Translational Research最新文献

{"title":"Angiogenic and reparative potency of a human cardiac CD90− mesenchymal subpopulation in heart ischemic model","authors":"Elisa Gambini ,&nbsp;Erica Rurali ,&nbsp;Veronica Barbagallo ,&nbsp;Sergio Pirola ,&nbsp;Alessandro Scopece ,&nbsp;Andrea Biondi ,&nbsp;Beatrice Bassetti ,&nbsp;Manuel Casaburo ,&nbsp;Luana Eramo ,&nbsp;Giorgio Pio Alberto Marinelli ,&nbsp;Diego Farinello ,&nbsp;Simona Rodighiero ,&nbsp;Yuri D’alessandra ,&nbsp;Mattia Chiesa ,&nbsp;Gabriella Spaltro ,&nbsp;Veronica Ricci ,&nbsp;Aoife Gowran ,&nbsp;Elisa Castiglioni ,&nbsp;Daniele Fileccia ,&nbsp;Giuseppe Nanci ,&nbsp;Giulio Pompilio","doi":"10.1016/j.trsl.2025.08.004","DOIUrl":"10.1016/j.trsl.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Despite recent significant therapeutic progress, cardiovascular diseases (CVD) remain an unmet clinical, economic, and social burden worldwide. Cell-based therapies have been proposed as therapeutic strategies, however, the overall efficacy was modest.</div></div><div><h3>Objective</h3><div>We aimed to fully characterize a novel subpopulation of CD90⁻ mesenchymal cells derived from human heart tissue (hCmPC90^-) and evaluate its ability to induce cardiac tissue repair and functional recovery.</div></div><div><h3>Methods</h3><div>We performed a comprehensive phenotypic characterization of the hCmPC90⁻ by flow cytometry and RNA sequencing. A direct comparison of hCmPC90⁻ with previously clinically tested bone marrow- and cardiac-derived cell types, has been conducted both <em>in vitro</em> by means of various assays of angiogenic potency, and <em>in vivo,</em> by testing the ability to ameliorate left ventricular function in a mouse model of acute myocardial infarction (AMI).</div></div><div><h3>Results</h3><div>hCmPC90⁻ showed distinct surface markers and transcriptional phenotype compared with unselected mesenchymal heart cells (hCmPCs) and the positive CD90 counterpart (hCmPC90⁺). When human hCmPC90⁻, hCmPC90⁺, hCmPC, cardiosphere-derived cells (CDCs), and bone marrow-derived CD34⁺ cells were functionally tested <em>in vitro</em>, hCmPC90⁻ revealed a superior endothelial differentiation ability, higher anti-inflammatory, cardio-protective capacity, and angiocrine activity. Moreover, hCmPC90⁻ showed specific immune-privileged features. When intramyocardially delivered into infarcted mouse hearts, hCmPC90⁻ outperformed three weeks after injection other clinical-grade cell types, as for left ventricular (LV) function and adverse LV remodeling recovery, infarct size reduction, and vascular density augmentation.</div></div><div><h3>Conclusion</h3><div>hCmPC90⁻ shows a superior biological potency which deserves clinical exploitation as an advanced therapy medicinal product in the context of refractory ischemic heart disease.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"283 ","pages":"Pages 22-35"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining computational target prioritization and a B cell maturation assay for target evaluation studies in systemic lupus erythematosus","authors":"Ming-Mei Shang ,&nbsp;Zhuang Liu ,&nbsp;Bogdan Knezevic ,&nbsp;Christine Möller Westerberg ,&nbsp;Sudeepta Kumar Panda ,&nbsp;Hai Fang ,&nbsp;Ning Xu Landén ,&nbsp;Michael Sundström ,&nbsp;Julian C. Knight ,&nbsp;Louise Berg","doi":"10.1016/j.trsl.2025.09.002","DOIUrl":"10.1016/j.trsl.2025.09.002","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving production of autoantibodies by B cells. This study aimed at identifying novel drug targets using a computational algorithm to select targets and thereafter validate the top ranked 11 targets by siRNA knockdown in a primary B cell maturation assay.