{"title":"PCBP2 promotes immune evasion via cGAS-STING pathway in biochemical recurrence of prostate cancer.","authors":"Zeng Zhou, Tiewen Li, Yichen Zhang, Xuehao Zhou, Xiaodong Song, Shiyu Ji, Yishu Huang, Yu Zhang, Yuan Ruan","doi":"10.1063/5.0250173","DOIUrl":"10.1063/5.0250173","url":null,"abstract":"<p><p>Immunotherapy resistance is a significant obstacle in the treatment of prostate cancer (PCa), primarily due to immune evasion mechanisms. This study aims to explore cancer-intrinsic immune evasion-related genes (CIERGs) in PCa and develop a predictive signature for biochemical recurrence (BCR). Bulk RNA-seq data and single-cell RNA-sequencing (scRNA-seq) were obtained from TCGA and Gene Expression Omnibus database. The scRNA-seq data analysis revealed higher immune evasion scores in tumor cells compared to normal cells. Differentially expressed genes from TCGA-PRAD and GSE70769 cohorts were intersected with 182 core immune evasion genes, followed by univariate Cox regression, identifying 48 CIERGs significantly associated with BCR. Nonnegative matrix factorization (NMF) clustering revealed two immune evasion-related PCa subtypes. A risk signature based on CIERGs was developed using LASSO regression, and a nomogram was created to predict BCR-free survival. Among the 48 identified CIERGs, poly(C)-binding protein 2 (PCBP2) emerged as a key risk factor associated with poor prognosis in PCa, and its function was validated <i>in vitro</i>. NMF clustering identified two subtypes, with the C1 subtype having a poorer prognosis. Gene Set Variation Analysis highlighted enrichment in cell cycle, extracellular matrix receptor interaction, and transforming growth factor-beta signaling pathways in the C1 subtype. A CIERGs-based risk signature, including six key genes, was developed and validated, with the nomogram showing high predictive accuracy. <i>In vitro</i> experiments showed PCBP2 promotes PCa cell proliferation, migration, and invasion by inhibiting the cyclic GMP-AMP synthase-STING pathway. The CIERGs signature provides a precise prediction of BCR, with PCBP2 emerging as a potential therapeutic target due to its inhibition of the cGAS-STING pathway in PCa.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016112"},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2025-03-05eCollection Date: 2025-03-01DOI: 10.1063/5.0250472
Xuefeng Wang, Yaqi Bai, Xiaoling Zhang, Wei Li, Jun Yang, Ning Hu
{"title":"Hydrodynamic efficient cell capture and pairing method on microfluidic cell electrofusion chip.","authors":"Xuefeng Wang, Yaqi Bai, Xiaoling Zhang, Wei Li, Jun Yang, Ning Hu","doi":"10.1063/5.0250472","DOIUrl":"10.1063/5.0250472","url":null,"abstract":"<p><p>Cell fusion is a widely employed process in various biological procedures, demonstrating significant application value in biotechnology. Cell pairing is a crucial manipulation for cell fusion. Standard fusion techniques, however, often provide poor and random cell contact, leading to low yields. In this study, we present a novel microfluidic device that utilizes a three-path symmetrical channel hydrodynamic capture method to achieve high-efficiency cell capture and pairing. The device contains several symmetrical channels and capture units, enabling three-path capture of two kinds of cells. To better understand the conditions necessary for effective cell pairing, we established a theoretical model of the three-path trapping flow field and conducted a qualitative force analysis on cells. Using K562 cells to explore the effect of different volumetric flow ratios of symmetric channels on cell capture and pairing efficiency, we finally got the optimized structure and obtained a single-cell capture efficiency of approximately 95.6 ± 2.0% and a cell pairing efficiency of approximately 83.3 ± 8.8%. Subsequently, electrofusion experiments were carried out on the paired cells, resulting in a fusion efficiency of approximately 77.8 ± 9.6%.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016111"},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2025-02-26eCollection Date: 2025-03-01DOI: 10.1063/5.0244026
Nadia O Abutaleb, Xin D Gao, Akhil Bedapudi, Leandro Choi, Kevin L Shores, Crystal Kennedy, Jordyn E Duby, Kan Cao, David R Liu, George A Truskey
