Clinical and Experimental Medicine最新文献

{"title":"Harnessing the gut microbiome for improved immune checkpoint inhibition in colorectal cancer immunotherapy: a narrative Review.","authors":"Desalegn Abebaw, Adane Adugna, Bantayehu Addis Tegegne, Zigale Hibstu Teffera, Bantegzie Selabat, Yonatan Kindie, Melkamu Tilahun, Habtamu Belew, Temesgen Baylie, Getachew Mengistu, Mohammed Jemal, Aytenew Atnaf","doi":"10.1007/s10238-026-02222-3","DOIUrl":"10.1007/s10238-026-02222-3","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains among the most prevalent and deadliest malignancies worldwide, with limited survival outcomes, particularly in patients with metastatic disease. Despite advances in immunotherapy, immune checkpoint inhibitors (ICIs) have shown efficacy mainly in mismatch repair-deficient (dMMR) CRC, while responses in mismatch repair-proficient (pMMR) microsatellite-stable (MSS) cases remain limited. Emerging evidence highlights the gut microbiome as a critical factor influencing CRC development, progression, and therapeutic response. In particular, the gut microbiota has been shown to affect the efficacy of ICIs, with dysbiosis contributing to treatment resistance and specific microbial taxa enhancing antitumor immune responses. Preclinical and clinical studies have demonstrated that microbiome-based interventions, including probiotics, fecal microbiota transplantation (FMT), dietary modulation, and traditional medicines, can restore immune function by modulating immune cell populations and producing immunoregulatory metabolites. These effects may enhance responsiveness to ICIs and contribute to the suppression of tumor growth. However, we also address key limitations in this field, including inconsistent findings and safety concerns, such as infection risks, to guide future translational efforts. Overall, while microbiome-based interventions represent a promising adjunct to CRC immunotherapy, rigorous clinical trials and mechanistic validation are required before their routine clinical implementation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338008","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":"Serum TIMP-1 shows a potential association with metastatic disease in patients with pancreatic cancer: a pilot analysis without a healthy control cohort.","authors":"Ivana Vecurkovska, Veronika Roskovicova, Tomas Gajdzik, Marek Soltes, Jana Maslankova, Ivana Kocanova, Jana Katuchova","doi":"10.1007/s10238-026-02241-0","DOIUrl":"10.1007/s10238-026-02241-0","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is most often diagnosed at an advanced stage, when distant metastases are already present and curative treatment options are limited. In this clinical context, biomarkers capable of reflecting tumor aggressiveness and metastatic potential are of particular relevance. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been implicated in tumor invasion and metastatic dissemination; however, its clinical significance in pancreatic cancer remains incompletely defined. We analyzed TIMP-1 concentrations in serum and pancreatic tissue of 154 patients (108 malignant tumors, 46 benign lesions) using ELISA. Associations with clinical stage and the presence of distant metastases were assessed using non-parametric tests and ROC curve analysis. TIMP-1 levels were significantly higher in malignant compared with benign tumors, both in tissue (24.28 vs. 21.62 ng/mL; p = 0.0318) and serum (28.03 vs. 25.52 ng/mL; p = 0.0106). Serum TIMP-1 showed superior diagnostic accuracy (AUC = 0.796) compared to tissue TIMP-1 (AUC = 0.745). Patients with distant metastases exhibited significantly higher serum TIMP-1 levels than non-metastatic cases (28.33 vs. 26.53 ng/mL; p = 0.0046; AUC = 0.785). Serum TIMP-1 is associated with malignant and metastatic pancreatic disease and reflects a more aggressive tumor phenotype in patients with established pancreatic cancer. While the observed differences are modest and limit its applicability as a stand-alone diagnostic or screening biomarker, TIMP-1 may provide clinically relevant information regarding metastatic status and could contribute to prognostic stratification or multimarker approaches in pancreatic cancer.