Pathology, research and practice最新文献

{"title":"Epigenetic regulation of circulating tumor cells in precision oncology","authors":"Husni Farah ,&nbsp;Munthar Kadhim Abosaoda ,&nbsp;Hayjaa Mohaisen Mousa ,&nbsp;S. Renuka Jyothi ,&nbsp;Priya Priyadarshini Nayak ,&nbsp;J. Bethanney Janney ,&nbsp;Gurjant Singh ,&nbsp;Ashish Singh Chauhan","doi":"10.1016/j.prp.2025.156282","DOIUrl":"10.1016/j.prp.2025.156282","url":null,"abstract":"<div><div>Cancer metastasis causes the majority of cancer-related deaths. During metastasis, invasive tumor cells enter the bloodstream and become circulating tumor cells. These cells eventually populate the secondary organs. In addition to genetic mutations, epigenetic changes (such as DNA methylation, histone modifications, and noncoding RNA-associated changes) are important for regulating gene expression and preserving chromatin integrity in tumor cells. Dysregulation of these epigenetic patterns is critical for carcinogenesis, tumor growth, and metastatic spread. We presented an overview of CTC biology, including essential mechanisms such as epithelial-mesenchymal transition (EMT) and immune evasion. We discussed how epigenetic reprogramming of CTCs also occurs post-transcriptionally via non coding RNAs, The subject then moves to how epigenetic changes in CTCs affect these processes throughout migration, survival in circulation, and metastatic seeding. The following sections discuss the clinical implications of addressing CTC epigenetics, proposing CTC epigenetic changes as prospective biomarkers for early cancer detection, prognosis, and targeted therapy intervention to improve patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156282"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Staphylococcal enterotoxins in cancer immunotherapy: An overview of translational advances and targeting strategies","authors":"Abbas Ali Imani Fooladi ,&nbsp;William C. Cho ,&nbsp;Russel J. Reiter ,&nbsp;Mina Alimohammadi ,&nbsp;Najma Farahani ,&nbsp;Kiavash Hushmandi","doi":"10.1016/j.prp.2025.156283","DOIUrl":"10.1016/j.prp.2025.156283","url":null,"abstract":"<div><div>Staphylococcal enterotoxins (SEs) are superantigens that polyclonally activate T cells by cross-linking MHC class II on antigen-presenting cells with T cell receptor (TCR) Vβ regions, generating potent IL-2/IFN-γ/TNF responses distinct from conventional peptide–MHC–restricted activation. This review synthesizes mechanistic and translational evidence for SEs in oncology, emphasizing disease-relevant contexts and advanced engineering strategies that improve therapeutic index. Preclinical studies demonstrate antitumor activity across melanoma, glioblastoma, renal cell carcinoma, bladder cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, squamous cell carcinoma, and hematologic malignancies (e.g., acute myeloid leukemia, lymphoma). Tumor-targeted superantigen platforms, such as antibody or ligand–SE fusion proteins and oncolytic vectors encoding Ses, concentrate activity intratumorally, increase intratumoral IFN-γ/TNF, reduce proliferation and angiogenesis, and enhance necrosis while limiting systemic exposure. Engineered SE variants (for example, SEB with attenuated pyrogenicity) and localized delivery further mitigate risks associated with cytokine release. Early clinical experiences with SE-based constructs and SE-modified tumor vaccines report feasibility and signals of activity in head and neck cancer, glioma, renal cell carcinoma, and myeloma, but small, heterogeneous studies limit definitive conclusions. Although SEs can trigger cytokine storm and off-target activation via MHC II on healthy tissues, risk can be reduced through intratumoral/regional dosing, tumor-targeted fusions, dose–schedule optimization, and indication selection informed by MHC II biology; paradoxical, disease-specific effects (e.g., in cutaneous T-cell lymphoma) highlight the importance of microbiome-aware protocols. Priorities for translation include disease-focused development in MHC II–II-permissive tumors, combinations with immune checkpoint inhibitors, and biomarker-anchored trials integrating multi-omics and patient selection. With targeted engineering and controlled delivery, SEs can evolve from broadly inflammatory agents into precise immuno-oncology tools with meaningful clinical impact. This review underscores that, with targeted engineering, controlled delivery, and biomarker-guided patient selection, SEs can be advanced from broadly inflammatory agents to precise immuno-oncology platforms ready for rigorous clinical evaluation.