Experimental and molecular pathology最新文献

{"title":"Identification of OTUD7a downregulation and global ubiquitination remodeling in a murine asthma model.","authors":"Yanbo Liu, Xuanyuan Pan, Haoyue Zhang, Ying Zhou, Juan Zhi, Jin Xu, Qianyu Wang, Quanle Liu, Kaixuan Zhao, Weipeng Xia, Haotian Chen, Dong Yang","doi":"10.1016/j.yexmp.2026.105073","DOIUrl":"https://doi.org/10.1016/j.yexmp.2026.105073","url":null,"abstract":"<p><p>Airway epithelial dysfunction is a hallmark of asthma, contributing to chronic inflammation and structural remodeling. Recent research suggests the role of post-translational modifications in regulating epithelial immune responses. However, the role of specific deubiquitinating enzymes (DUBs) remains unclear. In this study, we identified OTU deubiquitinase 7a (OTUD7a) as a gene that is significantly downregulated in a murine model of allergic asthma. Transcriptomic analysis of two independent datasets (GSE71822 and GSE9383) consistently revealed the suppression of OTUD7a in asthmatic lungs. Furthermore, immunofluorescence analysis suggested that OTUD7a was detected in CC10-positive bronchiolar epithelial cells, non-ciliated epithelial cells known for their anti-inflammatory functions. To explore the molecular associations of OTUD7a, we established a club cell line overexpressing Flag-tagged OTUD7a and performed co-immunoprecipitation-mass spectrometry (Co-IP/MS). We identified 1135 candidate interacting proteins. In parallel, LC-MS/MS-based ubiquitinome profiling in ovalbumin (OVA)-induced asthmatic lungs revealed widespread changes in protein ubiquitination, with more than 3000 differentially modified ubiquitination sites. These changes were enriched in pathways associated with immune signaling, cytoskeletal dynamics, and epithelial barrier function. Collectively, our findings suggest that OTUD7a, as a DUB detected in CC10-positive bronchiolar epithelial cells, is markedly decreased in asthma and they present a comprehensive landscape of ubiquitination changes in allergic airway inflammation. Therefore, our study offers new insight into post-translational regulation in the pathogenesis of asthma.</p>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"147 ","pages":"105073"},"PeriodicalIF":4.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886708","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":"Corrigendum to ‘Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms’ [Experimental and Molecular Pathology 94 (2013) 466–473]","authors":"Kang Cheng,&nbsp;Partab Rai,&nbsp;Andrei Plagov,&nbsp;Xiqian Lan,&nbsp;Dileep Kumar,&nbsp;Divya Salhan,&nbsp;Shabina Rehman,&nbsp;Ashwani Malhotra,&nbsp;Kuldeep Bhargava,&nbsp;Christopher J. Palestro,&nbsp;Sanjeev Gupta,&nbsp;Pravin C. Singhal","doi":"10.1016/j.yexmp.2026.105052","DOIUrl":"10.1016/j.yexmp.2026.105052","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"146 ","pages":"Article 105052"},"PeriodicalIF":4.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent cGAS–STING–IRF3 signaling profiles mark the transition from precancerous biliary lesions to cholangiocarcinoma","authors":"Parawee Artbua ,&nbsp;Naruemon Kentachalee ,&nbsp;Prakasit Sa-Ngiamwibool ,&nbsp;Sirinya Sitthirak ,&nbsp;Phongsathorn Wichian ,&nbsp;Raksawan Deenonpoe","doi":"10.1016/j.yexmp.2026.105054","DOIUrl":"10.1016/j.yexmp.2026.105054","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a highly lethal malignancy and often exhibits histological overlap with non-malignant bile duct lesions, including cholangitis and precancerous lesions. The lack of reliable markers to distinguish malignant from non-malignant biliary lesions underscores the need for improved diagnostic approaches. The cGAS–STING pathway, a key regulator of innate immune responses, may provide insight into inflammation-associated carcinogenesis.</div><div>This study aimed to compare the expression of cGAS, STING, IRF3, and IFN-α among CCA, precancerous lesions, and cholangitis, and to evaluate their potential diagnostic relevance. A total of 198 formalin-fixed paraffin-embedded (FFPE) tissue samples were analyzed, including 164 cases of cholangiocarcinoma, 26 precancerous lesions, and 8 cases of cholangitis. Immunohistochemistry for cGAS, STING, IRF3, and IFN-α was performed, and protein expression was quantitatively assessed using H-scores. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. ROC-derived H-score cut-off values were applied in logistic regression models to assess association with CCA. IRF3 and IFN-α expression were markedly increased in precancerous lesions compared with cholangitis. High cGAS and IRF3 expression at ROC-derived cut-off values showed association with CCA. Logistic regression analysis demonstrated that elevated cGAS (H-score ≥ 202; <em>p</em> = 0.026) and IRF3 (H-score ≥ 201; <em>p</em> = 0.032) expression were associated with increased odds of CCA. Although cGAS and IRF3 showed limited standalone diagnostic accuracy, their ROC-derived H-score thresholds were modestly associated with CCA. This work could provide adjunctive diagnostic information when integrated with routine histopathological assessment.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"146 ","pages":"Article 105054"},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028480","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":"LncRNA and mRNA m6A modification profile and functional network in sepsis-induced acute lung injury","authors":"Yanli Yang ,&nbsp;Ruo-Lan Xiang ,&nbsp;Yaqi Wang ,&nbsp;Kai-Feng Xu ,&nbsp;Xinlun Tian","doi":"10.1016/j.yexmp.2026.105053","DOIUrl":"10.1016/j.yexmp.2026.105053","url":null,"abstract":"<div><div>N⁶-methyladenosine (m⁶A) modification is crucial in sepsis-related organ damage, but its profiles in sepsis-induced acute lung injury (ALI) remain unclear. In this study, we elucidated the landscape and network of m⁶A modification in a rat model of lipopolysaccharide (LPS)-induced ALI. Total m⁶A levels in lung tissues from control and LPS-treated rats were determined using liquid chromatography tandem mass spectrometry. Epitranscriptomic microarray identified differentially m⁶A-modified mRNAs and long non-coding RNAs (lncRNAs). Bioinformatic analyses were performed to explore the functional implications of these differentially methylated transcripts. Selected methylated lncRNAs were further validated using m⁶A single-base site quantitative PCR. Results indicated significantly reduced total m⁶A levels in lung tissues from LPS-treated rats. 283 mRNAs showed decreased m⁶A modification levels and were enriched in immune response and inflammation pathways. Among the differentially expressed lncRNAs, LOC102551452 displayed m⁶A hypomethylation and negative correlation with neutrophil-related genes. These findings illuminate the potential role of m⁶A modification in immune and inflammation processes during sepsis-induced ALI, suggesting that targeting m⁶A modifications could be a potential therapeutic approach for sepsis-induced ALI.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"146 ","pages":"Article 105053"},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148014189","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":"Corrigendum to “A WNT/β-catenin-associated transcriptional program predicts survival outcomes in patients with hepatocellular carcinoma” [Exp Mol Pathol Volume 146, June 2026, 105049]","authors":"Stefano Scalera,&nbsp;Laura Cipriani,&nbsp;Andrea Scarinci,&nbsp;Giulia Schiavoni,&nbsp;Maurizio Fanciulli,&nbsp;Ludovica Ciuffreda,&nbsp;Francesca De Nicola,&nbsp;Frauke Goeman,&nbsp;Edoardo Pescarmona,&nbsp;Mariagrazia Diodoro,&nbsp;Elisa Melucci,&nbsp;Enzo Gallo,&nbsp;Patrizia Vici,&nbsp;Laura Pizzuti,&nbsp;Maddalena Barba,&nbsp;Eriseld Krasniqi,&nbsp;Emanuela Dell'Aquila,&nbsp;Chiara Manai,&nbsp;Giancarlo Paoletti,&nbsp;Federico Cappuzzo,&nbsp;Marcello Maugeri-Saccà","doi":"10.1016/j.yexmp.2026.105055","DOIUrl":"10.1016/j.yexmp.2026.105055","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"146 ","pages":"Article 105055"},"PeriodicalIF":4.