Biomedical Journal最新文献

{"title":"Regulatory T cells from concept to clinic: The 2025 Nobel Prize and its implications for immune-mediated diseases and cancer","authors":"Chien-Hao Huang ,&nbsp;Wei-Ting Ku ,&nbsp;Yung-Chang Lin ,&nbsp;Chun-Yen Lin","doi":"10.1016/j.bj.2026.100959","DOIUrl":"10.1016/j.bj.2026.100959","url":null,"abstract":"<div><div>The 2025 Nobel Prize in Physiology or Medicine, awarded to Shimon Sakaguchi, Mary E. Brunkow, and Fred Ramsdell, recognizes the discovery and molecular definition of regulatory T cells (Tregs) as the cornerstone of peripheral immune tolerance. This recognition honors a transformative journey marked by Sakaguchi's identification of CD4⁺CD25⁺ T cells as a regulatory population (1995), followed by Brunkow and Ramsdell's discovery that mutations in the <em>FOXP3</em> gene cause both the <em>scurfy</em> mouse phenotype and human IPEX syndrome (2001), and culminating in the demonstration that FOXP3 governs Treg development and function (2003).</div><div>This achievement crowns a turbulent half-century arc. The suppressor T-cell (Ts) hypothesis of the 1970s proposed an active T-cell brake on immunity but collapsed in the 1980s due to phenotypic ambiguity and reproducibility failures. Following this “dark age,” the concept of active suppression was kept alive through functional studies in organ-specific autoimmunity (Parish, Kong, Rose) and transplantation tolerance (Waldmann). However, it was Sakaguchi's discovery of CD25 as a specific marker that finally provided the physical identity of these cells, bridging the gap between functional observation and cellular definition. The subsequent identification of FOXP3 as the lineage-defining transcription factor transformed a disputed concept into a reproducible, engineerable immune module.</div><div>Today, this molecular precision drives broad clinical translation, ranging from Treg-based therapies in autoimmunity and transplantation to targeted Treg modulation in cancer immunotherapy. This Short Review traces the trajectory—from controversy to molecular definition—and frames a forward path for context-dependent modulation of Tregs in clinical medicine.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100959"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and genomic insights into persistent carbapenem-resistant Klebsiella pneumoniae bacteremia: risk factors, resistance mechanisms, and treatment challenges","authors":"Shian-Sen Shie ,&nbsp;Ya-Han Yang ,&nbsp;Yin-Hsiang Kung ,&nbsp;Chih-Jung Chen","doi":"10.1016/j.bj.2025.100905","DOIUrl":"10.1016/j.bj.2025.100905","url":null,"abstract":"<div><h3>Introduction</h3><div>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) is a major cause of nosocomial infections with high mortality rates. Persistent bacteremia, indicative of treatment failure, poses significant clinical challenges. This study aimed to identify clinical parameters for persistent CRKP bacteremia while exploring microbial and genetic characteristics.</div></div><div><h3>Materials and methods</h3><div>A case-control study was conducted on patients with CRKP bacteremia from January 2016 to July 2019 at a tertiary hospital in Taiwan. Clinical, demographic, and microbiological data were collected for 61 cases of persistent bacteremia and 122 matched controls without persistent infections. Conditional logistic regression was used to evaluate risk factors for persistent bacteremia. Whole-genome sequencing (WGS) was used to identify genotypes and factors mediating resistance and virulence in the strains.</div></div><div><h3>Results</h3><div>Persistent CRKP bacteremia was independently associated with mechanical ventilation (adjusted odds ratio [aOR] 11.007, 95 % confidence interval [CI] 2.137–56.693), a lower Pitt bacteremia score (aOR 0.642, 95 % CI 0.494–0.835), and the use of colistin (aOR 11.18, 95 % CI 2.988–41.787) and tigecycline (aOR 16.42, 95 % 4.495–60.0) in definitive therapy. Strains from either group shared similar capsular types. WGS identified three dominant multidrug-resistant clones, ST11, ST307, and ST15, harboring carbapenemase and virulence factors encoding yersiniabactin. A strain of hypervirulent clone ST23 exhibited high virulence but lacked carbapenemase genes, suggesting alternative resistance mechanisms of CR phenotype.