{"title":"Adenine base editing rescues pathogenic phenotypes in tissue engineered vascular model of Hutchinson-Gilford progeria syndrome.","authors":"Nadia O Abutaleb, Xin D Gao, Akhil Bedapudi, Leandro Choi, Kevin L Shores, Crystal Kennedy, Jordyn E Duby, Kan Cao, David R Liu, George A Truskey","doi":"10.1063/5.0244026","DOIUrl":"10.1063/5.0244026","url":null,"abstract":"<p><p>The rare, accelerated aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is commonly caused by a <i>de novo</i> c.1824 C > T point mutation of the <i>LMNA</i> gene that results in the protein progerin. The primary cause of death is a heart attack or stroke arising from atherosclerosis. A characteristic feature of HGPS arteries is loss of smooth muscle cells. An adenine base editor (ABE7.10max) corrected the point mutation and produced significant improvement in HGPS mouse lifespan, vascular smooth muscle cell density, and adventitial fibrosis. To assess whether base editing correction of human HGPS tissue engineered blood vessels (TEBVs) prevents the HGPS vascular phenotype and to identify the minimum fraction of edited smooth muscle cells needed to effect such changes, we transduced HGPS iPSCs with lentivirus containing ABE7.10max. Endothelial cells (viECs) and smooth muscle cells (viSMCs) obtained by differentiation of edited HGPS iPSCs did not express progerin and had double-stranded DNA breaks and reactive oxygen species at the same levels as healthy viSMCs and viECs. Editing HGPSviECs restored a normal response to shear stress. Normal vasodilation and viSMC density were restored in TEBVs made with edited cells. When TEBVs were prepared with at least 50% edited smooth muscle cells, viSMC proliferation and myosin heavy chain levels significantly improved. Sequencing of TEBV cells after perfusion indicated an enrichment of edited cells after 5 weeks of perfusion when they comprised 50% of the initial number of cells in the TEBVs. Thus, base editing correction of a fraction of HGPS vascular cells improves human TEBV phenotype.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016110"},"PeriodicalIF":6.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2025-02-25eCollection Date: 2025-03-01DOI: 10.1063/5.0235412
Long Chen, Ping Wu, Yu Zhu, Han Luo, Qiang Tan, Yongsong Chen, Dan Luo, Zhiyong Chen
{"title":"Electrospinning strategies targeting fibroblast for wound healing of diabetic foot ulcers.","authors":"Long Chen, Ping Wu, Yu Zhu, Han Luo, Qiang Tan, Yongsong Chen, Dan Luo, Zhiyong Chen","doi":"10.1063/5.0235412","DOIUrl":"https://doi.org/10.1063/5.0235412","url":null,"abstract":"<p><p>The high incidence and prevalence of diabetic foot ulcers (DFUs) present a substantial clinical and economic burden, necessitating innovative therapeutic approaches. Fibroblasts, characterized by their intrinsic cellular plasticity and multifunctional capabilities, play key roles in the pathophysiological processes underlying DFUs. Hyperglycemic conditions lead to a cascade of biochemical alterations that culminate in the dysregulation of fibroblast phenotype and function, which is the primary cause of impaired wound healing in DFUs. Biomaterials, particularly those engineered at the nanoscale, hold significant promise for enhancing DFU treatment outcomes. Electrospun nanofiber scaffolds, with their structural and compositional similarities to the natural extracellular matrix, serve as an effective substrate for fibroblast adhesion, proliferation, and migration. This review comprehensively summarizes the biological behavior of fibroblasts in DFUs and the mechanism mediating wound healing. At the same time, the mechanism of biological materials, especially electrospun nanofiber scaffolds, to improve the therapeutic effect by regulating the activity of fibroblasts was also discussed. By highlighting the latest advancements and clinical applications, we aim to provide a clear perspective on the future direction of DFU treatment strategies centered on fibroblast-targeted therapies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"011501"},"PeriodicalIF":6.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2025-02-20eCollection Date: 2025-03-01DOI: 10.1063/5.0239035
Yize Zhang, Ellen Y Zhang, Catherine Cheung, Yuna Heo, Bat-Ider Tumenbayar, Se-Hwan Lee, Yongho Bae, Su Chin Heo