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156283"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating biomarkers in osteoarthritis: a systematic review unveiling key trends and future prospects","authors":"Francesca Veronesi,&nbsp;Francesca Salamanna,&nbsp;Giulia Sacchi,&nbsp;Veronica Borsari,&nbsp;Gianluca Giavaresi","doi":"10.1016/j.prp.2025.156281","DOIUrl":"10.1016/j.prp.2025.156281","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive and chronic joint disorder characterized by cartilage degradation, joint inflammation, and pain, leading to reduced mobility and quality of life. One of the major challenges in OA management is the early diagnosis and effective monitoring of disease progression, due to the lack of specific and sensitive biomarkers. This systematic review aimed to evaluate circulating biomarkers, including serum proteins and microRNAs (miRNAs), for their potential diagnostic and prognostic value in OA. A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus for studies published from March 18, 2015, to March 18, 2025, resulting in 471 studies. After applying inclusion and exclusion criteria, 18 clinical studies and among them, 12 investigated circulating proteins and 6 focused on miRNAs. Several serum proteins such as interleukins (IL-6, IL-1β, IL-38), complement 3 (C3), autotaxin (ATX), pentraxin 3 (PTX3), hyaluronic acid (HA), and clusterin (CLU) showed significant elevation in OA patients and were linked to disease severity. Regarding miRNAs, some (e.g., let-7e, miR-33b-3p) were downregulated, while others (e.g., miR-146a-5p, miR-92a-3p) were upregulated in OA. Functional analyses using STRING and miRNet tools revealed that these biomarkers are not only diagnostic indicators but may actively contribute to OA pathogenesis, particularly through inflammation and cartilage-related pathways. In conclusion, circulating proteins and miRNAs hold promise as non-invasive biomarkers for knee OA. By integrating evidence from 18 clinical studies with network analyses, we identify two predominant molecular phenotypes: an inflammatory–metabolic axis and a cartilage-turnover axis. However, further large-scale, standardized studies are necessary to confirm their clinical applicability and integration into routine practice</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156281"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next generation DNA sequencing data analysis and its application in clinical genomics","authors":"Abhijit Beura ,&nbsp;Gowrang Kasaba Manjunath ,&nbsp;Shweta Mahalingam ,&nbsp;Mangesh Sudhakar Rajguru ,&nbsp;Tikam Chand Dakal ,&nbsp;Abhishek Kumar","doi":"10.1016/j.prp.2025.156280","DOIUrl":"10.1016/j.prp.2025.156280","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) has transformed genomics by enabling rapid, high-throughput analysis of DNA and RNA, driving significant progress across multiple fields, such as cancer research, rare disease diagnosis, and personalized medicine. This review discusses the wide-ranging applications of NGS, particularly in identifying genetic variants that guide the development of targeted therapies, improving patient outcomes. The NGS workflow involves crucial steps including data quality control, sequence alignment, and variant calling, supported by both open-source and commercial tools. Cloud-based platforms have further streamlined the storage, management, and processing of the vast datasets generated by NGS technologies. As NGS continues to evolve, ethical challenges, especially concerning genomic data privacy and informed consent, remain critical considerations. Looking ahead, the integration of multi-omics data and the advent of single-cell sequencing hold the potential to deepen our understanding of complex biological processes. Essential databases like dbSNP, COSMIC, and The Cancer Genome Atlas are key resources for interpreting NGS findings and their clinical significance. By effectively utilizing these tools and datasets, researchers can generate new genetic insights with far-reaching implications for advancing human health and understanding disease mechanisms.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156280"},"PeriodicalIF":3.