Clinical and Experimental Medicine最新文献

{"title":"Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.","authors":"Juairia Uddin Dekha, Amir Yami, Laura Quotti Tubi, Iris Haxhiu, Alessandro Carrer, Livio Trentin, Francesco Piazza, Sabrina Manni","doi":"10.1007/s10238-026-02169-5","DOIUrl":"10.1007/s10238-026-02169-5","url":null,"abstract":"<p><p>Lymphomas (Hodgkin lymphoma and non-Hodgkin lymphoma) constitute a heterogenous group of malignancies derived from immature and mature lymphoid cells. Despite improvements in therapeutic options in recent years, high rates of recurrence and resistance to current treatments remain a significant and unmet clinical eliminate s from needs. Past and recent studies have identified important molecular signatures playing a role in the pathophysiology of lymphomas, including the B-cell receptor, NF-κB, PI3K/AKT, Wnt/β-catenin cascades, and have pointed to protein kinases, such as BTK, PI3K, CK1α and CK2, as drivers and therefore potential therapeutic targets. It has also been extensively demonstrated that various epigenetic changes, including DNA methylation and histone modifications, play critical roles in sustaining cell survival, proliferation and perturbed differentiation of lymphoma cells. Moreover, the interplay between signal transduction and epigenetic modifications in lymphoma cells may influence the lymphoma-associated tumor microenvironment and immune cell function, shaping the anti-lymphoma immune response. Therefore, the identification of new targets for the therapy of lymphomas requires a comprehensive understanding of how cell signaling and epigenetic modifications interact. This review explores the function of newly recognized kinases in lymphoma pathogenesis, such as CK1, CK2 and others, highlighting their interaction with epigenetic regulation. The therapeutic potential of targeting simultaneously signaling and epigenetic pathways is proposed as a potential innovative strategy in the treatment of lymphomas.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13468871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197574","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":"Venetoclax, azacitidine, and chidamide in combination with cytarabine, aclarubicin, and G-CSF as induction chemotherapy for myelodysplasia-related acute myeloid leukemia.","authors":"Lei Lv, Jingjing Yang, Qingyang Liu, YanFen Li, Lingmin Xu, Meng Li, Ran Zhang, Sai Huang, Yu Jing, Liping Dou","doi":"10.1007/s10238-026-02200-9","DOIUrl":"https://doi.org/10.1007/s10238-026-02200-9","url":null,"abstract":"<p><p>Myelodysplasia-related acute myeloid leukemia (AML-MR) exhibits poor outcomes with intensive chemotherapy. This retrospective study was conducted to evaluate the clinical efficacy and safety of the Venetoclax, Azacitidine, and Chidamide in combination with Cytarabine, Aclarubicin, and G-CSF (CACAG-VEN) regimen in AML-MR patients. We included 14-75-year-old AML-MR patients (n = 30) treated with CACAG-VEN between January 1, 2023 and December 31, 2024. And compared this cohort with patients (n = 30) who received the standard \"3 + 7\" regimen (daunorubicin plus cytarabine) from January 1, 2018 to December 31, 2022. The primary endpoint was the complete remission rate(CR) after one cycle of induction. In this retrospective analysis of 30 patients treated with CACAG-VEN, the median age was 50.5 (range, 23-62) years. The CACAG-VEN achieved a high CR (83.3%, 95% CI, 66.4-92.7) and composite complete response (CRc, 93.1% [95% CI, 78.7-98.8]). The 1-year overall survival (OS) and relapse incidences (CIR) were 90.0% (95% CI: 72.1-96.7) and 18.0% (95% CI: 6.4-34.4), respectively. No significant differences in OS (1-year: 85.7% [non-HSCT] vs. 93.8% [HSCT]) or CIR (1-year: 29.3% [non-HSCT] vs. 7.1% [HSCT]) were observed, regardless of whether patients underwent HSCT. The most frequent grade 1-4 adverse events were febrile neutropenia (73.3%), sepsis (16.7%), and pneumonia (50.0%). The median time to recovery was 16.5 days for platelet counts ≥ 20,000/µL and 20.0 days for absolute neutrophil counts ≥ 1,000 cells/µL after induction therapy. The outcomes in the \"3 + 7\" group were inferior to those of patients who received the CACAG-VEN regimen (CR: 55.7%, p = 0.003; CRc: 56.4%, p = 0.005; 1-year OS: 73.3%, p = 0.039). The CACAG-VEN regimen is a potential frontline therapy for AML-MR, yielding superior response rates and longer survival durations than the standard \"3 + 7\" chemotherapy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155509","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":"Analysis