Experimental and molecular pathology最新文献

{"title":"Polymerase Ѳ inhibitors combinations with approved and investigational agents in patient-derived tumor multi-cell type (mct) spheroids","authors":"Beverly A. Teicher ,&nbsp;Thomas S. Dexheimer ,&nbsp;Li Chen ,&nbsp;Thomas Silvers ,&nbsp;Eric M. Jones ,&nbsp;Nathan P. Coussens ,&nbsp;J. Paul Eder ,&nbsp;James H. Doroshow","doi":"10.1016/j.yexmp.2025.104978","DOIUrl":"10.1016/j.yexmp.2025.104978","url":null,"abstract":"<div><div>The potential of novobiocin, recently identified to be a DNA POLѲ inhibitor, to augment cancer chemotherapy was explored in the late 1980s and early 1990s in tumor cells, tumor-bearing mice and in Phase 1 clinical trial in combination with cyclophosphamide or cisplatin. Genetic alterations which may increase or decrease POLѲ inhibitor effects have been elucidated. Thirty patient-derived tumor cell lines with known BRCA, ATM, ATR, POLѲ, XRCC1, PALB2, PARP1, LIG3 alterations as well as know gLOH% and MSI status were screened in a mct-spheroid assay (tumor cells, endothelial cells, mesenchymal stem cells) with a POLѲ inhibitor, novobiocin, ART-558, and RP6685, alone or in simultaneous combination with a FDA-approved or investigational anticancer small molecule with a 7-day exposure and a CellTiter-Glo 3D luminescence endpoint. As single agents, the POLѲ inhibitors had little or no cytotoxicity. In simultaneous combination with ART-558, talazoparib produced greater-than-additive cytotoxicity at the highest concentrations of the POLѲ inhibitors in the 922,993–354-T-J3-PDC endometrial serous carcinoma mct-spheroids. Activity of the Chk1/2 inhibitor prexasertib was potentiated by either ART-558 or RP6685 in the 922,993–354-T-J3 mct-spheroids. The combination of POLѲ inhibitors ART-558 and RP6685, and the Chk1/2 inhibitor prexasertib produced up to 1 log increase in cytotoxicity in the 922,993–354-T-J3 mct-spheroids. Regions of potentiation were evident in the 922,993–354-T-J3-PDC endometrial carcinoma survival surface plots at the highest concentration of paclitaxel tested, while regions of potentiation were evident in the paclitaxel mid-concentrations of the 299,254–011-R-J1-PDC melanoma mct-spheroids survival surface plots as determined by the Bliss independence calculation. DNA POLѲ is recruited to DNA double-strand breaks as a component of repair. POLѲ allosteric inhibitors, novobiocin, ART558 and RP-6685, have entered clinical trial. The current study explores the cytotoxicity of POLѲ inhibitors in combination with anticancer drugs and investigational agents in patient-derived cell lines grown as mct-spheroids.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104978"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501252","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":"Drug-eluting coronary stents mediate inflammation-associated protein signature in an experimental in vitro study.","authors":"Vera Paar, Xuanchao Feng, Kristen Kopp, Fitore Marmullaku, Uta C Hoppe, Lukas J Motloch, Michael Lichtenauer","doi":"10.1016/j.yexmp.2025.104991","DOIUrl":"10.1016/j.yexmp.2025.104991","url":null,"abstract":"<p><p>Drug eluting stents (DES) are a first-line treatment for ischemic heart diseases. Due to their direct contact with the blood stream, late stent thromboses are a common complication. Thrombosis and inflammation are tightly linked to each other, and are characterized by the activation of inflammatory cells and the secretion of cytokines and chemokines. To date, the influence of DES on the activation of the inflammatory cascade and its corresponding players has not yet been investigated. We performed an in vitro study to observe any potential response of isolated human peripheral blood mononuclear cells (PBMCs) to the structure and drug-coating of different DES. PBMCs from healthy volunteers were incubated with different DES types for 48 h. We measured the secretion of cytokines and chemokines, as well as cell adhesion molecules, and selected growth factors by ELISA. DES were found to significantly increase the cytokine and chemokine secretion of IL-1β, IL-6, IL-8, and ICAM-1, as well as the growth factors ANG and FGF-basic. We further showed that zotarolimus presents with the lowest inflammation-associated protein expression. Our data further revealed that the inflammatory reaction is highly dependent on the DES size, material, and the polymer type of the DES coating. Finally, we tendentially showed that thinner alloys are associated with a lower inflammatory reaction. Our results indicate that DES may potentially lead to an increased inflammatory reaction, considering the different DES designs and properties. This would potentially help to further improve composition and drug selection.