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338028","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":"The burden and unique patterns of extraintestinal manifestations in Chinese inflammatory bowel disease: a nationwide multicenter investigation.","authors":"Liuqing Zhao, Zhenzhen Fan, Jindan He, Lianlian Tian, Jun Shen, Hongliang Gao, Yanjun Chen, Xiaojing Zhao, Yan-Bo Yu, Yanyun Fan, Haitao Shi, Hailong Cao, Linglin Tian, Jie Liang","doi":"10.1007/s10238-026-02240-1","DOIUrl":"10.1007/s10238-026-02240-1","url":null,"abstract":"<p><p>Extraintestinal manifestations (EIMs) are a significant disease burden in inflammatory bowel disease (IBD). However, large-scale epidemiological data from the Chinese population remain scarce. This nationwide, multicenter, retrospective cross-sectional study included 2,252 adult IBD inpatients from 10 clinical centers. Data on demographics, clinical features, and EIMs were collected and analyzed using descriptive statistics and logistic regression. Of the 2252 patients, 384 (17.1%) reported at least one EIM. Among these, data on temporal sequence were available for 310 patients, of whom 70 (22.6%) developed their first EIM before the onset of intestinal symptoms. The overall prevalence of EIMs was significantly higher in Crohn's disease (CD) than in ulcerative colitis (UC) (20.5% vs. 15.4%, P = 0.003). Joint manifestations (10.0%) and aphthous ulcers (5.5%) were most common, with aphthous ulcers significantly more frequent in CD (11.2% vs. 2.8%, P < 0.001). The prevalence of classic EIMs such as arthritis/arthralgia (8.0%), uveitis (0.5%), and erythema nodosum (0.9%) fell within the low-to-mid range of global reports. Significant co-occurrence was observed among EIMs. For example, arthritis/arthralgia showed strong associations with uveitis (OR = 31.88) and erythema nodosum (OR = 13.34). Analysis of medication history revealed higher use of infliximab in patients with arthritis/arthralgia (47.0%) and pyoderma gangrenosum (71.4%), and frequent glucocorticoid use in those with venous thromboembolism (72.4%). In this inpatient-based cohort, the lower prevalence of classic EIMs in Chinese IBD patients may reflect clinical underdetection or genuine epidemiological differences. EIMs can precede intestinal symptoms and influence each other, underscoring the need for proactive, systematic assessment in clinical practice.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338012","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":"Decoding the immunometabolic landscape identifies SLC7A5 as a vulnerability in chemo-immunotherapy resistant TNBC.","authors":"Sen Zhong, Bolin Yu, Shengyi Zhou, Wenlong Chen, Fanglong Liu, Huanhuan Zhu, Fang Min, Fengyuan Qian","doi":"10.1007/s10238-026-02231-2","DOIUrl":"10.1007/s10238-026-02231-2","url":null,"abstract":"<p><p>Metabolic reprogramming within the tumor microenvironment (TME) limits the efficacy of chemo-immunotherapy in triple-negative breast cancer (TNBC). Despite advances in high-resolution profiling, the specific intercellular metabolic crosstalk driving immune evasion remains incompletely understood. Here, we present a comprehensive single-cell metabolic atlas of the TNBC ecosystem to decode spatial and cell-type-specific metabolic vulnerabilities. Our multidimensional analysis reveals a distinct paracrine metabolic communication axis: CXCL9⁺ macrophages upregulate rate-limiting enzymes (IDO1/2) to become a potential source of local kynurenine, which is subsequently imported by cytotoxic T cells. Through in vitro co-culture and in vivo models, we demonstrate that this kynurenine uptake triggers impaired effector function and phenotypic exhaustion. Crucially, pharmacological blockade of SLC7A5 with the specific inhibitor JPH203 abrogates this metabolic toxicity, restores T cell effector function, and enhances the anti-tumor efficacy of combined cisplatin and anti-PD-1 therapy. Collectively, our findings delineate the Kynurenine-SLC7A5 metabolic axis as a critical driver of immunosuppression, providing a compelling rationale for integrating amino acid transport blockade to overcome resistance to chemo-immunotherapy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316108","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":"Mapping the research landscape of myelodysplastic syndromes: a scientometric analysis (2014-2025).","authors":"Jieyun Li, Wei Song Seetoh, Hao Xu, Yuchen Tao, Milin Liu, Shuyang Cai, Jiahui Lu, Cuncun Lu","doi":"10.1007/s10238-026-02226-z","DOIUrl":"10.1007/s10238-026-02226-z","url":null,"abstract":"<p><p>This scientometric study critically evaluates the global evolution of myelodysplastic syndromes (MDS) research from 2014 to 2025, aiming to integrate fragmented knowledge and identify emerging trends. A scientometric analysis was conducted using data retrieved from the Web of Science Core Collection on August 2, 2025. The search was restricted to \"article\" and \"review\" in