Translational Research最新文献

{"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}

{"title":"Multiplexed imaging-driven single-cell analysis of abdominal aortic aneurysm according to C-reactive protein deposition","authors":"Eun Na Kim ,&nbsp;Hee Young Seok ,&nbsp;Jiwon Koh ,&nbsp;Jeong Mo Bae ,&nbsp;Wookyeom Yang ,&nbsp;Gyu Ho Lee ,&nbsp;Woo Hee Choi ,&nbsp;Joon Seo Lim ,&nbsp;You Jung Ok ,&nbsp;Jae-Sung Choi ,&nbsp;Donghee Kim ,&nbsp;Chong Jai Kim ,&nbsp;Lizhe Zhuang ,&nbsp;Young Hwan Chang ,&nbsp;Se Jin Oh","doi":"10.1016/j.trsl.2025.05.008","DOIUrl":"10.1016/j.trsl.2025.05.008","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) is an age-related, life-threatening condition characterized by the expansion of the abdominal aorta. Serum C-reactive protein (CRP) levels are a prognostic marker for AAA, and CRP accelerates tissue injury when deposited in damaged cell membranes in its monomeric form (mCRP). We previously showed that mCRP deposits in eroded atherosclerotic regions are associated with increases in inflammatory cell infiltration and aortic diameter. To investigate the changes in inflammatory-stromal cellular landscape associated with mCRP deposition, we used Co-Detection by Indexing (CODEX) tissue imaging with 31 nucleotide-barcoded antibodies and single-cell-based unsupervised clustering. AAA cases were categorized into High-CRP (<em>n</em> = 6) and Low-CRP (<em>n</em> = 3) groups based on serum levels and immunohistochemistry scores of mCRP. We identified 47 distinct immune and stromal cell types, revealing significant differences in protein expression between groups. In AAA, stromal cells decreased while immune cells increased. High-CRP cases showed increased M1-like and Ki67⁺ proliferating macrophages, and reduced αSMA⁺ cells, whereas Low-CRP cases exhibited intensified fibrosis with CD163⁺Ki67⁺ proliferating M2-like macrophages. Spatial neighborhood enrichment analysis highlighted the close proximity of CD4⁺FOXP3⁺PDL1⁺ T_reg cells to specific clusters: (1) CD57⁺granzyme <em>B</em>⁺ cytotoxic NK cells, (2) CD31⁺HLA-<em>A</em>⁺ endothelial cells, (3) CD45⁺lymphocytes/CD31⁺ endothelial cells, and (4) CD45⁺CD20⁺ <em>B</em> cells in High-CRP cases. Our findings demonstrate the varying distribution of immune cells and vascular wall phenotypes in AAA according to mCRP deposition levels. Targeting inflammation, specifically the immune cells, macrophages, and fibrosis affected by mCRP, may represent a novel approach to halting the pathogenesis of AAA.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 14-30"},"PeriodicalIF":6.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562453","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)00071-4","DOIUrl":"10.1016/S1931-5244(25)00071-4","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Pages iii-iv"},"PeriodicalIF":6.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480557","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)00072-6","DOIUrl":"10.1016/S1931-5244(25)00072-6","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Page IBC"},"PeriodicalIF":6.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480558","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)00070-2","DOIUrl":"10.1016/S1931-5244(25)00070-2","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Page ii"},"PeriodicalIF":6.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480555","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":"PHGDH alleviates DKD by regulating YB1/SLC7A11-mediated ferroptosis in podocytes","authors":"Yinghui Wang ,&nbsp;Qingqing Zhang ,&nbsp;Shasha Lv ,&nbsp;Xueling Wang ,&nbsp;Qingzhen Liu ,&nbsp;Xiangchun Liu ,&nbsp;Yaping Zhang ,&nbsp;Gang Liu","doi":"10.1016/j.trsl.2025.06.001","DOIUrl":"10.1016/j.trsl.2025.06.001","url":null,"abstract":"<div><div>Diabetic kidney disease (DKD) is a main cause of end-stage renal disorder, yet its pathogenesis is still incompletely understood. Ferroptosis has been implicated in DKD progression; however, its regulatory mechanisms remain unclear. Phosphoglycerate dehydrogenase (PHGDH), a key enzyme in serine biosynthesis, has been minimally studied in DKD development. To elucidate the roles of PHGDH in ferroptosis and its underlying mechanism in podocytes and DKD, we conducted this study. Our findings demonstrate that PHGDH deficiency exacerbates podocyte injury, characterized by cytoskeletal disorganization, and promotes ferroptosis in both podocytes and DKD renal tissues. Conversely, PHGDH overexpression alleviates podocyte injury, reduces ferroptosis, and improves renal function in DKD mice. Mechanistically, we identified that PHGDH mediates ferroptosis by regulating SLC7A11 expression, a key ferroptosis-related protein. Specifically, PHGDH stabilizes Y-box binding protein 1 (YB1) by inhibiting its K48-linked ubiquitination and degradation, thereby enhancing SLC7A11 mRNA stability and expression. In conclusion, our study reveals a novel PHGDH-YB1-SLC7A11 regulatory axis that is responsible for suppressing ferroptosis and protecting against podocyte and renal injury in DKD. Our findings shed new light into the molecular mechanism underlying ferroptosis in DKD and highlight PHGDH as a therapeutic target for mitigating ferroptosis-mediated renal damage.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"282 ","pages":"Pages 1-13"},"PeriodicalIF":6.