Translational Research最新文献

{"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}

{"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":"2025-03-12","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":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(25)00031-3","DOIUrl":"10.1016/S1931-5244(25)00031-3","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Pages iii-iv"},"PeriodicalIF":6.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580081","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)00032-5","DOIUrl":"10.1016/S1931-5244(25)00032-5","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Page IBC"},"PeriodicalIF":6.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580082","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)00030-1","DOIUrl":"10.1016/S1931-5244(25)00030-1","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Page ii"},"PeriodicalIF":6.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580080","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":"Caspase-12 exhibits non-redundant functions in response to endoplasmic reticulum stress to promote GSDMD-mediated NETosis, leading to thoracic aortic dissection","authors":"Hanchuan Chen ,&nbsp;Kun Yang ,&nbsp;Shumin Zhang ,&nbsp;Gulinazi Yesitayi ,&nbsp;Yunzhi Ling ,&nbsp;Rifeng Gao ,&nbsp;Yang Lyu ,&nbsp;Wei Wei ,&nbsp;Jiaran Shi ,&nbsp;Yulin Li ,&nbsp;Xiang Ma ,&nbsp;Pingjin Gao ,&nbsp;Junbo Ge ,&nbsp;Aijun Sun","doi":"10.1016/j.trsl.2025.02.005","DOIUrl":"10.1016/j.trsl.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Thoracic aortic dissection (TAD) is a highly lethal condition that is characterized by inflammatory cell infiltration. Recent evidence has indicated that Gasdermin D (GSDMD) plays an important role in vascular inflammation and degeneration. However, its effects on neutrophil extracellular trap formation and release (NETosis) during TAD remain unknown.</div></div><div><h3>Methods</h3><div>A TAD mouse model was generated using four-week-old male neutrophil-specific <em>GSDMD</em>-knockout mice (<em>GSDMD</em>^F/F; <em>Elane</em>^Cre) and dimethyl fumarate (DMF)-treated C57BL/6J mice by administering β-aminopropionitrile monofumarate (BAPN; 1 g/kg/day) in their drinking water for 4 weeks. Immunoprecipitation and immunofluorescence assays were performed to examine the role of the endoplasmic reticulum (ER) and its associated protein, caspase-12, in GSDMD-induced NETosis.</div></div><div><h3>Results</h3><div>GSDMD was elevated and co-localized primarily in neutrophils in the aortic tissues of patients with TAD and mice with BAPN-induced TAD. This was accompanied by increased NETosis. Neutrophil-specific <em>GSDMD</em> knockout and the NETosis inhibitor, GSK484, mitigated TAD development in mice. However, GSK484 did not provide additional therapeutic effects against TAD in the neutrophil-specific, <em>GSDMD</em> knockout mice. Mechanistically, ER stress promoted GSDMD cleavage by caspase-4/11, thereby inducing NETosis. Furthermore, caspase-12 exhibited non-redundant functions in the cleavage of GSDMD by caspase-4/11. The GSDMD inhibitor, DMF, partially prevented TAD development.</div></div><div><h3>Conclusions</h3><div>The ER stress/GSDMD/NETosis signaling pathway provides a potential therapeutic target for the prevention and treatment of TAD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Pages 48-60"},"PeriodicalIF":6.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525472","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":"Effects of senotherapeutics on gut microbiome dysbiosis and intestinal inflammation in Crohn's disease: A pilot study","authors":"Nannapat Sangfuang ,&nbsp;Laura E. McCoubrey ,&nbsp;Atheer Awad ,&nbsp;Massimo Marzorati ,&nbsp;Jonas Ghyselinck ,&nbsp;Lynn Verstrepen ,&nbsp;Julie De Munck ,&nbsp;Jelle De Medts ,&nbsp;Simon Gaisford ,&nbsp;Abdul W. Basit","doi":"10.1016/j.trsl.2025.02.004","DOIUrl":"10.1016/j.trsl.2025.02.004","url":null,"abstract":"<div><div>Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, and is usually accompanied by dysbiosis in the gut microbiome, a factor that contributes to disease progression. Excessive production of reactive oxygen species (ROS) because of gut microbiome dysbiosis—one of the hallmark features of IBD—promotes chronic inflammation and facilitates the transformation of normal cells into senescent cells. Cellular senescence is associated with the development of various chronic and age-related diseases. We hypothesise that senolytic agents, specifically dasatinib (D) and quercetin (Q), could have a beneficial effect on both the gut microbiome and intestinal cells in IBD. The modulatory effects of a combination of <em>D</em> + <em>Q</em> was assessed in the M-SHIME model with faecal microbiota sourced from Crohn's disease patients. <em>D</em> + <em>Q</em> significantly modulated butyrate and lactate levels in the samples from specific patients. In addition, metabolomic analysis showed that <em>D</em> + <em>Q</em> positively impacted the abundance of anti-inflammatory bacteria while also significantly reducing the several species of pathogenic bacteria. Findings from a Caco-2 cell/THP1 co-culture model of IBD demonstrated that <em>D</em> + <em>Q</em> exerted strong immunomodulatory effects on the gut epithelium, evidenced by reduced NF-kB activity, and lower levels of the pro-inflammatory markers TNF-α, CXCL-10, and MCP-1. Furthermore, <em>D</em> + <em>Q</em> induced the secretion of anti-inflammatory cytokines, including IL-6 and IL-10. However, it should be noted that <em>D</em> + <em>Q</em> also led to the secretion of the pro-inflammatory cytokines IL-8. These findings suggest that <em>D</em> + <em>Q</em> could offer a novel therapeutic approach for advanced IBD management by modulating both the gut microbiome and inflammatory pathways. The results support the potential repurposing of senotherapeutic agents as a strategy for addressing the chronic inflammation central to IBD pathogenesis</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Pages 36-47"},"PeriodicalIF":6.