English containing \"Myelodysplastic syndrome\" or \"Myelodysplastic syndromes\" in the abstract, covering the period from January 1, 2014 onward. Scientometric tools (VOSviewer, CiteSpace, R-bibliometrix) were employed to analyze annual publication trends, country/institution/author contributions, collaboration networks, journal distribution, reference co-citation clusters, emerging research topics. Analysis of 6,822 publications revealed that global MDS research output peaked in 2021. The USA dominated with 2,838 publications, followed by China (1,169) and Germany (717), while top institutions (e.g., University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center) and prolific authors (e.g., Garcia-Manero G, Kantarjian HM) were predominantly USA-based. Collaboration networks revealed a core-periphery structure with strong transatlantic ties and emerging Asian contributions. Thematic analysis identified research hotspots across multiple dimensions, including 5q deletion, trisomy 8, germline predisposition, TP53 mutation, clonal hematopoiesis, inflammation, venetoclax, luspatercept, targeted therapy, immunotherapy, pediatric population, VEXAS syndrome, IPSS-R, relapse, prognosis, overall survival, and artificial intelligence. MDS research is shifting toward precision medicine. Future advances are expected to rely on multi-ethnic cohort building, mechanism exploration, combined treatment regimen optimization and novel drug development. Strengthening multidisciplinary collaboration is anticipated to facilitate clinical translation and foster more precise, equitable and clinically practical management of MDS globally.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327178","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":"C-reactive protein-to-lymphocyte ratio and stroke: associations with prevalence and subsequent mortality in NHANES 1999-2010.","authors":"Yan Miao, Jianxin Chen, Zhiwei Zheng, Yunxiao Zhang, Ruiqi Liu, Junyi Chu, Sen Li, Ying Liu","doi":"10.1007/s10238-026-02225-0","DOIUrl":"10.1007/s10238-026-02225-0","url":null,"abstract":"<p><p>Early risk detection is critical for timely intervention to reduce stroke morbidity and recurrence rate. This study systematically investigated the association between the CRP-to-lymphocyte ratio (CLR) and stroke prevalence, aiming to evaluate whether CLR may serve as a convenient and readily accessible inflammatory biomarker for stroke prediction. Data were analyzed from the 23,483 participants in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010. Multivariable logistic regression models were employed to assess the relationship between CLR and prevalent stroke. Among 789 individuals with a history of stroke, Cox proportional hazards models were used to examine the association between CLR and all-cause as well as cause-specific mortality. Kaplan-Meier survival curves were constructed to compare survival outcomes across CLR strata defined by an optimal cutoff. Restricted cubic spline (RCS) analysis was applied to explore potential nonlinear relationships. The predictive value of CLR was compared with that of established inflammatory markers using receiver operating characteristic (ROC) curve analysis. After adjusting for potential confounders, elevated CLR is significantly and independently associated with higher odds of stroke prevalence in the fully adjusted model (OR = 1.005, 95% CI: 1.002-1.007, P < 0.001). Kaplan-Meier analysis demonstrates significantly higher mortality risks among stroke participants with CLR above the optimal threshold. RCS models showed no evidence of nonlinearity between the CLR and mortality risks. Furthermore, ROC analysis indicated that CLR exhibited superior predictive ability compared to the established inflammation markers, including the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), C-reactive protein (CRP), and lymphocyte counts (all P < 0.05). These findings suggest that CLR is an independent and significant predictor of both the stroke prevalence and all-cause mortality in stroke patients, highlighting its potential utility as a readily accessible inflammatory biomarker for stroke prevalence stratification. Given its ease of derivation from routine examination data, CLR holds promise for broad clinical applicability. Further prospective studies are warranted to elucidate the underlying mechanisms and to validate its predictive value in diverse populations.Trial registration: This study is a secondary analysis of publicly available NHANES data and does not constitute a clinical trial; therefore, trial registration is not applicable.