Frontiers in molecular medicine最新文献

{"title":"The potential of AI inspired approaches for patient monitoring in drug development for Huntington's disease: capturing the digital exhaust for activities of daily living.","authors":"Amit Khanna, Graham Jones","doi":"10.3389/fmmed.2026.1966010","DOIUrl":"10.3389/fmmed.2026.1966010","url":null,"abstract":"<p><p>Diagnosis, assessment and monitoring of Huntington's disease (HD) requires measurement of a complex array of motor, cognitive and psychiatric symptoms over sustained periods. However, the prodromal stages often span over a decade with symptoms presenting in a non-linear manner with short term fluctuations. This presents challenges for investigational drug development as treatment effects may become masked. To help address this issue, a number of digital health technology tools are being investigated for use in HD studies with increasing degrees of utility and sophistication. Herein we outline how remote passive monitoring technologies could be integrated into managed care of HD patients, and have the potential to inform algorithms and digital tools which could be used to improve our understanding of disease trajectories and improve early detection rates. Steps to implementation and the potential to derive learnings from adjacent technologies is presented, affording a key opportunity for next- generation approaches to patient monitoring. Measures derived from such technologies will also provide data to capture disease progression and treatment effects with high fidelity and granularity, and complement existing clinical research outcomes (clinROs) and patient reported outcomes (PRO's). Given the ethical, economic, and societal burden presented by neurodegenerative diseases, such developments could have long term impact in managed healthcare.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1966010"},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLDN18 and FGFR2 splicing variants are emerging tumor-associated antigens for cancer therapy.","authors":"Masuko Katoh, Masaru Katoh","doi":"10.3389/fmmed.2026.1927389","DOIUrl":"https://doi.org/10.3389/fmmed.2026.1927389","url":null,"abstract":"<p><p>Alternative splicing and alternative promoters generate splicing variants to expand proteomic and transcriptional diversity to orchestrate physiological activities and dictate tumorigenesis. Splicing variants are attractive tumor-associated antigens (TAAs) for the clinical development of cancer therapies. Here, recent progress in claudin-18 isoform 2 (CLDN18.2)- and fibroblast growth factor receptor 2 isoform b (FGFR2b)-targeted therapeutics is summarized, and perspectives in this field are discussed. Zolbetuximab and bemarituzumab are first-generation monoclonal antibodies (mAbs) targeting CLDN18.2 and FGFR2b, respectively, while next-generation biologics targeting these TAAs are emerging. Single-agent objective response rates of CLDN18.2-targeting mAb (omectatug), antibody-drug conjugates (ADCs, arcotatug tavatecan, BL-M05D1, garetatug rezetecan, JS107, sonesitatug vedotin and tecotabart vedotin), bispecific antibodies (emaretamig and givastomig) and chimeric antigen receptor T (CAR-T) cells (IMC002) were higher than that of zolbetuximab. Gastrointestinal toxicity, nausea and vomiting are common on-target/off-tumor adverse effects of CLDN18.2-targeted biologics, which are mitigated for arcotatug tavatecan and givastomig as a result of antibody engineering. Combination therapy of zolbetuximab plus chemotherapy is approved for the treatment of gastric and gastroesophageal junction cancer patients, while results of other CLDN18.2-targeting biologics in phase 3 clinical trials are anticipated with expectations for improved clinical activities and mitigated adverse events. Diagnostics detecting alternative isoforms and combination strategies using immune checkpoint inhibitors would address resistance mechanisms, such as epitope-losing isoform switching and immune evasion. Comparative studies on ADC monotherapy versus combination mAb-chemotherapy as well as the clinical development of bispecific ADCs and allogeneic CAR-T cells should further improve the clinical benefits of CLDN18.2- and FGFR2b-targeted therapies.