of clinical features of lupus mesenteric vasculitis.","authors":"Jiaojiao Han, Shanshan Li, Pengyu Xie, Yujie He, Tianfang Li","doi":"10.1007/s10238-026-02170-y","DOIUrl":"10.1007/s10238-026-02170-y","url":null,"abstract":"&lt;p&gt;&lt;p&gt;This study aimed to identify the clinical characteristics of systemic lupus erythematosus (SLE) patients with complicated with lupus mesenteric vasculitis (LMV), and to determine the impacts of the first-visit department, the number and duration of digestive system symptoms on disease activity, and imaging features of LMV patients. We expected that our study would keep clinicians across specialties vigilant for SLE-LMV, enabling early diagnosis and prompt treatment, thereby improving prognosis and reducing mortality from this potentially fatal condition. Clinical data of 174 patients with LMV admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2023 were collected and analyzed. The baseline clinical characteristics and laboratory data were analyzed and compared by the first-admission department: either the Rheumatology Department or other departments. In addition, the impact of the numbers and durations of various digestive system symptoms in these patients, as well as laboratory results, disease activity, and imaging findings, was analyzed. The independent-samples t-test and Mann-Whitney U-test were used to compare differences in continuous variables. In contrast, the Kruskal-Wallis test, chi-square test, or Fisher's exact test was used to compare differences in disease activity-related indicators, imaging features, and treatment regimens. A total of 174 patients with an initial diagnosis of LMV were included in this study. Among these patients, 87 (50.0%) had a prior SLE diagnosis, 76 (43.7%) were first diagnosed in the Rheumatology Department, and 36 (20.7%) and 31 (17.8%) were first diagnosed in the Departments of Gastroenterology and Emergency Medicine, respectively. All patients had mild to severe digestive symptoms, including abdominal pain, diarrhea, nausea, vomiting, and abdominal distension. Multiple digestive symptoms occurred in 151 (86.8%) patients. The patients were divided into two groups based on whether they were first diagnosed in the rheumatology department or other departments. The results showed that patients who were not initially diagnosed in the rheumatology department had longer hospital stays and lower disease activity. The patients were further categorized into groups based on the number and time of various digestive symptoms. Compared with those with fewer flares, the proportions of leukopenia, hypocomplementemia, and abdominal effusion were higher in those with frequent LMV recurrences. The white blood cell (WBC) and neutrophil counts in patients with abdominal pain of less than 7 days were higher than those with abdominal pain of more than 7 days. However, statistical analysis did not reveal significant differences among other inflammatory markers and the indices of disease activity. In terms of imaging features obtained by contrast-enhanced CT, a statistical difference was detected in patients with abdominal pain over 7 days compared to those with less than 7 days wit","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148840","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":"Circ-MAP4K3 promotes papillary thyroid cancer progression by sponging miR-758-3p to enhance RRM2 expression.","authors":"Yi Dong, Jiangnan Dong, Jun Li, Qi Qi, Lei Wei, Ying Chen, Xiaoyan Cai","doi":"10.1007/s10238-026-02140-4","DOIUrl":"10.1007/s10238-026-02140-4","url":null,"abstract":"<p><p>Papillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. PTC metastasizes more frequently in children and teenagers, although survival of these patients is usually considered excellent. Still, research on regulatory mechanisms has significant clinical implications. Circular RNAs (circRNAs) participate in PTC regulation. The present study analyzed the role of circ-MAP4K3 in PTC. High-throughput sequencing was used to determine circRNA expression differences between PTC and paracarcinoma tissues. The expression of circ-MAP4K3 was evaluated using RT-qPCR and FISH. TPC-1 and B-CPAP cell proliferation was analyzed utilizing CCK-8 and EdU, while cell migration was assessed based on Transwell and wound healing assays. The targeting relationship among circ-MAP4K3, miR-758-3p, and RRM2 was elucidated via dual-luciferase reporter assay. A xenograft mouse model was employed to determine the effect of circ-MAP4K3 on tumor formation in vivo. The expression of circ-MAP4K3 was increased in PTC tissues and cell lines compared to the levels in the control groups. Circ-MAP4K3 silencing inhibited PTC cell proliferation and migration and tumor growth both in vivo and in vitro. Bioinformatics analysis confirmed that both miR-758-3p and RRM2 were downstream targets of circ-MAP4K3. Inhibition of miR-758-3p or overexpression of RRM2 rescued the proliferation and migration abilities after circ-MAP4K3 downregulation. RRM2 overexpression also rescued the proliferation and migration abilities after miR-758-3p overexpression. Circ-MAP4K3 promotes PTC progression via the miR-758-3p/RRM2 signaling pathway.