Stem Cells International最新文献

{"title":"Mesenchymal Stem Cell Therapy for Type 2 Diabetes: Synergistic β-Cell Regeneration, Immune Modulation, and Exosome-Mediated Glucose Homeostasis.","authors":"Jia Yang, Yinglong Chen, Huanmei Jing, Chang Liu, Xiaoling Chen, Jiaju Chu, Liyun Chen, Shijie Tang, Fei Yu, Wancong Zhang","doi":"10.1155/sci/2759804","DOIUrl":"10.1155/sci/2759804","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and a progressive decline in pancreatic β-cell function, leading to impaired glucose regulation. It is often accompanied by severe complications, including cardiovascular diseases, nephropathy, and retinopathy. Conventional treatments, such as sulfonylurea pills, insulin injections, and GLP-1 receptor agonist injections, provide transient glycemic control but are often costly with unstable efficacy and long-term side effects. Pancreatic islet transplantation, while effective in some cases, is limited by donor scarcity, graft rejection, and the need for lifelong immunosuppression. Recently, mesenchymal stem cells (MSCs) have emerged as a promising alternative due to their multipotent differentiation potential, immunomodulatory properties, and regenerative capabilities. This review examines the therapeutic roles of MSCs in β-cell regeneration, inflammation modulation, and tissue repair while also addressing key challenges in clinical translation. However, given the lack of long-term clinical data, the conclusions presented remain preliminary and should be interpreted with caution. This article, therefore, aims to provide a foundational reference for future research, rather than definitive clinical guidance.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"2759804"},"PeriodicalIF":3.6,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253419","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}

{"title":"RETRACTION: Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes.","authors":"Stem Cells International","doi":"10.1155/sci/9841479","DOIUrl":"10.1155/sci/9841479","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1155/2019/9208173.].</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"9841479"},"PeriodicalIF":3.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253456","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}

{"title":"Sodium Nitrate Combined With Dental Pulp Stem Cells Alleviates Atherosclerosis Through Inhibiting Oxidative Stress.","authors":"Zhuang Mao, Han Duan, Zhichao He, Lin Lv, Haichao Yu, Hu Cao, Jingyuan Shao, Xuesong Zhang, Shunying Hu, Hua Wang","doi":"10.1155/sci/5785962","DOIUrl":"10.1155/sci/5785962","url":null,"abstract":"<p><p>Atherosclerosis (AS), a leading cause of cardiovascular disease (CVD), is closely associated with excessive oxidative stress. Dietary nitrate has emerged as a promising intervention for cardiovascular protection through the nitrate-nitrite-nitric oxide (NO) pathway. Meanwhile, dental pulp stem cell (DPSC) possess potent antioxidant properties. However, the potential synergistic effect of sodium nitrate (NaNO₃) and DPSC on AS remains unclear. In this study, ApoE^-/- mice were fed a high-fat diet (HFD) and treated with NaNO₃ and/or DPSC. The combined treatment markedly attenuated atherosclerotic plaque formation, reduced oxidative stress, increased endothelial NO synthase (eNOS) expression, and decreased circulating monocyte levels. Furthermore, in vitro assays revealed that NaNO₃ and DPSC synergistically alleviated oxidative stress and promoted macrophage polarization toward the M2 phenotype, thereby suppressing oxidized lipid uptake. Mechanistic studies revealed that these benefits were mediated by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the subsequent upregulation of heme oxygenase-1 (HO-1). Collectively, our findings unveil a novel therapeutic strategy that combines NaNO₃ with DPSC to alleviate oxidative stress and inflammation, presenting a promising approach for the treatment of AS.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"5785962"},"PeriodicalIF":3.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253458","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}

