Clinica Chimica Acta最新文献

{"title":"Beyond the glycation gap: A multicompartment framework for HbA1c-glycemia discordance in Pediatric type 1 diabetes.","authors":"Meiling Wang, Cunming Lv","doi":"10.1016/j.cca.2026.122898","DOIUrl":"10.1016/j.cca.2026.122898","url":null,"abstract":"<p><p>HbA1c is analytically standardized but biologically indirect: the measured value integrates glucose exposure through erythrocyte survival, age distribution, intracellular glucose handling, hemoglobin chemistry, and assay behavior. Continuous glucose monitoring (CGM) has made this indirection clinically visible by revealing recurrent disagreement between laboratory HbA1c and sensor-derived glycemia in children and adolescents with type 1 diabetes. This focused narrative review reframes pediatric HbA1c-glycemia discordance as a measurement-biology problem rather than a single 'glycation gap.' We separate three non-equivalent residual constructs, organize the evidence across glucose exposure, extracellular protein glycation, and erythrocyte-dependent glycation, and introduce a trait-state-measurement decomposition of discordance. We distinguish glycated albumin from fructosamine, separate CGM analytical error from interstitial-glucose physiology and temporal representativeness, and grade mechanistic claims as established, supported-but-incomplete, or hypothesis-generating. Direct pediatric evidence confirms that discordance is common and partly persistent, but mechanistic adjudication remains limited because most studies measure only two domains. We therefore propose a hypothesis-localization framework - not a validated diagnostic or therapeutic algorithm - in which analytical validity and temporal alignment precede triangulation. The central aim is explainable disagreement: understanding why valid measurements differ before allowing the difference to influence care.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122898"},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrolyte disturbance phenotypes and adverse outcomes in the intensive care unit: The role of magnesium and potassium abnormalities.","authors":"Nosayba Al-Azzam, Batool A Shhabat, Zainah O Aburashed, Buthaina Nusairat, Sayer Al-Azzam, Reema Karasneh","doi":"10.1016/j.cca.2026.122901","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122901","url":null,"abstract":"<p><strong>Background: </strong>Magnesium and potassium disturbances are common in critically ill patients, but the prognostic value of their co-occurrence is poorly defined.</p><p><strong>Objective: </strong>To evaluate the association of combined magnesium-potassium phenotypes at intensive care unit (ICU) admission with 30-day in-hospital mortality, acute kidney injury (AKI), and invasive mechanical ventilation.</p><p><strong>Methods: </strong>This retrospective cohort included 9462 adults admitted to the ICU of a tertiary hospital in Jordan (2012-2022) with admission magnesium and potassium, classified into nine phenotypes. Mortality was analyzed by Cox regression, censoring patients discharged alive at discharge, and AKI and ventilation by logistic regression, adjusted for age, sex, and modified APACHE II score.</p><p><strong>Results: </strong>Thirty-day mortality was 30.6%, ranging from 25.0% with normal magnesium and potassium to 63.6% with combined hypermagnesemia-hyperkalemia. The combined phenotype had the highest adjusted hazard of death (HR 3.01, 95% CI 2.60-3.49), with positive additive interaction (relative excess risk due to interaction 0.76, 95% CI 0.29-1.23). Isolated hyperkalemia (HR 1.63, 95% CI 1.46-1.82) and isolated hypermagnesemia (HR 1.62, 95% CI 1.42-1.86) were also associated with mortality. The combined phenotype was associated with AKI (aOR 2.66, 95% CI 2.09-3.38) and ventilation (aOR 1.51, 95% CI 1.17-1.94). Modeled continuously, potassium showed a U-shaped and magnesium a J-shaped association with mortality.</p><p><strong>Conclusion: </strong>Co-occurring hypermagnesemia and hyperkalemia at ICU admission identify a high-risk phenotype. Because both are measured routinely, this combination may serve as a simple marker for early risk stratification.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122901"},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Algorithm to detect IgA deficiency during automated tissue transglutaminase antibody testing.","authors":"Ilmavirta Heikki, Ristonmaa Ulla, Kurppa Kalle, Kinnunen Tuure","doi":"10.1016/j.cca.2026.122907","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122907","url":null,"abstract":"<p><strong>Background: </strong>Serological screening for celiac disease (CeD) relies on tissue transglutaminase IgA antibody (tTG-IgA) testing but may be compromised in individuals with total or partial IgA deficiency. Routine measurement of serum IgA (S-IgA) increases laboratory workload and costs. Signal intensity from automated tTG-IgA assays may provide an alternative means to identify individuals with low S-IgA levels requiring IgG-based testing for CeD diagnostics. Here, we evaluated an algorithm for detecting total IgA deficiency or low S-IgA levels during routine tTG-IgA measurement.