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1927389"},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic responses to intravenous rAAV administration in boys with Duchenne muscular dystrophy.","authors":"Brooke E Harris, Brooke M Seldin, Sam C Towne, Orinda R Hobson, Eli Zerpa, Victor Prima, H Lee Sweeney, David W Hammers","doi":"10.3389/fmmed.2026.1953867","DOIUrl":"10.3389/fmmed.2026.1953867","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic gene therapies utilizing recombinant adeno-associated virus (rAAV) are in the clinic for the treatment of rare monogenic diseases. This includes delandistrogene moxeparvovec for Duchenne muscular dystrophy (DMD), which uses AAVrh74 vector to deliver a micro-dystrophin transgene to striated muscle. While there have been cases of transformative benefits incurred from rAAV therapies, serious adverse events and mortalities have occurred. This study aimed to investigate short-term rAAV dynamics and long-term systemic responses to intravenous rAAV in the phase 1/2a delandistrogene moxeparvovec clinical trial (NCT03375164), which represents the most promising cases of micro-dystrophin gene therapy for DMD.</p><p><strong>Methods: </strong>Plasma and urine specimens from NCT03375164 were analyzed for rAAV using digital PCR and immunoblotting. The integrity and transduction competency of specimen-derived rAAV was evaluated <i>in vitro</i>. Systemic responses to rAAV treatment were investigated using the SomaScan proteomics platform. Preclinical antiviral responses to rAAV were assayed by real-time PCR in the livers of D2. <i>mdx</i> mice 1 week following systemic treatment with rAAV.</p><p><strong>Results: </strong>Digital PCR revealed high rAAV content in the plasma at Day 1 following treatment, which substantially reduced by Day 7. Urinary rAAV content was low and variable in all samples tested. The majority of detected vector genomes were packaged in AAVrh74 particles in these specimens, and the vector contained in Day 1 plasma samples was confirmed to be transduction competent. SomaScan data revealed highly significant changes in 99 circulating proteins, which include markers associated with immune activation, interferon responses, complement pathways, and organ injury. Most traditional markers of muscle damage were not changed across the time course, with the limitation that no healthy or untreated DMD samples were analyzed. Features of antiviral and interferon-associated responses were identified in D2. <i>mdx</i> mice.</p><p><strong>Conclusion: </strong>Systemic rAAV treatments result in high levels of circulating and transduction-competent vector early after treatment in DMD boys and result in wide-spread activation of immune-associated markers. These findings will provide insights for future investigational study design and efforts to improve safety of rAAV gene therapies.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1953867"},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to HPV16 VLP construction and production with improved accessibility and particle sorting potential.","authors":"Morgan Williamson, Caleb Boren, Rahul Kumar, Lauren Gollahon","doi":"10.3389/fmmed.2026.1941186","DOIUrl":"https://doi.org/10.3389/fmmed.2026.1941186","url":null,"abstract":"<p><p>Human papillomavirus (HPV), a member of the Papillomaviridae family, infects a broad range of animal hosts and is responsible for the majority of cervical cancers and a substantial proportion of oropharyngeal cancers. Current treatment strategies for HPV-associated cervical disease depend largely on disease stage, with preinvasive and early invasive lesions commonly managed through surgical excision or radiation. Additionally, more advanced cases often require chemotherapy, immunotherapy, or combination regimens. Prophylactic vaccination remains the most effective preventive approach, and currently available vaccines, including Gardasil, Gardasil-9, and Cervarix, rely on L1-based virus-like particles (VLPs) to induce protective immunity. At the same time, increasing interest has emerged in the use of nanomaterials and viral capsids as platforms for targeted drug and gene delivery, alongside the development of higher-throughput methods for nanoparticle and viral characterization. Modified HPV capsids have shown promise for cell-specific targeting and more efficient cargo delivery with reduced off-target cytotoxicity. In this study, the HPV16 structural proteins L1 and L2 were fused to the N- and C-terminal halves of the Venus fluorophore, respectively, using a specially designed linker intended to preserve capsid assembly while reducing VLP aggregation associated with current production methods. The resulting bimolecular fluorescence complementation (BiFC)-based VLPs demonstrated reduced aggregation and improved total particle yield. In addition, the particles generated a detectable YFP signal, supporting fluorescence-based monitoring of VLP assembly and providing a potential basis for high-throughput particle characterization and sorting. This intrinsic fluorescent signal may also reduce reliance on separately packaged reporter constructs for downstream analysis.