{"title":"MSC-EVs Prevent Abdominal Aortic Aneurysm Formation by Inhibiting Perivascular Adipose Tissue-Induced NET Release.","authors":"Xiaowei Sun, Changbo Zhao, Kunfeng Tu, Xun Guan, Lei Lv, Guanhua Xue, Shuofei Yang","doi":"10.1155/sci/8147359","DOIUrl":"10.1155/sci/8147359","url":null,"abstract":"<p><strong>Background: </strong>Perivascular adipose tissue (PVAT) envelops arteries and exerts paracrine effects, thereby modulating cardiovascular pathologies. Nevertheless, its precise role in abdominal aortic aneurysm (AAAs) pathogenesis remains elusive. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of neutrophil extracellular traps (NETs) formation. This investigation delineates PVAT's involvement in AAA, particularly in NETs regulation, and evaluates the modulatory impact of MSC-EVs on these processes.</p><p><strong>Methods: </strong>A comprehensive analysis of CT imaging and clinical datasets from AAA patients was undertaken. Subsequent RNA sequencing and transcriptomic profiling of PVAT from AAA animal models and controls were conducted. Both in vivo and in vitro assays were employed to determine whether PVAT-derived proteins influence NETs release within the abdominal aorta and contribute to AAA development. Additionally, MSC-EVs were administered via intravenous or intraperitoneal routes to assess their effects on PVAT accumulation and NETs formation.</p><p><strong>Results: </strong>A significant correlation was established between PVAT characteristics and clinical outcomes in AAA patients. Experimental findings reveal that PVAT-derived serum amyloid A (SAA) promotes PVAT accumulation and induces NETs release within the abdominal aorta during AAA formation. Intraperitoneal MSC-EVs administration mitigates AAA development by reducing PVAT accumulation, suppressing SAA expression in PVAT, and inhibiting NETs formation in the abdominal aorta.</p><p><strong>Conclusion: </strong>PVAT-derived SAA facilitates NETs formation during AAA pathogenesis. MSC-EVs, by targeting these mechanisms, offer a promising prophylactic strategy against AAA, opening new therapeutic avenues for future research.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"8147359"},"PeriodicalIF":3.6,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228502","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}

{"title":"Enamel Matrix Derivative in Dental Pulp Regeneration: Biological Basis, Mechanistic Insights, and Translational Considerations.","authors":"LinLin Zhang, KaiLiang Tang, XinYu Zhao, Yi Du","doi":"10.1155/sci/5777572","DOIUrl":"10.1155/sci/5777572","url":null,"abstract":"<p><p>Enamel matrix derivative (EMD) has attracted increasing attention in regenerative endodontics because of its potential to influence multiple biological processes involved in dental pulp healing. Derived from enamel matrix proteins (EMPs), EMD has been associated with the regulation of stem/progenitor cell migration, odontogenic differentiation, angiogenic activity, and inflammatory responses. This review summarizes current evidence regarding the role of EMD in dental pulp regeneration, with emphasis on its biological characteristics, underlying mechanisms, and integration with biomaterial systems. Available studies suggest that EMD may contribute to a regeneration-permissive microenvironment by modulating cellular behavior and extracellular matrix-related processes, while biomaterial-based delivery strategies have been explored to improve its stability and local bioactivity. However, most existing evidence is derived from in vitro studies or nonpulp regenerative models, and direct evidence supporting functional pulp regeneration remains limited. In addition, EMD, Emdogain, recombinant amelogenin (Am), and Am-derived peptides are closely related but should not be considered interchangeable interventions. Taken together, EMD represents a biologically relevant but not yet fully validated approach in regenerative endodontics, and further studies are required to clarify its mechanisms under clinically relevant conditions and to distinguish true pulp regeneration from partial reparative outcomes.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"5777572"},"PeriodicalIF":3.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212380","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}

{"title":"Stem Cell and Cell-Free Strategies for Osteoarthritis: Toward Durable Regenerative Therapies.","authors":"Andreas Pambis, Tianle Li, You Li, Biao Li, Christopher Kim","doi":"10.1155/sci/6699734","DOIUrl":"10.1155/sci/6699734","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most prevalent degenerative joint disease and a leading cause of pain and disability, yet current treatments remain largely palliative and fail to alter disease progression. Stem cell-based therapies offer a promising alternative, with mesenchymal stromal/stem cells (MSCs) representing the most clinically advanced approach. Preclinical and clinical studies demonstrate that MSCs exert anti-inflammatory, immunomodulatory, chondroprotective, and analgesic effects primarily through paracrine signaling rather than durable engraftment. Clinical trials consistently confirm intra-articular (IA) MSC safety and symptomatic benefit, though structural outcomes remain variable owing to heterogeneity in cell source, dose, and trial design. This recognition has fueled interest in cell-free derivatives, particularly extracellular vesicles (EVs), which recapitulate MSC paracrine functions while offering improved safety, scalability, and regulatory compatibility. In parallel, bioengineering innovations, including hydrogels, scaffolds, 3D bioprinting, nanotechnology, and genetic enhancement, are being leveraged to prolong persistence, optimize delivery, and enable adaptive, multimodal repair. Emerging sources such as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), and joint-resident progenitors further expand the regenerative toolkit. These developments suggest that future regenerative strategies for OA may combine cellular therapies, cell-free products, and biomaterial delivery systems to improve treatment durability and therapeutic control.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"6699734"},"PeriodicalIF":3.6,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199981","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}