</p><p><strong>Methods: </strong>A total of 11,596 serum samples submitted for routine tTG-IgA testing were analyzed by the EliA Celikey IgA assay. S-IgA concentrations were measured in samples yielding low assay response units (RU < 30; n = 271) and in a randomly selected subset (n = 226). Receiver operating characteristic analyses were used to determine RU cutoffs for identifying total IgA deficiency and low S-IgA levels.</p><p><strong>Results: </strong>RU values correlated with S-IgA concentrations, particularly at low S-IgA levels. RU cutoffs of <13.6 and < 19.2 identified total IgA deficiency and low S-IgA levels, respectively, with an estimated 100% sensitivity and ≥ 99.5% specificity. In addition, the built-in \"Low RU\" warning in the EliA Celikey IgA assay detected 86% of total IgA-deficient samples with an estimated 100% specificity. A few IgA-deficient samples, all of which were flagged by the \"Low RU\" warning, yielded IgG-based assay results suggestive of CeD.</p><p><strong>Conclusions: </strong>RU-based screening using the EliA Celikey IgA assay could enable a sensitive, specific and low-cost strategy for identifying individuals requiring IgG-based CeD diagnostics, minimizing the need for routine S-IgA testing.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122907"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNAs: Current and future diagnostic biomarkers in liver fibrosis.","authors":"Yongjie Liu, Min An, Huan Yang, Zhiyong Weng, Lihua Li, Guofu Chen","doi":"10.1016/j.cca.2026.122905","DOIUrl":"10.1016/j.cca.2026.122905","url":null,"abstract":"<p><p>Liver fibrosis is an abnormal response of the liver to various pathogenic factors. It represents a critical stage in the progression from chronic liver disease to cirrhosis and liver cancer. Without timely diagnosis and intervention, liver fibrosis can significantly reduce patients' survival rates and quality of life. In liver fibrosis, microRNA (miRNA) plays a dual role in disease progression by regulating gene expression and signaling pathways. Some miRNAs have antifibrotic effects by inhibiting the TGF-β/Smad signaling pathway or blocking the activation of hepatic stellate cells (HSCs). In contrast, other miRNAs accelerate fibrosis by activating the HIF-1α/VEGF pathway or promoting abnormal extracellular matrix deposition. This two-way relationship establishes a basis for investigating miRNAs as potential diagnostic markers. This narrative review synthesizes evidence on various miRNAs associated with liver fibrosis and their molecular mechanisms. It also evaluates their potential applications in serological testing. Research shows that miRNAs, because of their high stability and specificity, are likely to overcome the limitations of traditional methods for diagnosing liver fibrosis. Furthermore, this article evaluates the strengths and weaknesses of popular miRNA detection methods, such as real-time quantitative PCR, microarrays, and next-generation sequencing (NGS), emphasizing that optimizing standardized processes and high-throughput technologies is essential for facilitating the clinical use of miRNAs. In summary, miRNAs are promising non-invasive diagnostic tools for the early diagnosis and personalized treatment of liver fibrosis. Nonetheless, additional research is essential to improve the technology and clinical validation of miRNA detection for its widespread use in clinical settings.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122905"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of urinary biomarkers in relation to the serum sFlt-1/PlGF ratio in pregnant women with suspected placental dysfunction.","authors":"Eva Martinez-Marzo, Maria Peran, Juan Lerma-Irureta, Ana Medel-Martinez, Cristina Paules, Daniel Oros, Marta Fabre","doi":"10.1016/j.cca.2026.122891","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122891","url":null,"abstract":"<p><strong>Introduction: </strong>Urinary biomarkers may provide a non-invasive approach for assessing placental dysfunction. We evaluated their relationship with the clinically validated serum sFlt-1/PlGF ratio and clinically relevant pregnancy outcomes in women with suspected preeclampsia (PE) or fetal growth restriction (FGR).</p><p><strong>Materials and methods: </strong>This cross-sectional study included 151 pregnant women with suspected PE or FGR. Urinary placental growth factor (PlGF), myeloperoxidase (MPO), Serpin A7 (SA7), vascular endothelial growth factor A (VEGF-A), placental protein 13 (PP13) and endothelin-1 (ET-1) were evaluated according to a serum sFlt-1/PlGF ratio threshold of 38. ROC analyses assessed discriminatory performance overall and by gestational age at sampling (<34 and ≥ 34 weeks). Urinary PlGF was additionally evaluated against clinical outcomes and compared with the serum ratio for PE.