Pathology, research and practice最新文献

{"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":"2025-11-17","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":"FBXW7 promotes osteoarthritis injury by regulating SLC7A11 ubiquitination degradation and chondrocyte ferroptosis","authors":"Lijuan Yang,&nbsp;Dongli Wang,&nbsp;Nan Yu,&nbsp;Caixia Zhu","doi":"10.1016/j.prp.2025.156297","DOIUrl":"10.1016/j.prp.2025.156297","url":null,"abstract":"<div><div>F-box and WD repeat domain-containing 7 (FBXW7), a ubiquitinating enzyme, has been verified as a key factor linking to the mechanical overloading and chondrocyte senescence in the pathology of osteoarthritis (OA). Given the lack of deeply mechanism research on the regulation of OA by FBXW7, elucidation of the action mechanism of FBXW7 in OA could provide theoretical basis for the treatment of OA. OA model was established by injuring the anterior cruciate ligament (ACL). Ferrostatin-1 (Fer-1) was applied for analysis of ferroptosis. After overexpressed or silence of FBXW7, cell viability and apoptosis were determined via CCK-8 and TUNEL staining. The intracellular Fe^2 + , GSH concentration, ROS levels and mitochondrial membrane potential were assessed by iron determination kit, ELISA, C11-BODIPY/DCFH-DA and JC-1 staining methods. Western blot and RT-qPCR were carried out for determination of ferroptosis-correlated factors (SLC7A11 and GPX4) and ECM-related factors (collagen II (Col II) and ADAMTS5). The interaction between SLC7A11 protein and FBXW7 was detected by immunofluorescence (IF) and immunoprecipitation (IP). Up-regulation of FBXW7, and down-regulation of SLC7A11 and GPX4 were observed in OA groups, compared to that in Control group. Moreover, FBXW7 overexpression significantly hindered cell viability, injured cell morphology, promoted apoptosis and reduced Col II protein level, while Fer-1 treatment blocked the function of FBXW7 overexpression in OA injury. Additionally, silence of FBXW7 showcased the opposite results, meanwhile decreased Fe²⁺ level, increased GSH release, reduced ROS content, raised mitochondrial membrane potential and elevated SLC7A11 and GPX4 in OA chondrocytes. Furthermore, SLC7A11 and FBXW7 were co-localized in chondrocytes and exhibited protein interaction. The ubiquitination degradation of SLC7A11 was accelerated by FBXW7 in chondrocytes, which was intercepted by MG132 treatment. <em>In vivo</em> experimental results further uncovered the alleviated functions of FBXW7 knockdown in ferroptosis and cartilage damage in OA model. The finding demonstrated that FBXW7 aggravated OA injury and ferroptosis, which might be linked to the ubiquitination degradation of SLC7A11.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156297"},"PeriodicalIF":3.2,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145570118","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":"SCD1 drives bladder cancer progression and trametinib sensitivity","authors":"Yanping Zhang ,&nbsp;Shazhou Ye ,&nbsp;Suying Wang ,&nbsp;Qi Ding ,&nbsp;Jing Jin ,&nbsp;Ming Zhao","doi":"10.1016/j.prp.2025.156287","DOIUrl":"10.1016/j.prp.2025.156287","url":null,"abstract":"<div><div>Bladder cancer (BCa) is the most common malignancy of the urinary system. Despite advancements in novel targeted therapies and immunotherapy, the majority of patients remain incurable, and disease progression frequently occurs after treatment. Therefore, identifying new therapeutic strategies is crucial. Fatty acids are essential components of cell structure, playing roles in energy storage and serving as signaling molecules. In tumor tissues, due to abnormal blood vessel development, cancer cells primarily rely on de novo fatty acid synthesis to meet the demands of growth and proliferation. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme, widely recognized as a potential therapeutic target in various cancers. SCD1 promotes the synthesis of cell membranes by converting saturated fatty acids into monounsaturated fatty acids, thus supporting tumor cell growth. In this study, we conducted bioinformatics analysis using public datasets (including bulk RNA-seq and single-cell RNA-seq) and immunohistochemical examination of BCa tissues. Our findings reveal that SCD1 is specifically expressed in BCa cells and is associated with poor tumor grade and prognosis. Furthermore, drug sensitivity predictions and validations suggest that SCD1 enhances the sensitivity of BCa cells to trametinib. Therefore, SCD1 offers a promising new avenue for the early diagnosis, prognostic assessment, and optimization of personalized treatment strategies for BCa.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156287"},"PeriodicalIF":3.