</div></div><div><h3>Conclusions</h3><div>Antimicrobial regimens with tigecycline and colistin were insufficient for effectively managing CRKP bacteremia. The convergence of resistance and virulence in prevalent clones demands the urgent introduction of novel therapeutics. Aggressive and tailored strategies are critical for improving outcomes in high-risk patients.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100905"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-radiotherapy with tyrosine kinase inhibitors might benefit survival in hepatoma patients with portal vein tumor thrombosis","authors":"Hui-Ling Huang ,&nbsp;Wei-Ming Lin ,&nbsp;Chia-Hsuan Lai ,&nbsp;Te-Sheng Chang ,&nbsp;Sheng-Nan Lu","doi":"10.1016/j.bj.2025.100904","DOIUrl":"10.1016/j.bj.2025.100904","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is associated with a poor prognosis, and current treatment options yield suboptimal results. This article aims to share our treatment outcomes for PVTT using tyrosine kinase inhibitors (TKIs), radiation therapy (RT), and their combination.</div></div><div><h3>Methods</h3><div>From 2010 to 2021, a total of 160 Child-Pugh class A HCC patients with PVTT, but without extrahepatic spread, were enrolled. Among them, 26, 10, 81, and 43 patients underwent no treatment, RT, TKIs, and combination therapy, respectively.</div></div><div><h3>Results</h3><div>Compared to the no treatment group (median survival: 2 months), the RT group (4.5 months, <em>p</em> = 0.034), TKIs group (5.0 months, <em>p</em> = 0.0017), and combination group (15.0 months, <em>p</em> &lt; 0.001) all demonstrated a survival benefit. The multivariate Cox model showed adjusted hazard ratios and 95 % confidence intervals of 0.35 (0.16–0.78), 0.40 (0.25–0.63) and 0.26 (0.15–0.44) for RT, TKIs, combination groups, respectively. From clinical observation of patients who survived for two years, we found that 20 % of RT patients achieved good local control, and the RT group had longer durations of TKI use.</div></div><div><h3>Conclusions</h3><div>In this series, 26.9 % (43/160) of HCC patients with PVTT underwent combination treatment with TKIs and RT, achieving a median survival of 15.0 months. The contributions of RT were 20 % disease control rate and may extend the duration of TKIs use. Therefore, all candidates without contraindications should be considered for combination treatment.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100904"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNAs as modulators of metabolic reprogramming for endogenous heart regeneration: Mechanisms and therapeutic potential","authors":"Xueping Wu ,&nbsp;Yehui Lv ,&nbsp;Zhihong Li ,&nbsp;Zhifang Yang","doi":"10.1016/j.bj.2025.100914","DOIUrl":"10.1016/j.bj.2025.100914","url":null,"abstract":"<div><div>Myocardial infarction (MI) is one of the leading causes of death worldwide, with its high incidence and mortality posing a significant threat to human health. Despite some progress in the treatment of myocardial infarction, mortality rates remain alarmingly high. Adult mammals have limited myocardial regenerative capacity, and extensive cell death caused by myocardial ischemia severely impairs cardiac function, leading to heart failure or death. In contrast, neonatal myocardium possesses a robust regenerative ability, which gradually diminishes after birth. The loss of cardiomyocyte regenerative capacity is often accompanied by a shift in energy metabolism—from reliance on glucose (glycolysis) to fatty acid oxidation. This metabolic reprogramming significantly impacts CM proliferation. Long non-coding RNAs (lncRNAs) orchestrate cardiac regeneration through epigenetic control (e.g., Bvht/PRC2-mediated silencing), metabolic reprogramming (e.g., GATA6-AS1 suppression of FAO), and miRNA sponging (e.g., CAREL sequestration of miR-296). However, our understanding of the metabolic determinants and pathways that promote myocardial regeneration after myocardial infarction is still insufficient. This review investigates the interplay between lncRNAs and metabolic reprogramming in cardiovascular function, aiming to identify novel therapeutic targets and strategies to enhance myocardial regeneration post-MI.