</div></div><div><h3>Experimental Approach</h3><div>The top 1 % genes (∼150 genes) from SLE genome-wide association studies were ranked by Priority index (Pi), a computational tool integrating genomic and network information to prioritize disease-relevant genes. These were further filtered by network connectivity, drugability, for ranking highly in autoimmune diseases and for not directly interfering with the B cell stimulation cocktail used. From this, 11 genes were selected for validation by siRNA knockdown: <em>IFNGR1, IL-2, IRF4, IL-12A, IL-12B, VCAM-1, ATF6B, RELA, IKBKG, CHUK</em> and <em>MAPK14.</em> Effects on induced maturation and viability of primary blood B cells were analyzed by flow cytometry, and effects on IgG secretion were investigated by ELISA. RNA-sequencing of B cells treated with siRNA was performed to investigate molecular mechanisms underlying the functional alterations.</div></div><div><h3>Key Results</h3><div>Experimental results show that several of the targets (<em>IFNGR1, IL-2, IL-12A, MAPK14, IRF4, CHUK, ATF6B, IKBKG,</em> and <em>RELA</em>) are involved in B cell maturation, as knockdown caused reduced IgG production and/or decreased maturation of B cells. The observed variability of effects on IgG secretion and B cell maturation suggests differences in the mechanistic roles of the proteins encoded by these genes. RNA-seq analysis of cells where expression of the targeted genes had been modulated showed effects on the expression level of hundreds of genes involved in cellular processes important for B cell functions.</div></div><div><h3>Conclusion and Implications</h3><div>Combining the target prioritization algorithm with experimental functional validation studies by gene knockdown and whole transcriptomics profiling constitutes a promising approach to identify potential novel drug targets in immune disorders.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"283 ","pages":"Pages 36-46"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of thermogenic genes to metabolic tissues: Effects on body weight and glucose tolerance","authors":"Min-Jung Park ,&nbsp;Junhyeong Lee ,&nbsp;Merc Emil Matienzo ,&nbsp;Sangyi Lim ,&nbsp;Keon Kim ,&nbsp;Chang-Min Lee ,&nbsp;Dong-il Kim","doi":"10.1016/j.trsl.2025.09.003","DOIUrl":"10.1016/j.trsl.2025.09.003","url":null,"abstract":"<div><div>Adaptive thermogenesis, particularly via the β3-adrenergic receptor (ADRB3)–protein kinase A catalytic subunit α (PKA Cα)–uncoupling protein 1 (UCP1) pathway, promotes energy expenditure and contributes to metabolic homeostasis, thereby establishing this pathway as a promising therapeutic target for metabolic disorders associated with excessive energy intake. In this study, we aimed to evaluate the therapeutic potential of adeno-associated virus (AAV)-mediated gene therapy targeting thermogenic pathways in metabolic tissues for the treatment of obesity-related dysfunctions. We demonstrated that adipocyte-specific overexpression of UCP1 improved glucose tolerance. Similarly, ADRB3 overexpression significantly enhanced glucose tolerance. Furthermore, ectopic expression of UCP1 in hepatocytes and myofibers also led to improved glucose tolerance. These findings highlight the potential of AAV-mediated gene therapy targeting the ADRB3–PKA Cα–UCP1 axis as a promising strategy for the treatment of obesity-associated metabolic disorders.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"283 ","pages":"Pages 47-55"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of circulating tumor cells and circulating tumor DNA in peritoneal lavage fluid for predicting metachronous peritoneal metastasis of gastric cancer","authors":"Long Bai ,&nbsp;Bo Ni ,&nbsp;Xiaoyao Shen ,&nbsp;Yeqian Zhang ,&nbsp;Yujing Guan ,&nbsp;Jiayi Gu ,&nbsp;Haoyu Zhang ,&nbsp;Muerzhate Aimaiti ,&nbsp;Shuchang Wang ,&nbsp;Ben Yue ,&nbsp;Yanying Shen ,&nbsp;Zebing Liu ,&nbsp;Xiang Xia ,&nbsp;Zizhen Zhang","doi":"10.1016/j.trsl.2025.08.003","DOIUrl":"10.1016/j.trsl.2025.08.003","url":null,"abstract":"<div><h3>Background</h3><div>Peritoneal metastasis is a leading cause of death in gastric cancer (GC) patients, highlighting the need for early diagnosis and high-risk population identification. While circulating tumor DNA(ctDNA) and circulating tumor cells (CTC) have been widely studied in blood, their role in peritoneal lavage fluid (PLF) remains unexplored.