Pathology, research and practice最新文献

{"title":"CSB6B attenuates renal inflammation and fibrosis by inhibiting the activation of NLRP3 inflammasome through the NLRP3/Caspase-1/GSDMD/IL-1β signaling pathway","authors":"Shuo Chen ,&nbsp;Yonghong Zhu ,&nbsp;Tong Chen ,&nbsp;Yanyan Xu ,&nbsp;Qiuling Fan","doi":"10.1016/j.prp.2025.156286","DOIUrl":"10.1016/j.prp.2025.156286","url":null,"abstract":"<div><h3>Context</h3><div>Diabetic Kidney Disease (DKD) is a significant complication and leading cause of death in both type 1 and type 2 diabetes, as well as the primary cause of chronic kidney disease. Macrophage migration inhibitory factor (MIF) activates the NLRP3 inflammasome. Chicago sky blue 6B (CSB6B) is a MIF inhibitor with therapeutic potential in various inflammatory diseases, but its effect on DKD remains unexplored.</div></div><div><h3>Materials and methods</h3><div>HK-2 cell was used as the in vitro cell model. For the in vivo animal model, The db/db mice were randomly divided into three subgroups: the diabetic nephropathy model group, the low-dose CSB6B intervention group (2 mg/kg), and the high-dose CSB6B intervention group (8 mg/kg), with drug administration via intraperitoneal injection twice weekly for 12 weeks. CCK-8 assessed CSB6B toxicity, while qPCR measured MIF mRNA expression. Western blot, immunohistochemistry and ELISA detected protein expression level, and LDH release assessed membrane integrity. Histological analysis evaluated renal pathological changes.</div></div><div><h3>Results</h3><div>CSB6B significantly inhibited the secretion of inflammatory cytokines interleukin-1β (IL-1β) and TGF-β1 from high-glucose-stimulated HK-2 cells without affecting their viability. CSB6B effectively inhibited the expression and secretion of MIF in high-glucose-stimulated HK-2 cells, down-regulated the expression of NLRP3, suppressed the activation of NLRP3 inflammasomes, reduced the production of cell pyroptosis-related proteins, and significantly decreased collagen I and FN expression. CSB6B treatment significantly reduced the body weight, blood glucose, blood creatinine, urine ACR, and NGAL of db/db mice, and improved the pathological damage of diabetic nephropathy. CSB6B effectively reduced the expression level of MIF protein in diabetic nephropathy mice, down-regulated the expression of NLRP3, Caspase-1, GSDMD, IL-1β, Collagen I and FN in the renal cortex of diabetic nephropathy mice.</div></div><div><h3>Conclusions</h3><div>CSB6B mitigated DKD by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis signaling pathway, suppressed cell pyroptosis, reduced cytokine secretion, and decreasd extracellular matrix accumulation. CSB6B showed promise as a potential therapeutic for DKD.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156286"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518577","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":"EGCG inhibits hepatic stellate cell activity and liver fibrosis by targeting the MDM2/MUC5AC-mediated TGF-β1/Smad signaling pathway","authors":"Longbao Yang ,&nbsp;Fenrong Chen ,&nbsp;Xiong Li,&nbsp;Xiaoke Sun,&nbsp;Hong Li,&nbsp;Haitao Shi,&nbsp;Gang Zhao","doi":"10.1016/j.prp.2025.156298","DOIUrl":"10.1016/j.prp.2025.156298","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the intervention effect of epigallocatechin gallate (EGCG) on liver fibrosis and its underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>A mouse model of liver fibrosis induced by a high-fat diet was established, with groups divided into normal control, high-fat diet (HF) group, and HF + EGCG groups (low, medium, and high doses). The therapeutic effect of EGCG on liver fibrosis was evaluated by liver pathological scoring, detection of serum biochemical indicators, analysis of fibrotic markers, and Western blot for fibrotic protein expression. LX-2 cells were cultured in vitro and activated by TGF-β1. Molecular biology experiments (RT-qPCR, Western blot, immunofluorescence, co-immunoprecipitation, etc.) were used to explore the effects of EGCG on LX-2 cell activation, proliferation, migration, and its regulation of the TGF-β/Smad signaling pathway. Ubiquitination assays, molecular docking, and enzyme inhibitor interventions were performed to clarify the regulatory mechanism of EGCG on MUC5AC stability and its interaction with MDM2. Gene silencing/overexpression techniques were used to verify the critical role of the MDM2/MUC5AC axis in EGCG’s anti-fibrotic effect.</div></div><div><h3>Results</h3><div>In vivo experiments showed that EGCG dose-dependently improved liver histological damage in high-fat diet-fed mice, reduced serum levels of ALT, AST, and TBil, increased albumin and prothrombin time, decreased the expression of fibrotic markers such as hyaluronic acid (HA) and laminin (LN), and inhibited the expression of fibrotic proteins including α-SMA and collagen I. In vitro experiments confirmed that EGCG reduced activation, proliferation, and migration of LX-2 cells by inhibiting the TGF-β1/Smad signaling pathway (downregulating Smad2/3 phosphorylation and upregulating Smad7). Mechanistically, EGCG targeted and bound to MDM2, inhibiting MDM2-mediated ubiquitination and degradation of MUC5AC, thereby increasing MUC5AC protein stability. MUC5AC directly interacted with TGF-β1, further inhibiting the activation of the TGF-β1/Smad pathway. Additionally, overexpression of MDM2 reversed the upregulation of MUC5AC and the anti-fibrotic effect of EGCG, while supplementation of MUC5AC restored the intervention effect of EGCG, confirming that EGCG exerts its function through the MDM2/MUC5AC axis.