Pathology, research and practice最新文献

{"title":"Adult neurogenesis dysfunction in Parkinson’s disease: Molecular pathology and functional implications","authors":"Xiongjie He ,&nbsp;Tilong Huang ,&nbsp;Ai Yang ,&nbsp;Yafang Li ,&nbsp;Liping Bai ,&nbsp;Yanmei Chen ,&nbsp;Jie Bai ,&nbsp;Xianwen Zhang","doi":"10.1016/j.prp.2025.156340","DOIUrl":"10.1016/j.prp.2025.156340","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a neurodegenerative disorder marked by the accumulation of alpha-synuclein protein within dopamine-producing neurons and their consequent death. Although the specific etiology of PD remains unclear, emerging evidences suggest that disrupted neurogenesis plays a crucial role in pathophysiology of PD. Neurogenesis has a regenerative effect and is a promising therapeutic target for PD. Recent studies demonstrated that impaired neurogenesis in the subventricular zone (SVZ), hippocampus (HIP) and substantia nigra (SN) contributed to motor/nonmotor deficits in PD. However, the precise correlation between the pathogenesis of PD and neurogenesis remains to be explored. This study aimed to investigate the role of the dopaminergic signaling pathway, neurotrophic factors, gut microbiota, neuroinflammation, and mutations in PD-related genes in adult neurogenesis in PD. First, a comprehensive review of recent studies was carried out to explore how neurogenesis impacts PD pathophysiology. Then, the challenges and future perspectives associated with promoting endogenous neurogenesis to compensate for the loss of dopaminergic neurons in PD were investigated. The study offers promising therapeutic strategies to activate the endogenous neurogenesis in PD. Furthermore, it offers promising therapeutic strategies to activate the endogenous neurogenesis in PD. This article also emphasizes the importance of the precise manipulation of neurogenesis in PD with the aim of promoting the translation of these findings into clinical treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156340"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820492","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":"WTAP contributes to the malignancy and stemness of hepatocellular carcinoma through upregulating N6-methyladenosine modification of ITGB4","authors":"Jinlin Wang ,&nbsp;Kai Zhang ,&nbsp;Chen Zheng ,&nbsp;Xiao Chen","doi":"10.1016/j.prp.2025.156333","DOIUrl":"10.1016/j.prp.2025.156333","url":null,"abstract":"<div><h3>Background</h3><div>m6A modification is important in cancer progression. In the research, we explored the functions and mechanisms of WTAP (the key component of m6A) in HCC.</div></div><div><h3>Methods</h3><div>Expression of WTAP and ITGB4 was examined by qRT-PCR, western blot and IHC assays. Tumor cell proliferation, apoptosis, metastasis and stemness were investigated via colony formation, flow cytometry, transwell and sphere formation assays. The interaction between WTAP and ITGB4 was estimated by RIP, meRIP and dual-luciferase reporter experiments.</div></div><div><h3>Results</h3><div>ITGB4 was upregulated in HCC. Knockdown of ITGB4 repressed HCC cell growth, motility and stemness, accelerated HCC cell apoptosis <em>in vitro</em>, and blocked tumorigenesis <em>in vivo</em>. Through SRAMP website and a series experiments, WTAP catalysed m6A modification on ITGB4 mRNA, recognized by the reader YTHDF1, leading to increased mRNA stability. WTAP overexpression aggravated the malignant behaviors and stemness of HCC cells, with ITGB4 deficiency abrogated the effects. In addition, we demonstrated that WTAP could activate FAK/PI3K/AKT signaling pathway via regulating ITGB4 expression.