</div></div><div><h3>Methods</h3><div>Patients with stage III GC were enrolled, and preoperative/postoperative PLF was collected in this study. ctDNA in PLF supernatant was analyzed via next-generation sequencing (NGS), while CTC in the pellet were detected using Epithelial Cell Adhesion Molecule (EpCAM), Folate Receptor (FR), and Cytokeratin (CK) immunofluorescence.</div></div><div><h3>Results</h3><div>ctDNA-positive patients had higher peritoneal metastasis risk (preoperative HR: 4.82, 95% CI 1.03–22.54, p = 0.04; postoperative HR: 4.83, 95% CI 1.03–22.54, p = 0.04). CTC-positive patients also showed higher risk (preoperative HR: 6.76, 95% CI 0.92–49.74, p = 0.003; postoperative HR: 7.41, 95% CI 1.67–32.87, p = 0.02). Postoperative ctDNA had higher predictive efficacy for peritoneal metastasis compared to preoperative ctDNA, with AUC values of 0.93 and 0.86. Combined ctDNA/CTC positivity identified the highest recurrence risk (preoperative HR: 8.07, 95% CI 0.96–67.51, p = 0.0012; postoperative HR: 18.14, 95% CI 3.27–100.70, p = 0.0002).</div></div><div><h3>Conclusions</h3><div>The combination of postoperative ctDNA and CTC in PLF offered the highest accuracy (85%) and risk stratification in predicting peritoneal metastasis (30.30% vs. 66.67%, p = 0.0063). This method may guide the postoperative prophylactic intraperitoneal chemotherapy.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"283 ","pages":"Pages 13-21"},"PeriodicalIF":5.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive in vivo tracking of SPIONs-labeled CLDN18.2-targeted CAR-T cells in gastric cancer via magnetic particle imaging","authors":"Meng He ,&nbsp;Lijie Ge ,&nbsp;Hui Hui ,&nbsp;Yali Zhou ,&nbsp;Yingxiu Tang ,&nbsp;Lin Shen ,&nbsp;Jie Tian ,&nbsp;Bo Wu ,&nbsp;Changsong Qi ,&nbsp;Yang Du ,&nbsp;Lei Tang","doi":"10.1016/j.trsl.2025.08.002","DOIUrl":"10.1016/j.trsl.2025.08.002","url":null,"abstract":"<div><div>This study aims to employ magnetic particle imaging (MPI) for in vivo tracking and quantitative assessment of targeting capability of CLDN18.2-specific CAR-T cells. CLDN18.2-targeted CAR-T cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic particle imaging (MPI), and with the near-infrared fluorescent dye DiR for fluorescence molecular imaging (FMI) before infusion. SPIONs-labeled and unlabeled CAR-T cells were administered intravenously to NOD/SCID mice bearing HGC27 xenograft tumors, either independently or in combination with anti-PD-L1 (aPD-L1) antibody (n = 3 for imaging and n = 5 for treatment). The FMI and MPI successfully monitored the dynamic migration and tumor targeting of CAR-T cells towards CLDN18.2-overexpressing tumors. On the fifth day post-infusion, the MPI signal of SPIONs-labeled CAR-T cells was significantly higher in the tumor than that of labeled normal T cells. MPI combined with FMI successfully monitored the targeting of CLDN18.2-specific CAR-T cells in gastric cancer, providing a potential framework for evaluating CAR-T therapy combined with aPD-L1 immunotherapy.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"283 ","pages":"Pages 3-12"},"PeriodicalIF":5.