Journal of Translational Medicine最新文献

{"title":"ADSC-enriched adipose extract alleviates cartilage fibrosis in temporomandibular joint osteoarthritis by inhibiting chondrocyte senescence.","authors":"Zerou Zhang, Dan Jin, Bingshuai Jing, Shanluo Zhou, Yi Sun, Jeroen Van Dessel, Rui Ren, Fuwei Liu, Mian Zhang, Yunpeng Li","doi":"10.1186/s12967-025-07108-8","DOIUrl":"https://doi.org/10.1186/s12967-025-07108-8","url":null,"abstract":"<p><strong>Background: </strong>Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease causing chronic pain and restricted mandibular movement. Its complex pathology and lack of effective therapies make it a clinical challenge. Recent studies have demonstrated that cartilage fibrosis correlates closely with TMJOA progression. Inflammatory microenvironments induce chondrocyte senescence, altering secretory phenotypes and driving fibrocartilage formation, characterized by hardened texture and poor mechanical properties, compromising joint biomechanics. Targeting cartilage fibrosis represents a key therapeutic strategy. Stem cell therapies show antifibrotic potential but face clinical limitations due to complex preparation and safety risks.</p><p><strong>Methods: </strong>Synovial lavage fluid from TMJOA patients was collected and analyzed for fibrosis marker ACTA2 and inflammatory factor IL-1β expression to confirm intra-articular fibrosis and explore contributing factors. Adipose-derived mesenchymal stem cell (ADSC)-enriched adipose extract (ARDE) was prepared using mechanical emulsification with low-speed centrifugation. Its efficacy was assessed in a prospective clinical trial evaluating pain, mouth opening, and radiographic changes. ARDE's modulation of inflammation and repair of fibrocartilage were histologically assessed in a rabbit TMJOA model. In vitro TMJOA chondrocyte models induced by inflammatory factors (IL-1β, TNF-α) were co-cultured with ARDE's core component, ADSCs, to observe their impact on pathological chondrocytes. Transcriptome sequencing further explored their repair mechanisms.</p><p><strong>Results: </strong>TMJOA patient synovial lavage fluid showed elevated fibrotic markers correlating significantly with disease stage and inflammation levels. Prospective clinical trial follow-up demonstrated that ARDE injection substantially improved pain, mouth opening limitation, and quality of life, with reduced joint effusion radiographically evident in some patients. In vivo, intra-articular ARDE promoted histological cartilage repair and extracellular matrix redeposition while downregulating inflammatory factors and fibrotic markers in articular cartilage. Mechanistically, inflammatory cytokine-stimulated chondrocyte models exhibited upregulated fibrotic and senescence-associated pathways; ADSC co-culture suppressed fibrotic marker expression and attenuated cellular senescence.</p><p><strong>Conclusion: </strong>ARDE effectively alleviates cartilage fibrosis by suppressing chondrocyte senescence, significantly restoring cartilage structure and alleviating disease symptoms. The preparation process meets clinical requirements, and its demonstrated safety and efficacy indicate promising clinical translation prospects.</p><p><strong>Trial registration: </strong>Human studies were approved by the Medical Ethics Committee of The Third Affiliated Hospital of Air Force Medical University (Approval No: IRB-YJ-2022033) ","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1072"},"PeriodicalIF":7.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258529","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":"Conjunctival and retinal microvascular loss in systemic lupus erythematosus: a swept-source OCTA study.","authors":"Lulu Chen, Lu Sun, Lihui Meng, Chuting Wang, Youxin Chen","doi":"10.1186/s12967-025-07118-6","DOIUrl":"https://doi.org/10.1186/s12967-025-07118-6","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to characterize conjunctival and retinal microvascular alterations in Systemic lupus erythematosus (SLE) using swept-source optical coherence tomography angiography (SS-OCTA), and to evaluate their correlation with systemic clinical manifestations.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 32 SLE patients and 32 age, sex, and spherical equivalent matched controls. Participants underwent swept-source OCTA imaging of nasal and temporal conjunctiva (16 × 12 mm scans) and macula (6 × 6 mm scans). Vessel density of conjunctival vessel, superficial vascular plexus (SVP), and deep vascular plexus (DVP) were quantified using automated segmentation. Correlation analyses were conducted to evaluate the association between conjunctival and retinal vascular densities, as well as their relationships with clinical parameters of systemic involvement and disease activity.