</p>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"104991"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816114","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 interplay involving oxidative stress and autophagy: Mechanisms, implications, and therapeutic opportunities","authors":"Noha A. Gouda ,&nbsp;Assem Zhakupova ,&nbsp;Ahmed M. Abdelaal ,&nbsp;Firdos Ahmad ,&nbsp;Ahmed Elkamhawy","doi":"10.1016/j.yexmp.2025.104989","DOIUrl":"10.1016/j.yexmp.2025.104989","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) are extremely reactive molecules produced during cellular metabolism, which play important roles in signaling and immune responses. Excessive ROS accumulation results in oxidative stress and cellular damage. As a result, autophagy (a cellular recycling process) is induced to overcome oxidative stress conditions by eliminating impaired cellular components. By selectively targeting and degrading dysfunctional mitochondria and peroxisomes through mitophagy and pexophagy, respectively, cells can effectively reduce ROS accumulation. Conversely, oxidative stress can disrupt autophagy, impairing protein aggregate clearance and thereby exacerbating ROS accumulation. In this review, we discuss the complex correlation between oxidative stress and autophagy, highlighting the mechanisms of regulation and their pathological implications. Additionally, we discuss the latest advances and challenges in developing autophagy-modulating therapies.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104989"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757616","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":"Peroxidasin expression is increased in intratumoural capillaries and in proximal tubular cells adjacent to clear cell renal cell carcinoma.","authors":"Roberto Silva ,&nbsp;Jorge Reis Almeida ,&nbsp;Ana Rita Coelho ,&nbsp;Isabel Brandão ,&nbsp;Bárbara Gomes ,&nbsp;Inês Soares Alencastre ,&nbsp;João Paulo Oliveira","doi":"10.1016/j.yexmp.2025.104993","DOIUrl":"10.1016/j.yexmp.2025.104993","url":null,"abstract":"<div><div>Peroxidasin (PXDN), is a heme peroxidase with a critical role in the crosslinking of type IV collagen, being essential for basement membrane integrity. Overexpression of PXDN has been associated with poor clinical outcomes in many cancers; however, little is currently known about its role in renal cell carcinoma (RCC). In this study, we characterized the expression of PXDN in tumour tissue and adjacent non-neoplastic tissue from cases of clear cell renal cell carcinoma (ccRCC), chromophobe RCC (chRCC), and renal oncocytoma using immunohistochemistry. Our results revealed increased PXDN expression in the intratumoural capillaries of ccRCC compared to other tumour types, including oncocytoma. Additionally, there was a notable increase in PXDN expression in the proximal tubular epithelial cells of non-neoplastic adjacent parenchyma in ccRCC cases compared to the same region in oncocytomas. These findings suggest, for the first time, that PXDN may play a role in tumour angiogenesis, potentially promoting metastases and malignancy. Furthermore, PXDN may be involved in the crosstalk between the tumour and adjacent tissues, a mechanism warranting further investigation.