</div></div><div><h3>Conclusion</h3><div>WTAP mediated the m6A methylation modification of ITGB4 to promote HCC progression and tumor stemness, providing a new idea for HCC therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156333"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840857","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":"Targeting the NR4A3-RNF139-ATF6 pathway as a therapeutic and diagnostic strategy in bladder cancer","authors":"Haiyang Cui ,&nbsp;Xuejiao Fan","doi":"10.1016/j.prp.2025.156301","DOIUrl":"10.1016/j.prp.2025.156301","url":null,"abstract":"<div><h3>Background</h3><div>Bladder cancer (BCa) is a prevalent malignancy with high recurrence and metastasis rates. Nuclear receptor subfamily 4 group A member 3 (NR4A3), a member of the orphan nuclear receptor superfamily, is implicated in various cancers, but its functional role and mechanisms in BCa have not been well understood. This study aimed to explore the functional significance and diagnostic value of NR4A3 in BCa, with a focus on its regulation of endoplasmic reticulum (ER) stress and anoikis sensitivity via ATF6 and RNF139.</div></div><div><h3>Methods</h3><div>NR4A3 expression in BCa cell lines was assessed by qRT-PCR and Western blot. Gain-of-function assays were performed to evaluate cell proliferation, apoptosis, and anoikis sensitivity <em>in vitro</em>. ER stress markers and ATF6 degradation were examined by immunoblotting, cycloheximide chase, and ubiquitination assays. The role of RNF139 and its regulation by NR4A3 via KLF2 and KLF4 were determined via various biological assays. <em>In vivo</em> tumorigenesis was assessed using a xenograft mouse model. Additionally, the diagnostic performance of NR4A3 was evaluated in 100 clinical patients using serum ELISA and color Doppler ultrasound.</div></div><div><h3>Results</h3><div>NR4A3 was downregulated in BCa cells, and its overexpression suppressed cell proliferation, colony formation and promoted apoptosis and anoikis sensitivity. Mechanistically, NR4A3 inhibited ER stress by promoting ATF6 ubiquitination and degradation via transcriptional activation of RNF139 through KLF2 and KLF4. RNF139 directly interacted with ATF6 and mediated its ubiquitination at lysine 152. <em>In vivo</em>, NR4A3 overexpression inhibited tumor growth. Clinically, combining color Doppler ultrasound with serum NR4A3 levels significantly improved diagnostic accuracy for BCa (AUC = 0.986).</div></div><div><h3>Conclusion</h3><div>NR4A3 suppresses BCa progression via the KLF2/4-RNF139-ATF6 axis and enhances diagnostic efficacy when combined with ultrasound imaging.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156301"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775449","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":"Effect of Ferrostatin-1 on temporomandibular joint synovitis induced by abnormal flow fluid shear stress: An in vitro study","authors":"Peng Yu ,&nbsp;Chen‑xi Li ,&nbsp;Zhi‑qiang Song ,&nbsp;Zhong‑cheng Gong","doi":"10.1016/j.prp.2025.156330","DOIUrl":"10.1016/j.prp.2025.156330","url":null,"abstract":"<div><div>Synovitis of the temporomandibular joint (TMJ), a prevalent degenerative joint disease, plays an important role in the pathogenesis of TMJ osteoarthritis. This pathological condition arises from abnormal mechanical loading that induces a chronic low-grade inflammation within the synovial microenvironment through ferroptotic processes. Our research explores the impact of flow fluid-induced shear stress (FFSS) on ferroptosis in fibroblast-like synoviocytes (FLSs) and elucidates the relationship between mechanical overload and the development of TMJ synovitis. Experimental findings revealed progressive alterations in cellular morphology accompanied by significant elevations in intracellular ferrous ion (Fe^2 +) concentrations and reactive oxygen species (ROS) levels with increasing FFSS intensity (all <em>p</em> &lt; 0.05). Quantitative analysis showed upregulated expression of pro-inflammatory cytokines (IL-1β, IL-18), matrix-degrading enzymes (MMP-3, MMP-13), and ferroptosis-related markers (ACSL4, Nrf2), while antioxidant defense components (GPX4, system Xc-) were downregulated (all <em>p</em> &lt; 0.05). Pharmacological inhibition using Ferrostatin-1 (Fer-1) significantly attenuated intracellular Fe²⁺ and ROS accumulation. The treatment group demonstrated reduced expression of IL-1β (<em>p</em> &lt; 0.05) and ACSL4 (<em>p</em> &lt; 0.001), with concomitant upregulation of GPX4 (<em>p</em> &lt; 0.05) and Nrf2 (<em>p</em> &lt; 0.001), though IL-18 modulation did not reach statistical significance (<em>p</em> &gt; 0.05). These results establish that mechanical overload initiates ferroptosis in FLSs, driving inflammatory responses and extracellular matrix degradation through elevated Fe²⁺ and ROS production, ultimately contributing to TMJ synovitis pathogenesis. Our investigation provides novel mechanistic insights into FFSS-mediated ferroptosis in synovial cells, presenting foundational evidence for developing targeted therapeutic strategies that modulate this cell death pathway to enhance clinical management of TMJ synovitis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156330"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749026","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":"Primary Rosai-Dorfman disease of lung and mediastinum: A clinicopathological and immunohistochemical study of five cases","authors":"Jilong Qin ,&nbsp;Longguang Li ,&nbsp;Chi Sing Ng ,&nbsp;Xiaodong Lin ,&nbsp;Xina Lin ,&nbsp;Peng Hou ,&nbsp;Ping He","doi":"10.1016/j.prp.2025.156329","DOIUrl":"10.1016/j.prp.2025.156329","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the clinicopathological and immunohistochemical features of primary Rosai-Dorfman disease (RDD) in the lung and mediastinum.</div></div><div><h3>Methods</h3><div>Histological observation and immunohistochemical staining of 5 cases of pulmonary and mediastinal RDD, with a review of the related literature.</div></div><div><h3>Results</h3><div>Two cases were located in the trachea with involvement of the lung. One case was located in the left lower lung. Two cases were located in the mediastinum. Macroscopically, 1 case had clear boundaries, while 4 cases had unclear boundaries, and grayish-white on cut surfaces. Microscopically, low power view showing alternating light and dark areas. The dark areas comprise an admixture of lymphocytes and plasma cells. The light areas comprise the characteristic pale pink histiocytic cells. Histiocytes are large with round-to-oval nuclei, dispersed chromatin, prominent nucleoli, and abundant clear-to-foamy or vacuolated cytoplasm. Emperipolesis was observed in all five cases. All five cases showed interstitial fibrosis or sclerosis and Russell bodies. Four cases (4/5, 80 %) showed lymphoid follicles with germinal centers in the interstitium. Four cases showed (4/5, 80 %) interstitial neutrophil infiltration, with three cases accompanied by microabscess formation. Immunophenotypically, the histiocytes expressed Cyclin D1(5/5, 100 %), OCT2 (5/5, 100 %), S100 protein (5/5, 100 %), CD68 (5/5, 100 %), CD163 (5/5, 100 %), BCL2 (5/5, 100 %) and CD30 (3/5, 60 %), but did not express CD1a, Langerin, IgG4 and ALK.</div></div><div><h3>Conclusion</h3><div>RDD of the lung and mediastinum is rare, with a wide range of ages. Histologically, there are often lymphoid follicles with germinal centers and interstitial fibrosis or sclerosis. This together with the expression of BCL2 and CD30 in the histiocytes can lead to misdiagnosis of lymphomas or other lymphoproliferative diseases or missed diagnosis, particularly in the mediastinum. Careful histological examination for the diagnostic feature of emperipolesis together with characteristic Cyclin D1, OCT2, S100 protein, and CD68 positivity are important clues for accurate diagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156329"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749025","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":"Advancing glioblastoma immunotherapy: Molecular pathways and innovative therapeutic strategies","authors":"Min Tang ,&nbsp;Pengpeng Xu ,&nbsp;Xiaogang Zhang","doi":"10.1016/j.prp.2025.156326","DOIUrl":"10.1016/j.prp.2025.156326","url":null,"abstract":"<div><div>Glioblastoma (GBM) has been an aggressive brain tumor and it demonstrates poor prognosis and resistance to the traditional therapeutics. GBM is characterized by abnormal proliferation, high growth, and a significantly immunosuppressive tumor microenvironment (TME), making