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340733","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":"Epigenetically targeting PRMT5 promotes antitumor immunity by inducing endogenous retroviruses expression and triggering viral mimicry response","authors":"Hua Zhang ,&nbsp;Gang Shi ,&nbsp;Yamei Li ,&nbsp;Chao Wang ,&nbsp;Yong Zhang ,&nbsp;Yan Luo ,&nbsp;Jia Xu ,&nbsp;Yusha Qiu ,&nbsp;Jinhu Ma ,&nbsp;Jin Yang ,&nbsp;Dandan Liao ,&nbsp;Yihua Chen ,&nbsp;Hongxin Deng","doi":"10.1016/j.trsl.2025.05.007","DOIUrl":"10.1016/j.trsl.2025.05.007","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is one of the most common cancers worldwide. Although immune checkpoint blockade (ICB) has transformed CRC treatment, the low response rate and immune resistance remain significant challenges. In recent years, epigenetic therapies have been shown to induce viral mimicry response to overcome immune resistance and increase the effectiveness of ICB. However, as an epigenetic modifier, the intrinsic function of PRMT5 in controlling innate immune signaling, viral mimicry, and the tumor microenvironment in CRC remains to be elucidated. Here, we report that PRMT5 inhibition attenuates CRC growth and epigenetically targeting PRMT5 remolds the tumor immune microenvironment, thereby enhancing the therapeutic efficacy of ICB. Mechanistically, PRMT5 knockdown increases endogenous retroviruses (ERVs) expression and dsRNA formation and causes DNA repair incompetence and genomic instability. These changes, combined with the elevated expression of RIG-I/MDA5/STING, trigger innate immune activation and viral mimicry response, thereby facilitating immune cell infiltration and enhancing ICB effectiveness. Furthermore, PRMT5 knockdown reduces H3R2me2s and H3R8me2s levels, and epigenetically promotes innate immune responses. Our study reveals the tumor intrinsic role of PRMT5 in controlling ERVs and innate sensors expression, providing perspectives for the epigenetically targeting of PRMT5 to induce viral mimicry response and enhance antitumor immunity in CRC.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Pages 55-68"},"PeriodicalIF":6.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192640","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":"A novel rabbit model of severe ARDS: Synergistic effects of acid aspiration and harmful mechanical ventilation","authors":"Petra Košútová ,&nbsp;Nikollet Nemcová ,&nbsp;Maroš Kolomazník ,&nbsp;Andrea Čalkovská ,&nbsp;Pavol Mikolka","doi":"10.1016/j.trsl.2025.05.009","DOIUrl":"10.1016/j.trsl.2025.05.009","url":null,"abstract":"<div><h3>Background</h3><div>Acute respiratory distress syndrome (ARDS) is characterised by severe inflammation and pulmonary edema, often leading to respiratory failure. This study aims to develop a stable and relevant rabbit model of severe ARDS using hydrochloric acid (HCl) aspiration and ventilator-induced lung injury (VILI).</div></div><div><h3>Methods</h3><div>Adult New Zealand rabbits were divided into four groups: Saline (<em>n</em> = 9), 1-hit 3.0 (HCl 3 ml/kg, <em>n</em> = 7), 1-hit 6.0 (HCl 6 ml/kg, <em>n</em> = 7), and 2-hit (HCl 3 ml/kg and ventilation with V_T 20 ml/kg, zero PEEP, RR 20-30 bpm, and FiO₂ 1.0 to mimic VILI, <em>n</em> = 14). PaO₂/FiO₂ ratio, oxygenation index, oxygen saturation, PaCO₂, ventilation efficiency index and alveolar-arterial gradient were evaluated every hour for 4 h after induction of lung injury. The <em>post-mortem</em> analysis included total and differential cell counts in bronchoalveolar lavage fluid (BALF), evaluation of lung edema formation, biochemical and histological examination of lung tissue<em>.</em></div></div><div><h3>Results</h3><div>In the 2-hit group, we observed a significant deterioration of all lung function parameters (P/F ratio, oxygenation index, ventilation efficiency index, and alveolar-arterial gradient) compared to the saline group. Similarly, a deterioration was observed in the 1-hit 6.0 group. When analysing the inflammatory profile, we observed significantly increased levels of chemokines and cytokines (TNFα, IL-1β, IL-6, IL-8, ET-1, MCP, H1F, MIP) and oxidative stress parameters (3NT, MDA, AOPP, catalase and GSH/GSSG) in BALF in the 2-hit group compared to the saline group. Intratracheal administration of HCl alone did not have a significant impact on inflammation as the combination of two insults. An increased wet-to-dry lung weight ratio (W/D), indicative of pulmonary edema, was observed in both the 2-hit and 1-hit 6.0 groups compared to the saline group. An increased level of protein content in BALF and total lung injury score were observed in the 2-hit group compared to the saline group, 1-hit 3.0 and 1-hit 6.0.</div></div><div><h3>Conclusion</h3><div>The combination of hydrochloric acid aspiration and ventilator-induced lung injury reliably reproduces key features of severe ARDS, offering a robust and clinically relevant model for investigating its complex pathophysiology and evaluating novel therapeutic interventions.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Pages 43-54"},"PeriodicalIF":6.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192639","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)00060-X","DOIUrl":"10.1016/S1931-5244(25)00060-X","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Page IBC"},"PeriodicalIF":6.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147892","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)00059-3","DOIUrl":"10.1016/S1931-5244(25)00059-3","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Pages iii-iv"},"PeriodicalIF":6.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147891","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}