Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
High-throughput UHPLC-MS/MS method for 15 protein-bound uremic toxins in human serum.
Wu Q, Wan Z, Lan J … +7 more , Zhang X, Huang L, Ji B, Chen L, Sha Y, Pan Z, Shao Y
Clin Chim Acta · 2026 Jul · PMID 42044764 · Publisher ↗
Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a severe complication of chronic kidney disease (CKD), linked to the systemic accumulation of protein-bound uremic toxins (PBUTs). Current methods for PBUT an...
Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a severe complication of chronic kidney disease (CKD), linked to the systemic accumulation of protein-bound uremic toxins (PBUTs). Current methods for PBUT analysis are often constrained by limited analyte coverage and lack of integrated high-throughput quantification of multiple toxins. A high-throughput targeted Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the quantitative determination of PBUTs in human serum, including N-(carboxymethyl)lysine (CML) and pentosidine (PE). Reproducible sample preparation and reliable quantification were achieved using 96-well protein/phospholipid removal plates for sample preparation and optimizing chromatographic and mass spectrometric conditions. The method was validated, demonstrating acceptable linearity over the concentration range of 10-2000 ng/mL for all 15 analytes (R > 0.99), with lower limits of quantification (LLOQ) of 10-20 ng/mL. The limits of detection (LOD) ranged from 5 to 10 ng/mL, and the precision expressed as relative standard deviation (RSD) was below 15%. Application to serum samples from 40 uremic patients and 20 healthy controls revealed significantly elevated levels of 10 PBUTs, with p-cresyl sulfate (PCS) concentrations approximately 400-fold higher in patients. Five PBUTs were undetectable in healthy individuals. This study provides a reliable and accurate method for PBUTs quantification, offering valuable insights into the critical role of PBUTs in the pathogenesis of CKD-MBD, and advancing PBUT-related metabolomic research.
Automated ICAP AC-30/AC-2 discrimination on HEp-2 indirect immunofluorescence: development and clinical validation of a retrieval-based diagnostic system.
Wu C, Fang K, Li C … +2 more , Li Y, Wang J
Clin Chim Acta · 2026 Apr · PMID 42031356 · Publisher ↗
BACKGROUND: Accurate discrimination between the AC-2 nuclear dense fine speckled pattern and the AC-30 nuclear fine speckled pattern with mitotic plate on HEp-2 indirect immunofluorescence is required for ICAP-compliant...
BACKGROUND: Accurate discrimination between the AC-2 nuclear dense fine speckled pattern and the AC-30 nuclear fine speckled pattern with mitotic plate on HEp-2 indirect immunofluorescence is required for ICAP-compliant reporting but remains technically challenging. The 7th ICAP workshop established AC-30 as a distinct entity. Current automated systems operate at the competent level and do not address this expert-level distinction. In addition, the clinical interpretation of AC-2 depends on the complete autoantibody profile rather than pattern morphology alone, underscoring the need for precise and standardized pattern recognition. METHODS: We developed a retrieval-based diagnostic software module for second-stage AC-2 and AC-30 discrimination in specimens with confirmed mitotic plate positivity. The module integrates a MaxViT encoder with a Milvus vector database. It was developed on a retrospective cohort of 557 cases and independently validated on a prospective clinical cohort of 103 cases from a tertiary referral center. Performance was compared across six encoder architectures using both softmax classification and similarity-based retrieval. RESULTS: The optimal configuration achieved 95.1% overall accuracy on the internal hold-out validation set, with 100% precision and 90.6% recall for AC-30, resulting in no false-positive AC-30 assignments. Similarity-based retrieval consistently improved AC-30 precision across all evaluated architectures and demonstrated enhanced reproducibility across repeated runs. Each prediction was accompanied by a retrieved reference image, providing an interpretable and auditable evidence trail for laboratory quality assurance. CONCLUSION: This study presents a validated retrieval-based diagnostic software module for expert-level AC-2/AC-30 discrimination under updated ICAP nomenclature. The system improves class-specific precision while maintaining reproducibility and interpretability. Its vector database design enables incremental updates without retraining, supporting practical implementation in clinical laboratories as ICAP standards evolve. The module is designed as an assistive tool to support expert interpretation rather than replace clinical decision making.