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100914"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glibenclamide attenuates neuronal pyroptosis by modulating K_ATP channels in the hippocampus of palmitic acid-induced lipotoxic mice.","authors":"Chung-Lin Chen, Liang-Chu Chang, Chao-Yu Chen, Yen-Shuo Lai, Pei-Chun Chen, Ching-Han Lin","doi":"10.1016/j.bj.2026.100972","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100972","url":null,"abstract":"<p><p>Metabolic lipotoxicity contributes to neuroinflammation and cognitive dysfunction, yet the cellular mechanisms linking saturated fatty acids to hippocampal injury remain incompletely understood. In this study, we investigated whether glibenclamide (GB), a clinically used ATP-sensitive potassium (K_ATP) channel inhibitor, modulates hippocampal inflammatory responses induced by palmitic acid (PA). Male C57BL/6N mice were subjected to chronic PA injections with or without GB treatment for four weeks. Behavioral tests, histological analyses, and molecular assays were performed to evaluate hippocampal function and inflammatory signaling. Chronic PA exposure impaired recognition memory and was associated with neuronal apoptosis, microglial activation, and lipid accumulation in the hippocampus. PA treatment also increased the expression of inflammasome-associated markers, including NLRP3, caspase-1, gasdermin D (GSDMD), and IL-1β, together with elevated levels of pro-inflammatory cytokines (IL-6, MCP-1, TNF-α). GB treatment attenuated these changes and reduced markers of inflammasome activation in both hippocampal tissue and PA-treated BV2 microglial cells. Immunofluorescence analysis further revealed spatial proximity between SUR1/K_ATP channel components and GSDMD at the microglial cell surface following PA exposure. These findings indicate that PA-induced lipotoxic stress promotes microglial activation and inflammasome-associated pyroptotic signaling in the hippocampus. GB treatment mitigates these inflammatory responses, suggesting that modulation of microglial signaling pathways may represent a potential strategy for metabolic disorder-associated cognitive dysfunction.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100972"},"PeriodicalIF":4.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-Cas9-mediated elimination of plasmid-borne carbapenemase genes restores ertapenem susceptibility in clinical Klebsiella pneumoniae isolates.","authors":"Shu-Fang Kuo, Tsung-Yu Huang, Chih-Yi Lee, Fang-Ju Chen, Chen-Hsiang Lee","doi":"10.1016/j.bj.2026.100966","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100966","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its broad-spectrum antimicrobial resistance and capacity for horizontal gene transfer.</p><p><strong>Methods: </strong>Three clinical CRKP isolates, each carrying one of the three major classes of carbapenemase as class A (bla_KPC), class B (bla_NDM), and class D (bla_OXA) were selected. A CRISPR/Cas9-based system (pCasKP-pSGKP) was employed to target carbapenem resistance genes in these strains (KP21040 with bla_OXA-181, KP4-78 with bla_NDM-1, and KP5-4 with bla_KPC-2).</p><p><strong>Results: </strong>CRISPR/Cas9-mediated editing led to partial reduction or complete loss of resistance plasmids, as evidenced by S1 nuclease-pulsed-field gel electrophoresis. This plasmid elimination correlated with a marked restoration of susceptibility to ertapenem, showing a greater than 64-fold reduction in minimum inhibitory concentrations (MICs) across all strains. In KP21040, MICs for ertapenem and levofloxacin decreased to 0.006 μg/mL and 0.125 μg/mL, respectively. Whole-genome analysis revealed that bla_OXA-181 was flanked by insertion sequence (IS)26 elements, which mediated homologous recombination upon CRISPR-induced double-strand breaks, resulting in excision of a ∼15 kb segment including bla_OXA-181 and qnrS1. These findings suggest that ISs may enhance CRISPR efficacy by promoting recombination-driven deletion. Moreover, the complete removal of all three resistance plasmids was observed in the KP5-4 strain harboring bla_KPC-2.</p><p><strong>Conclusion: </strong>This study demonstrates that CRISPR/Cas9-based genome editing can eliminate plasmid-encoded carbapenemase genes in clinical CRKP isolates and, in specific genetic contexts, facilitate the concurrent removal of associated quinolone resistance determinants. These findings support CRISPR-based genome editing as a proof-of-concept strategy for addressing plasmid-mediated multidrug resistance in Gram-negative pathogens.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100966"},"PeriodicalIF":4.