Translational Research最新文献

{"title":"Peripheral PD-1⁺ T cell signatures predict immunotherapy response and survival in hepatobiliary cancers","authors":"Mingjian Piao ,&nbsp;Jiayu Xiao ,&nbsp;Nan Zhang ,&nbsp;Chengjie Li ,&nbsp;Jiongyuan Li ,&nbsp;Lihua Guan ,&nbsp;Shuofeng Li ,&nbsp;Zhe Zhu ,&nbsp;Shi Feng ,&nbsp;Boyu Sun ,&nbsp;Dandan Li ,&nbsp;Xuzhen Qin ,&nbsp;Ling Qiu ,&nbsp;Haitao Zhao","doi":"10.1016/j.trsl.2026.01.004","DOIUrl":"10.1016/j.trsl.2026.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) have shown efficacy in hepatobiliary malignancies; however, reliable biomarkers for predicting treatment response remain limited. Peripheral PD-1⁺ T cells, which reflect both T-cell exhaustion and reinvigoration, may serve as novel immune correlates of clinical benefit.</div></div><div><h3>Methods</h3><div>We prospectively enrolled 99 patients with advanced hepatocellular carcinoma (HCC) or biliary tract cancer (BTC) who received ICIs at Peking Union Medical College Hospital between December 2023 and December 2024. Peripheral blood was collected at baseline and during treatment for flow cytometric quantification of PD-1⁺ T-cell subsets. Patients were randomly divided into a training cohort (n=69) and a validation cohort (n=30). Survival outcomes were analyzed using the Kaplan–Meier method. Baseline predictors were identified by least absolute shrinkage and selection operator (LASSO) regression, followed by nomogram construction.</div></div><div><h3>Results</h3><div>Responders exhibited significantly longer progression-free survival (PFS; 16.4 vs. 3.5 months, p&lt;0.001) and overall survival (OS; not reached vs. 10.8 months, p&lt;0.001) than non-responders. Higher baseline CD3⁺PD-1⁺ T-cell percentages (32.8% vs. 24.5%, p&lt;0.001) and lower neutrophil-to-lymphocyte ratios (NLR, p=0.002) characterized responders. LASSO regression identified cirrhosis, CD3⁺PD-1⁺ T-cell percentage, and NLR as independent predictors (AUC 0.846 training; 0.670 validation). Longitudinal analysis showed that decreased PD-1⁺ T-cell levels post-treatment correlated with clinical response, while a post-/pre-treatment CD8⁺PD-1⁺ T-cell ratio above 0.07 predicted inferior PFS.</div></div><div><h3>Conclusions</h3><div>Baseline and dynamic circulating PD-1⁺ T-cell profiles robustly predict ICI response and survival in hepatobiliary cancers, supporting their potential as noninvasive biomarkers for individualized immunotherapy.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"288 ","pages":"Pages 12-20"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044383","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":"Ligand–receptor hotspots in dendritic–T cell niches expose targets in autoimmunity","authors":"Caio Santos Bonilha","doi":"10.1016/j.trsl.2026.01.006","DOIUrl":"10.1016/j.trsl.2026.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Dendritic cell–T cell (DC–T) co-signalling pathways are central switches directing immunity, tolerance, or evasion. Despite characterisation of known pathways, additional mediators that may contribute uniquely to regulating T-cell responses remain to be defined.</div></div><div><h3>Objective</h3><div>To identify emerging mediators of DC–T communication associated with autoimmune skin inflammation.</div></div><div><h3>Methods</h3><div>Spatial transcriptomic data from atopic dermatitis (AD) and psoriasis (PsO) skin were integrated with single-cell RNA sequencing to resolve ligand–receptor (LR) networks operating at DC–T interaction sites, including regions of DC–T co-occupation, defined as spots simultaneously enriched for DC and T-cell transcriptional signatures. LR-based ranking was used to prioritise canonical and emerging co-signalling mediators linked to autoimmune inflammation, which were subsequently validated in independent spatial and CITE-seq datasets.</div></div><div><h3>Results</h3><div>Top-ranked genes F11R and CDH3 localised to the epidermis, an area enriched in highly interactive DC–T regions, and correlated with PsO severity, establishing a link between spatial communication strength and clinical outcome. Among these, F11R also associated with cytokine signalling in severe PsO, linking its spatial enrichment to enhanced inflammatory states within interaction-rich niches. CITE-seq analysis showed that F11R RNA and protein expression correlate in PsO patients, with no upregulation observed in circulating DCs or T cells. In contrast, both F11R and co-signalling molecules were elevated in the arthritic form of the disease, characterised by systemic immune activation.