</p><p><strong>Results: </strong>SLE patients showed significant reductions in nasal (45.0% vs. 60.1%, p < 0.001) and temporal (51.8% vs. 60.5%, p = 0.009) conjunctival vascular density, alongside pan-retinal DVP attenuation (p < 0.05). Combined nasal conjunctival and retinal nasal DVP analysis yielded high diagnostic accuracy (AUC 0.897). Microvascular loss was independent of organ involvement or disease activity (p > 0.05).</p><p><strong>Conclusions: </strong>SLE is associated with significant reductions in conjunctival and retinal DVP vascular density. Combined multimodal SS-OCTA analysis achieved superior diagnostic accuracy, with microvascular loss independent of disease activity or organ-specific involvement, suggesting systemic microvascular injury as a unifying SLE feature. Conjunctival-retinal vascular metrics may serve as potential new biomarkers for SLE.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1073"},"PeriodicalIF":7.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258531","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":"Clinical trials and advanced MRI techniques with stem cell therapy for ischemic stroke: present and future perspectives.","authors":"Jiahui Liu, Liyuan Cheng, Changjun Ma, Xiulin Wang, Xiaofei Ji, Ying Li, Jing Liu","doi":"10.1186/s12967-025-07054-5","DOIUrl":"https://doi.org/10.1186/s12967-025-07054-5","url":null,"abstract":"<p><p>Ischemic stroke remains a leading cause of disability and mortality worldwide. Currently, there are no effective therapeutic strategies to promote post-stroke nerve repair and regeneration in clinical practice. Stem cells, characterized by self-renewal and differentiation capabilities, offer insights into the treatment of stroke. Over the past few decades, stem cell therapy has yielded promising results in preclinical and clinical studies for the treatment of ischemic stroke. However, various challenges to the clinical application of stem cell therapy remain. Herein, we review clinical trials of stem cell therapy for different stages of ischemic stroke. Based on this summary, we discussed the issues that need to be considered in future clinical trials, including determining the optimal cell types and doses, ideal transplantation routes and timing, and appropriate assessment methods. Additionally, as neuroimaging plays an increasingly critical role in humans, we elaborate on the application of advanced magnetic resonance imaging (MRI) techniques in clinical trials. In terms of the future outlook, we discuss technological advances, introducing machine learning in the field of stroke, and using this approach for integrating multi-omics data. These results may provide information for further development of clinical trials in this field and promote the future application of stem cell-based therapy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1069"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251737","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":"Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch^® 3-dimensional genomic regulatory immuno-genetic profiling.","authors":"Ewan Hunter, Heba Alshaker, Oliver Bundock, Cicely Weston, Shekinah Bautista, Abel Gebregzabhar, Anya Virdi, Joseph Croxford, Ann Dring, Ryan Powell, Dominik Vugrinec, Caroline Kingdon, Carol Wilson, Sarah Dowrick, Jayne Green, Alexandre Akoulitchev, Dmitri Pchejetski","doi":"10.1186/s12967-025-07203-w","DOIUrl":"10.1186/s12967-025-07203-w","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1048"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244881","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":"A multi-omics Mendelian randomization study reveals PAM as a potential therapeutic target for type 2 diabetes.","authors":"Ming Yi, Xingrong Feng, Qiuyue Guan, Yin Liu, Yunqiang Liu, Zhiguang Su","doi":"10.1186/s12967-025-07086-x","DOIUrl":"https://doi.org/10.1186/s12967-025-07086-x","url":null,"abstract":"<p><strong>Background: </strong>The progression of type 2 diabetes (T2D) is driven by pancreatic β-cell dysfunction and loss, yet current therapies fail to address this core pathophysiology.</p><p><strong>Methods: </strong>We implemented an integrative pipeline combining genetic and functional data to prioritize T2D targets. We leveraged genome-wide association study (GWAS) and protein quantitative trait loci (pQTL) summary data to infer causal associations between circulating proteins and disease risk. Phenome-wide association studies were conducted to evaluate pleiotropy and potential off-target effects. Single-cell RNA-seq was used to delineate cell-type-specific expression and identify biological pathways associated with candidate genes. Lead candidates were then validated by molecular docking and functional assays.