Yue Wu, Siyuan Wu, Yinghai Yu, Xiaojun Hu, Ting Zhao, Yan Jiang, Bilian Ke
{"title":"Blinking characteristics analyzed by a deep learning model and the relationship with tear film stability in children with long-term use of orthokeratology.","authors":"Yue Wu, Siyuan Wu, Yinghai Yu, Xiaojun Hu, Ting Zhao, Yan Jiang, Bilian Ke","doi":"10.3389/fcell.2024.1517240","DOIUrl":"10.3389/fcell.2024.1517240","url":null,"abstract":"<p><strong>Purpose: </strong>Using deep learning model to observe the blinking characteristics and evaluate the changes and their correlation with tear film characteristics in children with long-term use of orthokeratology (ortho-K).</p><p><strong>Methods: </strong>31 children (58 eyes) who had used ortho-K for more than 1 year and 31 age and gender-matched controls were selected for follow-up in our ophthalmology clinic from 2021/09 to 2023/10 in this retrospective case-control study. Both groups underwent comprehensive ophthalmological examinations, including Ocular Surface Disease Index (OSDI) scoring, Keratograph 5M, and LipiView. A deep learning system based on U-Net and Swim-Transformer was proposed for the observation of blinking characteristics. The frequency of incomplete blinks (IB), complete blinks (CB) and incomplete blinking rate (IBR) within 20 s, as well as the duration of the closing, closed, and opening phases in the blink wave were calculated by our deep learning system. Relative IPH% was proposed and defined as the ratio of the mean of IPH% within 20 s to the maximum value of IPH% to indicate the extent of incomplete blinking. Furthermore, the accuracy, precision, sensitivity, specificity, F1 score of the overall U-Net-Swin-Transformer model, and its consistency with built-in algorithm were evaluated as well. Independent t-test and Mann-Whitney test was used to analyze the blinking patterns and tear film characteristics between the long-term ortho-K wearer group and the control group. Spearman's rank correlation was used to analyze the relationship between blinking patterns and tear film stability.</p><p><strong>Results: </strong>Our deep learning system demonstrated high performance (accuracy = 98.13%, precision = 96.46%, sensitivity = 98.10%, specificity = 98.10%, F1 score = 0.9727) in the observation of blinking patterns. The OSDI scores, conjunctival redness, lipid layer thickness (LLT), and tear meniscus height did not change significantly between two groups. Notably, the ortho-K group exhibited shorter first (11.75 ± 7.42 s vs. 14.87 ± 7.93 s, p = 0.030) and average non-invasive tear break-up times (NIBUT) (13.67 ± 7.0 s vs. 16.60 ± 7.24 s, p = 0.029) compared to the control group. They demonstrated a higher IB (4.26 ± 2.98 vs. 2.36 ± 2.55, p < 0.001), IBR (0.81 ± 0.28 vs. 0.46 ± 0.39, p < 0.001), relative IPH% (0.3229 ± 0.1539 vs. 0.2233 ± 0.1960, p = 0.004) and prolonged eye-closing phase (0.18 ± 0.08 s vs. 0.15 ± 0.07 s, p = 0.032) and opening phase (0.35 ± 0.12 s vs. 0.28 ± 0.14 s, p = 0.015) compared to controls. In addition, Spearman's correlation analysis revealed a negative correlation between incomplete blinks and NIBUT (for first-NIBUT, r = -0.292, p = 0.004; for avg-NIBUT, r = -0.3512, p < 0.001) in children with long-term use of ortho-K.</p><p><strong>Conclusion: </strong>The deep learning system based on U-net and Swim-Transformer achieved optimal performance in the observation of blinking characteristics. Ch","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1517240"},"PeriodicalIF":4.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398728","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}
Kerstin Wendland, Lea Koblin, Dirk Stobbe, Anna Dahms, Debora Singer, Sander Bekeschus, Jan Wesche, Janosch Schoon, Konstanze Aurich
{"title":"Lyophilized human platelet lysate: manufacturing, quality control, and application.","authors":"Kerstin Wendland, Lea Koblin, Dirk Stobbe, Anna Dahms, Debora Singer, Sander Bekeschus, Jan Wesche, Janosch Schoon, Konstanze Aurich","doi":"10.3389/fcell.2025.1513444","DOIUrl":"10.3389/fcell.2025.1513444","url":null,"abstract":"<p><strong>Background: </strong>A significant number of platelet concentrates (PCs) is discarded daily in blood banks due to limited shelf life. Human platelet lysate (HPL), derived from expired PCs, has gained attention as an ethical and sustainable cell culture media supplement in biomedical research and cell therapy production. However, HPL is subject to decisive disadvantages such as batch differences and lack of storage stability. To overcome these limitations and to enhance the applicability of HPL, we developed an HPL manufacturing protocol including a lyophilization process. The aim of this study was to investigate the influence of HPL lyophilization on parameters of quality control, including growth factor concentrations and the culture of human mesenchymal stromal cells (hMSCs).