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316152","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":"Global trends in the burden of inflammatory bowel disease from 1990 to 2021: socioeconomic and sex-specific disparities with exploratory mendelian randomization analyses.","authors":"Yutong Cheng, Ziwei Wang, Yuxin Peng, Yongze Dang, Yingfan Deng, Sumei Sha, Xin Liu, Jinhai Wang, Haitao Shi, Ning Xie","doi":"10.1007/s10238-026-02224-1","DOIUrl":"10.1007/s10238-026-02224-1","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) shows substantial variation in burden across regions and populations worldwide. However, patterns of IBD b3urden across levels of socio-demographic development remain incompletely characterized, and complementary evidence on selected individual-level exposures is limited. Utilizing GBD 2021 data, we assessed age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and disability-adjusted life years rate (ASDR) from 1990 to 2021 across socio-demographic index (SDI) strata. Temporal trends were estimated using estimated annual percentage change and Joinpoint regression. Pearson analysis and frontier analyses assessed SDI correlations, while inequality was measured using the concentration index and slope index. Decomposition analysis was performed to identify the contributors of population growth, population aging, and epidemiological change. Two-sample Mendelian randomization (MR) analysis was conducted to examine potential associations between selected exposures and IBD. From 1990 to 2021, the global ASIR rose by 0.29 annually, while ASPR, ASMR and ASDR decreased by 0.13, 0.31 and 0.52. Burden patterns differed across SDI strata. High SDI regions had the highest age-standardized burden in 2021. The largest increases in ASIR and ASPR were observed in middle SDI regions, and declines in ASMR and ASPR began later in low SDI regions than in high SDI regions. ASDR was positively correlated with SDI in females but not in males, and cross-country inequality in ASDR was greater in females than in males. Decomposition analysis showed that population aging contributed more to changes in ASMR and ASDR in high SDI regions, while population growth was the dominant contributor in low SDI regions. Fifteen countries showed large effective differences between observed ASDR and frontier values at comparable SDI levels. In MR analyses, several nominal associations were observed, but none remained significant after false discovery rate (FDR) correction. The burden of IBD showed substantial heterogeneity across SDI levels and between sexes in GBD 2021, with a more pronounced inequality pattern in disability burden among women. The MR findings did not remain significant after FDR correction and should therefore be interpreted cautiously as exploratory signals. These findings underscore the importance of context-specific strategies to reduce inequalities in IBD burden across populations and between women and men.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327186","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":"GRP78 in viral pneumonia: dual regulatory mechanisms and translational prospects.","authors":"Hang Ruan, Qian-Rui Huang, Li-Juan Zou, Shu-Sheng Li","doi":"10.1007/s10238-026-02228-x","DOIUrl":"10.1007/s10238-026-02228-x","url":null,"abstract":"<p><p>Glucose-regulated protein 78 (GRP78), a core molecular chaperone governing the endoplasmic reticulum (ER) stress response, exerts dual regulatory effects during the pathogenesis of viral pneumonia. Beyond serving as a critical cofactor that promotes viral invasion and replication, GRP78 functions as an indispensable protective chaperone that preserves pulmonary cellular homeostasis and attenuates lung injury. This review characterizes two distinct subcellular localizations of GRP78 in viral pneumonia, namely ER-resident GRP78 and cell surface GRP78 (csGRP78), and systematically summarizes its dual regulatory mechanisms. Specifically, csGRP78 mediates viral adhesion and internalization, whereas ER-GRP78 promotes viral replication and aggravates pulmonary inflammation by modulating ER stress and the unfolded protein response. Meanwhile, GRP78 alleviates pulmonary tissue damage via suppressing lung cell apoptosis and restraining excessive ERS activation. Moreover, this review provides a comprehensive overview of advances in GRP78-targeted therapeutic strategies. The covered therapeutic modalities include small-molecule inhibitors, biological macromolecular drugs, indirect regulatory compounds, and natural products. This review also elaborates their specific molecular targets, core mechanisms, and preclinical findings. Additionally, the current research trends, existing limitations, and future perspectives of GRP78-related investigations are critically discussed. This review aims to clarify the central regulatory role of GRP78 in viral pneumonia, providing theoretical basis and innovative research directions for the precision targeted therapy of viral pneumonia.