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104993"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866366","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":"Estrogen induces the alternative activation of macrophages through binding to estrogen receptor-alpha","authors":"Amina Belboul ,&nbsp;Jason Ashworth ,&nbsp;Abdulmannan Fadel ,&nbsp;Jessica Mcloughlin ,&nbsp;Ayman Mahmoud ,&nbsp;Mohamed El Mohtadi","doi":"10.1016/j.yexmp.2025.104971","DOIUrl":"10.1016/j.yexmp.2025.104971","url":null,"abstract":"<div><div>Age-related impaired wounds represent a major health burden resulting in considerable morbidity and mortality in the elderly. When injury occurs, monocytes migrate to the damaged site and undergo differentiation into tissue-resident macrophages, which are crucial for wound repair. For proper resolution of the inflammatory response, macrophages differentiate into two distinct phenotypes classified as classically-activatedpro-inflammatory and alternatively-activatedanti-inflammatory macrophages. Pro-inflammatory macrophages are commonly linked with pro-inflammatory events, while anti-inflammatory macrophages are known to be pro-regenerative. The age-related delay in wound repair is often attributed to the age-related decrease in local and systemic estrogen levels in both genders. However, despite its well-documented anti-inflammatory effect in wound healing, the role of estrogen and involvement of Estrogen Receptors (ERs) in macrophage polarization has gained little attention to date. To investigate the impact of estrogen and ERs on the polarization of macrophages, monocyte-derived macrophages were pre-treated with estrogen, ER-alpha agonist/antagonist or ER-beta agonist/antagonist prior to stimulation with LPS/IFN-γ or IL-4/IL-13 to produce pro-inflammatory or anti-inflammatory macrophages. Our findings confirm that estrogen promotes the alternative activation of macrophages <em>via</em> possible ER-α signalling. Selective targeting of ER-α with agents like PPT could potentially lead to the development of novel therapies to treat excessive inflammation in impaired wounds.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104971"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098790","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":"Platelet-derived growth factor-C contributes to kidney inflammation in experimental hypertension with little effect on the peritubular capillary network","authors":"Ina V. Martin ,&nbsp;Christian Dippel ,&nbsp;Eva M. Buhl ,&nbsp;Robert Göllinger ,&nbsp;Katja Ermert ,&nbsp;Jürgen Floege ,&nbsp;Eleni Stamellou ,&nbsp;Ute Raffetseder ,&nbsp;Rafael Kramann ,&nbsp;Tammo Ostendorf","doi":"10.1016/j.yexmp.2025.104994","DOIUrl":"10.1016/j.yexmp.2025.104994","url":null,"abstract":"<div><h3>Background and aims</h3><div>Platelet-Derived Growth Factor (PDGF)-C plays a significant role in kidney fibrosis, angiogenesis, and hypertension. While its involvement in the healing of damaged glomerular capillaries is well recognized, its function in kidney peritubular capillaries (PTCs) remains less understood. Therefore, this study investigates the role of PDGF-C in PTCs under both homeostatic conditions and experimentally angiotensin II (AngII)-induced hypertension.</div></div><div><h3>Materials and methods</h3><div>We utilized mice with systemic PDGF-C antagonism or conditional deletion of endothelial-derived PDGF-C (<em>Cdh5-cre::Pdgfc</em>^{<em>flox/flox</em>}) in an AngII-induced hypertension model. The PTC network, glycocalyx, and inflammatory parameters in the kidneys were analyzed and quantified using qPCR, electron microscopy, and fluorescence microscopy.</div></div><div><h3>Results</h3><div>Systemic antagonism of PDGF-C in the AngII model reduced peritubular accumulation of PDGF receptor-expressing mesenchymal cells and the expression of <em>Ccl2</em>, <em>Plat</em> and <em>Nos3</em>, while PTC density and glycocalyx-regulating genes remained unaffected. Conditional deletion of endothelial cell-derived PDGF-C did not affect peritubular accumulation of mesenchymal cells, blood pressure or genes associated with angiogenesis; it also had no impact on the PTC network or glycocalyx. Notably, a reduction in inflammatory infiltrates was observed in the hypertensive <em>Cdh5-cre::Pdgfc</em>^{<em>flox/flox</em>} -mice.</div></div><div><h3>Conclusion</h3><div>Despite influencing certain parameters critical for endothelial homeostasis, such as PDGFR⁺ pericyte recruitment following systemic PDGF-C antagonism during hypertension, PDGF-C has minimal effects on the PTC network. Conversely, both systemic and endothelial cell-derived PDGF-C modulate the inflammatory response associated with hypertension in the kidney. Our findings help mitigate safety concerns about pharmacological PDGF-C targeting and its impact on peritubular capillaries.