Defining age partitions for thyrotropin (TSH) reference intervals in infancy: a robust statistical approach.
Senarathne U, Lu Z, Doery J … +13 more , Heather N, Kyle C, Heron R, Smith J, Coates P, Saleem M, Lim EM, Wijeratne N, McNeil A, Gangodaliyanage D, Brown J, Sikaris K, Hewitt J
Clin Chim Acta · 2026 Jul · PMID 42025902 · Publisher ↗
Age-specific thyrotropin (TSH) reference intervals (RIs) during the first year of life remain inadequately defined, posing a significant challenge given the essential role of thyroid hormones in normal growth and neurode...
Age-specific thyrotropin (TSH) reference intervals (RIs) during the first year of life remain inadequately defined, posing a significant challenge given the essential role of thyroid hormones in normal growth and neurodevelopment. Therefore, applying age-specific TSH RIs in the paediatric population is essential for accurate interpretation and to prevent diagnostic uncertainty and unnecessary testing. This indirect RI study aimed to establish statistically derived age partitions for TSH RIs that reflect thyroid physiology during the first year of life. De-identified TSH results from infants were extracted from a tertiary-care public hospital in Victoria, Australia. After excluding results from infants with repeat testing, extreme TSH values, and conditions affecting thyroid physiology, the remaining data were analysed using the Mann-Whitney U test, applied sequentially across 3-monthly, weekly, and daily intervals to identify physiologically relevant inflection points for age partitioning. The derived partitions were then validated using the proportion criteria described by Lahti et al., and TSH RIs were calculated as the 2.5th-97.5th percentiles. Of 17,525 TSH results from 11,045 infants, 7708 met the inclusion criteria. Five age partitions were established: days 0-1, 2, 3, 4-89, and 90-365. TSH peaked on days 0-1 (RI: 1.9-40.1 mIU/L), declined sharply by day 2, and decreased more gradually to near-adult levels by days 90-365 (RI: 0.7-5.7 mIU/L). No clinically significant sex differences were observed. This study presents a robust, data-driven framework for defining age-specific TSH RIs during the first year of life. The proposed methodology enhances diagnostic accuracy for thyroid disorders in infants and provides a reproducible approach for defining physiologically meaningful age partitions for other age-dependent analytes.
Efficacy of oncolytic viruses (OVs) in malignant tumor therapy: a review on its therapeutic aspects.
Das S, Goswami HR, Barman I … +1 more , Talukdar N
Clin Chim Acta · 2026 Jul · PMID 42025901 · Publisher ↗
Despite the life-saving potential of mainstream cancer therapies like surgery, chemotherapy and radiation, the clinical effectiveness is often limited by systemic toxicity, a lack of specificity and the survival of resis...