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol targeting Smad4 via a concentration-dependent biphasic effect regulates stem cells-mediated regeneration","authors":"Ziqing Zhou ,&nbsp;Shaoming Wu ,&nbsp;Xiaoran Zhang ,&nbsp;Guanbin Chen ,&nbsp;Hengyue Ma ,&nbsp;Ming Li ,&nbsp;Yuchuan Liu ,&nbsp;Ting Wang","doi":"10.1016/j.yexmp.2026.105035","DOIUrl":"10.1016/j.yexmp.2026.105035","url":null,"abstract":"<div><div>Resveratrol (RSV), a globally utilized nutraceutical compound, is primarily recognized for its human health benefits, contributing to its widespread and often unregulated use in daily life and clinical settings. However, its influence on cellular stemness remains poorly understood. While numerous reports suggest anti-tumor properties, systematic and robust evidence is lacking. This study employed high-throughput RNA sequencing, RNA interference, RT-qPCR, and whole-mount in situ hybridization, and used the planarian <em>Dugesia japonica</em> as a stem cell model, aiming to investigate the effects of varying RSV concentrations on blastema regeneration following amputation and analyze the associated mechanism. We demonstrated a biphasic effect of RSV on anterior blastema regeneration: low-concentration RSV (5 μM) promoted regeneration, whereas high-concentration RSV (50 μM) caused significant inhibition. RNA-seq identified <em>Smad4</em> as a key mediator; its inhibition exacerbated the regenerative deficit under low concentration. Intriguingly, <em>PiwiA</em> expression increased in the anterior blastema at both RSV concentrations, most notably at low concentration condition. Conversely, the late stem cell marker <em>Agat1</em> was significantly suppressed by high-concentration RSV. These findings indicated that RSV promoted stem cell proliferation. Critically, low-concentration RSV enhanced both proliferation and differentiation, while high-concentration RSV inhibited differentiation independently of <em>Smad4</em>. This study provided the first <em>in vivo</em> evidence at the whole-organism level that RSV concentration dictated divergent stem cell differentiation fates, offering a scientific basis for its rational evaluation and application.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105035"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200660","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":"Hyperuricemia-induced renal fibrosis: Mechanisms and advances in pharmacological studies using uricase-deficient animal models","authors":"Jiaxiang Zhang ,&nbsp;Yu Yun ,&nbsp;Weigang Duan","doi":"10.1016/j.yexmp.2026.105030","DOIUrl":"10.1016/j.yexmp.2026.105030","url":null,"abstract":"<div><div>The high incidence of hyperuricemia (HUA) is largely attributed to imbalances between uric acid production, distribution, and excretion. HUA can lead to renal fibrosis, which in turn causes a progressive decline in kidney function and the development of serious conditions such as chronic kidney disease (CKD). Therefore, the effective prevention and treatment of HUA-induced renal fibrosis is of critical importance. Elevated serum uric acid acts as a key trigger for HUA-induced renal fibrosis, while uric acid accumulation in kidney tissues, especially in the medulla, may play an even essential role in this process. However, few studies have focused on the role of tissue uric acid, even though increased tissue uric acid can activate macrophages and mediate chronic inflammation as well as other mechanisms that initiate or worsen renal fibrosis. Moreover, current clinical drug interventions yield unsatisfactory outcomes and are often associated with numerous adverse effects, emphasizing the urgent need for new therapeutic agents. In recent years, the use of clinically relevant uricase-deficient animal models in pharmacological studies has increased, potentially representing the forefront of research in HUA-induced renal fibrosis. However, a comprehensive review of these studies is still needing. This review explains how uric acid affects the kidney and induces renal fibrosis, summarizes the underlying mechanisms to inform clinical diagnosis, treatment, and drug development, and consolidates the current status of clinical therapies and pharmacological research using uricase-deficient animal models, with the aim of identifying promising agents for the effective prevention and treatment of HUA-induced renal fibrosis.