Translational Research最新文献

{"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}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S1931-5244(25)00058-1","DOIUrl":"10.1016/S1931-5244(25)00058-1","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Page ii"},"PeriodicalIF":6.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147890","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":"Predictive modeling of ARDS mortality integrating biomarker/cytokine, clinical and metabolomic data","authors":"Ruslan Rafikov ,&nbsp;Debrah M. Thompson ,&nbsp;Olga Rafikova ,&nbsp;Sara M. Camp ,&nbsp;Roberto A. Ribas ,&nbsp;Ramon C. Sun ,&nbsp;Matthew S. Gentry ,&nbsp;Nancy G. Casanova ,&nbsp;Joe G N Garcia","doi":"10.1016/j.trsl.2025.05.005","DOIUrl":"10.1016/j.trsl.2025.05.005","url":null,"abstract":"<div><div>Acute Respiratory Distress Syndrome (ARDS), characterized by the rapid onset of respiratory failure and mortality rates of ∼40%, remains a significant challenge in critical care medicine. Despite advances in supportive care, accurate prediction of ARDS mortality remains challenging, resulting in delayed delivery of targeted interventions and effective disease management. Traditional critical illness severity scores lack specificity for ARDS, underscoring the need for more precise prognostic tools for ARDS mortality. To address this crucial gap, we employed a multimodal approach to predict ARDS patients utilizing a comprehensive dataset comprised of integrated clinical, metabolomic, and biochemical/cytokine data from ARDS patients (collected within hours of ICU admission) to develop and validate predictive models of ARDS mortality risk. The most robust multimodal data model generated demonstrated superior predictive capability with an area under the curve (AUC) of 0.868 on the test set and 0.959 on the validation set. Notably, this model achieved perfect specificity in identifying non-survivors in the validation cohort, highlighting potential utility in guiding early and targeted interventions in ICU settings. Metabolomic analysis revealed significant alterations in crucial pathways associated with ARDS mortality with tryptophan metabolism, particularly the kynurenine pathway, emerging as the most significantly enriched metabolic route, as well as the NAD+ metabolism/nicotinamide phosphoribosyltransferase (NAMPT) and glycosaminoglycan biosynthesis pathways. These metabolic derangements were strongly confirmed by lipidomic/metabolomic analysis of lung tissues from a porcine sepsis/ARDS model. Together, these findings demonstrate the promise of integrating multimodal data to improve ARDS prognostication and to provide important insights into the complex metabolic derangements underlying severe ARDS. Identification of metabolic signatures, such as kynurenine and NAD+ metabolism/NAMPT pathways, may serve as a foundation for developing personalized and effective targeted interventions and management strategies for ARDS patients.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Pages 31-42"},"PeriodicalIF":6.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153286","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":"sFRP5 ameliorates atherosclerosis by suppressing the JNK/TLR9 pathway in macrophages","authors":"Yue Yu ,&nbsp;Han Chen ,&nbsp;Rui Wang ,&nbsp;Fei Xu,&nbsp;Jiasheng Yin,&nbsp;Tongtong Zang,&nbsp;Changyi Zhou,&nbsp;Chengpeng Liu,&nbsp;Chaofu Li,&nbsp;Li Shen,&nbsp;Junbo Ge","doi":"10.1016/j.trsl.2025.05.004","DOIUrl":"10.1016/j.trsl.2025.05.004","url":null,"abstract":"<div><div>Secreted frizzled related protein 5 (sFRP5), an anti-inflammatory adipokine, plays a crucial role in various diseases, and its serum levels are low in patients with coronary artery disease (CAD). However, its role in atherosclerosis remains unclear. Therefore, we investigated the correlation between sFRP5 and plaque stability, along with the molecular mechanisms underlying atherosclerosis. In patients with CAD, serum sFRP5 levels were positively correlated with plaque stability, a predictor of thin-cap fibroatheromas (TCFAs). Recombinant sFRP5 (r-sFRP5) supplementation significantly increased plaque stability and ameliorated atherosclerosis progression in <em>ApoE^-/-</em> mice. Aortic RNA-sequencing (RNA-seq) revealed sFRP5-mediated regulation in inflammatory cells. Our experiments