{"title":"Derivation and Pluripotency Validation of Six iPSC Lines From Amniotic Fluid Carrying Intermediate α-Thalassemia Genotypes (--^3.7/α^SEA and --^4.2/α^SEA).","authors":"Qingyun Chen, Xinxing Jiang, Xinhuai Xue, Yao Zhou, Yuanhua Huang, Fei Sun, Yanlin Ma","doi":"10.1155/sci/9951684","DOIUrl":"10.1155/sci/9951684","url":null,"abstract":"<p><strong>Purpose: </strong>Thalassemia intermedia (TI), or hemoglobin H (Hb H) disease, presents significant clinical heterogeneity, and its pathogenesis remains unclear. This study aimed to establish induced pluripotent stem cells (iPSCs) from amniotic fluid (AF) cells of fetuses diagnosed with intermediate α-thalassemia genotypes (-α^3.7/--^SEA and -α^4.2/--^SEA) to provide a robust in vitro model for investigating disease mechanisms and exploring therapeutic strategies.</p><p><strong>Methods: </strong>AF cells from six TI fetuses were reprogrammed using nonintegrating episomal vectors via electro-transfection. The resulting iPSC lines underwent comprehensive characterization, including alkaline phosphatase (AP) staining, immunofluorescence (IF) for pluripotency markers (e.g., OCT-4, SOX-2, and TRA-1-60), quantitative reverse transcription real-time PCR (RT-qPCR) for the expression of pluripotency genes, G-band karyotyping, and genetic analysis for thalassemia. Differentiation potential was assessed in vivo via teratoma formation in immunodeficient mice and in vitro through directed hematopoietic differentiation.</p><p><strong>Results: </strong>Six stable iPSC lines were successfully established. All lines retained the progenitor's intermediate α-thalassemia genotype and exhibited normal karyotypes. They displayed typical embryonic stem cell (ESC)-like morphology, were positive for AP, and expressed key pluripotency markers. In vivo, all lines robustly formed teratomas containing tissues derived from all three germ layers (endoderm, mesoderm, and ectoderm). Furthermore, in vitro hematopoietic differentiation protocols successfully induced the iPSCs to generate CD34⁺/CD43⁺ hematopoietic progenitors, which were functionally validated by their ability to form hematopoietic colonies in colony-forming unit (CFU) assays.</p><p><strong>Conclusion: </strong>We have successfully derived and comprehensively characterized six patient-specific iPSC lines from intermediate α-thalassemia fetuses. These cell lines demonstrate robust pluripotency and maintain the capacity for hematopoietic differentiation. They represent a valuable resource for investigating TI pathophysiology, screening novel drugs, and developing future cell-based therapeutic strategies.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"9951684"},"PeriodicalIF":3.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199895","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}