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1941186"},"PeriodicalIF":0.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future directions of CAR-T Cell therapy: unlocking the potential of immunotherapy in cancer treatment.","authors":"Angel Alberto Justiz-Vaillant, Sachin Soodeen, Rodolfo Arozarena-Fundora, Patrick Eberechi Akpaka, Chandrashekhar Unakal","doi":"10.3389/fmmed.2026.1931159","DOIUrl":"10.3389/fmmed.2026.1931159","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for relapsed and refractory haematological malignancies, producing durable clinical responses in patients with otherwise limited therapeutic options. Despite these advances, significant biological, clinical, and economic barriers continue to limit its broader application, particularly in solid tumours. This literature review critically evaluates recent developments in CAR-T cell therapy, with emphasis on areas that have received limited discussion in previous reviews. Multi-target CAR strategies, including bispecific, tandem, and pooled CAR-T cell approaches, are comparatively assessed with respect to antigen escape, manufacturing complexity, therapeutic efficacy, and safety. Current challenges in solid tumour treatment are examined through evidence from clinical trials, highlighting key obstacles such as antigen heterogeneity, the immunosuppressive tumour microenvironment, poor cellular trafficking, and treatment-related failures that have informed the development of next-generation CAR constructs. Emerging approaches to overcoming antigen loss, including γδ CAR-T cells, are reviewed alongside their current limitations, including restricted <i>ex vivo</i> expansion, donor variability, isolation challenges, and uncertain long-term persistence. The review also addresses the growing importance of improving affordability and accessibility through allogeneic \"off-the-shelf\" CAR-T products, genome editing technologies, automated manufacturing platforms, and rational combination therapies designed to enhance efficacy while reducing treatment costs. In addition, advances in toxicity prediction are evaluated, focusing on biomarkers beyond interleukin-6, including ferritin, C-reactive protein, soluble interleukin-2 receptor alpha, and multiparametric cytokine signatures for the early identification of severe cytokine release syndrome. Collectively, these developments demonstrate that future progress in CAR-T cell therapy will depend not only on enhancing antitumour efficacy but also on improving safety, accessibility, manufacturing efficiency, and equitable global implementation through evidence-based innovation.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1931159"},"PeriodicalIF":0.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal muscular atrophy in the disease-modifying therapy era: successes, limitations and future directions.","authors":"Madison M Sexton, Emma W Crow, Congyue Annie Peng","doi":"10.3389/fmmed.2026.1901311","DOIUrl":"10.3389/fmmed.2026.1901311","url":null,"abstract":"<p><p>Spinal Muscular Atrophy (SMA) is a rare and debilitating neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, leading to muscle weakness, respiratory failure, and premature mortality. The pathogenesis of SMA is highly complex and the investigation of downstream pathways and specific cellular mechanisms is still ongoing. In recent years, three FDA-approved disease-modifying therapies, nusinersen, risdiplam, and onasemnogene abeparvovec, have improved the quality of life for patients with SMA and have eased the management of associated symptoms. However, unmet needs remain as comorbidities become increasingly apparent in the era of disease-modifying therapies. Despite the remarkable progress achieved over the past decade, continued research is essential to further improve the quality of life, clinical outcomes, and standard of care for individuals living with SMA.