</p><p><strong>Methods: </strong>We performed a paired comparison of six batches of HPL and lyophilized HPL (L-HPL) regarding the quality parameters pH, total protein, osmolality, sodium, potassium and chloride concentration. Concentrations of 11 growth factors and cytokines were compared between HPL and L-HPL. Additionally, we determined cell yield, proliferation capacity, viability and trilineage differentiation potential of hMSCs following expansion in HPL- and L-HPL-supplemented cell culture media.</p><p><strong>Results: </strong>Quantification of the quality parameters revealed non-altered pH, osmolality and potassium concentrations and slightly lower total protein, sodium and chloride concentrations of L-HPL compared to HPL. Growth factor and cytokine concentrations did not differ between HPL and L-HPL. Cell yield, division cycles and viability of hMSCs cultured in either HPL- or L-HPL-containing media were comparable. Cells differentiated in medium containing L-HPL showed a slightly higher capacity for osteogenic differentiation, while adipogenic differentiation and chondrogenic differentiation potentials remained unchanged.</p><p><strong>Conclusion: </strong>We successfully developed a method to produce well-applicable L-HPL. The comparison of L-HPL with HPL did not reveal any relevant differences regarding quality control parameters of routine testing, growth factor concentrations and hMSC functionality, demonstrating the suitability of L-HPL as a cell culture supplement. These results emphasize the potential of L-HPL as a sustainable and ethical alternative to animal-derived serum products in biomedical research and drug development.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1513444"},"PeriodicalIF":4.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390631","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>Fosab</i>, but not <i>fosaa</i>, plays important role in learning and memory in fish-insights from zebrafish gene knockout study.","authors":"Qiuling Wang, Lixin Zhang, Chenyuan Zhu, Ke Lu, Jiaqi Wu, Xu-Fang Liang","doi":"10.3389/fcell.2025.1503066","DOIUrl":"10.3389/fcell.2025.1503066","url":null,"abstract":"<p><p><b>Introduction:</b> Learning and memory allow individuals to adapt to their environmental needs and survive. Fish have the ability to solve complex learning tasks, associative learning, and flexible spatial memory. The proto-oncogene fos (<i>c-fos</i>) has been reported to be involved in brain development, learning and memory in mammals. However, whether the c-fos plays a vital role in learning and memory in fish is unclear. <b>Methods:</b> Almost all fish have two paralogues of <i>c-fos</i> named <i>fosaa</i> and <i>fosab</i>. We used CRISPR/Cas9 technology to generate <i>fosaa</i> and <i>fosab</i> knockout zebrafish models. <b>Results:</b> In this study, we discovered the brain weight marked reduction in <i>fosaa</i> <sup>-/-</sup> and <i>fosab</i> <sup>-/-</sup> zebrafish compared with the wild-type (WT) (AB strain) zebrafish. In the T-maze behavioral assay, the <i>fosab</i> <sup>-/-</sup> zebrafish took significantly more than the average time to complete the assigned trial as the increase in the days compared to WT zebrafish, while the <i>fosaa</i> <sup>-/-</sup> zebrafish did not show a notable variance. The average time to complete the trial in <i>fosab</i> <sup>-/-</sup> zebrafish was significantly higher than in WT zebrafish. The relative mRNA expression level of c-<i>jun</i> in <i>fosab</i> <sup>-/-</sup> zebrafish was significantly higher than that in WT zebrafish, while the <i>fosaa</i> <sup>-/-</sup> zebrafish has no discernible trend. Additionally, the phylogenetic and multiple amino acid alignment results indicated that fish <i>fosab</i> has a higher identity with mammals Fos. <b>Discussion:</b> By integrating the above results, we found that <i>fosab</i>, but not fosaa, may possess a learning and memory function in fish. For the first time, we illustrated the role of <i>fosaa</i> and <i>fosab</i> in learning and memory via <i>c-fos</i> knockout in fish, which can provide new insights into environmental adaptation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1503066"},"PeriodicalIF":4.