</p><p><strong>Results: </strong>Urinary PlGF concentrations were lower in women with a serum sFlt-1/PlGF ratio > 38 (17.15 vs 32.13 pg/mL, p < 0.001) and showed the highest discriminatory performance among urinary biomarkers (AUC 0.73; 95%CI: 0.64-0.82), increasing to 0.85 (95%CI, 0.74-0.97) before 34 weeks. Urinary PlGF correlated negatively with the serum ratio before 34 weeks in women with a ratio ≤ 38 (rho = -0.77, p < 0.001). Urinary PlGF showed modest discrimination for PE (AUC 0.67) and FGR (AUC 0.64). For PE, the serum ratio outperformed urinary PlGF overall (AUC 0.82 vs 0.67; p = 0.001), whereas their AUCs did not differ significantly before 34 weeks (0.88 vs 0.80, p = 0.175).</p><p><strong>Conclusions: </strong>Urinary PlGF may provide a feasible non-invasive biomarker of placental angiogenic imbalance, particularly before 34 weeks. It could complement serum-based assessment, although validation in larger independent cohorts is required.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122891"},"PeriodicalIF":4.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond blood pressure: AI-assisted multi-omics biomarker stratification for stroke risk in hypertension: clinical chemistry, analytical validation, and translational perspectives.","authors":"Zhaohong Gao, Junfeng Li, Deyou Jiang","doi":"10.1016/j.cca.2026.122885","DOIUrl":"10.1016/j.cca.2026.122885","url":null,"abstract":"<p><strong>Background: </strong>Hypertension remains a major contributor to stroke burden; however, conventional blood pressure measurements do not fully capture the heterogeneous biological processes underlying cerebrovascular risk. Residual risk may persist despite apparently controlled blood pressure due to vascular, inflammatory, metabolic, cardiac, renal, and neurovascular abnormalities.</p><p><strong>Objective: </strong>This review summarizes emerging multi-omics biomarker strategies for biological stratification of stroke risk in hypertension, emphasizing mechanistic interpretation, analytical validation, artificial intelligence (AI)-assisted integration, and clinical translation.</p><p><strong>Methods: </strong>Relevant literature on genomic, epigenomic, transcriptomic, proteomic, metabolomic, lipidomic, extracellular vesicle biomarkers, clinical chemistry approaches, and AI-assisted integration was reviewed. Evidence was synthesized according to biological relevance, analytical readiness, validation status, and translational potential.</p><p><strong>Key findings: </strong>Multi-omics approaches provide complementary information regarding vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, thrombosis, metabolism, and target-organ injury. However, biological associations do not necessarily establish predictive validity, and predictive performance alone does not demonstrate clinical utility. Translation requires analytical validation, standardized workflows, external validation, and evidence of improved clinical decision-making.</p><p><strong>Limitations: </strong>Most proposed biomarkers remain in exploratory or early translational stages, with limitations including analytical variability, limited external validation, and insufficient prospective clinical utility studies.</p><p><strong>Conclusions: </strong>Multi-omics biomarkers offer a promising framework for understanding biological heterogeneity in hypertensive stroke risk. Future studies should prioritize standardized measurement, prospective validation, and demonstration of clinical utility before routine implementation.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122885"},"PeriodicalIF":4.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating artificial intelligence into medical laboratories: A structured implementation framework.","authors":"Avi Peretz, Hanoch Goldshmidt, Sari Peretz, Marielle Kaplan, Orna Schwartz, Ronit Marco, Maya Azrad","doi":"10.1016/j.cca.2026.122884","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122884","url":null,"abstract":"<p><p>This article presents a structured framework for integrating artificial intelligence (AI) into medical laboratory workflows. As laboratories face increasing demands, workforce shortages, and technological complexity, AI offers promising solutions to enhance efficiency, diagnostic accuracy, and predictive capabilities. The paper outlines key benefits of AI, including automation, quality assurance, and administrative optimization, while also addressing critical challenges such as bias, legal and ethical concerns, workforce disruption, and over-reliance on automated systems. A multi-level implementation strategy is proposed, spanning international, national, and organizational domains, with emphasis on standards, guidelines, training, and oversight. Importantly, the article underscores that AI is a supportive tool, not a replacement for laboratory professionals, whose expertise remains essential for validation and interpretation. The framework aims to guide responsible AI adoption while safeguarding quality and patient safety.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122884"},"PeriodicalIF":4.