{"title":"Investigation Into the Association Between Neurotransmitters, Immune Features, and Lung Adenocarcinoma: Identifying GABA-Related Features Using Machine Learning Methods.","authors":"Jiangtao You, Tianren Wang, Qingshi Wang, Yong Zhang, Rui Zhao, Wei Cui, Huan Chen","doi":"10.1155/sci/3060138","DOIUrl":"10.1155/sci/3060138","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung adenocarcinoma (LUAD), a predominant subtype of non-small cell lung cancer (NSCLC), is associated with a high mortality rate. Currently, there are no reliable or sensitive biomarkers or prognostic methodologies available for its early detection or diagnosis. Gamma-aminobutyric acid (GABA), a pivotal inhibitory neurotransmitter within the central nervous system (CNS), primarily exerts its effects through interactions with GABA receptors (GABARs). Recent studies have increasingly highlighted GABA's significant role in mediating the initiation and progression of various tumors beyond the CNS. Nonetheless, research investigating the role of GABA in LUAD is limited, and the specific molecular and cellular mechanisms underlying its interactions remain to be fully elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We developed an innovative machine learning framework designed to screen GABA-related genes (GABARgenes) at both single-cell and large transcriptomic levels. This framework encompasses 10 algorithms and 101 combinatorial pairing patterns, which facilitate the construction of consistent GABA-related features (GABARFs). The framework's performance was assessed using both a training set and an external validation set. To provide a quantitative prognostic tool for clinical application, we established a nomogram that incorporates GABARF. Additionally, we conducted multiomics analyses, including genomics, single-cell transcriptomics, and comprehensive transcriptomics, to derive and consolidate more extensive prognostic features. We also evaluated the response of GABARF-defined risk subgroups to immunotherapy and identified potential personalized therapeutic agents for specific risk categories.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 124 GABARgenes analyzed, 38 demonstrated a significant correlation with overall survival (OS) in patients. Our machine learning-derived GABARF exhibited exceptional performance in predicting prognosis and clinical outcomes, showing promise in forecasting the onset and progression of LUAD. Multivariate analysis confirmed that GABARF serves as an independent prognostic factor for OS in LUAD. Furthermore, distinct GABARF risk subgroups exhibited significant differences in biological function, mutation status, and tumor immune infiltration. Notably, there were significant variations in the immunophenoscore (IPS) across the risk subgroups. GABARF risk stratification aligns with stemness properties of tumor cells, indicating that high-risk patients may harbor tumors with enhanced stemness features that contribute to their poor prognosis and reduced immunotherapy response. Sensitivity analyses of conventional LUAD therapies indicated that patients in the low-risk group may derive greater benefit from immune checkpoint inhibitors (ICIs), while those in the high-risk group may exhibit heightened sensitivity to first-line chemotherapy agents. Furthermore, LDHA overexpression was found to promote pro","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"3060138"},"PeriodicalIF":3.6,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13191820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017311","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}

{"title":"<i>Plastrum Testudinis</i> Extract Promotes Endogenous Bone Marrow Mesenchymal Stem Cell Migration in Osteoporotic Fracture Repair Partly by Activating the SDF-1/CXCR4 Axis.","authors":"Xingda Chen, Hang Zhuo, Peng Zhang, Jizhi Ma, Guibo Liang, Riwei Tan, Yan Gong, Yifei Wang, Weicheng Qin, Jiahui Dai, Zilan Zhong, Hongze Wang, Ruicheng Lin, Zheng Kuang, Liang De, Yongchao Tang, Jinyong Ding, Zixian Wu, Xiang Yu","doi":"10.1155/sci/3033093","DOIUrl":"10.1155/sci/3033093","url":null,"abstract":"<p><p>Osteoporotic fracture (OPF) is a major global health concern, particularly among aging populations, and the compromised migration and osteoblast differentiation potential of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis significantly hinder fracture repair. The stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis is vital for guiding BMSC migration and bone regeneration. However, <i>Plastrum Testudinis</i> (PT) extract (PTE), a traditional Chinese medicine (TCM) derived from turtle shell, has revealed promise in promoting BMSC proliferation and differentiation, although its mechanism of regulating endogenous stem cell migration in OPF remains unclear. To address this, we combined bioinformatics screening, molecular docking, clinical tissue analysis, and in vivo experiments to identify key pathways via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We established a bilateral ovariectomy-induced osteoporotic mouse model with tibial defects and treated the mice with PTE alone or with the CXCR4 inhibitor AMD3100, followed by histological, micro-CT, immunofluorescence, and in vitro Transwell assays. Bioinformatics analysis revealed enriched chemokine signaling pathways and identified CXCR4 as a key target of PTE. Molecular docking confirmed stable binding between PTE's active components (phenylalanine, methionine, threonine, and aspartic acid) and CXCR4. PTE significantly improved bone volume/total volume (BV/TV) and trabecular microarchitecture in osteoporotic tibial defect (OTD) mice, reversed reduced SDF-1/CXCR4 expression in osteoporotic tissues, and enhanced BMSC migration and SDF-1/CXCR4 mRNA levels in vitro; these effects were blocked by AMD3100. In summary, PTE effectively rescues the migration deficit of endogenous BMSCs under osteoporotic conditions by targeting the SDF-1/CXCR4 axis. This enhanced recruitment accelerates OPF healing, highlighting the potential of PTE as a regenerative therapeutic strategy.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"3033093"},"PeriodicalIF":3.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983330","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}