Despite the life-saving potential of mainstream cancer therapies like surgery, chemotherapy and radiation, the clinical effectiveness is often limited by systemic toxicity, a lack of specificity and the survival of resistant cancer stem cells. With a global cancer burden projected to exceed over 30 million new cases by 2050, oncolytic virotherapy has emerged as a significant development in cancer treatment. These viruses - either natural or genetically modified, selectively infect the cancer cells, replicate within them and destroy while sparing the healthy tissue. This review examines the therapeutic effectiveness and biological mechanisms of oncolytic viruses (OVs) as a modern approach to treating cancer aiming to discuss the engineered strategies that improve viral potency and safety, explore current clinical progress, and assess the potential of combination treatments. OVs mainly work through a two-pronged approach by direct killing or immunogenic cytolysis. By releasing tumor-specific antigens and pro-inflammatory signals, OVs change the cold tumor microenvironment into a hot one, drawing T-cells to attack both the main tumors and distant metastases. This review also explores key viral platforms, including the common viruses like the Adenovirus, Vaccinia virus, Herpes Simplex Virus (HSV-1) and Reovirus, across various cancers such as melanoma, glioblastoma and solid tumors. Clinical translation has advanced from anecdotal reports to over 250 active trials worldwide. While Imlygic remains a landmark FDA-approved treatment for melanoma, newer platforms like Delytact and H101 have received regional approvals. Key findings show that OVs are more effective when they are in synergy with immune checkpoint inhibitors like Pembrolizumab, that helps in achieving objective response rates (ORR) of up to 62% in advanced melanoma. However, challenges persist, including neutralization by host antibodies, physical barriers like high interstitial fluid pressure and scalability issues in manufacturing. Oncolytic virotherapy is now progressing to its next iteration, evolving from simple cytolytic agents to advanced programmable, biological platforms. Emerging trends, such as personalized neoantigen encoding and real-time monitoring with reporter genes, may help overcome existing delivery challenges. Integrating OVs with precision medicine and multimodal therapies is shaping the strategy for achieving durable clinical responses in the changing field of oncology.
Potential value of serum IL-6 and IL-8 as biomarkers for screening and severity stratification of diabetic retinopathy.
Wang YL, Su H, Hou LY … +2 more , Zhang CX, Dong YF
Clin Chim Acta · 2026 Jul · PMID 42019754 · Publisher ↗
Diabetic retinopathy (DR) remains a leading cause of vision impairment, and early detection with accurate staging is essential for effective intervention. Inflammation plays a pivotal role in DR pathogenesis, with interl...
Diabetic retinopathy (DR) remains a leading cause of vision impairment, and early detection with accurate staging is essential for effective intervention. Inflammation plays a pivotal role in DR pathogenesis, with interleukin-6 (IL-6) and interleukin-8 (IL-8) implicated in retinal microvascular dysfunction. However, their potential as biomarkers for DR screening and staging remains unclear. In this study, a total of 136 participants were enrolled, including 28 healthy controls (NC) and 108 patients with diabetes, stratified according to DR severity: no DR (NDR, n = 38), non-proliferative DR (NPDR, n = 40), and proliferative DR (PDR, n = 30). Serum IL-6 and IL-8 levels were measured using flow cytometry-based immunoassays. Reference intervals (2.5th-97.5th percentiles) were established for each stage, and receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance. In vitro validation was performed using high-glucose-stimulated 661 W photoreceptor and Müller glial cells. We found that serum IL-6 and IL-8 levels increased progressively with DR severity (P < 0.001). IL-6 and IL-8 median concentrations rose from 0.98 and 1.36 pg/mL in NC to 6.15 and 9.60 pg/mL in PDR, respectively. ROC analysis revealed remarkable discriminatory power for disease staging (IL-6: AUC = 1.00; IL-8: AUC = 0.96-1.00). High-glucose stimulation significantly upregulated IL-6 and IL-8 secretion in vitro. Our research provisionally demonstrates that serum IL-6 and IL-8 levels are closely associated with DR progression and exhibit promising potential as biomarkers for early screening and precise disease stratification, supporting their translational value in DR management.
Right ventricular-centered metabolomics: A promising tool for phenotyping pulmonary arterial hypertension.
Vicenzi A, Pagnoni G, Coppi F
Clin Chim Acta · 2026 Jul · PMID 42019753 · Publisher ↗
Recent advances in plasma metabolomics have highlighted the potential role of right ventricular-centered metabolic profiling in pulmonary arterial hypertension associated with atrial septal defect. By commenting on a tra...
Recent advances in plasma metabolomics have highlighted the potential role of right ventricular-centered metabolic profiling in pulmonary arterial hypertension associated with atrial septal defect. By commenting on a trans-cardiac metabolomic gradient approach, this letter discusses how right ventricular metabolic signatures may reflect adaptive and maladaptive mechanisms beyond hemodynamic burden alone. We contextualize these findings within emerging evidence from lipidomics, endothelial biomarkers, and systemic disease models, emphasizing the translational value of integrating metabolomics into phenotyping and risk stratification strategies for pulmonary hypertension.