</p><p><strong>Findings: </strong>Mendelian randomization and colocalization analyses prioritized 14 circulating proteins with causal links to T2D, nine of which shared strong causal variants (PPH4 > 0.8). Phenome-wide association studies (PheWAS) excluded off-target effects for 2 candidates (HP and SVEP1). Among the remaining 7 candidates (ENG, GOLM1, GSTA1, HIBCH, PAM, PLXND1, and PTN), PAM (peptidylglycine α-amidating monooxygenase) was found to be expressed in over 80% of β-cells, as revealed by single-cell RNA-sequencing. Moreover, genes co-expressed with PAM were functionally clustered in pathways related to insulin secretion and protein processing. Notably, PAM expression was significantly downregulated in islets of diabetic mice. Molecular docking simulations identified a high-affinity interaction between PAM and oleic acid (OA), a metabolite linked to β-cell function. Strikingly, pharmacological PAM inhibition in INS1 β-cells induced deficits in cell proliferation and survival that were unresponsive to OA supplementation, underscoring PAM's indispensable role in β-cell integrity.</p><p><strong>Interpretation: </strong>This study positions PAM as a clinically relevant therapeutic target for T2D, offering new opportunities for β-cell preservation therapies and diagnostic biomarker development.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1067"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251713","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":"Plant-derived extracellular vesicles: composition, function and clinical potential.","authors":"Defa Huang, Jie Chen, Minghong Zhao, Haibin Shen, Qing Jin, Dewang Xiao, Zongbo Peng, Tao Chen, Yilei Zhang, Dingyu Rao, Meijin Liu","doi":"10.1186/s12967-025-07101-1","DOIUrl":"https://doi.org/10.1186/s12967-025-07101-1","url":null,"abstract":"<p><p>As membrane structural bodies secreted by cells, extracellular vesicles (EVs) have become a hot topic in the field of plant science in recent years. Plant-derived extracellular vesicles (PDEVs) play a key role in both plant physiological activities and the interaction between plants and the environment. These vesicles are involved in plant growth, development, and response to adversity by delivering signaling molecules, proteins, and other bioactive substances. Current studies have shown that PDEVs also exhibit promising potential for clinical applications, including as drug carriers, vaccine development, and biomarkers for disease diagnosis. In this paper, we review studies related to compositional characterization, isolation and purification methods, biological roles, and clinical applications of PDEVs. We aim to provide a systematic theoretical basis and practical guidance for future studies to promote their application in biomedical fields.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1065"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251776","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":"Mucoadhesive polydopamine-coated nanoparticle-mediated inner ear drug delivery for hearing loss treatment.","authors":"Subin Kim, Seo Young Cheon, Keum-Jin Yang, Seong Su Won, Simin Chun, Hyorim Nam, Dong-Kee Kim, Heebeom Koo","doi":"10.1186/s12967-025-07103-z","DOIUrl":"https://doi.org/10.1186/s12967-025-07103-z","url":null,"abstract":"<p><p>This study investigated the potential of mucoadhesive polymeric nanoparticles coated with polydopamine (Dopa-NPs) for inner ear drug delivery. Dopa, inspired by mussel adhesion proteins, leveraged the mucoadhesive properties of NPs and enhanced their retention within the cochlea. Dopa-NPs were compared with non-adhesive uncoated control NPs to reveal their safety and drug delivery efficiency. The safety evaluation demonstrated no toxicity during in vitro test using HEI-OC1 cells and in vivo test using mouse with auditory function assessment. When coumarin-encapsulated NPs were administered through intratympanic injection to mice, Dopa-NPs provided intense fluorescence in the inner ear compared to non-adhesive control NPs. Furthermore, dexamethasone (Dex)-encapsulated Dopa-NPs exhibited significantly higher drug concentrations in the cochlea than dexamethasone sodium phosphate and uncoated NPs. Finally, in vivo test using an ototoxicity-induced animal model showed that Dopa-NPs improved hearing protection, as indicated by the auditory brainstem response (ABR) test. In conclusion, mucoadhesive Dopa-NPs exhibit enhanced drug delivery efficiency and safety, offering a promising strategy for inner ear drug delivery and chemotherapy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1066"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251796","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":"Mn-Zn ferrite nanoparticles inducing ferroptosis to reverse the resistance in CML cells.","authors":"Miao Zhu, Yanqian Zhao, Li Xu, Mei Sun, Yuxiang Sun","doi":"10.1186/s12967-025-07107-9","DOIUrl":"https://doi.org/10.1186/s12967-025-07107-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic myeloid leukemia (CML) is a malignant clonal disease of hematopoietic stem cells driven by the BCR-ABL fusion gene. Although tyrosine kinase inhibitors (TKIs) serve as targeted therapies, drug resistance remains one of the key challenges affecting the long-term survival of CML patients. A novel iron-based nano-reagent of Mn-Zn Ferrite was constructed to explore its role in regulating the redox homeostasis of CML cells and to clarify its therapeutic potential in reversing drug resistance in CML.</p><p><strong>Methods: </strong>CCK8 experiments were used to evaluate the effect of Mn-Zn Ferrite nanoparticles (Nano-Iron) on the drug sensitivity of adriamycin in K562 cells and adriamycin-resistant K562 cells (K562/ADR). Apoptosis, reactive oxygen species (ROS) levels, superoxide dismutase (SOD) levels in K562 cells and K562/ADR cells were measured after treatment of Nano-Iron and adriamycin. Further detection was conducted on the levels of glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio in K562 cells and K562/ADR cells after combined intervention. Meanwhile, the expression of glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) levels after combined intervention were determined. In vivo experiments involved in constructing systemic metastasis tumor models of K562 and K562/ADR in mice, which were treated with Nano-Iron and adriamycin. On the 10th, 15th and 20th day after tumor formation, in vivo imaging and medial canthal vein blood collection were performed to evaluate the proportion of tumor cells in peripheral blood. All mice were weighed regularly and euthanized when showing mental depression, at the same time, another batch of mice were used to calculate their survival period. Spleens and femurs were collected for hematoxylin-eosin (HE) and GPX4 staining.</p><p><strong>Results: </strong>Mn Zn ferrite (Nano-Iron) enhances the sensitivity of K562/ADR cells to adriamycin. After co-treatment with Nano-Iron and adriamycin, more apoptosis of K562/ADR cells was induced and accompanied with an increase of ROS and MDA levels, as well as a decrease of GSH/GSSG ratio and GPX4 expression. In vivo experiments have shown that the combination therapy of Nano-Iron and adriamycin prolongs the survival period of mice, significantly inhibits the infiltration of tumor cells in the bone marrow and suppresses the expression of GPX4 in the femur of mice.</p><p><strong>Conclusion: </strong>Mn-Zn Ferrite (Nano-Iron) enhances the therapeutic sensitivity of K562/ADR cells to adriamycin by inducing ferroptosis, demonstrating the therapeutic potential in reversing drug resistance.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1071"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251719","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":"Systemic inflammation and fibrocalcific remodeling in aortic stenosis: the interplay of Lipoprotein(a), sex, and valve morphology.","authors":"Veronika A Myasoedova, Vincenza Valerio, Valentina Rusconi, Francesca Bertolini, Ilaria Massaiu, Sergio Pirola, Paola Gripari, Valentina Mantegazza, Francesco Cannata, Kamil Stankowski, Saima Mushtaq, Gianluca Pontone, Paolo Poggio","doi":"10.1186/s12967-025-07061-6","DOIUrl":"https://doi.org/10.1186/s12967-025-07061-6","url":null,"abstract":"<p><strong>Background: </strong>Aortic valve stenosis (AS) is a progressive valvular disease characterized by fibrocalcific remodeling of the aortic valve leaflets, contributing to significant cardiovascular morbidity and mortality. While valve calcification has been extensively studied, the relationship between valve fibrosis, lipoprotein(a) [Lp(a)], systemic inflammation, sex differences, and valve morphology remains less explored.