</div></div><div><h3>Conclusion</h3><div>This study establishes a spatial framework for identifying immune communication mediators and highlight F11R as a potential target linked to autoimmune skin inflammation severity.</div></div><div><h3>Capsule summary</h3><div>Mapping dendritic–T cell communication in psoriasis identifies F11R as a spatially enriched signature associated with disease severity, offering insight into local immune amplification and highlighting potential targets for precision modulation of autoimmune inflammation.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"288 ","pages":"Pages 21-32"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081012","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":"IgG from anti-MDA5⁺ CADM patients impairs NK cell function via CD16 in RP-ILD","authors":"Yiying Yang ,&nbsp;Ke Liu ,&nbsp;Muyuan Li ,&nbsp;Caiyan Li ,&nbsp;Li Wang ,&nbsp;Meidong Liu ,&nbsp;Hui Luo ,&nbsp;Yisha Li ,&nbsp;Xiaoxia Zuo ,&nbsp;Quanzhen Li ,&nbsp;Chuyi Tan ,&nbsp;Huali Zhang","doi":"10.1016/j.trsl.2026.01.003","DOIUrl":"10.1016/j.trsl.2026.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate natural killer (NK) cell dysfunction in anti-MDA5 autoantibody-positive (anti-MDA5⁺) clinically amyopathic dermatomyositis (CADM) patients with rapidly progressive interstitial lung disease (RP-ILD), and explore potential mechanisms related to macrophage activation.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from anti-MDA5⁺ CADM and anti-Jo1-positive (anti-Jo-1⁺) dermatomyositis patients were profiled using the Illumina HT-12 v4 chip. Cytokine profiles were analyzed using ELISA, and flow cytometry was performed to assess PBMC subsets, NK cell cytotoxicity, and the activation of PLC-γ2 and MAPK signaling. IgG purified from patient serum was used to assess antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) in THP-1/THP-1–like macrophages under poly(I:C) stimulation.</div></div><div><h3>Results</h3><div>Anti-MDA5⁺ CADM patients exhibited downregulated expression of NK cell activation receptor genes and elevated cytokines such as sCD163 and ferritin compared to anti-Jo-1⁺ patients. NK cell percentages in PBMCs were prominently decreased in anti-MDA5⁺ patients with RP-ILD compared to those without, and NK cell cytotoxicity or degranulation was weakened, as shown by decreased CD107a and perforin expression, while monocyte populations were increased in RP-ILD patients. IgG purified from anti-MDA5⁺ patient serum impaired NK-cell degranulation <em>in vitro</em> and enhanced ADCC/ADCP activity of THP-1 macrophages following poly(I:C) stimulation. These effects were reduced by CD16 knockdown, indicating involvement of FcγRIII (CD16) dependent interactions. PBMCs from RP-ILD patients exhibited hypophosphorylation of PLCγ2 and ERK, along with hyperphosphorylation of p38, consistent with altered downstream signaling associated with CD16 engagement.</div></div><div><h3>Conclusion</h3><div>NK-cell dysfunction and enhanced macrophage activation in anti-MDA5⁺ CADM patients with RP-ILD are associated with dysregulated CD16-dependent IgG–cell interactions and perturbations in downstream PLCγ2–MAPK signaling. These findings highlight FcγR-mediated immune dysregulation as a potential contributor to the severe inflammatory phenotype characteristic of RP-ILD, while not establishing antigen-specific mechanisms.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"288 ","pages":"Pages 1-11"},"PeriodicalIF":5.