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307182","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":"Decoding the association between microorganisms and autoimmunity: a multifaceted review of evidence on specific pathogens that trigger autoimmune diseases.","authors":"Haixiang Zhang, Jun Hu, Jingying Sun, Lijun Sun, Cuixiang Xu","doi":"10.1007/s10238-026-02206-3","DOIUrl":"10.1007/s10238-026-02206-3","url":null,"abstract":"<p><p>The occurrence and progression of autoimmune diseases (AIDs) result from the combined effects of genetic susceptibility, immune response defects, and environmental triggers. Among these, microorganisms, as key environmental factors, have been widely hypothesized to play a role in initiating AIDs, but the exact causal relationship remains to be demonstrated. This review aims to deeply explore the core role of specific microbial infections in triggering AIDs by integrating evidence from three dimensions: epidemiological investigations, clinical studies, and animal model research. We focused on analyzing nine AIDs, including Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, and confirmed that specific pathogens such as Campylobacter jejuni, Epstein-Barr virus, and Porphyromonas gingivalis can induce corresponding autoimmune pathological damage in susceptible individuals through mechanisms including molecular mimicry and bystander activation. Nevertheless, the field still faces important gaps that caused the chain from mechanism association to clinical application to break.This review integrates existing evidence and demonstrates that microbial infections are one of the important triggers for AIDS. It provides a new theoretical basis and direction for mechanistic research, risk early warning, and targeted intervention of related diseases.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307143","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":"Patient-derived tissue slice cultures from endoscopic biopsies as a translational ex vivo model for inflammatory bowel diseases.","authors":"Julia Werner, Laura Schiller, Claudia Müller, Jörg Lehmann, Jens Przybilla, Tobias Schlosser, Albrecht Hoffmeister, Sonja Kallendrusch, Cica Vissiennon","doi":"10.1007/s10238-026-02209-0","DOIUrl":"10.1007/s10238-026-02209-0","url":null,"abstract":"<p><p>Effective inflammatory bowel disease (IBD) management increasingly relies on patient-stratified therapeutic approaches, yet clinically accessible platforms for ex vivo pharmacological evaluation remain limited. This study establishes patient-derived tissue slice cultures from routine endoscopic biopsies (ePDTC), as a potential translational platform for individualized drug response assessment. ePDTC were generated from routine colonic biopsies of ulcerative colitis (UC, N = 11), Crohn's disease (CD, N = 7), and non-IBD control patients (N = 3). Tissue slices (350 μm high) were cultured at an air-liquid interface for 24 and 48 h, assessed for viability, immune cell composition, transcription factor activation, and mediator release profiles. Pharmacological responsiveness was evaluated using budesonide (1 µM) and myrrh extracts (50-100 µg/mL). Structural integrity was preserved in 88.4% of ePDTC at 24 h after start of cultivation with low apoptosis rates (median: 1.21%), but declined to 56.0% of tissues at 48 h. ePDTC preserved disease-specific inflammatory signatures, including distinct neutrophil patterns between UC and CD subtypes. Budesonide significantly reduced 17 of 24 inflammatory mediators after 24 h (adjusted P < 0.001) with indication of disease subtype-specific response patterns in principal component analysis. Myrrh extracts demonstrated concentration-dependent responses. Biopsy-derived ePDTC provide a clinically accessible ex vivo platform that preserves native tissue complexity and demonstrates the capacity to capture inter-individual pharmacodynamic heterogeneity within a 24-hour experimental window. This provides a biological basis for future patient-stratified pharmacological evaluation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293659","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}