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An MRI radiomics approach to predict the efficacy of chemotherapy for osteosarcoma","authors":"Danna Liu ,&nbsp;Xue Zhou ,&nbsp;Yixiong Liu ,&nbsp;Hong Wang ,&nbsp;Jixin Liu ,&nbsp;Zhengyuan Li ,&nbsp;Yanfei Liu ,&nbsp;Xin Hou ,&nbsp;Yuewen Hao","doi":"10.1016/j.prp.2025.156279","DOIUrl":"10.1016/j.prp.2025.156279","url":null,"abstract":"<div><h3>Objectives</h3><div>Magnetic resonance imaging (MRI) and dynamic contrast enhancement MRI(DCE-MRI) data of osteosarcoma patients prior to neoadjuvant chemotherapy (NAC) were compared in order to investigate the value of imaging histological features in predicting the rate of tumor necrosis in osteosarcoma and patients' postoperative survival.</div></div><div><h3>Methods</h3><div>We enrolled 28 osteosarcoma patients who received three courses of NAC followed by tumor resection. Prior to chemotherapy both conventional MRI and DCE-MRI scans were performed Quantitative analysis of histological features within the tumor region was conducted using T1-weighted, T2-weighted, and DCE-MRI images. Recursive feature elimination guided the selection of relevant features, and a prediction model was constructed using five machine learning algorithms (Random Forest, Logistic Regression, Decision Tree, Gradient Boosting, and Bagging Decision Tree). Model performance was assessed using receiver operating characteristic (ROC) curves, area under the curve (AUC), and accuracy. The five imaging features with the strongest predictive capability were identified, and their association with postoperative survival was explored using Kaplan-Meier survival analysis.</div></div><div><h3>Results</h3><div>Among the five prediction models, the decision tree, gradient boosting and bagging decision tree models showed high prediction performance, with AUC values of 0.850, 0.856 and 0.872, respectively, and an accuracy of 0.857. Notably, Kaplan-Meier survival analysis highlighted the significance of two features extracted from DCE-MRI images -\"Small Dependence Low Gray Level Emphasis\" (based on the Gray Level Cooccurrence Matrix, GLCM）and \"Run Length Non-Uniformity\" (based on the Gray Level Run Length Matrix, GLRLM), were significantly predictive of postoperative survival (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>DCE-MRI-based imaging histology models of osteosarcoma patients prior to NAC can be a useful tool for predicting tumour necrosis rates and patient survival after surgery.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156279"},"PeriodicalIF":3.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into plant-derived natural compounds for the treatment of skin cancer: Targeting molecular signaling for therapeutic intervention","authors":"Ashutosh Pathak ,&nbsp;G. Surendra ,&nbsp;Sathvik Belagodu Sridhar ,&nbsp;Patibandla Jahnavi ,&nbsp;Jeetendra Kumar Gupta ,&nbsp;P. Balaji ,&nbsp;N. Juniorsundresh ,&nbsp;Konatham Teja Kumar Reddy ,&nbsp;Abdul Ajeed Mohathasim Billah ,&nbsp;Karthickeyan Krishnan","doi":"10.1016/j.prp.2025.156277","DOIUrl":"10.1016/j.prp.2025.156277","url":null,"abstract":"<div><div>Skin cancer, a prevalent global cancer, is primarily caused by chronic environmental exposures and cellular signaling pathway deregulation. Traditional therapies like radiation, chemotherapy, and surgery face toxicity, resistance, and recurrence issues. Natural compounds, with their diverse biological activity and minimal side effects, are increasingly recognized as potential therapeutic agents. This review explores the potential of natural compounds in treating skin cancer by modifying key molecular signaling pathways, including MAPK/ERK, PI3K/Akt, NF-κB, STAT3, and Wnt/β-catenin. Curcumin, resveratrol, quercetin, epigallocatechin gallate, and genistein are natural substances known to have potent anticancer effects by inhibiting cell proliferation, promoting apoptosis, and preventing metastasis. These substances regulate inflammation, prevent angiogenesis, enhance drug effectiveness, combat multidrug resistance, and have low toxicity to healthy skin cells, indicating potential therapeutic use. Additionally, their compatibility with current chemotherapeutic drugs underscores their significant role in combating drug resistance. The review underscores the importance of understanding the molecular mechanisms underlying phytochemicals' anticancer properties to facilitate their integration into modern treatment methods. Future initiatives should focus on clinical validation, increasing bioavailability, and targeting administration schemes to maximize the therapeutic potential of natural chemicals against skin cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156277"},"PeriodicalIF":3.