</div></div><div><h3>Conclusion</h3><div>EGCG targets MDM2 to prevent MUC5AC from ubiquitination and degradation. The upregulated MUC5AC binds to TGF-β1 and inhibits the TGF-β1/Smad signaling pathway, thereby suppressing hepatic stellate cell activation and liver fibrosis progression. This study provides new potential targets and experimental basis for the prevention and treatment of liver fibrosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156298"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605549","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":"Molecular regulation and therapeutic targeting of programmed cell death in hepatocellular carcinoma","authors":"Yu Zhao ,&nbsp;Liuxin Yang ,&nbsp;Peng Wang ,&nbsp;Shuang Huo ,&nbsp;Xingxing Yuan ,&nbsp;Jiakang Jiang","doi":"10.1016/j.prp.2025.156310","DOIUrl":"10.1016/j.prp.2025.156310","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a global health challenge with limited treatment options, largely due to the ability of tumor cells to evade programmed cell death (PCD). Dysregulation of key PCD pathways; apoptosis, necroptosis, pyroptosis, and autophagy plays a pivotal role in hepatocarcinogenesis, progression, and therapy resistance.</div></div><div><h3>Objective</h3><div>This review comprehensively elucidates the molecular mechanisms governing these PCD pathways, their dysregulation in HCC, and the resulting therapeutic opportunities.</div></div><div><h3>Methods</h3><div>We systematically analyzed current literature to detail the core regulators of each PCD pathway, summarize how HCC cells evade them, and evaluate preclinical and clinical strategies for therapeutic targeting.</div></div><div><h3>Key findings</h3><div>HCC cells hijack multiple mechanisms to suppress apoptosis and divert necroptosis. Pyroptosis exhibits a dual role, acting as a tumor suppressor but also contributing to an immunosuppressive microenvironment in established tumors. Autophagy serves a context-dependent function, preventing tumor initiation but sustaining advanced tumors. Promisingly, preclinical studies demonstrate that resensitizing HCC cells to PCD, particularly through combination therapies, can overcome resistance. Early-phase clinical trials targeting these pathways, especially with autophagy inhibitors, have shown manageable safety profiles and hints of efficacy, though larger trials are needed.</div></div><div><h3>Conclusion</h3><div>The precise modulation of PCD pathways represents a promising frontier in HCC therapy. Future efforts must focus on patient stratification, biomarker development, and rational combination strategies that exploit the crosstalk between different PCD modalities to improve clinical outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156310"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615954","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":"Pitfalls in MLH1 promoter methylation assessment, including POLEmut/MLH1meth endometrial adenocarcinoma","authors":"Amelia Flaus ,&nbsp;Zhi Cui ,&nbsp;Mirko Miladinovic ,&nbsp;Ju-Yoon Yoon","doi":"10.1016/j.prp.2025.156303","DOIUrl":"10.1016/j.prp.2025.156303","url":null,"abstract":"<div><div><em>MLH1</em> promoter methylation status may serve as an important diagnostic, prognostic, and predictive biomarker in management of mismatch repair (MMR)-deficient cancers. A new commercial assay for detection of <em>MLH1</em> promoter hyper-methylation (EntroGen), which interrogates regions C and D, was assessed for its performance characteristics. False positive results were obtained in 5/21 non-lesional cases, with signals limited to region C. Three were explained by overloaded reactions. Two unexplained cases were both muscle samples (2/6 muscle samples, one each of skeletal and smooth). The assay was 100 % concordant (52/52) for lesional samples with expected <em>MLH1</em> promoter methylation status. These included two exceptional cases—one Lynch-associated, and one <em>POLE</em>-mutated endometrial carcinoma; thus expanding the spectrum of extreme cases, and demonstrate neither germline or somatic NGS results completely rule out <em>MLH1</em> promoter methylation, and vice versa. The <em>POLE</em>^mut/<em>MLH1</em>^meth carcinoma was notable for molecular features in keeping with POLE dysfunction, accompanied by multiple, additional genetic lesions in the MMR pathway. Exploring the TCGA dataset, 1/8 cases of POLE (ultramutated) endometrial carcinoma was notable for <em>MLH1</em> silencing. Comprehensive genomic profiling assay was informative, allowing for correlation of <em>MLH1</em> methylation and <em>POLE</em> genotype results with tumor mutation burden and mutational signature. Taken together, our data highlight the need for integrated approach in endometrial carcinoma biomarker testing, integrating NGS and <em>MLH1</em> promoter methylation status, the latter of which benefits from assessing both regions C and D. Finding of <em>MLH1</em> promoter methylation does not rule out either Lynch syndrome or ultramutated (POLE) carcinoma.