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1901311"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-titer human packaging cells producing γ-retroviral vectors pseudotyped with engineered baboon endogenous retrovirus (BaEV) envelope proteins.","authors":"Angelina Hallik, Mona Pißarreck, Mats Jürgen Grummel, Yasemin van Heuvel, Jörn Stitz","doi":"10.3389/fmmed.2026.1888550","DOIUrl":"10.3389/fmmed.2026.1888550","url":null,"abstract":"<p><p>Lentiviral, α-retroviral, and γ-retroviral vector particles pseudotyped with envelope (Env) proteins of baboon endogenous retrovirus (BaEV) were shown to mediate highly efficient gene transfer into a range of primary human hematopoietic cell types in gene therapeutic strategies. However, the fusogenicity of utilized Env proteins mediated syncytia formation, hindering the establishment of stable viral packaging cell lines (VPCLs). Consequently, we used another BaEV Env variant, termed BaEV-TR-previously reported not to induce cell-to-cell fusion-and assessed its utility in stable producer cell line development. The absence of syncytia formation was reconfirmed in human 293T and HT1080 cell lines. Using HT1080 host cells, the stable VPCL HT/BaEV-TR was established. Conducting a Western blot analysis, BaEV-TR protein incorporation into vector particles was readily detected. Murine leukemia virus (MLV) pseudotype vectors efficiently transduced a variety of human target cell lines, reaching high vector titers of more than 3.0 × 10⁶ transducing units per mL (TU/mL) in 293T target cells. In summary, this proof-of-concept study underlines the utility of the Env variant BaEV-TR for the establishment of stable pseudotype VPCLs and the utilization of HT1080 cells as an alternative to frequently used 293T host cells.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1888550"},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumour DNA in mCRPC: bridging tumour biology and real-time treatment monitoring.","authors":"Chimbabantu Kaoma, Mike Sathekge, Joseph Chalwe, Kgomotso Mokoala, Mankgopo Kgatle","doi":"10.3389/fmmed.2026.1852641","DOIUrl":"https://doi.org/10.3389/fmmed.2026.1852641","url":null,"abstract":"<p><p>Metastatic castration-resistant prostate cancer (mCRPC) is associated with poor prognosis. Currently, treatment selection and response assessment in mCRPC still rely largely on prostate-specific antigen (PSA) and imaging tools, which may be insensitive and biologically noninformative. Liquid biopsy (LB), particularly circulating tumor DNA (ctDNA), offers a minimally invasive and reproducible approach for real-time assessment of tumor burden and tumor genomics. Across major treatment classes, ctDNA tumor fraction has shown consistent prognostic value, while selected genomic alterations may provide therapy-specific predictive information. Early on-treatment ctDNA kinetics are also emerging as dynamic markers of response, although prospective validation is required before routine clinical implementation. In this narrative review, we synthesize current evidence on ctDNA biology, detection methods, and its clinical utility across key mCRPC treatment classes, including androgen receptor pathway inhibitors (ARPIs), taxane chemotherapy, PARP inhibitors, and PSMA-targeted radioligand therapy (RLT). We critically examine ctDNA tumor fraction as a pan-therapy prognostic biomarker, genomic alterations as potential predictors of treatment sensitivity or resistance, early kinetic changes as surrogate markers of response, and the biological and technical limitations that currently restrict clinical adoption. Overall, the current evidence base for ctDNA in mCRPC remains predominantly prognostic rather than definitively predictive. Its integration into routine clinical practice will require prospective biomarker-driven trials, assay standardization, and a clear demonstration of clinical utility. At present, ctDNA is best positioned as a complementary tool for risk stratification and disease monitoring, with the potential to evolve into a clinically actionable biomarker for treatment decision-making.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1852641"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of plant-based interventions on gynecological cancers: a narrative review of mechanistic interplays and clinical evidence.","authors":"Fidelis Batale Fabrael, John Sotunsa, Kehinde Samuel Olaniyi, Onome Bright Oghenetega, Oluwatobi Adewale, Blessing Monica Akindele, Faith Olanrewaju, Nekabari Lekpa Gbimadee, Seyi Olayemi, Abosede Oreoluwa Bolaji, Marvellous Osewe Iyobhebhe, Emmanuel Mololuwa Adegbotoluwa, Emmanuel Damilare Folahanmi, John Ahmadu Kaisar, Precious Adeoye Oyedokun","doi":"10.3389/fmmed.2026.1832188","DOIUrl":"10.3389/fmmed.2026.1832188","url":null,"abstract":"<p><p>Gynecological cancers account for approximately 1.4 million new cases and 680,000 deaths