immunotherapy as an ideal treatment for GBM. The recent advances in the field of immunotherapy such as vaccines, and CAR-T cell treatments, have demonstrated significant efficacy in accelerating anticancer immune responses and improving survival outcomes. Immune checkpoint drugs targeting CTLA-4 and PD-1/PD-L1 have demonstrated synergistic effects in enhancing T cell activation and infiltration. Vaccines such as DCVax-L and oncolytic viruses including G47Δ have demonstrated promising outcomes in the clinical studies. CAR-T cell treatments have been directed against particular antigens such as EGFRvIII and IL13Rα2 and have demonstrated considerable antitumor efficacy. Nonetheless, there are a number of challenges to be considered including the immunosuppressive TME, the blood-brain barrier (BBB), and the molecular heterogeneity of GBM. Addressing these challenges requires a versatile strategy, encompassing the development of innovative combination drugs, complicated imaging methodologies to evaluate treatment efficacy, and the discovery of biomarkers to predict patient responses to immunotherapy. The future research can focus on highlighting the complicated connections between the immune system and GBM, utilizing perspectives from preclinical models and clinical studies to formulate more effective and customized treatment options. This review emphasizes on the recent research results and clinical data, providing insights into prospective developments in GBM immunotherapy and highlighting the necessity of a comprehensive strategy to enhance patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156326"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743703","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":"KDM2A demethylase: A versatile epigenetic regulator in development, cancer, and therapeutic horizons","authors":"Tajrin Sultana ,&nbsp;Md Sadikul Islam ,&nbsp;S.M. Abdus Salam ,&nbsp;Eshrat Jahan ,&nbsp;Md Khalesur Rahman ,&nbsp;Md Shiblee Sadik Sabuj ,&nbsp;Byung-Yong Park ,&nbsp;Tanvir Ahmed ,&nbsp;Md Jamilur Rahman ,&nbsp;Md Rashedunnabi Akanda","doi":"10.1016/j.prp.2025.156336","DOIUrl":"10.1016/j.prp.2025.156336","url":null,"abstract":"<div><div>Lysine demethylase 2A (KDM2A), a crucial member of the histone demethylase family, plays a vital role in epigenetic regulation by modifying histone methylation and the chromatin structure. It regulates key cellular activities, including development, differentiation, and metabolism, by controlling gene expression and transcriptional silencing, and maintaining genomic stability through the demethylation of histone H3 at lysine 36 (H3K36). In addition to its canonical enzymatic role, KDM2A is involved in diverse biological processes, together with embryonic development, stem cell maintenance, DNA damage response, and metabolic homeostasis. Throughout development, it facilitates gene silencing and activation by engaging DNA regions rich in cytosine-guanine (CpG) dinucleotides and attracting polycomb repressive complexes (PRC), which affect lineage specification and organogenesis. Here, we outline the disease-related effects of KDM2A dysregulation related to developmental disorders, cancers, and metastasis. KDM2A aids in tumor development by influencing cell cycle regulators, oncogenes, and chromatin accessibility while also being involved in preserving cancer stem cell characteristics and facilitating epithelial-mesenchymal transition (EMT), metabolic reprogramming, and interactions with cancer-associated fibroblasts (CAFs). Its dual function as an oncogene and tumor suppressor, which varies with the cellular context, highlights its drug complexity and resistance. This review discusses the multifaceted epigenetic functions of KDM2A under both normal and diseased conditions, emphasizing its increasing importance as a potential epigenetic target. It also summarizes the progress in KDM2A-targeted therapies, including inhibitors, RNA interference, CRISPR-Cas9, and immunoepigenetic strategies, with a focus on future applications of KDM2A modulation in clinical