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039944","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":"Predicting exercise pulmonary hypertension: the right-net machine learning model a pilot study","authors":"Francesco Ferrara ,&nbsp;Rossana Castaldo ,&nbsp;Luna Gargani ,&nbsp;Nicola Benjamin ,&nbsp;Andreina Carbone ,&nbsp;Erberto Carluccio ,&nbsp;Antonio Cittadini ,&nbsp;Veronica Codullo ,&nbsp;Anna D’Agostino ,&nbsp;Michele D’Alto ,&nbsp;Ekkehard Grünig ,&nbsp;Alessandra Maria Esposito ,&nbsp;Giovanni Esposito ,&nbsp;Stefano Ghio ,&nbsp;Jaroslaw D. Kasprzak ,&nbsp;Graziella Lacava ,&nbsp;Alberto Maria Marra ,&nbsp;Marco Matucci-Cerinic ,&nbsp;Antonella Moreo ,&nbsp;Eugenio Picano ,&nbsp;Monica Franzese","doi":"10.1016/j.trsl.2025.12.007","DOIUrl":"10.1016/j.trsl.2025.12.007","url":null,"abstract":"<div><h3>Background</h3><div>Exercise-transthoracic Doppler echocardiography (Ex-TTE) determination of mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope may offer key diagnostic and prognostic information in cardiorespiratory diseases. However, its applicability and reliability in routine clinical practice remain to be established. Herein, the aim of the present study was to apply a machine learning (ML) model to predict abnormal exercise TTE-derived mPAP/CO slope (&gt;3 mmHg/L·min) in individuals at risk of pulmonary hypertension (PH), based only on clinical and resting TTE parameters.</div></div><div><h3>Methods</h3><div>The study population (221 healthy adults and 196 patients with connective tissue disease) was grouped according to mPAP/CO slope ≤3 vs. &gt;3 mmHg/L·min (<em>n</em> = 222 and <em>n</em> = 195, respectively). Three different ML models (Elastic Net-Regularized Generalized Linear Model, Classification and Regression Tree, LogitBoost) were trained on resting clinical and TTE parameters to predict mPAP/CO slope &gt;3 mmHg/L·min. Data were split into training/test sets to evaluate performance. The model with the highest area under the curve (AUC) on the test set was selected.</div></div><div><h3>Results</h3><div>The Elastic Net model achieved the best performance (AUC=0.92). Lower tricuspid annular plane systolic excursion/systolic PAP ratio, female sex, and smaller left ventricular outflow tract diameter were the key features predicting TTE-derived mPAP/CO slope &gt;3 mmHg/L·min.</div></div><div><h3>Conclusions</h3><div>An ML algorithm using resting clinical and TTE parameters can effectively predict exercise TTE-derived mPAP/CO slope &gt;3 mmHg/L·min, supporting its use as a noninvasive tool to identify individuals at risk of exercise PH.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Pages 12-21"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890849","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":"B-cell activation underpins Rituximab response in focal segmental glomerulosclerosis","authors":"Liangjian Lu ,&nbsp;Chang Yien Chan ,&nbsp;Mya Than ,&nbsp;Sharon Teo ,&nbsp;Perry YW Lau ,&nbsp;Kong-Peng Lam ,&nbsp;Kar Hui Ng ,&nbsp;Hui Kim Yap","doi":"10.1016/j.trsl.2026.01.002","DOIUrl":"10.1016/j.trsl.2026.01.002","url":null,"abstract":"<div><div>The pathogenesis of primary focal segmental glomerulosclerosis (FSGS) is incompletely understood, and outcomes remain poor. Some patients respond to Rituximab, especially patients who have hyporesponsive T-cells, but the underlying mechanism is unknown. This study aimed to investigate the association between B-cell activation and T-cell hypo-responsiveness as well as Rituximab response. A cohort of 33 patients with childhood-onset FSGS receiving Rituximab were recruited. T-cell hypo-responsiveness was defined as stimulated T-cell IFNγ &lt;2.5%, and B-cell activation was characterized by CD80 expression and cytokine production. T-cell hypo-responsiveness was associated with Rituximab response (OR: 5.4 (95% CI: 1.2-25), <em>p</em> = 0.028). Compared to T-cell normo-responsive patients, T-cell hypo-responsive patients had elevated activated CD19+CD80+ <em>B</em>-cells (16% (IQR 6-25) vs 5% (IQR: 1-9), <em>p</em> = 0.009), and upregulation in resting B-cell cytokine production (15/27 cytokines, <em>p</em> &lt; 0.05). Rituximab selectively restored T-cell responsiveness and abolished elevated B-cell CD80 expression and resting cytokine production in these patients, although nascent B-cell activation could still be detected on <em>in vitro</em> stimulation (6/27 cytokines, <em>p</em> &lt; 0.05). Resting B-cell culture supernatants from patients with hypo-responsive T-cells (<em>p</em> = 0.02) but not normo-responsive T-cells were able to induce cytoskeletal rearrangements in cultured podocytes. Together with T-cell responsiveness, resting B-cell cytokine production was able to strongly predict Rituximab response (AUC 0.922±0.077, <em>p</em> = 0.002), and also the duration of Rituximab response (AUC 0.958±0.062, <em>p</em> = 0.019). Rituximab response in childhood-onset FSGS occurs in a subgroup of patients with B-cell mediated disease characterized by B-cell activation and the production of podocyte damaging factors. Resting B-cell cytokine production can predict Rituximab response, and if it will be long-lasting.