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD47/HIF-1α circuit promotes cell proliferation in hepatocellular carcinoma","authors":"Cuicui Xu ,&nbsp;Yuhui Pei ,&nbsp;Xiaoman Zhang ,&nbsp;Cuicui Wang ,&nbsp;Min He ,&nbsp;Zhicheng Wan ,&nbsp;Ganyu Miao ,&nbsp;Jun Hou ,&nbsp;Lianghai Wang","doi":"10.1016/j.prp.2025.156275","DOIUrl":"10.1016/j.prp.2025.156275","url":null,"abstract":"<div><h3>Objective</h3><div>Hepatocellular carcinoma (HCC) is a prevalent digestive system malignancy with a poor prognosis. Previous studies suggested that elevated CD47 expression, a member of the immunoglobulin superfamily, is correlated with poor outcomes in various cancers. However, the precise mechanisms through which CD47 influences HCC progression remain unclear.</div></div><div><h3>Methods</h3><div>CD47 expression in tumor and adjacent tissues was assessed using online databases and immunohistochemical staining. The effects of CD47 on tumor cell proliferation were evaluated through cell counting kit-8 and colony formation assays. Bioinformatics analyses, qRT-PCR, and western blotting were employed to investigate the underlying mechanisms by which CD47 regulates tumor progression.</div></div><div><h3>Results</h3><div>CD47 expression was significantly elevated in HCC tissues compared to normal counterparts, and its level was closely associated with tumor stage. Overexpression of CD47 enhanced HCC cell growth, whereas silencing CD47 inhibited proliferation. Mechanistically, HIF-1α directly binds to the CD47 promoter, regulating its transcription. Additionally, CD47 stabilizes HIF-1α protein by inhibiting autophagy-lysosome-mediated degradation, establishing a positive feedback loop that promotes HCC cell proliferation.</div></div><div><h3>Conclusion</h3><div>CD47 is upregulated in HCC tissues, and its interaction with HIF-1α accelerates tumor growth through a positive feedback loop. Targeting both CD47 and HIF-1α may offer a promising therapeutic strategy for patients with HCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156275"},"PeriodicalIF":3.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP5 influences immune infiltration and prognosis in non-small-cell lung cancer","authors":"Yonghong Xu ,&nbsp;Yifei Xie ,&nbsp;Jian Zhao ,&nbsp;Jiansheng Zhang ,&nbsp;Jie Zhao ,&nbsp;Yongliang Du ,&nbsp;Jianjie Zhu ,&nbsp;Yuanyuan Zeng ,&nbsp;Jian-an Huang ,&nbsp;Zeyi Liu","doi":"10.1016/j.prp.2025.156276","DOIUrl":"10.1016/j.prp.2025.156276","url":null,"abstract":"<div><h3>Background</h3><div>USP5, a deubiquitinating enzyme, is linked to various cancers. However, its relationship with immune infiltration and its prognostic significance in non–small-cell lung cancer (NSCLC) remains to be determined.</div></div><div><h3>Methods</h3><div>USP5 expression patterns in NSCLC were analyzed using data sourced from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Functional enrichment analyses were performed to predict the role of USP5 in NSCLC development, and Hub genes were identified through a protein–protein interaction (PPI) network. Immune cell infiltration was assessed via single-sample gene set enrichment analysis, while the prognostic significance of USP5 was evaluated using the Kaplan–Meier method and Cox regression analysis. To facilitate survival rate predictions at different time points, a prognostic model was developed. Previous findings were validated using real-time PCR and <em>in vitro</em> functional assays in NSCLC cell lines.</div></div><div><h3>Results</h3><div>USP5 expression was found to be markedly elevated in NSCLC tissues when compared to normal tissues. Functional enrichment analysis revealed the involvement of USP5 in regulating key pathways linked to lung adenocarcinoma development. PPI network analysis revealed several potential interactions contributing to NSCLC progression. A correlation was observed between higher USP5 levels and the reduced presence of immune cells (e.g., macrophages, CD8 +T cells, NK cells, and iDCs) within the tumor microenvironment. ROC curves confirmed the prognostic value of USP5 for NSCLC. Functional studies in NSCLC cell lines confirmed the molecular effects of USP5 on NSCLC development.