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615958","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":"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":"2025-11-09","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":"Therapeutic potential of natural compounds in the management of chronic diseases: Targeting PINK1–Parkin pathway","authors":"Naglaa F. Khedr ,&nbsp;Hend M. Selim ,&nbsp;Gamal A. Abourayya","doi":"10.1016/j.prp.2025.156284","DOIUrl":"10.1016/j.prp.2025.156284","url":null,"abstract":"<div><div>Chronic diseases like neurodegenerative disorders, musculoskeletal issues, metabolic diseases, cancer, liver and kidney disorders are increasingly linked to mitochondrial dysfunction. PINK1-Parkin-mediated mitophagy, a vital autophagic process, plays a central role in maintaining cellular homeostasis by selectively eliminating damaged mitochondria, which is crucial for preserving mitochondrial integrity and preventing reactive oxygen species accumulation. Activation of the PINK1-Parkin signaling pathway has emerged as a promising therapeutic strategy to restore mitochondrial function and attenuate disease progression. Recent studies have demonstrated that natural PINK1-Parkin activators offer significant therapeutic potential for treating a wide range of chronic diseases by modulating mitochondrial dynamics, alleviating cellular inflammation, and preventing mitochondrial damage. This review provides an in-depth analysis of the molecular mechanisms underlying PINK1-Parkin signaling, discusses the therapeutic benefits of natural activators, and presents them as a compelling strategy for addressing mitochondrial dysfunction and mitigating the progression of chronic diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156284"},"PeriodicalIF":3.2,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506307","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":"Oxidative stress and neuronal alteration: Mitochondrial dysfunction as a key player in intractable epilepsy - a narrative review","authors":"Muhammad Liaquat Raza ,&nbsp;Mustafa Hussain Imam ,&nbsp;Warisha Zehra ,&nbsp;Insa Binte Anwar ,&nbsp;Rukhsar Mehdi","doi":"10.1016/j.prp.2025.156285","DOIUrl":"10.1016/j.prp.2025.156285","url":null,"abstract":"<div><div>Drug-resistant epilepsy (DRE) still poses one of the greatest therapeutic challenges, afflicting about one-third of all patients with epilepsy in the world. Despite spectacular advances in the fields of anti-seizure medications and neurostimulation techniques, treatment outcomes in DRE have reached plateau levels, signifying an urgent need for better mechanistic understanding and therapeutic strategies. New evidence increasingly elucidates mitochondrial dysfunction as a lens through which to understand seizure generation, pharmacoresistance, and disease progression. Mitochondria are regulators of ATP production, calcium buffering, and redox homeostasis; disruption of any such pathway will result in neuronal hyperexcitability, oxidative injury, and cell death. Moreover, mitochondrial DNA mutations and heteroplasmy threshold can correlate with seizure onset, seizure severity, and <strong>Response</strong> to treatment, thus being potential biomarkers for risk stratification. This narrative review surveys both preclinical and clinical evidence for mitochondrial dysfunction in epilepsy, examining oxidative stress pathways, mitophagy, and mitochondrial permeability transition pore opening as key mechanisms of neuronal vulnerability. We subsequently analyze various preclinical models of mitochondrial dysfunction, pointing out their respective strengths and weaknesses. Emerging therapeutic strategies, encompassing pharmacological agents, gene therapy, diet, and natural compounds, are then reviewed, which aim to resolve issues surrounding mitochondrial health on a molecular basis. By straddling the mechanistic and clinical narratives, this work foregrounds mitochondrial-centered approaches as promises for both the diagnostic and therapeutic arsenal in the management of DRE.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156285"},"PeriodicalIF":3.2,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518578","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":"PTEN mutation status in uterine carcinosarcomas: A comprehensive overview and a new diagnostic approach","authors":"Maccio Livia ,&nbsp;Bragantini Emma ,&nbsp;Piermattei Alessia ,&nbsp;Santoro Angela ,&nbsp;Zannoni Gian Franco","doi":"10.1016/j.prp.2025.156278","DOIUrl":"10.1016/j.prp.2025.156278","url":null,"abstract":"<div><div>Uterine carcinosarcomas (UCS), also known as malignant mixed Müllerian tumors, are rare and aggressive neoplasms characterized by the coexistence of carcinomatous (epithelial) and sarcomatous (mesenchymal) components. PTEN (Phosphatase and Tensin Homolog) mutations, a hallmark of endometrioid-type carcinomas, play a significant role in the pathogenesis and histological presentation of a subset of uterine carcinosarcomas, contributing to their aggressive behavior and poor prognosis. This overview synthesizes the current understanding of PTEN mutations in carcinosarcomas and their implications for clinical management and therapy. A new approach based on morphological, immunohistochemical, and molecular characteristics is proposed.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156278"},"PeriodicalIF":3.2,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467116","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":"2025-10-30","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}