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":"2025-06-27","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":"Effect of Clostridium butyricum and antibiotics using simultaneous simple suspension in mice with Clostridioides difficile infection","authors":"Hideo Kato ,&nbsp;Mao Hagihara ,&nbsp;Chihiro Shiraishi ,&nbsp;Yuki Asai ,&nbsp;Hiroshige Mikamo ,&nbsp;Takuya Iwamoto","doi":"10.1016/j.yexmp.2025.104979","DOIUrl":"10.1016/j.yexmp.2025.104979","url":null,"abstract":"<div><h3>Background</h3><div>A simple suspension method, wherein tablets and capsules are disintegrated in warm water (55 °C), is increasingly used in clinical settings. Previously, we demonstrated that probiotic strains were reduced or below limit of detection in a simultaneous simple suspension of probiotic preparations and metronidazole or fidaxomicin. This study investigated its effectiveness in mice with <em>C. difficile</em> infection (CDI).</div></div><div><h3>Methods</h3><div><em>Clostridium butyricum</em> products and antibiotics used in this study were the Miya-BM tablet (CBM), metronidazole (Flagyl 250-mg oral tablet), and fidaxomicin (Dafclir 200-mg tablet). Non-infected mice received a simple suspension of CBM and antibiotics simultaneously to assess probiotic viability in the feces. Additionally, <em>C. difficile</em> counts and cytokine production were investigated in CDI-infected mice treated with these suspensions.</div></div><div><h3>Results</h3><div><em>C. butyricum</em> was detectable in the feces of non-infected mice receiving simultaneous suspensions of CBM and antibiotics. In CDI-infected mice, simultaneous suspensions significantly reduced <em>C. difficile</em> colony counts in feces compared to CBM or antibiotics alone. Furthermore, suspensions downregulated tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10 levels, while upregulating interferon-γ (IFN-γ) levels in colon tissues, indicating reduced inflammation and an enhanced immune response.</div></div><div><h3>Conclusions</h3><div>This study using mice demonstrates the effectiveness of simultaneous simple suspensions of CBM and antibiotics in treating CDI. This approach significantly reduces <em>C. difficile</em> counts, modulates cytokine levels, and maintains probiotic viability, potentially making it a viable option for administration via gastric tubes in clinical settings.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104979"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501079","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 \"Characteristics of liver fibrosis associated with chronic Opisthorchis felineus infection in Syrian hamsters and humans\" [Experimental and Molecular Pathology 110 (2019) 104274].","authors":"Anna V Kovner, Maria Y Pakharukova, Galina A Maksimova, Viatcheslav A Mordvinov","doi":"10.1016/j.yexmp.2025.104975","DOIUrl":"https://doi.org/10.1016/j.yexmp.2025.104975","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":" ","pages":"104975"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265790","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 \"Upregulation of CDK7 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis\" [Experimental and Molecular Pathology 100 (2016) 514-521].","authors":"Qiuhong Wang, Manhua Li, Xunlei Zhang, Hua Huang, Jianfei Huang, Jing Ke, Haifang Ding, Jinzhang Xiao, Xiaohang Shan, Qingqing Liu, Bojun Bao, Lei Yang","doi":"10.1016/j.yexmp.2025.104974","DOIUrl":"https://doi.org/10.1016/j.yexmp.2025.104974","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":" ","pages":"104974"},"PeriodicalIF":2.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224873","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":"Retraction notice to “Matrine protects neuro-axon from CNS inflammation-induced injury” [Experimental and Molecular Pathology 98 (2015) 124–130]","authors":"Quan-Cheng Kan ,&nbsp;Peng Lv ,&nbsp;Xiao-Jian Zhang ,&nbsp;Yu-Ming Xu ,&nbsp;Guang-Xian Zhang ,&nbsp;Lin Zhu","doi":"10.1016/j.yexmp.2025.104968","DOIUrl":"10.1016/j.yexmp.2025.104968","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104968"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971564","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: \"Matrine ameliorates experimental autoimmune encephalomyelitis by modulating chemokines and their receptors\" [Experimental and Molecular Pathology 99 (2015) 212-219].","authors":"","doi":"10.1016/j.yexmp.2025.104962","DOIUrl":"10.1016/j.yexmp.2025.104962","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"104962"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247185","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: \"Upregulation of immunomodulatory molecules by matrine treatment in experimental autoimmune encephalomyelitis\" [Experimental and Molecular Pathology 97 (2014) 470-476].","authors":"","doi":"10.1016/j.yexmp.2025.104961","DOIUrl":"10.1016/j.yexmp.2025.104961","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"104961"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247186","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":"Evaluation of direct-to-PCR (D2P) method for molecular diagnosis of infectious diseases","authors":"Rahul Sharma ,&nbsp;Vaibhav K. Tamrakar ,&nbsp;Rob E. Carpenter ,&nbsp;Aditya Sharma ,&nbsp;Kamalpreet Suri ,&nbsp;Salima Karki ,&nbsp;Katelyn Kyser ,&nbsp;Randy Sronce ,&nbsp;Sadia Almas","doi":"10.1016/j.yexmp.2025.104972","DOIUrl":"10.1016/j.yexmp.2025.104972","url":null,"abstract":"<div><div>This study evaluates the performance of the Direct-to-PCR (D2P) method as a streamlined, extraction-independent alternative to conventional nucleic acid extraction techniques for diagnosing urinary tract infections, sexually transmitted infections, and respiratory tract infections. The D2P approach employs proprietary antimicrobial peptide-based lysis buffers tailored for bacterial, fungal, and viral targets, enabling direct amplification from clinical and contrived specimens without column- or bead-based purification. Comparative analyses were conducted against silica column-based (QIAGEN) and magnetic bead-based (KingFisher) extraction methods using both microbial reference isolates and 116 residual clinical samples. Results demonstrate that the D2P method yields comparable sensitivity and specificity to conventional extraction workflows across a diverse panel of pathogens—including Gram-negative and Gram-positive bacteria, <em>Candida</em> species, ssRNA viruses (e.g., CoV-229E, Parainfluenza Virus 1 and 2), and dsDNA viruses (e.g., HSV, HAdV). Notably, D2P outperformed both QIAGEN and KingFisher in extracting nucleic acids from <em>Candida auris</em>, a multidrug-resistant fungal pathogen. Limit of detection and amplification efficiency remained within acceptable ranges across all platforms, with R² values between 0.92 and 0.99, and slopes consistent with MIQE standards. The D2P protocol reduced total sample processing time from ∼120 min to ∼45 min, minimized hands-on steps, and demonstrated effective performance in turbid or hemolyzed samples—making it suitable for high-throughput and resource-limited settings. However, limitations were observed in samples with high PCR-inhibitor content or low target yield, and broader validation across additional matrices is recommended. These findings support D2P as a reliable, efficient, and scalable molecular diagnostic alternative with broad clinical utility. Integration of D2P into diagnostic workflows could enhance access to rapid, cost-effective pathogen detection in both centralized laboratories and decentralized or point-of-care environments.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104972"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134740","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":"2025-05-20","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":"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":"2025-05-20","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}