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474855","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":"Tailored CD4+ lymphocytes expressing human CHAT protein as a novel vasodilator in attenuating RV pressure in PAH animal model","authors":"Akash Gupta ,&nbsp;Nahla Zaghloul ,&nbsp;Senthil Kumar Thulasingam ,&nbsp;Ian Richard Robbins ,&nbsp;Geetanjali Gupta ,&nbsp;Jad Bader ,&nbsp;Joe GN Garcia ,&nbsp;Mohamed Ahmed","doi":"10.1016/j.trsl.2025.02.001","DOIUrl":"10.1016/j.trsl.2025.02.001","url":null,"abstract":"<div><div>ChAT-expressing T cells represent ∼0.01 % of total circulating T lymphocytes in adult wild-type mice. However, we previously reported that systemic infusion of ChAT+ve Jurkat T cells into adult mice elicits vasodilation and instantaneous decline in the mean systolic blood pressure, suggesting potential as a biologic therapeutic to attenuate pathologic increases in pulmonary arterial pressures. We now report that ChAT gene-expressing Jurkat cells dose-dependently decrease right ventricular systolic pressures (RVSP) in hypoxic mice and that transgenic mice with ChAT KO restricted to endothelial cells (KO END/ChAT-/-) exhibit significantly elevated pulmonary arterial pressure and peripheral systemic resistance (compared to WT mice). To rigorously characterize the role of CD4 ChAT+ T cells in regulating pulmonary arterial hypertension (PAH) hemodynamics and molecular signatures, we infused CD4+ ChAT+ve cells (0.5 to 2.0 million cells/animal) into adult PAH mice and noted significant reductions in RVSP within 2-3 min post injection (∼ 50 % reduction). The tailored tail vein injection effect was sustained until the animal was euthanized (30-40 min). Mice KO END/ChAT-/-showed a significant and severe hypoxia-induced PAH phenotype compared to WT adult mice. Tail vein injection of biologically active CD4 ChAT+ve cells into either KO END/ChAT-/-mice with hypoxia-induced PAH or into adult rats with hypoxia/Sugen-induced PAH resulted in significant attenuation of RVP elevations. RNA seq data analysis of human pulmonary endothelial cells (HPAECs) incubated with CD4 ChAT+ve T cells showed significant differential regulation of pathways involved in systemic and pulmonary pressure regulation, NO synthesis/regulation, antioxidant expression, and vasodilation. In conclusion, CD4 ChAT+ve T cells have a unique, vasodilating innate immunity mechanism to augment nitric oxide release and potentially mitigate molecular and genetic pathways involved in PAH pathogenesis.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Pages 22-35"},"PeriodicalIF":6.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443109","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":"Macrophage-driven inflammation in acute kidney injury: Therapeutic opportunities and challenges","authors":"Ya-Fan Mu ,&nbsp;Zi-Hui Mao ,&nbsp;Shao-Kang Pan ,&nbsp;Dong-Wei Liu ,&nbsp;Zhang-Suo Liu ,&nbsp;Peng Wu ,&nbsp;Zhong-Xiuzi Gao","doi":"10.1016/j.trsl.2025.02.003","DOIUrl":"10.1016/j.trsl.2025.02.003","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is increasingly being recognized as a systemic disorder associated with significant morbidity and mortality. AKI manifests with extensive cellular damage, necrosis, and an intense inflammatory response, often leading to late-stage interstitial fibrosis. Although the mechanisms underlying renal injury and repair remain poorly understood, macrophages (pivotal inflammatory cells) play central roles in AKI. They undergo polarization into pro-inflammatory and anti-inflammatory phenotypes, contributing dynamically to both the injury and repair processes while maintaining homeostasis. Macrophages modulate microenvironmental inflammation by releasing extracellular vesicles (EVs) containing pro- or anti-inflammatory signaling molecules, thereby influencing the regulation of tissue injury. The injured tissue cells release EVs and activate local macrophages to initiate these responses. Our bibliometric analysis indicated that a shift has occurred in AKI macrophage research towards therapeutic strategies and clinical translation, focusing on macrophage-targeted therapies, including exosomes and nanoparticles. This review highlights the roles and mechanisms of macrophage activation, phenotypic polarization, and trans-differentiation in AKI and discusses macrophage-based approaches for AKI prevention and treatment. Understanding the involvement of macrophages in AKI contributes to the comprehension of related immune mechanisms and lays the groundwork for novel diagnostic and therapeutic avenues.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"278 ","pages":"Pages 1-9"},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418852","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}