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Clinical Microbiology and Artificial Intelligence: An Image-Based Deep Learning Framework for Automated Antimicrobial Susceptibility Testing.","authors":"Fatih Ciftci, Kadriye Yasemin Usta Ayanoğlu, Azime Erarslan","doi":"10.1016/j.bj.2026.100965","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100965","url":null,"abstract":"<p><p>The rising threat of antimicrobial resistance has underscored the urgent need for rapid, standardized, and automated antimicrobial susceptibility testing (AST) solutions. Leveraging recent advances in computer vision and deep learning, this study introduces a fully image-based diagnostic framework that integrates a YOLOv8n object detection model with a Convolutional Neural Network (CNN) to perform end-to-end bacterial identification and susceptibility classification directly from Petri dish images. The YOLOv8n model accurately localizes handwritten bacterial species labels with a mean Average Precision (mAP@0.50) exceeding 0.93, demonstrating robustness across diverse handwriting styles and imaging conditions. Complementarily, the CNN achieves a balanced accuracy of 94.7% and 100% sensitivity for susceptible cases by analyzing inhibition zone morphology without manual measurements or interpretive rules. Notably, the system achieved a 0% Very Major Error (VME) rate, ensuring no resistant isolates were misclassified as susceptible. The dual-model system generalizes effectively across experimental variations and produces high-confidence predictions, highlighting its potential to streamline AST workflows, minimize human variability, and enhance diagnostic reliability in clinical microbiology.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100965"},"PeriodicalIF":4.4,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complex interplay between hepatitis D virus and the interferon response.","authors":"Claudie Eber, Eloi R Verrier","doi":"10.1016/j.bj.2026.100964","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100964","url":null,"abstract":"<p><p>Hepatitis D virus (HDV) infection represents a major global public health challenge and is responsible for the most severe form of chronic viral hepatitis. Affecting an estimated 12 million individuals worldwide, chronic hepatitis D is associated with rapid progression to advanced liver disease, including cirrhosis and hepatocellular carcinoma. Despite its clinical burden, therapeutic options for HDV remain limited. In this context, pegylated interferon alpha (PEG-IFN-α) continues to be the most widely used treatment globally, particularly outside Europe where access to newly approved therapies is restricted. However, PEG-IFN-α is characterized by modest and heterogeneous antiviral efficacy, frequent viral relapse, and a high rate of adverse effects, highlighting the need for improved therapeutic strategies. A better understanding of the mechanisms underlying interferon responsiveness and resistance in HDV infection is therefore essential. The complex interplay between HDV and the innate immune response plays a central role in determining viral persistence and treatment outcome. HDV is sensed by innate immune receptors and induces type I and type III interferon responses, yet these responses are insufficient to control viral replication. Viral nuclear replication, interferon-stimulated gene accessibility, and active interference with interferon signaling pathways contribute to the limited antiviral activity of interferons against HDV. This review synthesizes current knowledge on the interactions between HDV and the interferon response, discusses experimental models used to study these mechanisms, and highlights key limitations and open questions that must be addressed to optimize future interferon-based and combination therapies.