,"abstract":"<p><p>Transient receptor potential (TRP) channels, particularly those involved in nociception (nociceptive TRP channels), are implicated in both pain and cancer development. Activation of these channels by diverse stimuli triggers calcium influx, leading to mitochondrial oxidative stress and reactive oxygen species (ROS) accumulation. This ROS production contributes to both nociceptive signaling (causing pain) and aging processes, including genomic instability, a key driver of carcinogenesis. Although a direct causal link between pain and cancer onset remains elusive, the shared involvement of nociceptive TRP channels strongly suggests a correlation. This opinion article proposes targeting the crosstalk between nociceptive TRP channels and ROS as a promising therapeutic strategy to mitigate cancer and cancer-associated pain simultaneously. While further research is needed to definitively establish a causal relationship between pain and cancer risk, the available evidence suggests that inhibiting this pathway may offer significant benefits for both cancer prevention and treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"31328"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Zhou, Hongsheng Li, Chen Chen, Hao Yang, Guicheng Zhang, Qin Zhang, Mengnan Wen, Lei Shi, Tong Xing, Ming Fan, An Qin, Jie Zhao, Shen'ao Zhou
{"title":"A Quality by Design (QbD) Project of Human Dermal Fibroblast and its Therapeutic Effects on Managing Degenerative Intervertebral Disc Fibrosis in Rabbit and Cynomolgus Monkey.","authors":"Li Zhou, Hongsheng Li, Chen Chen, Hao Yang, Guicheng Zhang, Qin Zhang, Mengnan Wen, Lei Shi, Tong Xing, Ming Fan, An Qin, Jie Zhao, Shen'ao Zhou","doi":"10.31083/FBL28062","DOIUrl":"10.31083/FBL28062","url":null,"abstract":"<p><strong>Background: </strong>Low back pain (LBP) is the leading cause of disability among the elderly, placing significant social and economic burdens on societies globally. A common cause of chronic LBP is lumbar disc degeneration. Previously, we reported that autologous or allogenic fibroblast injections could treat intervertebral disc degeneration (IVDD) in preclinical studies by maintaining disc height and stability through fibrosis. However, the pathway to successful drug development remains unclear.</p><p><strong>Methods: </strong>To develop a novel human allogenic fibroblast injection, we launched a quality-by-design (QbD) project focusing on human dermal fibroblasts (HDFs).</p><p><strong>Results: </strong>We developed a tissue separation process, HDF culture process, and HDF cryopreservation process. The tissue disinfection method used 5% povidone-iodine solution and 75% alcohol for 3-5 min each; the tissue digestion conditions used neutral protease AF followed by overnight soaking plus collagenase NB6 digestion for 2-3 h; the non-animal component medium contained high glucose dulbecco's modified eagle medium (DMEM) + 7.5% human platelet lysate (hPL); A cell density of 14,000-18,000 cells/cm<sup>2</sup> was used; the cell cryopreservation solution contained 75% CS10 + 10% human serum albumin (HSA) + 15% saline (NaCl). Finally, we explored its therapeutic effects by treating IVDD in rabbits.</p><p><strong>Conclusions: </strong>The model of lumbar disc degeneration in rabbits was induced by acupuncture, and HDF was injected into the intervertebral disc. The therapeutic effect of HDF was observed by imaging and histopathology at 1, 3, and 6 months after administration. HDF treatment significantly improved the water content of degenerative intervertebral discs and maintained the height and stability of intervertebral discs. Signal pathway analysis in cynomolgus monkeys suggested that the primary mechanism involves promoting disc fibrosis. Therefore, this study demonstrated the feasibility and cost-effectiveness of manufacturing FibroCell<sup>TM</sup>, a foreskin-derived human dermal fibroblast injection. FibroCell<sup>TM</sup> shows promise as a cell-based therapy for IVDD treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"28062"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Historical View and Some Unsolved Problems in Red Blood Cell Membrane Research.","authors":"Ingolf Bernhardt, Lars Kaestner","doi":"10.31083/FBL25331","DOIUrl":"10.31083/FBL25331","url":null,"abstract":"<p><p>The article provides a comprehensive overview of biological membrane lipid composition and distribution and ion transport processes, focusing particularly on red blood cells (RBCs). It begins with a historical perspective, detailing the introduction of the terms 'cell' and 'membrane' in biological sciences, and the