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104994"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907621","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":"Small intestinal bacteria accelerate aspirin-induced small intestinal injuries","authors":"Fumio Kakizaki ,&nbsp;Teruo Miyazaki ,&nbsp;Hajime Ueda ,&nbsp;Junichi Iwamoto ,&nbsp;Akira Honda ,&nbsp;Tadashi Ikegami","doi":"10.1016/j.yexmp.2025.104984","DOIUrl":"10.1016/j.yexmp.2025.104984","url":null,"abstract":"<div><h3>Background</h3><div>Small intestinal mucosal injuries are observed during treatment with enteric-coated, low-dose aspirin (LDA) through uncertain mechanism(s). Because aspirin (acetylsalicylic acid, ASA) is an acetylated form of the highly cytotoxic salicylic acid (SA), we hypothesized that SA deacetylated by esterases in the small intestine directly causes mucosal injuries. This study explored the mechanism(s) of ASA deacetylation to SA in the small intestinal environment.</div></div><div><h3>Methods</h3><div>ASA was added to the x, and deacetylation of added ASA and cell damage were evaluated. To explore the ASA deacetylation mechanism(s) in the intestinal environment, ASA was incubated with different pH phosphate buffers (4.01–9.10), pancreatic enzymes, homogenates of pancreas and IEC-6 cell, and caecum bacterial suspension (CBS). ASA and CBS were co-injected into the murine duodenum, and small intestinal damage was evaluated after an hour by histological observation.</div></div><div><h3>Results</h3><div>Intestinal cell damage was caused dependently on the deacetylation rate of added ASA to SA in the cell and culture media. In vitro, almost ASA was not deacetylated by incubation with different pH buffer, pancreatic enzymes, or IEC-6 cell homogenate, but deacetylation of ASA was significantly promoted with CBS. ASA deacetylation by bacterial esterases(s) was confirmed by adding an esterase-specific inhibitor, potassium fluoride. Furthermore, severe injuries throughout the entire murine small intestine were found after co-injection of ASA and CBS, but not after ASA alone.</div></div><div><h3>Conclusions</h3><div>Enteric-coated, LDA-induced mucosal injuries in the small intestine are mainly caused by direct cytotoxicity of SA deacetylated by enterobacterial esterase in the small intestine.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104984"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614742","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":"Modulating cellular deformability via 3D dextran hydrogel cultivation to regulate the microcirculation of mesenchymal stem cells in murine spleen and liver","authors":"Xiaolu Zhu ,&nbsp;Zheng Wang ,&nbsp;Yuanping Shi ,&nbsp;Shuang Yao ,&nbsp;Fengliang He ,&nbsp;Xiuli Cong ,&nbsp;Fang Teng","doi":"10.1016/j.yexmp.2025.104987","DOIUrl":"10.1016/j.yexmp.2025.104987","url":null,"abstract":"<div><div>For mesenchymal stem cell (MSC) therapy to be effective, the vascular system may be used to deliver and steer the cells to the target tissue. However, the expanded MSCs in petri dishes typically exhibit limited deformability and commonly excluded by the capillary networks when homing to the downstream organs via microcirculation. Here, we propose to utilize specially designed 3D dextran hydrogels and tuning the microscopic heterogeneity of hydrogel composition to make the administrated cells mechanically comply with the structure and mechanics of the capillary. The deformability of cells cultured in petri dishes, microcosmically homogeneous (HOM), and heterogeneous (HET) dextran hydrogels was investigated in vitro by measuring cell moduli through atomic force microscope (AFM), analyzing the expression of cytoskeletal protein via flow cytometry and fluorescent imaging. The in vitro experimental results demonstrate a progressive increase in cell deformability from 2D dishes, to HOM-hydrogel derived cells, and then to HET-hydrogel derived cells. The in vivo mouse experiment indicates the cells could deform accordingly and pass through easily with reduced resistance inside the mouse organs. It is suggested that the main destination of hMSC microcirculation could be selected between the spleen and liver of mice, by tuning cell mechanics that depends on the stimulus from HOM or HET hydrogel, which lays a potential foundation for the mechanically modified MSC therapy targeting organ lesions.