</p><p><strong>Methods: </strong>We prospectively enrolled 45 patients with severe AS undergoing preoperative echocardiography and contrast-enhanced cardiac computed tomography (CT) at Centro Cardiologico Monzino. Aortic valve calcium and fibrosis volumes were quantified using threshold-based segmentation on CT images. Lp(a) was measured by ELISA, while a multiplex Luminex assay measured a panel of 44 cytokines. Patients were stratified by Lp(a) levels (≤ 50 vs. > 50 mg/dL), sex, and valve morphology (bicuspid vs. tricuspid) to explore associations with the fibrocalcific components of stenotic aortic valves.</p><p><strong>Results: </strong>The median Lp(a) level was 34.4 mg/dL (12.6; 93.4). No significant differences in valvular calcium load were observed between low and high Lp(a) groups. However, a modest increase in fibrotic volume was noted in patients with elevated Lp(a), particularly among men (p = 0.075). Several cytokines, including IL-1RA, IL-8, and TGF-α in men, and EGF, GM-CSF, IP-10, and IL-10 in women, were positively correlated with calcium burden. Fibrotic volume was associated with elevated eotaxin and PDGF-AA levels, with sex-specific patterns. Patients with bicuspid valve exhibited higher fibrocalcific volumes but lower circulating levels of several cytokines compared to patients with tricuspid valve morphology.</p><p><strong>Conclusions: </strong>In patients with severe AS, circulating cytokine profiles show sex- and valve-morphology-specific associations with the fibrocalcific composition of the valve. However, Lp(a) was not associated with valvular calcification, and any relationship with fibrosis appeared at most modest, more evident in men. These results support the relevance of inflammatory profiling in assessing AS pathophysiology.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1070"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251747","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":"Cardiovascular comorbidities are risk factors for increased oxidative stress and DNA damage in migraine patients: a prospective cohort study.","authors":"Mustafa Gokce, Muhammed Yunus Bektay, Mustafa Uzun, Can Ulutas, Ferda Uslu, Eray Metin Guler","doi":"10.1186/s12967-025-07055-4","DOIUrl":"https://doi.org/10.1186/s12967-025-07055-4","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a prevalent neurovascular disorder frequently linked with oxidative stress and an elevated risk of cardiovascular diseases (CVDs), particularly in patient with comorbidities. This study aimed to investigate the relationships between oxidative stress and DNA damage biomarkers, cardiovascular comorbidities, and the effects of six months of migraine prophylaxis.</p><p><strong>Methods: </strong>A prospective cohort study was conducted between January and September 2024 at a tertiary neurology clinic, enrolling 75 women who were divided into three groups: migraine with cardiovascular comorbidities (MC, n = 25), migraine without comorbidities (M, n = 25), and age-matched healthy controls (C, n = 25). Migraine diagnosis was confirmed according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), and patients with renal/hepatic dysfunction, active infections, migraine with aura, pregnancy, or other neurological/psychiatric disorders were excluded. Venous blood samples were obtained during the interictal period (≥ 72 h migraine-free) at baseline and after 6 months of standard acute migraine treatment. Biochemical analyses included total oxidant status (TOS), total antioxidant status (TAS), and calculation of oxidative stress index (OSI) using automated colorimetric assays. DNA damage was quantified by comet assay (single-cell gel electrophoresis), whereas ischemia-modified albumin (IMA) and hypoxia-inducible factor-1α (HIF-1α) were measured via ELISA. Statistical analyses were performed using ANOVA, paired and independent t tests, and Pearson correlation, with p < 0.05 considered significant.</p><p><strong>Results: </strong>Migraine patients exhibited significantly higher oxidative stress and DNA damage levels compared to controls, with the highest levels in those with cardiovascular comorbidities. After six months of treatment, biomarker levels decreased but remained elevated relative to controls. Ischemic markers (IMA and HIF-1α) were consistently higher in migraine patients, especially in the MC group, and although reduced post-treatment, did not normalise to control values.</p><p><strong>Conclusions: </strong>Cardiovascular comorbidities substantially increase oxidative stress and DNA damage in migraine patients, potentially heightening long-term cardiovascular risks. Monitoring these biomarkers may facilitate personalised risk stratification and management in clinical practice.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1068"},"PeriodicalIF":7.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251763","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}