Translational Research最新文献

{"title":"tiRNA-HAR contributes to ischemic myocardial injury via facilitating HuR-mediated stability of p53","authors":"Changhao Wang ,&nbsp;Yuelin Gao ,&nbsp;Kuiwu Liu ,&nbsp;Yaozhi Zhang ,&nbsp;Zhiyong Sun ,&nbsp;Min Huang ,&nbsp;Zhezhe Qu ,&nbsp;Shuting Yu ,&nbsp;Jiaqi Han ,&nbsp;Zhongting Mei ,&nbsp;Shunkang Dou ,&nbsp;Jianhao Jiang ,&nbsp;Ying Li ,&nbsp;Na Li ,&nbsp;Chuanhao Huang ,&nbsp;Yuechao Dong ,&nbsp;Baofeng Yang ,&nbsp;Weijie Du","doi":"10.1016/j.trsl.2025.04.002","DOIUrl":"10.1016/j.trsl.2025.04.002","url":null,"abstract":"<div><div>Cardiomyocyte death due to heart occlusion of coronary artery is the main driver to myocardial infarction (MI) and subsequent heart failure progression. tsRNA, a small RNA fragment from tRNA, has been shown to be implicated in many physiological and pathological processes by exerting different biological functions, but the roles of tsRNA in ischemic cardiac injury remain to be determined. The present study identified a hypoxia responsive-tiRNA (tiRNA-HAR) was markedly upregulated in ischemic mouse myocardium and hypoxic cardiomyocytes, respectively. Enforced expression of tiRNA-HAR by transfecting its mimic caused and aggravated, while knockdown of tiRNA-HAR mitigated cardiomyocyte apoptosis upon hypoxia. Cardiac specific knockdown of tiRNA-HAR mediated by AAV9 (adeno-associated virus 9) harboring an antisense oligonucleotide reduced cardiomyocytes apoptosis and improved cardiac function after MI. Mechanistically, tiRNA-HAR directly bound to HuR and enhanced the binding capacity of HuR and p53, thereby increasing the stability of p53. Silencing of HuR partially reversed the aggravative effects of tiRNA-HAR overexpression on cardiomyocyte apoptosis in the context of hypoxia. Collectively, our study reveals that tiRNA-HAR play a critical role in regulating cardiomyocytes apoptosis and cardiac injury via targeting HuR/p53 signaling axis after MI, and tiRNA-HAR might be a novel therapeutic target for treatment of ischemic heart disease.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Pages 17-28"},"PeriodicalIF":6.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906469","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":"2025-06-01","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":"Loss of peptidylarginine deiminase 4 mitigates maladaptive cardiac remodeling after myocardial infarction through inhibition of inflammatory and profibrotic pathways","authors":"Michelle Holthaus ,&nbsp;Xiaolin Xiong ,&nbsp;Kaveh Eghbalzadeh ,&nbsp;Clara Großmann ,&nbsp;Simon Geißen ,&nbsp;Fabian Piontek ,&nbsp;Martin Mollenhauer ,&nbsp;Ali T. Abdallah ,&nbsp;Thomas Kamphausen ,&nbsp;Markus Rothschild ,&nbsp;Thorsten Wahlers ,&nbsp;Adnana Paunel-Görgülü","doi":"10.1016/j.trsl.2025.04.003","DOIUrl":"10.1016/j.trsl.2025.04.003","url":null,"abstract":"<div><div>Inflammation and progressive fibrosis represent predictive risk factors for heart failure (HF) development following myocardial infarction (MI). Peptidylargininine deiminase 4 (PAD4) catalyzes the citrullination of arginine residues in polypeptides and has recently been identified as a contributor to HF pathogenesis. This study aimed to evaluate the role of PAD4 in monocytes / macrophages (Mo/Mφ) and cardiac fibroblasts (CFs) for cardiac repair following MI and HF progression. Cardiac <em>Padi4</em> expression significantly increased in mice subjected to MI by permanent coronary artery ligation as well as in humans who died from MI. Transcriptome analysis revealed marked downregulation of inflammation-related genes in infarcted hearts and cardiac Mo/Mφ from global PAD4 knockout (PAD4^−/−) mice on day 7 post-MI accompanied by increased frequency of reparative CD206⁺ macrophages. Mechanistically, pharmacological and genetic PAD4 inhibition abrogated nuclear NF-κB translocation and inflammatory gene expression in bone marrow-derived macrophages (BMDM). Simultaneously, reduced inflammation and diminished cardiac levels of transforming growth factor-β (TGF-β) along with impaired IL-6 / TGF-β signaling in PAD4^−/− CFs were associated with decreased expression of fibrotic genes, reduced collagen deposition, improved cardiac function, and enhanced 28-day survival in PAD4^−/− mice. Strikingly, whereas pharmacological PAD inhibition in the acute phase after MI exacerbated cardiac damage, treatment starting on day 7 ameliorated cardiac remodeling and improved long-term survival in mice. Collectively, we here identified PAD4 as a critical regulator of inflammatory genes in Mo/Mφ and of profibrotic pathways in CFs. Thus, therapeutic approaches directed against PAD4 are promising interventions to alleviate adverse cardiac remodeling and subsequent HF development.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Pages 1-16"},"PeriodicalIF":6.