</div></div><div><h3>Conclusions</h3><div>USP5 appears to be a reliable marker for diagnosing NSCLC and predicting its prognosis. Further investigation into the role of USP5 in immune responses may aid in the development of immunotherapies for NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156276"},"PeriodicalIF":3.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of C-reactive protein in cervical intraepithelial neoplasia/cancer","authors":"Adriana Pedreañez ,&nbsp;Yenddy Carrero ,&nbsp;Renata Vargas ,&nbsp;Juan P.Hernández Fonseca ,&nbsp;Jesús Mosquera","doi":"10.1016/j.prp.2025.156274","DOIUrl":"10.1016/j.prp.2025.156274","url":null,"abstract":"<div><div>Cervical cancer is one of the most common malignancies in women. This pathology originates from the progression of cervical intraepithelial neoplasia (CIN), induced by high-risk human papillomavirus (HPV) infection. During CIN, an inflammatory process characterized by immune system activation and increased levels of C-reactive protein (CRP) occurs. This protein, generally an indicator of inflammatory processes, also has functions that can influence the pathogenesis of several diseases. This review summarizes the current published literature (searched on Pubmed, EMBASE and Web of Science) regarding the factors that affect pathogenesis of cervical intraepithelial neoplasia/cancer mediated by CRP searched up to 2025. This review highlights the events present in CIN/cancer where CRP may be involved. CRP may induce progression of CIN to cervical cancer through its action on its lectin-like receptor oxidized low-density lipoprotein receptor-1 (LOX-1) and influence events involving complement activation, immune system activation, apoptosis induction, oxidative stress, and modulation of HPV biology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156274"},"PeriodicalIF":3.2,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chuanxing Qingfei Syrup ameliorates acute lung injury by suppressing BCL10 expression and blocking the IKK/IκBα/NF-κB pathway","authors":"Yuanyuan Song ,&nbsp;Heng Li ,&nbsp;Yanyun Zhao ,&nbsp;Chen Cheng ,&nbsp;Weiwei Zhang ,&nbsp;Yingying Sun ,&nbsp;Taiyu Jin","doi":"10.1016/j.prp.2025.156273","DOIUrl":"10.1016/j.prp.2025.156273","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is a potentially lethal condition with a considerable mortality rate. This study aims to determine the protective effect of Chuanxing Qingfei Syrup (CQS) against ALI.</div></div><div><h3>Methods</h3><div>An ALI model was constructed by dropping lipopolysaccharide (LPS) into the trachea of mice, and mice were treated with low, medium, and high doses of CQS to evaluate the therapeutic effect of CQS. LPS-treated A549 cells were used to construct an <em>in vitro</em> ALI model, and low, medium, and high doses of CQS were used to treat A549 cells. The cytotoxicity and therapeutic efficacy of CQS were verified. Bioinformatic analysis was employed to predict the downstream targets of CQS. BCL10 expression in mouse lung tissues and A549 cells was detected. The phosphorylation level of IKKβ, IκBα, and NF-κB p65, and the nuclear translocation of NF-κB p65 were measured. BCL10 overexpression and treatment with the NF-κB pathway inhibitor PDTC were performed to explore their effects on A549 cell injury. Intranasal instillation of overexpressed BCL10 adeno-associated virus was performed to observe its effect on ALI mice.</div></div><div><h3>Results</h3><div>CQS effectively alleviated the infiltration of inflammatory cells, reduced levels of inflammatory factors, inhibited apoptosis, and alleviated lung edema in mice. CQS inhibited apoptosis in A549 cells. CQS inhibited BCL10, and BCL10 activated the IKK/IκBα/NF-κB pathway. Overexpression of BCL10 aggravated A549 cell injury and pathological changes in ALI mice. PDTC treatment mitigated LPS-induced injury in A549 cells overexpressing BCL10.</div></div><div><h3>Conclusion</h3><div>CQS inhibits ALI progression by targeting BCL10 and suppressing the IKK/IκBα/NF-κB pathway.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156273"},"PeriodicalIF":3.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}