annually. Cervical, ovarian, endometrial, vulvar, and vaginal cancers collectively impose a major and disproportionate burden on women in low- and middle-income countries. Conventional treatments, including surgery, platinum-based chemotherapy, and radiotherapy, are limited by systemic toxicity, acquired chemoresistance, recurrence, and financial inaccessibility in resource-limited settings. Approximately 80 percent of patients with advanced ovarian cancer eventually develop platinum resistance, and cervical cancer persists as a leading cause of cancer death in regions with inadequate screening and vaccination infrastructure. Plant-derived phytochemicals have attracted substantial scientific attention as adjunct or complementary anticancer strategies. This review synthesizes preclinical, epidemiological, and emerging clinical evidence for alkaloids, flavonoids, terpenoids, polyphenols, coumarins, and organosulfur compounds in gynecological cancer prevention and management. These compounds modulate multiple oncogenic pathways relevant to gynecological malignancies: tumor cell proliferation, intrinsic and extrinsic apoptosis, angiogenesis, oxidative stress, inflammation, hormone receptor signaling, HPV E6/E7 oncoprotein expression, and epigenetic regulation. Paclitaxel, a taxane terpenoid, serves as the definitive proof of concept that plant-derived compounds can achieve gold-standard clinical status in gynecological oncology. Critical barriers limit clinical translation for most non-approved phytochemicals: oral bioavailability is poor, botanical preparations are unstandardized, randomized trial data in gynecological cancer populations are scarce, and herb-drug interaction profiles are incompletely characterized. Nanoformulation approaches, including liposomal encapsulation, PLGA nanoparticles, and phytosomes, offer practical routes to overcome these pharmacokinetic obstacles. Future work should prioritize biomarker-embedded clinical trials, molecular subtype-stratified patient selection, and rigorous evaluation of phytochemical-chemotherapy combination regimens.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1832188"},"PeriodicalIF":0.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood biomarkers and atrial remodeling in patients at risk of atrial fibrillation.","authors":"Filip Loncaric, Ilana Forado Benatar, Maria Mimbrero Guillamon, Loredana Nunno, Rafael Jimenez-Arjona, Laia Tirapu, Sílvia Montserrat, Laura Sanchis, Adelina Doltra, Bart Bijnens, Marta Sitges","doi":"10.3389/fmmed.2026.1801523","DOIUrl":"10.3389/fmmed.2026.1801523","url":null,"abstract":"<p><strong>Introduction: </strong>Arterial hypertension and endurance training are related to left atrial (LA) remodeling and risk of atrial fibrillation (AF). Serum blood biomarkers have been explored in relation to cardiovascular risk. Our aim was to assess the influence of patient and echocardiographic characteristics on serum blood biomarkers in individuals at risk for AF.</p><p><strong>Methods: </strong>A population of 511 subjects was analyzed: 286 endurance athletes and 225 patients with arterial hypertension. Participants underwent 2D and 3D echocardiography with speckle-tracking analysis. Blood samples were obtained to evaluate biomarkers of myocardial damage (Brain Natriuretic Peptide, troponin I, Oncostatin M, heart-type Fatty Acid-Binding Protein and Placenta Growth Factor), vascular endothelial dysfunction (Endothelial cell-specific molecule 1), and fibrosis (Matrix Metalloproteinase 1, 2 and 9, C-X-C motif chemokine ligand 6 and 16, and Galectin-3 (Gal-3)). Linear regression models were fitted to discern the relationship of patient and echo characteristics and serum biomarker levels.</p><p><strong>Results: </strong>The results revealed the significant influence of age, gender, body mass index and renal function on biomarker levels. Parameters of myocardial damage showed a limited range of values in our cohort with no differences between groups. Biomarkers of fibrosis were uniformly elevated in hypertension, with Gal-3 levels independently associated with LA reservoir strain.</p><p><strong>Conclusion: </strong>Serum levels of fibrosis biomarkers differ between populations at risk for AF. In hypertension Gal-3 levels are associated with LA reservoir function, making it a potential biomarker for LA remodeling in this setting. Clinical follow-up is needed to relate these findings with clinical outcomes.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1801523"},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}