{"title":"Epigenetic dynamics in meniscus cell migration and its zonal dependency in response to inflammatory conditions.","authors":"Yize Zhang, Ellen Y Zhang, Catherine Cheung, Yuna Heo, Bat-Ider Tumenbayar, Se-Hwan Lee, Yongho Bae, Su Chin Heo","doi":"10.1063/5.0239035","DOIUrl":"10.1063/5.0239035","url":null,"abstract":"<p><p>Meniscus injuries are challenging to treat due to the tissue heterogeneity and limited treatment efficacy. Understanding meniscus cell migration, crucial for healing, remains incomplete, especially its zonal dependency. This study explores how epigenetic mechanisms affect meniscus cell migration under inflammation, focusing on healing implications. Distinct histone modifications and chromatin dynamics between inner and outer cells were observed during migration, emphasizing the need to consider these differences in repair strategies. Furthermore, tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine, slows inner meniscus cell migration, while outer cells remain unaffected, indicating a zonal response. Interestingly, TNF-α differentially alters histone modifications, particularly H3K27me3, between the cell types. Transcriptome analysis showed significant gene expression changes with inner cells more affected than outer cells. Gene cluster analysis revealed different responses in chromatin remodeling, extracellular matrix assembly, and wound healing between zones. We further identified potential therapeutic targets by using epigenetic drugs, GSKJ4 (a histone demethylase inhibitor) and C646 (a histone acetyltransferase inhibitor), which restored inner meniscus cell migration under inflammatory conditions, highlighting their potential in treating meniscus tears. This highlights their potential utility in treating meniscus tear injuries. Overall, our findings elucidate the intricate interplay between epigenetic mechanisms and meniscus cell migration, along with its meniscus zonal dependency. This study provides insight into potential targets for enhancing meniscus repair and regeneration, which may lead to improved clinical outcomes for patients with meniscus injuries and osteoarthritis.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016109"},"PeriodicalIF":6.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-12-24eCollection Date: 2024-12-01DOI: 10.1063/5.0233737
Antonina P Maxey, Sage J Wheeler, Jaya M Travis, Megan L McCain
{"title":"Contractile responses of engineered human <i>μ</i>myometrium to prostaglandins and inflammatory cytokines.","authors":"Antonina P Maxey, Sage J Wheeler, Jaya M Travis, Megan L McCain","doi":"10.1063/5.0233737","DOIUrl":"10.1063/5.0233737","url":null,"abstract":"<p><p>Preterm labor is a prevalent public health problem and occurs when the myometrium, the smooth muscle layer of the uterus, begins contracting before the fetus reaches full term. Abnormal contractions of the myometrium also underlie painful menstrual cramps, known as dysmenorrhea. Both disorders have been associated with increased production of prostaglandins and cytokines, yet the functional impacts of inflammatory mediators on the contractility of human myometrium have not been fully established, in part due to a lack of effective model systems. To address this, we engineered human myometrial microtissues (<i>μ</i>myometrium) on compliant hydrogels designed for traction force microscopy. We then measured <i>μ</i>myometrium contractility in response to a panel of compounds with known contractile effects and inflammatory mediators. We observed that prostaglandin F2α, interleukin 6, and interleukin 8 induced contraction, while prostaglandin E1 and prostaglandin E2 induced relaxation. Our data suggest that inflammation may be a key factor modulating uterine contractility in conditions including, but not limited to, preterm labor or dysmenorrhea. More broadly, our <i>μ</i>myometrium model can be used to systematically identify the functional impact of many small molecules on human myometrium.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046115"},"PeriodicalIF":6.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-12-12eCollection Date: 2024-12-01DOI: 10.1063/5.0240772
Fei Wu, Yue Xu
{"title":"Immunogenic cell death-related cancer-associated fibroblast clusters and prognostic risk model in cervical cancer.","authors":"Fei Wu, Yue Xu","doi":"10.1063/5.0240772","DOIUrl":"10.1063/5.0240772","url":null,"abstract":"<p><p>Cervical cancer (CC) remains a leading cause of female cancer mortality globally. Immunogenic cell death (ICD) influences the tumor microenvironment (TME) and adaptive immune responses. Cancer-associated fibroblasts (CAFs) within the TME suppress anti-tumor immunity and contribute to CC progression. This study identified three ICD-related CAF clusters linked to patient survival, including IL6+CAF and ILR1+CAF, which were associated with clinical outcomes. Using a nine-gene risk model, patients were stratified into risk groups, with high-risk individuals showing worse survival and correlations with pathways such as hypoxia and TGFβ. The model also predicted immunotherapy responses, highlighting immune infiltration differences across risk groups. These findings provide insights into the role of CAF clusters in CC and present a risk model that supports prognosis prediction and personalized therapy.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046114"},"PeriodicalIF":6.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-12-06eCollection Date: 2024-12-01DOI: 10.1063/5.0240444