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Pages 1-11"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936872","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":"Neutrophil extracellular traps exacerbate endothelial tight junction dysfunction via the Wnt7a/β-catenin/HDAC5 pathway in sepsis-associated lung injury","authors":"Qianya Hong ,&nbsp;Shuainan Zhu ,&nbsp;Chenning Li ,&nbsp;Heyang Sun ,&nbsp;Zhenzhen Zhan ,&nbsp;Hao Zhang ,&nbsp;Kefang Guo","doi":"10.1016/j.trsl.2026.01.001","DOIUrl":"10.1016/j.trsl.2026.01.001","url":null,"abstract":"<div><div>Sepsis is a complicated clinical disease caused by an infection-related host response, which results in acute organ dysfunction and a high mortality risk. Among the affected organs, the lungs are particularly susceptible to sepsis. Sepsis-induced acute lung injury (SI-ALI) is a common and severe complication observed among septic patients. Neutrophil extracellular traps (NETs) serve a significant role in immune and inflammatory regulation. Our previous studies have shown a close association between NETs and SI-ALI. However, the mechanism by which NETs mediate the interaction between endothelial cell (EC) barrier integrity and inflammatory responses remains incompletely understood. By reanalyzing our RNA-seq data, we discovered that NET-stimulated HUVECs had an increased cell adhesion molecules pathway, and the differentially expressed genes Wnt7a, HDAC5, and Claudin-5 were screened out. The relationships between differentially expressed genes were further established by STRING analysis. The expression levels of Claudin-5 and Wnt7a/β-catenin/HDAC5 signaling pathway proteins were evaluated by quantitative PCR (qPCR), western blotting, and immunofluorescence staining. At the same time, a cecal ligation and puncture (CLP) model was used to induce sepsis in mice to investigate the function of NETs in vivo. In our research, we demonstrated that NETs activate HDAC5 gene expression through the Wnt7a/β-catenin signaling activation, which subsequently downregulated the expression of tight junction (TJ) proteins, including Claudin-5, ZO-1, and Occludin. This led to impaired barrier function in lung microvascular endothelial cells and worsened the prognosis in a murine model of SI-ALI. Moreover, the NETs disruption and Wnt7a or HDAC5 inhibition mitigated the degradation of tight junction proteins in endothelial cells and improved outcomes in septic mice. In conclusion, our findings indicate that NETs contribute to lung endothelial barrier dysfunction via the Wnt7a/β-catenin/HDAC5 axis during the progression of SI-ALI.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Pages 22-37"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936953","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":"Inhibiting CCR3 expands cancer stem cells via c-Myc–NTSR1 axis and associates with tumor innervation features","authors":"Ta-Jung Peng ,&nbsp;Wei-Lun Hwang ,&nbsp;Wan-Hsuan Sun ,&nbsp;Shye-Jye Tang ,&nbsp;Kuang-Hui Sun","doi":"10.1016/j.trsl.2025.12.005","DOIUrl":"10.1016/j.trsl.2025.12.005","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) drive intra-tumor heterogeneity, therapy resistance, and relapse. Chemokines regulate cancer stemness via intercellular signaling within the tumor microenvironment. However, the role and clinical relevance of CCR3 in tumor subpopulations remain unexplored. In this study, we enriched CSCs by serum-free spheroid culture as spheroid-derived CSCs (SDCSCs). Cell proliferation, clonogenicity, migration/invasion, tumorsphere formation, chemo-drug resistance, in vivo tumorigenicity, signaling activity, and transcriptomic landscape were characterized. TCGA databases were