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104987"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662203","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":"Mitochondrial dysfunction in fibrotic diseases: Research progress and MSC-exos therapy","authors":"Xiaoyun Zhang ,&nbsp;Yingyu Wang ,&nbsp;Xinyi Guo ,&nbsp;Yu Xiao ,&nbsp;Weiguo Wan ,&nbsp;Hejian Zou ,&nbsp;Xue Yang","doi":"10.1016/j.yexmp.2025.104983","DOIUrl":"10.1016/j.yexmp.2025.104983","url":null,"abstract":"<div><div>Fibrosis is a common pathological feature of most chronic diseases progressing to the end stage, with its specific pathogenesis still unclear and lacking effective therapeutic approaches. Mitochondria are essential organelles responsible for energy production and the maintenance of cellular homeostasis. Increasing evidence indicates that mitochondrial dysfunction is closely associated with the onset and progression of fibrotic diseases. In this review, we explore the relationship between mitophagy, oxidative stress, mitochondrial dynamics, mtDNA release, and progression of fibrosis from the perspective of mitochondrial dysfunction. Furthermore, we summarized the latest research advances of mitochondrial dysfunction in lung, liver, kidney and skin fibrosis, and provided an overview of the potential therapeutic use of mesenchymal stem cell-derived exosomes in the treatment of fibrotic diseases by improving mitochondrial function, aiming to deepen the understanding of mitochondrial dysfunction in the pathogenesis of fibrotic diseases and provide new insights into targeting mitochondria in the treatment of fibrotic diseases.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104983"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588196","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":"From asbestos exposure to carcinogenesis: Transcriptomic signatures in malignant pleural mesothelioma","authors":"Diletta Rosati ,&nbsp;Bianca Giulia Maurizi ,&nbsp;Viola Bianca Serio ,&nbsp;Debora Maffeo ,&nbsp;Angela Rina ,&nbsp;Francesca Mari ,&nbsp;Maria Palmieri ,&nbsp;Antonio Giordano ,&nbsp;Elisa Frullanti","doi":"10.1016/j.yexmp.2025.104973","DOIUrl":"10.1016/j.yexmp.2025.104973","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of malignant pleural mesothelioma (MPM) has surged due to widespread asbestos exposure, particularly since the mid-20th century. Despite significant advancements in cancer treatment, an effective cure for MPM remains elusive, largely due to a limited understanding of the molecular mechanisms underlying asbestos-related carcinogenesis. This exploratory study aims to uncover gene expression patterns uniquely altered in mesothelioma patients with documented asbestos exposure, providing a solid foundation for future research focused on identifying novel prognostic and predictive biomarkers.</div></div><div><h3>Methods</h3><div>Publicly available RNA sequencing data were analyzed through a bioinformatics pipeline to perform differential gene expression analysis. Additionally, functional enrichment analysis was applied to highlight significantly enriched Gene Ontology (GO) terms related to biological processes, molecular functions, and cellular components, offering insights into the molecular pathways involved in MPM development.</div></div><div><h3>Results</h3><div>The analysis uncovered a set of differentially expressed genes (DEGs) in MPM patients with documented asbestos exposure, as well as key GO terms. These enriched biological terms reflect processes such as ion homeostasis and oxidative stress response, providing crucial information on the cellular alterations driven by asbestos exposure.</div></div><div><h3>Conclusion</h3><div>This study's findings deepen our understanding of the molecular landscape underlying asbestos-induced carcinogenesis in MPM. The identification of specific DEGs and enriched GO terms lays the foundation for future investigations, including the development of biomarkers, with potential implications for the diagnostic and prognostic assessment of MPM.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104973"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098789","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}