Chun-Liang Lai, Riya Karmakar, Arvind Mukundan, Ragul Kumar Natarajan, Song-Cun Lu, Cheng-Yi Wang, Hsiang-Chen Wang
{"title":"Advancing hyperspectral imaging and machine learning tools toward clinical adoption in tissue diagnostics: A comprehensive review.","authors":"Chun-Liang Lai, Riya Karmakar, Arvind Mukundan, Ragul Kumar Natarajan, Song-Cun Lu, Cheng-Yi Wang, Hsiang-Chen Wang","doi":"10.1063/5.0240444","DOIUrl":"10.1063/5.0240444","url":null,"abstract":"<p><p>Hyperspectral imaging (HSI) has become an evident transformative apparatus in medical diagnostics. The review aims to appraise the present advancement and challenges in HSI for medical applications. It features a variety of medical applications namely diagnosing diabetic retinopathy, neurodegenerative diseases like Parkinson's and Alzheimer's, which illustrates its effectiveness in early diagnosis, early caries detection in periodontal disease, and dermatology by detecting skin cancer. Regardless of these advances, the challenges exist within every aspect that limits its broader clinical adoption. It has various constraints including difficulties with technology related to the complexity of the HSI system and needing specialist training, which may act as a drawback to its clinical settings. This article pertains to potential challenges expressed in medical applications and probable solutions to overcome these constraints. Successful companies that perform advanced solutions with HSI in terms of medical applications are being emphasized in this study to signal the high level of interest in medical diagnosis for systems to incorporate machine learning ML and artificial intelligence AI to foster precision diagnosis and standardized clinical workflow. This advancement signifies progressive possibilities of HSI in real-time clinical assessments. In conclusion despite HSI has been presented as a significant advanced medical imaging tool, addressing its limitations and probable solutions is for broader clinical adoption.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"041504"},"PeriodicalIF":6.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1063/5.0227135
Federico Cantoni, Laurent Barbe, Ananya Roy, Grzegorz Wicher, Stina Simonsson, Karin Forsberg-Nilsson, Maria Tenje
{"title":"On-chip fabrication of tailored 3D hydrogel scaffolds to model cancer cell invasion and interaction with endothelial cells.","authors":"Federico Cantoni, Laurent Barbe, Ananya Roy, Grzegorz Wicher, Stina Simonsson, Karin Forsberg-Nilsson, Maria Tenje","doi":"10.1063/5.0227135","DOIUrl":"10.1063/5.0227135","url":null,"abstract":"<p><p>The high mortality associated with certain cancers can be attributed to the invasive nature of the tumor cells. Yet, the complexity of studying invasion hinders our understanding of how the tumor spreads. This work presents a microengineered three-dimensional (3D) <i>in vitro</i> model for studying cancer cell invasion and interaction with endothelial cells. The model was generated by printing a biomimetic hydrogel scaffold directly on a chip using 2-photon polymerization that simulates the brain's extracellular matrix. The scaffold's geometry was specifically designed to facilitate the growth of a continuous layer of endothelial cells on one side, while also allowing for the introduction of tumor cells on the other side. This arrangement confines the cells spatially and enables <i>in situ</i> microscopy of the cancer cells as they invade the hydrogel scaffold and interact with the endothelial layer. We examined the impact of 3D printing parameters on the hydrogel's physical properties and used patient derived glioblastoma cells to study their effect on cell invasion. Notably, the tumor cells tended to infiltrate faster when an endothelial cell barrier was present. The potential for adjusting the hydrogel scaffold's properties, coupled with the capability for real-time observation of tumor-endothelial cell interactions, offers a platform for studying tumor invasion and tumor-endothelial cell interactions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046113"},"PeriodicalIF":6.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}