confirmed that sFRP5 inhibits inflammation and macrophage migration. Mechanistically, Toll-like receptor 9 (TLR9) was identified as a downstream target of sFRP5, and sFRP5 suppressed TLR9 expression by decreasing c-Jun N-terminal kinase (JNK) phosphorylation. These findings suggest that serum sFRP5 levels are associated with plaque stability and play a protective role in atherosclerosis by attenuating inflammation and macrophage infiltration via inhibition of the JNK/TLR9 pathway, thereby ameliorating the progression of atherosclerosis. This study highlights the potential of sFRP5 as both a biomarker and therapeutic target for plaque stability in atherosclerosis.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Pages 1-13"},"PeriodicalIF":6.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133401","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":"Mechanism of adipose-derived stem cell-derived extracellular vesicles affecting macrophage efferocytosis by mediating ADAM17/MerTK in the apoptosis of tubular epithelial cells after sepsis-associated acute kidney injury","authors":"Zhixiang Bian,&nbsp;Xiangxiang Wang,&nbsp;Xiaoxuan Su,&nbsp;Ming Yang,&nbsp;Rui Zhu,&nbsp;Shunjie Chen","doi":"10.1016/j.trsl.2025.05.002","DOIUrl":"10.1016/j.trsl.2025.05.002","url":null,"abstract":"<div><h3>Objective</h3><div>This study explored the molecular mechanism of adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) improving post-sepsis-associated acute kidney injury (S-AKI) tubular epithelial cell (TEC) apoptosis by modulating ADAM17/MerTK-mediated macrophage efferocytosis.</div></div><div><h3>Methods</h3><div>The S-AKI mouse model was established by caecal ligation and puncture and intravenously injected with ADSC-EVs. Mouse kidney macrophages were cultured with LPS, cultured with EVs while transfecting with oe-ADAM17 or si-MerTK, then incubated with Jurkat cells. Mouse serum urea and creatinine, and KIM-1, efferocytosis- and apoptosis-related protein, inflammatory factor, cytokine, and soluble MerTK (sMerTK) levels were determined using colorimetric assay, immunohistochemistry, Western blot, and ELISA. Renal tubular injury, TEC apoptosis, macrophage efferocytosis, and M1/M2 polarization levels were assessed via HE staining, TUNEL staining, immunofluorescence, and flow cytometry, respectively. <em>In vivo</em> validation experiments were conducted.</div></div><div><h3>Results</h3><div>S-AKI mice displayed elevated levels of serum urea, creatinine, KIM-1, pro-inflammatory factors, pro-apoptotic proteins and ADAM17 protein, decreased anti-apoptotic protein and MerTK protein levels, and diminished M2 polarization. ADSC-EVs down-regulated ADAM17 and sMerTK, and increased cell membrane MerTK, macrophage recognition of apoptotic cells and efferocytosis, and M2 polarization in renal tissues of S-AKI mice and LPS-induced mouse renal macrophages, indicating that ADSC-EVs regulated ADAM17/MerTK-mediated macrophage efferocytosis and promoted M2 polarization. MerTK silencing partially reversed ADSC-EVs-regulated LPS-induced mouse renal macrophage efferocytosis and M2 polarization. <em>In vivo</em>, ADAM17 upregulation partly averted ADSC-EVs-regulated post-S-AKI TEC apoptosis in mouse renal tissues.</div></div><div><h3>Conclusion</h3><div>ADSC-EVs down-regulated sMerTK level and up-regulated macrophage membrane MerTK protein level by modulating ADAM17 to promote macrophage efferocytosis and ameliorate post-S-AKI TEC apoptosis and inflammation.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"281 ","pages":"Pages 14-30"},"PeriodicalIF":6.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129922","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":"Modeling diabetic epitheliopathy using 3D-Organotypic corneal epithelium","authors":"Grazia Maugeri ,&nbsp;Agata Grazia D’Amico ,&nbsp;Salvatore Saccone ,&nbsp;Francesca Bruno ,&nbsp;Elisabetta Pricoco ,&nbsp;Davide Scollo ,&nbsp;Teresio Avitabile ,&nbsp;Antonio Longo ,&nbsp;Velia D’Agata","doi":"10.1016/j.trsl.2025.05.003","DOIUrl":"10.1016/j.trsl.2025.05.003","url":null,"abstract":"<div><div>Diabetic keratopathy (DK) is a degenerative corneal disease occurring in more than 50 % of diabetic patients. DK is correlated with the hyperglycemic state causing morphological and functional changes in corneal layers. Currently, most studies