development of the fluid-mosaic model of membrane structure. Early findings on ion transport highlighted the non-equilibrium distribution of Na<sup>+</sup> and K<sup>+</sup> across cell membranes, leading to the discovery of the Na<sup>+</sup>/K<sup>+</sup> pump. The article delves into the lipid composition of RBC membranes, emphasising the roles of various lipids, including cardiolipin, and the concept of lipid rafts. These rafts, enriched with sphingolipids and cholesterol, play crucial roles in cellular processes. Variations in RBC shapes are discussed, with biophysical theories explaining transformations and pathological conditions affecting RBC morphology, such as sickle cell anaemia. Na<sup>+</sup> and K<sup>+</sup> transporters in RBC membranes are explored, highlighting the almost ubiquitous presence of the Na<sup>+</sup>/K<sup>+</sup> pump (absent in Carnivora RBCs) and various ion channels, including the Gárdos and Piezo1 channels. The article notes species-specific differences in ion transport mechanisms and the activation or suppression of transporters during RBC maturation. The mechanism of residual ion transport is examined, questioning whether a Na<sup>+</sup>(K<sup>+</sup>)/H<sup>+</sup> antiporter exists in the human RBC membrane. Residual ion fluxes are mediated by this antiporter, influenced by the fatty acid composition of the RBC membrane. The outlook section underscores the need for further research to fully understand the complexities of RBC membrane structure and function, suggesting that many questions remain unanswered despite significant advances.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"25331"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiting Zhao, Lingyi Chen, Yantuanjin Ma, Shufen Wang
{"title":"Scutellarin Attenuates Pro-Inflammatory Foam Cell Formation and Facilitates M2 Polarization in Microglia during Copper Homeostasis Imbalance via the MAPK Signaling Pathway.","authors":"Qiting Zhao, Lingyi Chen, Yantuanjin Ma, Shufen Wang","doi":"10.31083/FBL36255","DOIUrl":"10.31083/FBL36255","url":null,"abstract":"<p><strong>Background: </strong>Clinical and experimental evidence indicates that copper has the ability to promote the progressive development of demyelinating diseases such as multiple sclerosis. Microglia-mediated neuroinflammation is believed to play a crucial role in this process. Scutellarin, a flavonoid compound, has anti-inflammatory, antioxidative, and neuroprotective effects.</p><p><strong>Aim: </strong>We investigated the effect of scutellarin on copper-induced inflammatory foam cell formation in microglia.</p><p><strong>Methods: </strong>We exposed BV2 murine microglial cells to copper, then collected the conditioned medium and co-cultured it with MO3.13 human glial cells to mimic myelin damage <i>in vitro</i>. The Cell Counting kit-8 assay, quantitative (polymerase chain reaction) PCR, enzyme-linked immunosorbent assay, Luxol fast blue staining, and western blotting were used to detect the cell phenotype. To investigate whether exposure of BV2 cells to copper can cause neurotoxicity and indirect damage to myelin cells, we determined whether BV2 cells promote inflammation through foam cell formation by oil red O staining and detection of malondialdehyde (MDA) content. Finally, we treated cells with scutellarin to investigate its therapeutic effects.</p><p><strong>Results: </strong>Exposure to copper activated the pro-inflammatory phenotype of microglia, as assessed by measuring the transcription of M1/M2-related biomarkers. In addition, increased copper intake by microglia promoted intracellular lipid accumulation and oxidation, facilitating foam cell formation. Rescue experiments showed that copper chelator ammonium tetrathiomolybdate (ATTM) and the lipid oxidation inhibitor ferrostatin-1 (Fer-1) significantly inhibited copper-induced inflammation, reduced intracellular lipid accumulation and MDA levels, and decreased foam cell formation. Moreover, copper-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in microglia led to a shift towards the M1 phenotype and foam cell transformation, which were effectively inhibited by ATTM, Fer-1, and the p38 MAPK inhibitor SB203580. Lastly, after treatment with scutellarin, copper-induced foam microglia exhibited inhibited p38 MAPK phosphorylation, increased production of neurotrophic factors, decreased expression of inflammatory mediators, reduced lipid accumulation, and induced polarization towards the M2 phenotype.