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390625","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":"Human-based complex <i>in vitro</i> models: their promise and potential for rare disease therapeutics.","authors":"Surat Parvatam, Francesca Pistollato, Lindsay J Marshall, Fabia Furtmann, Devashree Jahagirdar, Mohua Chakraborty Choudhury, Sujata Mohanty, Harshita Mittal, Saveetha Meganathan, Rakesh Mishra","doi":"10.3389/fcell.2025.1526306","DOIUrl":"10.3389/fcell.2025.1526306","url":null,"abstract":"<p><p>Rare diseases affect a small percentage of an individual country's population; however, with over 7,000 in total, rare diseases represent a significant disease burden impacting up to 10% of the world's population. Despite this, there are no approved treatments for almost 95% of rare diseases, and the existing treatments are cost-intensive for the patients. More than 70% of rare diseases are genetic in nature, with patient-specific mutations. This calls for the need to have personalised and patient-specific preclinical models that can lead to effective, speedy, and affordable therapeutic options. Complex <i>in vitro</i> models (CIVMs), including those using induced pluripotent stem cells (iPSCs), organoids, and organs-on-chips are emerging as powerful human-based pre-clinical systems with the capacity to provide efficacy data enabling drugs to move into clinical trials. In this narrative review, we discuss how CIVMs are providing insights into biomedical research on rare diseases. We also discuss how these systems are being used in clinical trials to develop efficacy models for rare diseases. Finally, we propose recommendations on how human relevant CIVMs could be leveraged to increase translatability of basic, applied and nonclinical research outcomes in the field of rare disease therapeutics in developed as well as middle-and low-income countries.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1526306"},"PeriodicalIF":4.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390629","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}
Lingyun Liu, Shuo Guan, Yizhuo Xue, Yijia He, Liang Ding, Yong Fu, Sheng Chen, Zhiyong Wang, Yi Wang
{"title":"The immunological landscape of CCL26<sup>High</sup> invasive oral squamous cell carcinoma.","authors":"Lingyun Liu, Shuo Guan, Yizhuo Xue, Yijia He, Liang Ding, Yong Fu, Sheng Chen, Zhiyong Wang, Yi Wang","doi":"10.3389/fcell.2025.1502073","DOIUrl":"10.3389/fcell.2025.1502073","url":null,"abstract":"<p><strong>Background: </strong>Our previous study demonstrated that CCL26 secreted by cancer-associated fibroblasts (CAF) promoted the invasive phenotype of oral squamous cell carcinoma (OSCC), however, more comprehensive clinical expression patterns of CCL26 and its role in immunotherapy remains ambiguous.</p><p><strong>Methods: </strong>CCL26 levels in different cancer and normal tissues were analyzed and validated in 67 OSCC patients through immunohistochemical staining (IHC). The clinical spatial distribution pattern of CCL26 in tumor microenvironment was determined, and its clinical outcomes were investigated. We also determined the invasive phenotype of tumor cells with distinct CCL26 level and explored its immune checkpoint and immunocytes relevance by differentially expressed gene (DEG) analysis, GSEA, and GO analysis. We collected peripheral blood from 28 OSCC patients to assess the percentage and absolute number of lymphocytes by flow cytometry.</p><p><strong>Results: </strong>CCL26 was upregulated in HNSC and preferentially high-expressed on CAFs and tumor cells in OSCC patients, which exhibits a trend toward decreased overall survival. CCL26<sup>high</sup> OSCC had a characteristic of tumor invasive phenotype with upregulated CLDN8/20 and reduced keratin KRT36, which was significantly associated with EMT markers (CDH1, CDH2, VIM, SNAI2). In addition, CCL26<sup>high</sup> OSCC was found to be associated with immunoglobulin mediated immune response, B cell mediated immunity et al. Indeed, immune checkpoint molecules (PD-L1, PD-L2, et al.) also decreased in CCL26<sup>high</sup> OSCC. However, CCL26 did not affect T/B/NK lymphocytes in peripheral blood of OSCC patients.</p><p><strong>Conclusion: </strong>CCL26 could regulate Immune balance and promote invasiveness of OSCC, which gave a new insight into a potential immunotherapy strategy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1502073"},"PeriodicalIF":4.