on the cornea are performed on two-dimensional (2D) cultures <em>in vitro</em> or animal models. Although 2D culture models can provide large amounts of data at low cost, they poorly represent the complex pathophysiology of the human cornea and hardly predict <em>in vivo</em> responses that can be achieved with animal model studies. However, the use of the latter presents ethical problems. Therefore, it is necessary to identify new strategies and models that can integrate the information validly and effectively, to reduce the number of animals used. Here, we used human corneal epithelial cells (hCECs) derived from donor cornea differentiated into three-dimensional (3D)-organotypic air-liquid interface (ALI), which resemble the features of the corneal epithelium. The 3D-organotypic ALI corneal epithelium was subjected to high-glucose conditions to generate a model of diabetic epitheliopathy. Our model showed well-established molecular and cellular characteristics of this pathology, such as epithelial defects and inflammation, with increased expression of IL-1β, TNF-<span><math><mi>α</mi></math></span>, p-NF-kB, COX-2, MMP-2 and MMP-9. The data provided highlight the utility of 3D-organotypic corneal epithelium in modeling diabetic epitheliopathy, offering new avenues in drug screening, as well as in precision and personalized medicine.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Pages 55-63"},"PeriodicalIF":6.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103120","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":"Abundance of dopamine and its receptors in the brain and adipose tissue following diet-induced obesity or caloric restriction","authors":"Fleur W Hukema ,&nbsp;Susanne Hetty ,&nbsp;Christakis Kagios ,&nbsp;Sofia Zelleroth ,&nbsp;Giovanni Fanni ,&nbsp;Maria J Pereira ,&nbsp;Maria K Svensson ,&nbsp;Magnus Sundbom ,&nbsp;Anna Nilsson ,&nbsp;Per E Andrén ,&nbsp;Erika Roman ,&nbsp;Jan W Eriksson","doi":"10.1016/j.trsl.2025.05.001","DOIUrl":"10.1016/j.trsl.2025.05.001","url":null,"abstract":"<div><div>While obesity and type 2 diabetes (T2D) are associated with altered dopaminergic activity in the central nervous system and in adipose tissue (AT), the directions and underlying mechanisms remain inconclusive. Therefore, we characterized changes in the abundance of dopamine, its metabolites, and receptors DRD1 and DRD2 in the brain and AT upon dietary intervention or obesity. Male Wistar rats were fed either a standard pellet diet, a cafeteria diet inducing obesity and insulin resistance, or a calorie-restricted diet for 12 weeks. Abundance of dopamine and its receptors DRD1 and DRD2 were examined in brain regions relevant for feeding behavior and energy homeostasis. Furthermore, DRD1 and DRD2 protein levels were analyzed in rat inguinal and epidydimal AT and in human subcutaneous and omental AT from individuals with or without obesity. Rats with diet-induced obesity displayed higher dopamine levels, as well as DRD1 or DRD2 receptor levels in the caudate putamen and the nucleus accumbens core. Surprisingly, caloric restriction induced similar changes in DRD1 and DRD2, but not in dopamine levels, in the brain. Both diets reduced DRD1 abundance in inguinal and epidydimal AT, but upregulated DRD2 levels in inguinal AT. Furthermore, in human obesity, DRD1 protein levels were elevated only in omental AT, while DRD2 was upregulated in both omental and subcutaneous AT. These findings highlight dopaminergic responses to changes in energy balance, occurring both in the brain and AT. We propose that dopaminergic pathways are involved in tissue crosstalk during the development of obesity and T2D.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Pages 41-54"},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948444","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)00045-3","DOIUrl":"10.1016/S1931-5244(25)00045-3","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Page IBC"},"PeriodicalIF":6.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886500","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)00043-X","DOIUrl":"10.1016/S1931-5244(25)00043-X","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Page ii"},"PeriodicalIF":6.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886498","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}