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of external quality assessment results of 15 clinical laboratory quality indicators in China from 2019 to 2021.","authors":"Yuxuan Du, Zhiguo Wang, Zhixin Zhang, Wei Wang, Jiali Liu, Jie Ma","doi":"10.1016/j.cca.2026.122865","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122865","url":null,"abstract":"<p><strong>Objectives: </strong>This study analyzed external quality assessment (EQA) results for 15 clinical laboratory quality indicators (QIs) in China from 2019 to 2021 to evaluate error-influencing factors, benchmark performance against international standards and inform preliminary quality specifications.</p><p><strong>Methods: </strong>Data for 15 QIs were collected via a web-based EQA system from 2019 to 2021. Variations across years were analyzed using descriptive statistics and Kruskal Wallis H test.</p><p><strong>Results: </strong>Participation rates exceeded 75% for most indicators. Specimen acceptability indicators improved significantly over time. Pre-examination and intra-laboratory turnaround times (TATs) for routine and stat samples remained generally stable over the study period, except for a slight but significant increase in intra-laboratory TAT for stat samples (p < 0.001). The median rate of tests covered by an EQA-proficiency testing (PT) control reached 100%, whereas the rates of tests covered by internal quality control (IQC) and inter-laboratory comparison required improvement. The median rate of unacceptable performances in EQA-PT schemes from 2019 to 2021 was 0%, while the 75th percentile reached nearly 4%. This finding reveals considerable performance variation among individual laboratories. Reporting-related indicators yielded satisfactory results. Most laboratories achieved 100% for timely critical value notification, despite statistically significant inter-annual variations (p < 0.05).</p><p><strong>Conclusions: </strong>Overall laboratory quality improved from 2019 to 2021. Deficiencies in tests covered by IQC and inter-laboratory comparison require targeted improvements and sustained monitoring of quality indicators.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122865"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application progress and prospects of non-invasive preimplantation genetic testing (niPGT): A review","authors":"Shaozhe Yang ,&nbsp;Rongxiang Li ,&nbsp;Bo Xu ,&nbsp;Yongyong Wu ,&nbsp;Junfeng Li ,&nbsp;Xiuhong Fu","doi":"10.1016/j.cca.2026.120945","DOIUrl":"10.1016/j.cca.2026.120945","url":null,"abstract":"<div><div>Preimplantation genetic testing (PGT) is a critical tool in reproductive medicine for selecting genetically healthy embryos, thereby reducing the risk of congenital disabilities. However, conventional PGT relies on invasive embryo biopsy, which carries risks of embryo damage and diagnostic challenges related to mosaicism. Non-invasive preimplantation genetic testing (niPGT), which analyzes embryonic cell-free DNA (cfDNA) from spent culture medium or blastocoel fluid, has emerged as a promising and safer alternative. This review provides a comprehensive overview of the principles, clinical applications, challenges, and future prospects of niPGT. Although some initial studies have indicated a correlation between niPGT for aneuploidy and the overall embryo or inner cell mass, its potential as an embryo sorting tool is hindered in clinical practice by the lack of reliability in its results. This issue could result in inaccurate assessments of viable embryos. Key challenges hindering its widespread adoption include low cfDNA yield leading to amplification failure, maternal and exogenous DNA contamination, the diagnostic dilemma of embryonic mosaicism, and a profound lack of standardized laboratory protocols. Future progress in the field will depend on technological innovations in cfDNA analysis, the integration of multi-omics data with artificial intelligence for comprehensive embryo assessment, and, most critically, large-scale clinical validation through randomized controlled trials. Establishing standardized guidelines and robust ethical frameworks is imperative for the responsible transition of niPGT from a promising research method to a reliable clinical tool.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"587 ","pages":"Article 120945"},"PeriodicalIF":2.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles as emerging biomarkers and therapeutic targets in neurodegenerative diseases","authors":"Askarova Zebo Zafarjonovna ,&nbsp;Elmuratova Aysulu ,&nbsp;Sanoeva Matlyuba ,&nbsp;Hamroyev Rashid ,&nbsp;Jurakulov Bakhrom Azamatovich ,&nbsp;Ahmadjonov Ahmadjon ,&nbsp;Amirullayeva Barno ,&nbsp;Azimova Mayram Kurbanovna ,&nbsp;Mahsudali Rohataliyev Mahmudali ugli ,&nbsp;Iskandarova Shaxodat ,&nbsp;Turakulov Rustam ,&nbsp;Matrizaeva Gulnara Jumaniyazovna ,&nbsp;Alisher Ishankulov","doi":"10.1016/j.cca.2026.120932","DOIUrl":"10.1016/j.cca.2026.120932","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood–brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"587 ","pages":"Article 120932"},"PeriodicalIF":2.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}