analyzed for clinical relevance. We found that CCR3 silencing increased self-renewal capability, stemness markers expression, chemoresistance, and <em>in vivo</em> tumorigenicity in SDCSCs; however, it inhibited proliferation, colony formation, and invasion in parental cancer cells. Transcriptomic analysis revealed that CCR3 silencing induced pro-tumoral features in SDCSCs, while it resulted in anti-proliferative and anti-invasive profiles in parental cancer cells by oppositely regulating oncogenic signaling, including c-Myc, KRAS, mTORC, and HIF pathways. In SDCSCs, CCR3 silencing induced c-Myc nuclear expression and transcriptional activation, leading to NTSR1 upregulation and enhanced cancer stemness, which was hindered by a c-Myc inhibitor (10058-F4). Clinically, tumors with low CCR3 expression exhibited a transcriptomic landscape with enhanced cell growth and suppressed immune surveillance, accompanied by activated stemness-related signalings and tumor innervation signatures. High NTSR1 expression further exacerbated the poorer survival in patients with low CCR3 expression. In summary, CCR3 inhibition elicits divergent functional and transcriptomic responses in tumor subpopulations and is associated with stemness- and innervation-related signatures that predict poor prognosis. Combined targeting of CCR3 and the c-Myc–NTSR1 axis may eliminate CSCs.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Pages 55-68"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835806","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":"PIM3 enhances nucleus pulposus cell function and extracellular matrix integrity via kinase-dependent activation of the Akt/mTOR signaling axis in intervertebral disc degeneration","authors":"Qianshi Zhang ,&nbsp;Jia Hu ,&nbsp;Ziqi Liu ,&nbsp;Siwen Wu ,&nbsp;Fusheng Liu ,&nbsp;Yanlin Tan ,&nbsp;Chao Wei ,&nbsp;Xiaobin Wang ,&nbsp;Jing Li","doi":"10.1016/j.trsl.2025.12.006","DOIUrl":"10.1016/j.trsl.2025.12.006","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IDD), a condition characterized by extracellular matrix (ECM) degradation and nucleus pulposus (NP) cell senescence, compromises disc function. The Akt signaling pathway is essential for NP cell viability and ECM homeostasis. This study identifies the serine/threonine kinase PIM3 as significantly downregulated in degenerated human NP tissues. Notably, PIM3 mRNA expression levels were found to be negatively correlated with the clinical severity of IDD (Pfirrmann grade). The functional role of PIM3 was investigated through knockdown and overexpression experiments in human NP cells. PIM3 overexpression restored cell viability, suppressed senescence, and enhanced ECM protein levels in degenerated NP cells, while its knockdown in normal cells produced the opposite results. These protective effects were critically dependent on the kinase activity of PIM3. Mechanistically, PIM3 was found to physically interact with and activate the Akt signaling pathway, thereby regulating downstream molecules, including mTOR and FoxO1, to modulate cell viability and senescence. In an IDD rat model, AAV-mediated PIM3 overexpression improved ECM integrity, reduced senescence and activated the Akt pathway, mitigating disc degeneration. In conclusion, this study establishes PIM3 as a key regulator of NP cell homeostasis that acts through direct engagement with the Akt/mTOR/FoxO1 axis. Its correlation with disease severity and the kinase-dependent nature of its function highlight PIM3 as a promising, mechanistically-defined therapeutic target for treating IDD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Pages 38-54"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890830","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(26)00026-5","DOIUrl":"10.1016/S1931-5244(26)00026-5","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Pages iii-iv"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090137","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(26)00025-3","DOIUrl":"10.1016/S1931-5244(26)00025-3","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"287 ","pages":"Page ii"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090140","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}