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389886","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":"Biophysical aspects of mechanotransduction in cells and their physiological/biological implications in vocal fold vibration: a narrative review.","authors":"Junseo Cha, Susan L Thibeault","doi":"10.3389/fcell.2025.1501341","DOIUrl":"10.3389/fcell.2025.1501341","url":null,"abstract":"<p><p>Mechanotransduction is a crucial property in all organisms, modulating cellular behaviors in response to external mechanical stimuli. Given the high mobility of vocal folds, it is hypothesized that mechanotransduction significantly contributes to their tissue homeostasis. Recent studies have identified mechanosensitive proteins in vocal fold epithelia, supporting this hypothesis. Voice therapy, which, involves the mobilization of vocal folds, aims to rehabilitate vocal function and restore homeostasis. However, establishing a direct causal link between specific mechanical stimuli and therapeutic benefits is challenging due to the variability in voice therapy techniques. This challenge is further compounded when investigating biological benefits in humans. Vocal fold tissue cannot be biopsied without significant impairment of the vibratory characteristics of the vocal folds. Conversely, studies using vocal fold mimetic bioreactors have demonstrated that mechanical stimulation of vocal fold fibroblasts can lead to highly heterogeneous responses, depending on the nature and parameters of the induced vibration. These responses can either aid or impede vocal fold vibration at the physiological level. Future research is needed to determine the specific mechanical parameters that are biologically beneficial for vocal fold function.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1501341"},"PeriodicalIF":4.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390627","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":"Non-histone lactylation: unveiling its functional significance.","authors":"Pusong Shi, Yongjie Ma, Shaolu Zhang","doi":"10.3389/fcell.2025.1535611","DOIUrl":"10.3389/fcell.2025.1535611","url":null,"abstract":"<p><p>Lactylation, a newly discovered protein posttranslational modification (PTM) in 2019, primarily occurs on lysine residues. Lactylation of histones was initially identified, and subsequent studies have increasingly demonstrated its widespread presence on non-histone proteins. Recently, high-throughput proteomics studies have identified a large number of lactylated proteins and sites, revealing their global regulatory role in disease development. Notably, this modification is catalyzed by lactyltransferase and reversed by delactylase, with numerous new enzymes, such as AARS1/2, reported to be involved. Specifically, these studies have revealed how lactylation exerts its influence through alterations in protein spatial conformation, molecular interactions, enzyme activity and subcellular localization. Indeed, lactylation is implicated in various physiological and pathological processes, including tumor development, cardiovascular and cerebrovascular diseases, immune cell activation and psychiatric disorders. This review provides the latest advancements in research on the regulatory roles of non-histone protein lactylation, highlighting its crucial scientific importance for future studies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1535611"},"PeriodicalIF":4.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381989","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}
Jung-Mi Lee, Hunmin Jung, Bruno de Paula Machado Pasqua, Yungki Park, Qinghuang Tang, Shin Jeon, Soo-Kyung Lee, Jae W Lee, Hyuk-Jae Edward Kwon
{"title":"MLL4 regulates postnatal palate growth and midpalatal suture development.","authors":"Jung-Mi Lee, Hunmin Jung, Bruno de Paula Machado Pasqua, Yungki Park, Qinghuang Tang, Shin Jeon, Soo-Kyung Lee, Jae W Lee, Hyuk-Jae Edward Kwon","doi":"10.3389/fcell.2025.1466948","DOIUrl":"10.3389/fcell.2025.1466948","url":null,"abstract":"<p><p>MLL4, also known as KMT2D, is a histone methyltransferase that acts as an important epigenetic regulator in various organogenesis programs. Mutations in the <i>MLL4</i> gene are the major cause of Kabuki syndrome, a human developmental disorder that involves craniofacial birth defects, including anomalies in the palate. This study aimed to investigate the role of MLL4 and the underlying