treatments for cancer and other epigenetic-associated diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156336"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782388","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":"Nodal T-follicular helper cell lymphoma with hodgkin/reed-sternberg-like cells: Clinicopathologic and molecular characterization of 11 cases","authors":"Linlin Huang ,&nbsp;Jing Li ,&nbsp;Huawen Wang ,&nbsp;Mei Tang ,&nbsp;Min Jing ,&nbsp;Xinyi Shi ,&nbsp;Yongkun Xiao ,&nbsp;Lu Bai ,&nbsp;Ling Wang ,&nbsp;Dong Liu ,&nbsp;Tao Wu ,&nbsp;Chao Ding ,&nbsp;Jinglong Lv ,&nbsp;Huami Ye ,&nbsp;Jing Li ,&nbsp;Jiamei Fan ,&nbsp;Pengchun Wu ,&nbsp;Wenbo Zhou ,&nbsp;Xiaohui Wu ,&nbsp;Hongwei Wang","doi":"10.1016/j.prp.2025.156327","DOIUrl":"10.1016/j.prp.2025.156327","url":null,"abstract":"<div><h3>Background</h3><div>Angioimmunoblastic T-cell lymphoma (AITL), a subtype of nodal T-follicullar helper (TFH) cell lymphoma, may pccasionally contain Hodgkin/Reed-Sternberg (HRS)-like cells, which poses significant diagnostic challenges. These large atypical cells ofthen express CD30 and weak PAX5, making classical Hodgkin lymphoma (CHL) and increasing the risk of misdiagnosis. Accurate recognition requires integration of histological, immunophenotypic, viral, and molecular features.</div></div><div><h3>Method</h3><div>We retrospectively analyzed 11 patients diagnosed with AITL containing HRS-like cells between January 2020 and January 2025. All cases were consultation cases from a regional lymphoma diagnostic center, with available formalin-fixed, paraffin-embedded lymph node tissue. A comprehensive review included histomorphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization, T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangement studies, and targeted next-generation sequencing (NGS) of lymphoma-associated genes.</div></div><div><h3>Results</h3><div>The cohort included 7 men and 4 women, with a median age of 63 years. Histologically, all cases showed partial to complete effacement of nodal architecture, proliferation of high endothelial venules, expansion of follicular dendritic cell (FDC) meshworks, and scattered HRS-like cells. Immunophenotypically, HRS-like cells were consistently CD30-positive, weak PAX5-positive (9/11), and variably CD15-positive. Background T cells expressed TFH markers including CD4, PD-1, CD10, BCL-6, CXCL13, and ICOS. EBER was positive in 10 cases. TCR gene clonality was detected in 9 patients, while 2 also showed B-cell clonality. NGS identified frequent mutations in <em>TET2</em> (11/11) and <em>RHOA</em> (8/11), with additional alterations in <em>DNMT3A, KMT2D, CREBBP, BRD4</em>, and <em>PLCG1</em>.</div></div><div><h3>Conclusions</h3><div>AITL with HRS-like cells is prone to misdiagnosis as CHL due to overlapping morphological and immunophenotypic features. Integration of EBER, TCR/IG clonality assessment, and molecular profiling, particularly the identification of <em>TET2</em> and <em>RHOA</em> mutations is essential for accurate classification. Recognizing this entity is critical for avoiding diagnostic pitfalls and guiding appropriate therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156327"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743809","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 interpretable model based on weakly supervised learning for uterine smooth muscle tumor diagnosis: A multi-center study","authors":"Xiaoxi Wang ,&nbsp;Xiaochen Shen ,&nbsp;Moxuan Yang ,&nbsp;Ling Yang ,&nbsp;Ying He ,&nbsp;Yanni Ren ,&nbsp;Shuhao Wang ,&nbsp;Dayi Wu ,&nbsp;Yuanyuan Guo ,&nbsp;Yiru Niu ,&nbsp;Kaiyue Peng ,&nbsp;Zhihui Wang ,&nbsp;Jingpeng Wu ,&nbsp;Jiacheng Li ,&nbsp;Wei Wang ,&nbsp;Feng Wang ,&nbsp;Lijuan Cui ,&nbsp;Wei Wang ,&nbsp;Congrong Liu ,&nbsp;Dingrong Zhong","doi":"10.1016/j.prp.2025.156337","DOIUrl":"10.1016/j.prp.2025.156337","url":null,"abstract":"<div><div>Uterine smooth muscle tumors (USMTs) are the most common tumors of the female reproductive system, but remain diagnostically challenging due to morphological