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906470","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":"2025-06-01","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":"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":"2025-06-01","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":"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":"2025-06-01","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":"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":"Role of DNMT3a expression and nuclear translocation under ELAVL1 mediation for dendritic cell function and Th17/Treg balance in COPD","authors":"Dan Huang ,&nbsp;Bin Tang ,&nbsp;Qiugen Li ,&nbsp;Bo Tong ,&nbsp;Na Liu","doi":"10.1016/j.trsl.2025.03.002","DOIUrl":"10.1016/j.trsl.2025.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. The DNA methyltransferase DNMT3a has been implicated in COPD, however its upstream regulation and downstream mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>Relative mRNA and protein levels of indicated genes in lung tissues and dendritic cells (DCs) were tested via qRT-PCR and western blot, respectively. Cellular distribution of DNMT3a in DCs was determined by immunofluorescence staining. COPD mouse model was established by exposing mice to cigarette smoke (CS) via nose. The Th17/Treg cell ratio was examined using flow cytometry. Production of indicated cytokines was assessed by corresponding commercial ELISA kit. Interplay between DACH1 and c-Jun was verified by Co-immunoprecipitation, ChIP and luciferase reporter assays. Methylation level of DACH1 was tested by methylation specific PCR.</div></div><div><h3>Results</h3><div>DNMT3a expression was upregulated and negatively correlated with lung function in COPD patients. CS exposure increased pulmonary DNMT3a in mice. DNMT3a was predominantly expressed in the nucleus and CS exposure promoted its translocation to cytoplasm. RNA binding protein ELAVL1 upregulated DNMT3a expression, induced its nuclear translocation and increased its enzyme activity. DNMT3a promoted Th17 differentiation while inhibited Treg differentiation. DNMT3a methylated DACH1 and inhibited its expression, resulting in c-Jun pathway activation. In vivo DNMT3a knockdown ameliorated lung injury and Th17/Treg imbalance in COPD mice.</div></div><div><h3>Conclusion</h3><div>This study suggests that ELAVL1 regulates DNMT3a expression and nuclear translocation to modulate dendritic cell function and Th17/Treg balance through DACH1/c-Jun pathway in COPD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Pages 1-15"},"PeriodicalIF":6.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631160","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":"Optical coherence tomography for the qualitative analysis of thyroid tissue images: Feasibility, features, and clinical potential","authors":"Yun Shao ,&nbsp;Qianru Xu ,&nbsp;Cuixia Feng ,&nbsp;Yang Liu ,&nbsp;Baolei Jia ,&nbsp;Yuning Song ,&nbsp;Yuxuan Qiu ,&nbsp;Qing Xu ,&nbsp;Yanhong Tai ,&nbsp;Feng Liang","doi":"10.1016/j.trsl.2025.03.003","DOIUrl":"10.1016/j.trsl.2025.03.003","url":null,"abstract":"<div><div>The most important steps in thyroid surgery include distinguishing benign from malignant lesions and identifying the parathyroid glands. Optical coherence tomography (OCT) provides technical support for intraoperative guidance owing to its real-time, three-dimensional imaging capability. Benign and malignant diagnoses can be confirmed with intraoperative frozen sections; however, current approaches are time-consuming and labor-intensive and do not allow comprehensive, nondestructive tissue assessments. This study aimed to explore the use of OCT for imaging the thyroid tissue by verifying its clinical feasibility and qualitatively analyzing the OCT imaging characteristics of pathological thyroid glands. A customized swept-source OCT (SS-OCT) system was used to collect OCT data corresponding to the pathologies of 61 freshly excised tissue blocks containing either benign or malignant lesions from 45 patients. The OCT images were highly consistent with the H&amp;E histological images, verifying the feasibility of OCT in producing suitable images for analysis. The OCT-derived characteristics of the thyroid tissue were as follows: normal thyroid follicles presented with regularly arranged honeycomb structures; follicular nodular disease (FND) was characterized by heterogeneous nodules composed of follicles of different sizes, with multiple nodules also differing in size and consisting of varied reticular structures and a focally solid appearance; lymphocyte aggregation led to a gray‒black appearance in Hashimoto's thyroiditis tumors; and papillary thyroid carcinoma lesions were characterized by a heterogeneous texture and a low penetration depth. These results demonstrate the imaging capabilities of OCT for thyroid tissue with different pathological conditions and its broad prospects for clinical application.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Pages 27-39"},"PeriodicalIF":6.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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}