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148786","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":"Adipose-derived mesenchymal stem cell-derived extracellular vesicles reduce glycolysis and polarize macrophages toward M2 phenotype in sepsis-associated acute kidney injury via the miR-574-5p/GLUT1 axis.","authors":"Jinbo Zhang, Jinling Li, Xiaohong Jin, Jinqiang Zhu","doi":"10.1007/s10238-026-02165-9","DOIUrl":"10.1007/s10238-026-02165-9","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) may exert a therapeutic benefit in sepsis-associated organ dysfunction by delivering cargos to target cells. The aims of this study were to explore the therapeutic efficacy and potential mechanism of microRNA (miR)-574-5p delivered by ADSC-EVs in sepsis-associated acute kidney injury (SA-AKI). EVs were isolated from mouse ADSCs and characterized by multilineage differentiation potency, morphology, and surface markers. miR-574-5p expression in ADSC-EVs was analyzed by biochemical testing. Luciferase reporter and RNA pull-down assays were employed to identify the binding relation between miR-574-5p and glucose transporter 1 (GLUT1). Cecal ligation and puncture (CLP)-induced mouse SA-AKI model administered with ADSC-EVs was used to evaluate therapeutic effects on kidney injury. ADSC-EVs were co-cultured with RAW264.7 macrophages to assess effects on inflammation, glycolysis (lactate levels, extracellular acidification rate), and macrophage polarization. ADSC-EVs elevated miR-574-5p expression and polarized macrophages toward M2 phenotype, reducing kidney dysfunction and inflammatory response in CLP mice. In vitro, ADSC-EVs arrested lipopolysaccharide-induced M1 macrophage polarization and induced M2 macrophage polarization by upregulating miR-574-5p expression. Mechanistically, ADSC-EVs transferred miR-574-5p into macrophages, where miR-574-5p targeted GLUT1 and limited its expression. This effect contributed to the inhibition of glycolysis and promotion of M2 macrophage polarization. In vivo studies confirmed these positive effects of ADSC-EVs in SA-AKI via the miR-574-5p/GLUT1 pathway. Altogether, our findings suggest that ADSC-EVs carrying miR-574-5p target GLUT1 to restrain glycolysis and prime M2 macrophage polarization in a SA-AKI model, paving the way for establishing a therapeutic approach for SA-AKI.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148814","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":"Analysis of the clinical characteristics of warfarin-associated purple toe syndrome.","authors":"Can Shi, Siyi Zhang, Songhua Chen, Ren Guo, Tian Wu","doi":"10.1007/s10238-026-02196-2","DOIUrl":"10.1007/s10238-026-02196-2","url":null,"abstract":"<p><p>Purple toe syndrome (PTS) represents a critical yet underrecognized complication of warfarin therapy. To characterize this condition, we conducted a retrospective analysis of all reported warfarin-associated PTS cases through April 30, 2025, without language restrictions. A total of 26 patients (17 male, 9 female) with a median age of 68 years were identified. Of these, 76.9% had pre-existing atherosclerotic disease and 66.7% showed elevated serum creatinine. Symptom onset occurred within three months of warfarin initiation in 53.9% of cases, with 84.0% exhibiting classic bilateral lower extremity involvement characterized by painful violaceous discoloration. Management strategies included warfarin discontinuation (88.5%), dose reduction (7.7%), renal replacement therapy (15.4%), LDL apheresis (11.5%), surgical or endovascular interventions (7.7%), and transition to alternative anticoagulant therapy. Notably, no cross-reactivity between anticoagulant classes was observed, and warfarin rechallenge was not categorically contraindicated in all cases. Outcomes were favorable in 69.2% of patients (symptom resolution), though 3.8% required amputation and 19.2% died within one year, suggesting this complication carries substantial morbidity despite therapeutic intervention. These finding suggest that warfarin-associated PTS warrants clinical awareness, particularly in elderly patients with pre-existing atherosclerotic disease and renal impairment. Early detection, warfarin cessation, and initiation of alternative anticoagulation appear important to help prevent irreversible outcomes.