overlap among leiomyosarcoma (LMS), various leiomyoma (LM) subtypes, and smooth muscle tumors of uncertain malignant potential (STUMP). This study aimed to develop a weakly supervised artificial intelligence (AI) model for classifying USMTs as benign or malignant using only slide-level labels. A multi-center dataset comprising 94 LMS cases (408 whole-slide images, WSIs) and 634 benign cases (1389 WSIs) was used for model training and internal testing, with an independent external test set including 27 LMS cases (54 WSIs) and 90 benign cases (248 WSIs). The CAMEL2-based model achieved excellent diagnostic performance, with AUCs of 0.9976 and 0.9889 on the internal and external test sets, respectively, and accuracies exceeding 0.97. Heatmaps frequently highlighted regions enriched for key pathological features of LMS, while benign tissues were consistently assigned low-suspicion regions. In STUMP cases, heatmaps emphasized morphologically suspicious regions that often overlapped with areas identified by pathologists, supporting their potential as decision-support visualizations. In the AI–human collaboration study, model assistance was associated with improved diagnostic accuracy and reduced diagnostic time. This represents the first weakly supervised learning model for USMT diagnosis, achieving high accuracy and interpretability with minimal annotation requirements.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156337"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798004","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":"Glutamine metabolites promote the progression of cervical cancer by inducing M2 macrophage polarization","authors":"Tingting Liu ,&nbsp;Lanyue Zhang ,&nbsp;Yang Li,&nbsp;Wenxin Liao,&nbsp;Juexiao Deng,&nbsp;Hua Liang,&nbsp;Fujin Shen","doi":"10.1016/j.prp.2025.156348","DOIUrl":"10.1016/j.prp.2025.156348","url":null,"abstract":"<div><h3>Background</h3><div>Tumour-associated macrophages (TAMs) within the tumour microenvironment play crucial roles in tumour initiation, invasion, and metastasis. While glutamine synthetase (GS) is expressed predominantly in the tumour stroma, particularly in TAMs, the role of glutamine metabolism in regulating TAM polarization and function in cervical cancer (CC) remains poorly understood. This study aims to clarify this role and its implications for cancer progression.</div></div><div><h3>Methods</h3><div>CD68 and GS expression in cervical tissues was detected using immunofluorescence staining. The effects of glutamine metabolism on TAM polarization were investigated via RT<img>qPCR, flow cytometry, Western blotting and NAA treatment analyses. CCK8, colony formation, and Transwell assays were conducted to determine the effects of MSO-treated macrophages on tumour cell proliferation, migration, and invasion.</div></div><div><h3>Results</h3><div>We observed a significant increase in GS expression in TAMs within cervical cancer (CC) tissues, particularly in M2-like TAMs. Glutamine synthesized by TAMs with high GS expression was found to increase the proliferation, migration, and invasion of CC cells. Inhibition of GS in TAMs notably reduced their tumour-promoting effects. Additionally, the byproducts of glutamine metabolism in CC cells contributed to the polarization of TAMs towards the M2 phenotype. This polarization was completely abrogated when SNAT1, a key glutamine transporter, was inhibited in CC cells.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that glutamine synthesized by TAMs with high GS expression promotes tumour progression in CC. Furthermore, glutamine byproducts produced by CC cells induce TAM polarization towards the M2 phenotype, suggesting crucial metabolic crosstalk between tumour cells and macrophages that supports tumour progression. These results highlight the potential of targeting glutamine metabolism to modulate TAM function and inhibit tumour growth.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156348"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884322","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}