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Information for Readers","authors":"","doi":"10.1016/S1931-5244(25)00084-2","DOIUrl":"10.1016/S1931-5244(25)00084-2","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Page IBC"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-34 is expressed in the pancreas and regulates local inflammation","authors":"Chloé M Delépine ,&nbsp;Emilie Courty ,&nbsp;Laurence Preisser ,&nbsp;Raffaella Soleti ,&nbsp;Laetitia Basset ,&nbsp;Audrey Le Guernic ,&nbsp;Laure Rolland ,&nbsp;Marine Monnier ,&nbsp;Gianni Pasquetti ,&nbsp;Simon Blanchard ,&nbsp;Pascale Pignon ,&nbsp;Nathalie Merillon ,&nbsp;Julie Kerr-Conte ,&nbsp;Charline Miot ,&nbsp;Dominique Couez ,&nbsp;Aline Schmidt-Tanguy ,&nbsp;Elise Dalmas ,&nbsp;Pascale Jeannin ,&nbsp;Jean-Sébastien Annicotte ,&nbsp;Yves Delneste ,&nbsp;Celine Beauvillain","doi":"10.1016/j.trsl.2025.07.002","DOIUrl":"10.1016/j.trsl.2025.07.002","url":null,"abstract":"<div><div>Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of <em>Il34</em> in mice (IL-34^ΔPdx) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34^ΔPdx mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, <em>ex vivo</em> murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of <em>Il-34</em> mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 56-67"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S1931-5244(25)00082-9","DOIUrl":"10.1016/S1931-5244(25)00082-9","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Page ii"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(25)00083-0","DOIUrl":"10.1016/S1931-5244(25)00083-0","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages iii-iv"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet bound B cells and their role in SSc: Implications for disease subtypes and clinical outcomes","authors":"Rubén Osuna-Gómez ,&nbsp;Ivan Castellví ,&nbsp;Maria Mulet ,&nbsp;Jose Luis Tandaipan ,&nbsp;Carlos Zamora ,&nbsp;Helena Codes-Mendez ,&nbsp;Mª Àngels Ortiz ,&nbsp;Cesar Diaz-Torné ,&nbsp;Elisabet Cantó ,&nbsp;Berta Magallares ,&nbsp;Albert Guinart-Cuadra ,&nbsp;Patricia Moya ,&nbsp;Hector Corominas ,&nbsp;Silvia Vidal","doi":"10.1016/j.trsl.2025.07.001","DOIUrl":"10.1016/j.trsl.2025.07.001","url":null,"abstract":"<div><h3>Objectives</h3><div>Systemic sclerosis (SSc) is a complex autoimmune disease characterized by microvascular damage, immune dysregulation, and tissue fibrosis. While lymphocyte-platelet (PLT) complexes have been implicated in autoimmune diseases, their role in SSc is not well understood. Methods: In a study of 21 predominantly female SSc patients, 66.7 % had limited SSc (lcSSc), with anti-centromere antibodies (ACA) being the most common autoantibody pattern. We applied flow cytometry to analyze B cells with bound PLTs, enzyme-linked immunosorbent assay (ELISA) to determine plasma levels of activated PLT soluble factors, and co-culture assays to evaluate B cell cytokine secretion and plasma cell differentiation. Results: SSc patients had a higher percentage of B cells, but not T cells, with bound PLTs compared to healthy donors (HD). Despite similar PLT counts, SSc patients showed higher plasmatic levels of P-selectin (CD62P), soluble CD40 ligand (sCD40L), platelet-derived growth factor (PDGF), and transforming growth factor–β (TGF-β). Plasma IL-10 levels were also higher in SSc patients, with increased intracellular IL-10 in B cells with bound PLTs. We observed an increased IL-10 production and plasma cell differentiation when B cells were co-cultured with PLTs, especially from SSc patients. B cells with bound PLTs were associated with calcinosis, digital ulcers, and ACA status, with no effect from previous corticosteroid or aspirin therapy. Logistic regression identified B cells with bound PLTs as a predictor for distinguishing lcSSc patients. Conclusions: B cells with bound PLTs play a significant role in SSc by modulating B cell function and contributing to disease pathogenesis. Their association with clinical parameters suggests their potential as biomarkers for disease severity and subtype classification in SSc.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 31-40"},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}