Translational Research最新文献

{"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}

{"title":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(25)00044-1","DOIUrl":"10.1016/S1931-5244(25)00044-1","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Pages iii-iv"},"PeriodicalIF":6.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886499","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":"Cardioprotective effects of PARP Inhibitors: A meta-analysis of animal studies","authors":"Seong Kyung Kim ,&nbsp;Jae Hyun Kim ,&nbsp;Inyeong Moon ,&nbsp;Jiwon Min ,&nbsp;Jieun Park ,&nbsp;Myeong Gyu Kim","doi":"10.1016/j.trsl.2025.04.004","DOIUrl":"10.1016/j.trsl.2025.04.004","url":null,"abstract":"<div><div>Poly(adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitors are expected to provide benefits to the cardiovascular system. However, the cardioprotective effect of PARP inhibitors has not been systematically reviewed or quantitatively analyzed. This study aimed to assess the cardioprotective effects of PARP inhibitors through a meta-analysis of animal studies. Three databases PubMed, Web of Sciences, and Embase were searched until September 1, 2023. The risk of bias was assessed using SYRCLE’s Risk of Bias. A total of 74 animal studies that investigated the cardiac function of PARP inhibitors compared to placebo or vehicle, were included. Outcome measures were hemodynamic indexes, cardiac contractility, and biomarkers of myocardial injury. Pooled effect size was estimated using a random-effects model with RevMan 5.4. PARP inhibitors were associated with enhanced hemodynamic indexes, including cardiac output (standardized mean difference, 0.86 [95 % CI, 0.54 to 1.17]; <em>p</em> &lt; 0.00001) and stroke volume (0.42 [0.07 to 0.76]; <em>p</em> = 0.02). PARP inhibitors were associated with increased cardiac contractility, including ejection fraction (0.71 [0.42 to 1.01]; <em>p</em> &lt; 0.00001) and fractional shortening (0.96 [0.62 to 1.31]; <em>p</em> &lt; 0.00001). PARP inhibitors were associated with decreased troponin І (-1.42 [-2.16 to -0.68]; <em>p</em> = 0.0002), plasma B-type natriuretic peptide (-0.95 [-1.56 to -0.33]; <em>p</em> = 0.003), creatine kinase (-1.81 [-2.63 to -0.99]; <em>p</em> &lt; 0.0001), and infarct size (-1.58 [-2.01 to -1.14]; <em>p</em> &lt; 0.00001). PARP inhibitors improve cardiac functions and attenuate myocardial injury in animals, which indicate the cardioprotective effects. Further human studies are necessary.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"280 ","pages":"Pages 29-40"},"PeriodicalIF":6.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921176","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":"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":"2025-04-17","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":"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":"2025-04-17","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":"Kv1.3 expression on CD4 (+) T cells promotes interleukin-17A-associated airway inflammation and airway remodeling in asthma","authors":"Bingqing Sun ,&nbsp;Jiangtao Lin","doi":"10.1016/j.trsl.2025.04.001","DOIUrl":"10.1016/j.trsl.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div>Different types of T helper cells play an important role in disease severity and treatment response in patients with asthma. The potassium channel Kv1.3 is a type of potentially therapeutic target in T-cell-mediated inflammatory diseases.</div></div><div><h3>Objective</h3><div>This study aimed to explore the potential of Kv1.3 as a therapeutic target for asthma and to assess the efficacy of the Kv1.3 inhibitor PAP-1 in the treatment of asthma.</div></div><div><h3>Methods</h3><div>Kv1.3 expression on CD4⁺T cells was determined using data from public databases. CD4⁺T cells were isolated from peripheral blood samples obtained from healthy individuals and patients with asthma. The mouse models of OVA-induced asthma and Kv1.3 knockout were established. The underlying mechanism was investigated using mouse splenic CD4⁺T cells and BEAS-2B cells. OVA-induced asthmatic mice were treated with the Kv1.3 selective blocker PAP-1.</div></div><div><h3>Results</h3><div>Based on public data, we determined the distribution of Kv1.3 on CD4⁺T cells, its up-regulation in asthma, and its correlation with Th17/Treg balance. Upregulation of Kv1.3 in CD4⁺T cells was associated with enhanced activation of these cells and airway inflammation in patients and mice with asthma, accompanied by increased IL-17A levels in alveolar lavage fluid. Conversely, Kv1.3 deficiency significantly attenuated airway inflammation, lowered IL-17A levels in bronchoalveolar lavage fluid, and inhibited airway epithelial-mesenchymal transition in asthmatic mice. Furthermore, treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice.</div></div><div><h3>Conclusions</h3><div>Kv1.3 expression on CD4⁺ T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma.</div></div><div><h3>Translational significance</h3><div>Based on our study, Kv1.3 expression on CD4⁺T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma. The treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice. Our discoveries offer novel perspectives for a better understanding of IL-17A-associated airway remodeling in asthma. The development of drugs targeting Kv1.3 holds application value for IL-17A-associated asthma.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Pages 40-54"},"PeriodicalIF":6.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860264","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":"2025-03-25","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":"Soluble ST2 is an early marker and treatment target for hypertensive nephrosclerosis signatured in glomerular mesangial cells","authors":"Jeong Min Cho ,&nbsp;Seong Joon Park ,&nbsp;Young Joo Kim ,&nbsp;Saram Lee ,&nbsp;Sunhwa Lee ,&nbsp;Dha Woon Im ,&nbsp;Semin Cho ,&nbsp;Ran-hui Cha ,&nbsp;Jae Wook Lee ,&nbsp;Dong Ki Kim ,&nbsp;Kook-Hwan Oh ,&nbsp;Kwon Wook Joo ,&nbsp;Yon Su Kim ,&nbsp;Yong Chul Kim ,&nbsp;Seung Hee Yang","doi":"10.1016/j.trsl.2025.03.001","DOIUrl":"10.1016/j.trsl.2025.03.001","url":null,"abstract":"<div><div>The absence of a biologic marker for hypertensive nephrosclerosis (HN) remains a challenge. This study aimed at exploring the relationship between sST2 and early HN and examining their interaction in glomerular mesangial cells. The serum sST2 levels of healthy controls (HC; n=9), patients with HN (n=15), and patients with lupus nephritis (LN; n=27) were measured using ELISA. The association between the serum sST2 levels and clinicopathologic characteristics, including kidney function and mesangial proliferation, were assessed. The expression of ST2 and fibrotic markers in glomerular mesangial cells in hypertensive conditions was evaluated using a 5/6 nephrectomy rat model. To mimic intraglomerular hypertension, human primary glomerular mesangial cells (hPGMCs) were subjected to a 3-mmHg pressure using a newly developed mechanical pressurizing device. The cells were then treated with anti-ST2 antibody (0.5 and 1 μg/mL) to examine inflammation, apoptosis, and necrosis. The serum sST2 levels were significantly higher in the HN and LN groups than in the HC group. Increased expression of ST2 and fibrotic markers in glomerular mesangial cells was observed in the hypertension-induced animal model. In the <em>in vitro</em> study, pressure-stimulated hPGMCs exhibited increased population of early and late apoptosis, which were markedly reduced after treatment with anti-ST2 antibody (1.0 μg/mL). ST2 indicates the early pathologic changes of hypertensive kidney damage and may serve as a mesangial cell-specific marker for HN in terms of determining kidney function and pathologic findings. Thus, ST2 blockade could be a novel therapeutic approach for HN.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"279 ","pages":"Pages 16-26"},"PeriodicalIF":6.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653032","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}