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100964"},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From inhibition to regulation: serpins in health and disease","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2026.100950","DOIUrl":"10.1016/j.bj.2026.100950","url":null,"abstract":"<div><div>This issue of the Biomedical Journal highlights regulatory mechanisms that shape aging, disease progression, and biological complexity across molecular, cellular, and systems levels. A central theme is plasminogen activator inhibitor-1 (PAI-1) as a multifunctional regulator linking fibrinolysis, cellular senescence, stem cell dynamics, fibrosis, and tumor biology. Contributions examine structure-guided development of small-molecule PAI-1 inhibitors and their therapeutic potential across thrombotic disease, chronic myeloid leukemia, systemic sclerosis, lung cancer, and skin cancer, emphasizing controlled modulation of PAI-1 activity to preserve physiological balance while overcoming disease-associated dysregulation. Beyond protease signaling, several studies address regulatory layers governing cellular state and adaptability. Epitranscriptomic remodeling via N6-methyladenosine (m6A) emerges as a key mechanism in protozoan parasites and host–pathogen interactions, including parasite-driven reprogramming of host leukocytes. In cancer biology, ferroptosis susceptibility is shown to be regulated through SLC7A11-associated protein interactions, linking redox homeostasis, cell survival, and tumor progression in hepatocellular carcinoma. Exosome-mediated intercellular communication is further examined as a mechanism regulating tissue repair, inflammation, and systemic crosstalk, including gut microbiota–dependent effects on bone homeostasis. Methodological advances further underscore the importance of precision and interpretability in modern biomedical research. These include accessible platforms for reproducible single-cell RNA sequencing analysis, robot-assisted quantification of acupuncture mechanics underlying analgesic responses, and interpretable deep-learning frameworks combining classification and segmentation in medical imaging. Quantitative three-dimensional imaging approaches are also applied to craniofacial surgery, where cone-beam computed tomography–based analyses identify determinants of lip cant and facial midline correction following bimaxillary surgery. A conceptual synthesis places living systems and learning systems within shared theoretical frameworks, highlighting the convergence of physics, information theory, and artificial intelligence in understanding biological organization.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100950"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of PAI-1 in the progression and treatment resistance of non-small cell lung cancer","authors":"Takeshi Masuda ,&nbsp;Noboru Hattori","doi":"10.1016/j.bj.2025.100911","DOIUrl":"10.1016/j.bj.2025.100911","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is the leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs), chemotherapy, and molecular targeted therapies have improved survival rates, therapeutic resistance remains a major barrier to curative outcomes. Recently, plasminogen activator inhibitor-1 (PAI-1) has been implicated in lung cancer progression and treatment resistance.</div></div><div><h3>Material and methods</h3><div>This review summarizes the recent evidence from preclinical and clinical studies on the role of PAI-1 in the progression and treatment resistance in lung cancer, focusing on its contribution to tumor aggressiveness and resistance to therapy. As limited evidence is available regarding its role in small cell lung cancer, this review focuses on the findings reported to date for non-small cell lung cancer (NSCLC).</div></div><div><h3>Results</h3><div>PAI-1 promoted tumor invasion, angiogenesis, and epithelial–mesenchymal transition (EMT), thereby facilitating cancer progression. Elevated PAI-1 expression in tumor tissues and plasma is correlated with advanced disease stages and poor prognosis. Genetic polymorphisms such as A15T, which affect PAI-1 stability, are also associated with unfavorable outcomes. PAI-1 contributes to radiotherapy resistance through the hypoxia-induced upregulation of AKT/ERK signaling, chemotherapy by activating cancer-associated fibroblasts, and targeted therapies via integrin-mediated EMT. Moreover, it enhances immune evasion by promoting programmed cell death-ligand 1 expression and creating an immunosuppressive tumor microenvironment.</div></div><div><h3>Conclusions</h3><div>PAI-1 is a key regulator of tumor progression and therapeutic resistance in NSCLC. Targeting PAI-1 may offer a novel strategy to overcome resistance to multiple treatment modalities, and future research should focus on developing PAI-1–based biomarkers and therapeutic combinations for both NSCLC.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100911"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}