mechanisms in the development and growth of the palate. We generated a novel conditional knockout (cKO) mouse model with tissue-specific deletion of <i>Mll4</i> in the palatal mesenchyme. Using micro-computed tomography (CT), histological analysis, cell mechanism assays, and gene expression profiling, we examined palate development and growth in the <i>Mll4</i>-cKO mice. Gross craniofacial examination at adult stages revealed mild midfacial hypoplasia and midline defects of the palate in <i>Mll4</i>-cKO mice, including a widened midpalatal suture and disrupted midline rugae pattern. Micro-CT-based time-course skeletal analysis during postnatal palatogenesis through adulthood demonstrated a transverse growth deficit in overall palate width in <i>Mll4</i>-cKO mice. Whole-mount and histological staining at perinatal stages identified that the midline defects in the <i>Mll4</i>-cKO mice emerged as early as 1 day prior to birth, presenting as a widened midpalatal suture, accompanied by increased cell apoptosis in the suture mesenchyme. Genome-wide mRNA expression analysis of the midpalatal suture tissue revealed that MLL4 is essential for the timely expression of major cartilage development genes, such as <i>Col2a1</i> and <i>Acan</i>, at birth. Immunofluorescence staining for osteochondral differentiation markers demonstrated a marked decrease in the chondrogenic marker COL2A1, while the expression of the osteogenic marker RUNX2 remained unchanged, in the <i>Mll4</i>-cKO midpalatal suture. Additionally, SOX9, a master regulator of chondrogenesis, exhibited a significant decrease in protein expression. Indeed, time-course histological analysis during postnatal palate growth revealed retardation in the development of the suture cartilage in <i>Mll4</i>-cKO mice. Taken together, our results demonstrate that MLL4 is essential for orchestrating key cellular and molecular events that ensure proper midpalatal suture development and palate growth.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1466948"},"PeriodicalIF":4.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381985","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}
Pierre Cybulski, Maria Bravo, Jim Jui-Kai Chen, Indra Van Zundert, Sandra Krzyzowska, Farsai Taemaitree, Hiroshi Uji-I, Johan Hofkens, Susana Rocha, Beatrice Fortuni
{"title":"Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge.","authors":"Pierre Cybulski, Maria Bravo, Jim Jui-Kai Chen, Indra Van Zundert, Sandra Krzyzowska, Farsai Taemaitree, Hiroshi Uji-I, Johan Hofkens, Susana Rocha, Beatrice Fortuni","doi":"10.3389/fcell.2024.1520078","DOIUrl":"10.3389/fcell.2024.1520078","url":null,"abstract":"<p><p>Preclinical studies have demonstrated that nanoparticles (NPs) hold significant potential for advancing cancer therapy by enhancing therapeutic efficacy while reducing side effects. Their effectiveness in solid tumors is, however, often constrained by insufficient accumulation and penetration. Understanding how the physicochemical properties of NPs - such as size, shape, and surface charge - influence their interaction with cells within the tumor is critical for optimizing NP design. In this study, we addressed the challenge of inconsistent NP behavior by systematically evaluating NP uptake in both 2D and 3D tumor models, and NP penetration in spheroids. Our results showed that larger NPs exhibited higher internalization rates in 2D models but limited penetration in 3D spheroids. Furthermore, negatively charged NPs consistently achieved superior accumulation and deeper penetration than neutral and positively charged NPs. Spherical NPs outperformed rod-shaped NPs in tumor accumulation and penetration. These findings underscore the importance of carefully tailoring NP properties to the complex tumor microenvironment for improved therapeutic outcomes in real tumors.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1520078"},"PeriodicalIF":4.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381927","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: Advancements in proteomics and PTMomics: unveiling mechanistic insights and targeted therapies for metabolic diseases.","authors":"Xiulan Chen, Yanchang Li, Daniela Braconi","doi":"10.3389/fcell.2025.1556129","DOIUrl":"10.3389/fcell.2025.1556129","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1556129"},"PeriodicalIF":4.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381930","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}