</p><p><strong>Conclusions: </strong>Here, we demonstrated that copper can induce microglia to damage myelinating cells, with the key mechanism involving the phosphorylation of p38 MAPK. Scutellarin partially reversed the positive effects of copper on promoting microglial M1 polarization, lipid deposition, and lipid oxidation by mediating the p38 MAPK signaling pathway. Taken together, these results suggest that scutellarin may be a promising drug for the treatment of demyelinating diseases such as multiple sclerosis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36255"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Loss of Atoh8 Affects Neurocranial and Axial Skeleton Development in Zebrafish.","authors":"Ninfa Fragale, Satya Srirama Karthik Divvela, Victoria Clare Williams-Ward, Beate Brand-Saberi","doi":"10.31083/FBL26806","DOIUrl":"10.31083/FBL26806","url":null,"abstract":"<p><strong>Background: </strong>The basic helix-loop-helix (bHLH) transcription factor atonal homologue 8 (Atoh8) has been implicated in various developmental and physiological processes by means of transient knockdown and conditional knockout approaches in zebrafish, chick and mouse. Despite its demonstrated involvement in multiple tissues, the role of Atoh8 remains elusive in zebrafish. A recent permanent knockout study in zebrafish investigated the role of Atoh8 on the background of previous morpholino studies which demonstrated various developmental defects but could not find any of the morpholino-based effects in the mutant. In mice, a knockout study demonstrated involvement of the transcription factor in skeletal development, showing that disruption of the <i>atoh8</i> gene results in reduction of skeletal size. We investigated a mutant fish line generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9)-technology for possible phenotypic effects on zebrafish skeletogenesis.</p><p><strong>Methods: </strong>Here, we present a CRISPR/Cas9-generated <i>atoh8</i> permanent zebrafish mutant and investigate the phenotypic effects of the knockout on the developing zebrafish craniofacial and axial skeleton. We investigated the expression pattern of the gene in wildtype and conducted detailed morphometric analysis for a variety of bone and cartilage elements of the developing skeleton at 12 days post fertilisation (dpf) in zebrafish siblings from a heterozygous mating using detailed morphometric measurements and statistical analysis of the results.</p><p><strong>Results: </strong>Homozygous mutants are viable into late adulthood and show no overt morphological phenotype. Despite the prominent appearance of <i>atoh8</i> signal in various embryonic and larval craniofacial and axial skeletal structures, detailed morphometric analysis revealed only subtle phenotypic effects of the mutation on skeletal development in zebrafish. We found the formation of the orbital cartilages of the developing neurocranium and the progress of chordacentra mineralisation to be negatively affected by loss of the transcription factor.</p><p><strong>Conclusions: </strong>Despite the very subtle phenotypic effect of our mutation, we were able to show involvement of <i>atoh8</i> in the skeletal development of zebrafish. We attribute the mild phenotype to a compensatory mechanism induced by nonsense-mediated degradation of messenger ribonucleic acid (mRNA) as suggested in the recent literature. The effect of <i>atoh8</i>-disruption on zebrafish skeletal development suggests that the loss of <i>atoh8</i> cannot be compensated for at interfaces where more than one embryonic cell lineage contributes to bone and cartilage formation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26806"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huiyang Li, Xin Wang, Xinping Luo, Haiming Shi, Jian Li
{"title":"cGAS/STING/NLRP3 Signaling Pathway-Mediated Pyroptosis in Hypertrophic Cardiomyopathy Radiotherapy.","authors":"Huiyang Li, Xin Wang, Xinping Luo, Haiming Shi, Jian Li","doi":"10.31083/FBL26084","DOIUrl":"10.31083/FBL26084","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is a commonly employed treatment modality for cancer; however, its radiobiological effects in hypertrophic cardiomyopathy (HCM) remain unclear. Radiation exposure activates the cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, which is functionally associated with the activation of NOD-like Receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes, known mediators of pyroptotic cell death. Nonetheless, the underlying mechanism requires further investigation. Therefore, the objective of this study is to elucidate the role of the cGAS/STING/NLRP3 pathway in the process of cardiomyocyte pyroptosis during radiotherapy for HCM.