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105030"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118309","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 characterization of non-muscle invasive tumor from N-methyl-N-nitrosourea (MNU)-induced urothelial carcinoma in a rat model reveals hallmarks of both luminal and basal subtypes","authors":"Kara A. Lombardo ,&nbsp;Takahiro Yoshida ,&nbsp;Evan Johnson ,&nbsp;Kate Fitzgerald ,&nbsp;Max Kates ,&nbsp;William R. Bishai ,&nbsp;Alex S. Baras ,&nbsp;Trinity J. Bivalacqua","doi":"10.1016/j.yexmp.2026.105032","DOIUrl":"10.1016/j.yexmp.2026.105032","url":null,"abstract":"<div><div>With the advances in molecular classification of bladder cancer subtypes, pre-clinical rodent models used to study urothelial tumorigenesis must be profiled to reflect clinical relevance and optimize translational research strategies. Murine models of bladder cancer such as the autochthonous N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) model and genetically-engineered Upk3a-Cre^ERT2; Trp53^L/L; Pten^L/L; Rosa26^LSL-Luc (UPPL) model are muscle invasive models which have been found to correlate with basal and luminal subtypes, respectively. The rat MNU model has been used to represent non-muscle invasive bladder cancer, however the MNU non-muscle invasive tumors have not been fully molecularly characterized. Intravesical MNU instillations were administered to female rats to induce bladder tumors which were harvested for pathologic staging and immunohistochemistry. Bulk RNA sequencing was performed on non-muscle invasive (stage T1) tumors and compared to gene expression data from human and murine bladder cancer datasets. Rat MNU-treated bladders showed step-wise progression from non-muscle invasive tumor over 16 weeks which progressed to muscle invasive blader cancer over 30 weeks. Luminal and basal protein marker expression was positively expressed in all stages of MNU-induced tumors. Cluster analysis of gene expression data from non-muscle invasive MNU-induced T1 tumors more closely resemble luminal papillary and stroma-rich human bladder cancer subtypes as well as murine UPPL luminal-like tumors, while inference of immune cell markers reveals MNU-induced T1 tumors are more immune infiltrated, similar to human basal/squamous and murine BBN basal-like tumors. These data reveal the rat MNU model of non-muscle invasive bladder cancer (NMIBC) harbors characteristics of both basal and luminal bladder cancer subtypes and provide a framework for how this model may be used to guide clinically relevant investigations aimed at improving and developing novel therapies for more luminal like-immune infiltrated NMIBC.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105032"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156395","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":"Expression of concern: \"The critical roles of lncRNAs in the pathogenesis of melanoma\" [Experimental and Molecular Pathology 117 (2020) 104558].","authors":"","doi":"10.1016/j.yexmp.2025.105019","DOIUrl":"10.1016/j.yexmp.2025.105019","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"105019"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456661","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":"The role of myotubularin-related lipid phosphatases in cancer pathogenesis","authors":"Lenka Doubravská,&nbsp;Marie Macůrková","doi":"10.1016/j.yexmp.2026.105022","DOIUrl":"10.1016/j.yexmp.2026.105022","url":null,"abstract":"<div><div>Myotubularin-related proteins (MTMRs) comprise a family of lipid phosphatases using phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate as their substrate. Several members have a well-established role in the pathogenesis of human myopathies and neuropathies. There is a growing body of evidence that the portfolio of diseases where MTMRs play a role should be extended to cancer. MTMRs are thus closing the gap on their functional counterparts, the phosphatidylinositol kinases. MTMRs do not contribute to cancer initiation through driver mutations, but their expression in tumours is frequently altered, leading to defects in cell proliferation, migration or cell death. In some instances, MTMR misexpression contributes to resistance to cancer treatment. In this review we summarize the current knowledge with the emphasis on the molecular mechanisms underlying the MTMR function in cancer pathogenesis.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105022"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911202","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}