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148850","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":"Integrated multi-omics analysis: exploring the molecular regulatory mechanisms of HIV infection and identifying the key gene WFDC2.","authors":"Bingqing Yan, Tiantian Jiang, Yayun Wu, Renfei Zhu, Shifang Wang, Yihua Sun","doi":"10.1007/s10238-026-02197-1","DOIUrl":"10.1007/s10238-026-02197-1","url":null,"abstract":"<p><p>Although substantial progress has been made in the treatment of HIV infection, the regulatory mechanisms linking genetic variation, transcriptomic alterations, immune-cell changes, and post-transcriptional control remain poorly defined. A systematic multi-omics framework is needed to identify key molecular drivers and candidate biomarkers associated with HIV infection. We performed an integrated multi-omics analysis combining protein quantitative trait locus (cis-pQTL)-based summary-data Mendelian randomization (SMR) for 555 plasma proteins with multiple HIV-related genome-wide association study (GWAS) outcomes, followed by HEIDI testing to exclude linkage. In parallel, we conducted differential expression analyses of mRNA and miRNA from blood of healthy controls (n = 7), individuals with low viral load (n = 14), and individuals with high viral load (n = 16). Weighted gene co-expression network analysis (WGCNA) was used to define co-expression modules, which were overlaid with SMR hits and differentially expressed genes (DEGs) and further embedded into transcription-factor (TF) regulon networks. Plasma WFDC2 levels were quantified by ELISA in untreated HIV-infected, ART-treated, and control cohorts. Immune-cell deconvolution, gene set enrichment, and miRNA-mRNA network modeling were used to characterize the functional context of candidate genes.Lastly, HIV-associated cellular models were constructed, followed by functional validation experiments based on WFDC2 overexpression. Transcriptomic profiling revealed strong concordance between the HVL-CON and LVL-CON contrasts, identifying 803 commonly up-regulated and 1,108 commonly down-regulated genes. Integration of SMR results with DEGs highlighted eight overlapping candidate genes-including WFDC2-whose encoded proteins were supported by both genetic instruments and transcriptional deregulation. These genes were embedded in immune-related co-expression modules and TF regulons. Among them, WFDC2 emerged as a key candidate, showing consistent down-regulation at the mRNA and protein levels, extensive correlations with inferred immune-cell subsets, and co-expressed genes enriched for chromatin remodeling, antiviral defense, RNA processing, and translation. Plasma WFDC2 concentrations were reduced in untreated HIV-infected individuals and partially restored under ART compared with healthy controls. Differentially expressed miRNAs potentially targeting WFDC2 and its co-expressed partners suggested additional post-transcriptional regulation. This multi-omics framework delineates a layered network connecting genetic regulation, transcriptional changes, immune-cell shifts, and miRNA-mediated control in HIV infection. Within this network, WFDC2 stands out as a putative hub integrating immune modulation and RNA metabolic pathways, and may represent a promising biomarker and potential therapeutic targets in HIV.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136733","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":"B3GNT7 preserves intestinal barrier integrity: a key defense mechanism against acute pancreatitis progression.","authors":"Jia Hu, Yang Fu, Zehua Huang, Nuoming Yin, Binqiang Xu, Huizhen Huang, Mengyan Cui, Qixiang Mei, Chunlan Huang, Yue Zeng, Junjie Fan","doi":"10.1007/s10238-026-02186-4","DOIUrl":"10.1007/s10238-026-02186-4","url":null,"abstract":"<p><p>Mucin-2 (MUC2) plays a crucial role in maintaining intestinal homeostasis during acute pancreatitis (AP). We aimed to investigate the role of B3GNT7 (β-1,3-N-acetylglucosamine transferase) in the O-glycosylation of MUC2 in AP. We used two mouse models of AP induced by caerulein/lipopolysaccharide or L-arginine, and observed colonic goblet cells using electron microscopy, noting that Golgi damage was linked to decreased levels of mature MUC2. Golgi