</p><p><strong>Methods: </strong>Transverse aortic constriction surgery was conducted to establish a mouse model of pressure overload-induced HCM, followed by the administration of 30 Gray (Gy) radiation one-week post-surgery. Cardiac morphology and function were evaluated through echocardiographic techniques. Hematoxylin & Eosin staining, along with Wheat Germ Agglutinin (WGA) staining, were utilized to quantify the cross-sectional area of cardiomyocytes and the degree of left ventricular hypertrophy. The HL-1 mouse cardiac muscle cell line was subjected to 40 Gy of radiation using an X-ray irradiator to establish an <i>in vitro</i> model of HCM, with or without the application of the NLRP3 inhibitor MCC950 and cGAS overexpression. Various assays, including the Cell Counting Kit-8 (CCK8), enzyme-linked immunosorbent assay (ELISA), and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi- dazolylcarbocyanine iodide (JC-1) probe assays, were performed to assess cell viability, the concentrations of Interleukin (IL)-1β, IL-18, and cGAMP, as well as mitochondrial membrane potential. The morphology of cell membranes and mitochondria was analyzed using scanning electron microscopy (SEM) and fluorescence <i>in situ</i> hybridization (FISH) dual labelling techniques. The expression levels of cGAS, STING, and NLRP3 were evaluated through by western blot analysis.</p><p><strong>Results: </strong>Radiotherapy reduced cardiac hypertrophy, improved cardiac function, and decreased fibrotic changes in HCM mice when compared to control groups. The application of radiation resulted in pyroptosis in HL-1 cells and a reduction in cell viability; this effect that was alleviated by the inhibition of NLRP3, while overexpression of cGAS exacerbated the situation. Furthermore, radiation led to a decline in mitochondrial membrane potential and the leakage of mitochondrial DNA into the cytoplasm, which activated the cGAS-STING signaling pathway, thereby initiating pyroptosis. This activation was corroborated by elevated levels of pyroptosis-associated proteins, including cGAS, STING, NLRP3, caspase-1, Gasdermin D (GSDMD), cGAMP, IL-18, and IL-1β. Notably, the inhibition of NLRP3 effectively abolished the upregulation of IL-1","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26084"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD47 Contributes to the Proliferation of Breast Cancer.","authors":"Junbin Wang, Xia Wu, Xuejian Liu, Ying Xu","doi":"10.31083/FBL28210","DOIUrl":"10.31083/FBL28210","url":null,"abstract":"<p><strong>Background: </strong>The <i>CD47</i> molecule (<i>CD47</i>) performs a novel role in regulating immunoreactions by binding to signal-regulatory protein alpha (<i>SIRPα</i>), resulting in the tumorigenesis of multiple malignant neoplasms. However, its effects and mechanisms in breast cancer (BC) remain unknown.</p><p><strong>Methods: </strong>To explore the molecular mechanisms and explicit impacts of CD47, we screened two databases for <i>CD47</i>-associated signaling pathways and cellular functions. BC samples and patients' basic information were collected to identify the statistical significance of <i>CD47</i> expression. We also constructed experiments to validate the regulatory role of <i>CD47</i> in BC cell proliferation.</p><p><strong>Results: </strong>Analysis of the TCGA-BRCA, GSE42568, and GSE15852 datasets demonstrated an elevated level of <i>CD47</i> in BC tissues. A Venn diagram revealed 11,194 co-expressed genes, and pathway analysis linked elevated <i>CD47</i> levels to critical signaling pathways, such as cytokine-receptor interactions and Janus kinase/signal transducer and activator of transcription (<i>JAK/STAT</i>) signaling, which are integral to cell proliferation and invasiveness. Clinical data from 108 BC specimens showed that <i>CD47</i> localization was primarily membranous, with higher levels correlating with proliferation marker Ki-67 (<i>Ki-67</i>) expression (<i>p</i> < 0.0001) and advanced tumor/node/metastasis (TNM) stage (<i>p</i> < 0.0001). Additionally, functional assays demonstrated that <i>CD47</i> depletion reduced cell viability (<i>p</i> < 0.01), migration (<i>p</i> < 0.001), and invasion (<i>p</i> < 0.05 in 4T1 cells; <i>p</i> < 0.001 in MDA-MB-231 cells) <i>in vitro</i> and led to smaller tumor volumes (<i>p</i> < 0.0001) <i>in vivo</i>.</p><p><strong>Conclusion: </strong><i>CD47</i> is a key regulator of BC cell proliferation and invasiveness and serves as a potential marker for assessing tumor aggressiveness and guiding therapeutic strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"28210"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}