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156303"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615955","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":"2026-01-01","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":"Assessing large language model for automated diagnosis of benign and malignant lung tumors","authors":"Yinghan Jiang ,&nbsp;Jianzhong He ,&nbsp;Bingsen He ,&nbsp;Lingyan Liu ,&nbsp;Li Wang ,&nbsp;Huan Li ,&nbsp;Yanan Li ,&nbsp;Yuebin Shi ,&nbsp;Rongsheng Liu ,&nbsp;Peiren Tang ,&nbsp;Ying Li ,&nbsp;Ji Du ,&nbsp;Jun Peng ,&nbsp;Jie Li ,&nbsp;Yang Chen","doi":"10.1016/j.prp.2025.156306","DOIUrl":"10.1016/j.prp.2025.156306","url":null,"abstract":"<div><h3>Background</h3><div>Differentiating benign from malignant lung tumors remains a critical and often challenging task in histopathological diagnosis. With the advancement of artificial intelligence (AI), large language models such as ChatGPT offer novel opportunities for assisting in diagnostic workflows.</div></div><div><h3>Methods</h3><div>This study retrospectively collected 250 histopathological images, including 50 cases each of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), lung neuroendocrine neoplasms, bronchiolar adenoma, and pulmonary hamartoma. ChatGPT-4o was applied to analyze hematoxylin–eosin (HE) stained images and generate diagnostic interpretations. Its performance was compared to diagnoses made by two experienced pathologists, with evaluations based on accuracy, sensitivity, specificity, F1 score, misdiagnosis rate, and diagnostic time.</div></div><div><h3>Results</h3><div>ChatGPT-4o achieved an overall accuracy of 79.6 %, sensitivity of 81.3 %, specificity of 77.0 %, and F1 score of 82.7 %, significantly lower than the performance of human pathologists (p &lt; 0.001). While its diagnostic accuracy for benign lesions such as bronchiolar adenoma was comparable to human experts, misclassifications frequently occurred in highly differentiated malignancies and poorly visualized neuroendocrine tumors. Notably, ChatGPT-4o achieved near real-time diagnostic speed (&lt;10 s), vastly outperforming human diagnostic time.</div></div><div><h3>Conclusion</h3><div>ChatGPT-4o shows promise as a rapid, scalable AI-assisted diagnostic tool for lung tumors, particularly for benign lesions that are morphologically challenging. Although not yet a replacement for expert pathologists, it may serve as a valuable adjunct to support decision-making and improve diagnostic efficiency in clinical pathology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156306"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615956","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":"2025-12-01","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":"CircRBM33 facilitates colorectal cancer progression by regulating the miR-512–5p/SLC1A5 axis","authors":"Juan Zhang ,&nbsp;Li Zhang ,&nbsp;Kiyohito Tanaka ,&nbsp;Feiyu Shi ,&nbsp;Junjun She ,&nbsp;Shuixiang He","doi":"10.1016/j.prp.2025.156248","DOIUrl":"10.1016/j.prp.2025.156248","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with high morbidity and mortality. Previous studies have shown that circular RNA (circRNA) circRBM33 (also known as hsa_circRNA_104532) was implicated in the pathogenesis of various human cancers. This study aims to investigate the potential function and working mechanism of circRBM33 in CRC.</div></div><div><h3>Methods</h3><div>circRBM33, microRNA-512–5p (miR-512–5p), and solute carrier 1 family member 5 (SLC1A5) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, apoptosis, and migration were analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, and wound healing assay. C-myc, CyclinD1, and SLC1A5 protein levels were measured using Western blot. The glycolysis levels were evaluated using specific kits. The biological role of circRBM33 on CRC tumor growth was assessed using the xenograft tumor model <em>in vivo.</em> After circular RNA Interactome and Targetscan prediction, the binding between miR-512–5p and circRBM33 or SLC1A5 was verified using a dual-luciferase reporter assay.</div></div><div><h3>Results</h3><div>CircRBM33 and SLC1A5 were increased, and miR-512–5p was decreased in CRC tissues and cells. From a functional perspective, circRBM33 knockdown could hinder cell proliferation, migration, glutamine metabolism, and boost apoptosis in CRC cells. Also, circRBM33 silencing could suppress the cell growth of CRC <em>in vivo.</em> The mechanical analysis suggested that circRBM33 could increase SLC1A5 expression via sponging miR-512–5p.</div></div><div><h3>Conclusion</h3><div>CircRBM33 boosted CRC development partly by regulating the miR-512–5p/SLC1A5 axis, providing a promising therapeutic target for CRC therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156248"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293388","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":"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":"2025-12-01","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":"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":"2025-12-01","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}