{"title":"Unraveling the Predictive Value of <i>HGF</i>, <i>RECK</i>, <i>CYP1B1</i>, and <i>ZEB2</i> for Cancer Stemness and Immune Microenvironment in Pancreatic Adenocarcinoma.","authors":"Hongxi Chen, Shenglei Song, Chenglong Li, Zhige Yu","doi":"10.1155/sci/2402325","DOIUrl":"10.1155/sci/2402325","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The progression of pancreatic adenocarcinoma (PAAD) is closely linked to autophagy and microRNA (miRNA) regulation. Therefore, constructing miRNA regulatory networks based on PAAD autophagy-related genes is essential for improving targeted therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we downloaded PAAD-related data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), PAAD-related miRNA data from Gene Expression Omnibus (GEO), and mined autophagy from existing literature reports for autophagy-related genes. Autophagy signature scores were assessed employing single-sample gene set enrichment analysis (ssGSEA) and screened for autophagy-associated candidate genes via weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Bioinformatics tools such as CIBERSORT and ESTIMATE were employed to assess the level of immune infiltration. The Encori database and Cytoscape 3.8.0 tools were used to construct the miRNA regulatory network. The PubChem website and AutoDockTools were used for targeted drug prediction and molecular docking of PAAD autophagy-related genes. Cell counting kit-8 (CCK-8), scratch healing assay, transwell assay, etc. were used to investigate the regulatory effect of biomarkers on the PAAD cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;WGCNA combined differential expression analysis obtained candidate genes related to PAAD autophagy, which were primarily implicated in the pathways of phagocytosis and miRNAs in cancer. Among them, four characteristic genes (&lt;i&gt;HGF&lt;/i&gt;, &lt;i&gt;RECK&lt;/i&gt;, &lt;i&gt;CYP1B1&lt;/i&gt;, and &lt;i&gt;ZEB2&lt;/i&gt;) contained in the miRNAs in cancer pathway will be included in the subsequent analyses as biomarkers affecting PAAD autophagy. The expressions of these biomarkers were positively linked to all immune-relevant indicators (Stromal, Immune, and ESTIMATE scores) of PAAD. The regulatory network of miRNAs and four biomarkers in PAAD was constructed, and it was elucidated that hsa-miR-222-3p and hsa-miR-377-3p had targeting relationship to &lt;i&gt;RECK&lt;/i&gt; and &lt;i&gt;CYP1B1&lt;/i&gt;, respectively. Moreover, results showed that &lt;i&gt;HGF&lt;/i&gt;, &lt;i&gt;RECK&lt;/i&gt;, and &lt;i&gt;ZEB2&lt;/i&gt; were significantly positively correlated with cancer stem cell (CSC) scores (&lt;i&gt;R&lt;/i&gt; &gt; 0.3), and the high expressions of &lt;i&gt;HGF&lt;/i&gt;, &lt;i&gt;RECK&lt;/i&gt;, and &lt;i&gt;ZEB2&lt;/i&gt; genes all led to the significant enrichment of EPITHELIAL_MESENCHYMAL_TRANSITION and TGF_BETA_SIGNALING. Molecular docking revealed that &lt;i&gt;CYP1B1&lt;/i&gt;, &lt;i&gt;HGF&lt;/i&gt;, and &lt;i&gt;RECK&lt;/i&gt; all stably bound resveratrol. &lt;i&gt;ZEB2&lt;/i&gt; is significantly associated with proliferation, migration, and invasion in the PAAD cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The present study elucidated genes associated with autophagy features in PAAD by bioinformatics and constructed corresponding miRNA networks and molecular docking models, and predicted potential target drugs for PAAD, which will guide the development of prognostic therapeutic strategies for PAAD.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"2402325"},"PeriodicalIF":3.6,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964490","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}