stress-associated proteins (reduced GM130 and elevated GOLPH3) were identified using immunofluorescence. Transcriptome analysis revealed the downregulation of B3gnt7, a glycosyltransferase that is highly enriched in the Golgi apparatus of goblet cells in AP mice. B3GNT7 expression was negatively correlated with pancreatic and colonic pathological scores. In patients with AP, intestinal B3GNT7 levels are markedly reduced and correlated with Ranson scores, C-reactive protein levels, and intestinal permeability markers (serum diamine oxidase and D-lactate). Adeno-associated virus (AAV)-mediated knockdown of B3GNT7 reduced O-glycosylated MUC2 levels, exacerbated pancreatic and systemic inflammation, and worsened intestinal permeability and dysbiosis. In vitro, LPS-treated HT-29 cells exhibited Golgi stress (decreased levels of B3GNT7 and O-glycosylated MUC2) that was reversed by L-glutathione (GSH). These findings demonstrate that B3GNT7 downregulation, mediated by Golgi stress, disrupts MUC2 O-glycosylation, exacerbating AP by impairing intestinal homeostasis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101206","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":"Morpho-functional plasticity of tumour-associated macrophages: linking cell shape, ultrastructure, and immune regulation in cancer.","authors":"Keerthana Suresh Kizhakkanoodan, Vidhula Jessica Inigo, Sindhura Lakshmi Koulmane Laxminarayana, Raviraja N Seetharam, Kanive Parashiva Guruprasad, Bharath Raja Guru","doi":"10.1007/s10238-026-02190-8","DOIUrl":"10.1007/s10238-026-02190-8","url":null,"abstract":"<p><p>Macrophages are highly adaptable immune cells that play dual roles in the tumor microenvironment (TME), either promoting or restraining tumor progression. Their polarization into M1 and M2 tumor-associated macrophage (TAM) phenotypes is classically defined by molecular and biochemical cues. Recent evidence shows that morphology also significantly influences the macrophage function and behavior. This review highlights the correlation between macrophage shape and function, and how cytoskeletal remodeling, extracellular matrix (ECM) stiffness, and topographical patterning regulate macrophage polarization under in vitro and in vivo conditions. We further discuss the ultrastructural features of distinct phenotypes and their mechanistic links to tumor growth and metastasis. Therapeutic strategies that target morphology through ECM modulation, engineered biomaterials, and nanoparticle platforms are examined alongside modern imaging and machine learning tools that enable precise morphometric analysis. Finally, we address the translational progress and limitations of current 2D versus 3D model systems. Overall, this review emphasizes macrophage morphology as a critical yet underexplored determinant of immune function and tumor dynamics.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136771","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":"Exosomal integrin αvβ3 derived from colorectal cancer promotes the liver pre-metastatic niche formation by inducing cancer-associated fibroblasts activation.","authors":"Jing Yu, Jiangning Xiang, Lin Yao, Shan Wang, Yifan Liu, Enli Chen, Xiaolin Liu, JinXiang Wu, Yuhao Wang, Lei Zhao","doi":"10.1007/s10238-026-02193-5","DOIUrl":"10.1007/s10238-026-02193-5","url":null,"abstract":"<p><p>The formation of the liver pre-metastatic niche (PMN) is a critical factor in the development of colorectal cancer liver metastasis (CRLM), so understanding the mechanism of the liver PMN is crucial for the prevention and treatment of CRLM. Hepatic stellate cells (HSCs) can promote CRLM by forming cancer-associated fibroblasts (CAFs), but the mechanism remains unclear. In this study, we found that integrin αvβ3 is associated with CRLM and the poor clinical prognosis. Exosomal integrin αvβ3 derived from CRC can target HSCs via fibronectin to mediate their activation. We further explored the mechanism and found that exosomal integrin αvβ3 activates the MEK-ERK signaling pathway through the vitronectin-Integrin αvβ3-FAK axis, thereby promoting HSCs activation. After HSCs become CAFs, they promote the formation of the PMN through EMT, angiogenesis, and inflammatory factors, thereby promoting CRLM. In summary, this study clarifies that exosomal integrin αvβ3 derived from CRC can promote the formation of liver PMN by mediating HSC activation into CAFs, providing a novel therapeutic strategy for the prevention and treatment of CRLM.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136768","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}