Exosomes for myasthenia gravis: unraveling pathogenic insights and pioneering therapies.
Roudsari ZO, Hashemi Motahar H, Anarjan FS … +5 more , Rahdan F, Shodikulova G, Badr IH, Movahedpour A, Ehtiati S
Clin Chim Acta · 2026 Jul · PMID 42019752 · Publisher ↗
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by pathogenic autoantibodies targeting the neuromuscular junction, leading to fatigable muscle weakness. While traditional and novel biologic t...
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by pathogenic autoantibodies targeting the neuromuscular junction, leading to fatigable muscle weakness. While traditional and novel biologic therapies have advanced management, the complex immunopathology necessitates deeper mechanistic insights and improved diagnostic tools. Exosomes-small extracellular vesicles secreted by virtually all cell types-have emerged as pivotal players in intercellular communication, immune regulation, and disease propagation. This review synthesizes current evidence on the multifaceted roles of exosomes in MG. We detail their therapeutic potential, highlighting how engineered exosomes from tolerogenic dendritic cells or mesenchymal stem cells can deliver immunomodulatory cargo (e.g., miR-146a, caspase-1 inhibitors) to restore immune tolerance, suppress pathogenic antibody production, and ameliorate disease in experimental models. We explore their diagnostic utility as reservoirs of stable biomarkers, where dysregulated exosomal microRNAs (e.g., miR-106a-5p, miR-150-5p) and long non-coding RNAs correlate with disease severity, subtype, and treatment response, offering promise for non-invasive monitoring, especially in seronegative MG. Furthermore, we examine pathogenic mechanisms, whereby exosomal cargos may disrupt central thymic tolerance, amplify B- and T-cell activation via lncRNA-mediated miRNA sequestration, and contribute to neuromuscular dysfunction. By integrating findings across these domains, this review positions exosomes as critical mediators linking immune dysregulation to clinical manifestations in MG. Their dual nature as both disease contributors and therapeutic vehicles underscores their translational significance, paving the way for novel biomarker-driven strategies and targeted, cell-free immunotherapies in the precision medicine era.
Neuropeptide Y: a promising multifunctional neurotransmitter.
Xie Q, Zhong J, Yu S … +1 more , Qiu L
Clin Chim Acta · 2026 Jul · PMID 42019751 · Publisher ↗
Neuropeptide Y (NPY) is a neurotransmitter widely expressed in the central and peripheral sympathetic nervous systems. By binding to widely distributed G protein-coupled receptors, active NPY is involved in regulating va...
Neuropeptide Y (NPY) is a neurotransmitter widely expressed in the central and peripheral sympathetic nervous systems. By binding to widely distributed G protein-coupled receptors, active NPY is involved in regulating various physiological processes, including energy homeostasis, insulin secretion, vasoconstriction, angiogenesis, cell proliferation and differentiation. Consequently, it plays an important role in the pathophysiology of obesity, diabetes, heart failure, myocardial infarction and cancers. However, most existing studies are limited to the preclinical stage, clinical evidence remains relatively scarce, and inconsistencies exist among some findings. Therefore, this review aims to provide a more comprehensive perspective from the following three aspects: (1) the biosynthesis and metabolic pathways for NPY; (2) the current status of detection methods for NPY; and (3) the key physiological roles and molecular mechanisms underlying its involvement in diseases. Collective analysis reveals that different NPY peptide forms (NPY, NPY, NPY) exhibit significantly different physiological roles in the central nervous system and peripheral tissues, highlighting the need to accurately distinguish these peptides. Currently, enzyme-linked immunosorbent assay remains the primary method for NPY quantification, yet results derived from human samples are highly heterogeneous. Methodological limitations may represent a major reason why preclinical findings are difficult to be consistently validated in clinical studies. Thus, it is necessary to establish more accurate, stable, and standardized strategies for quantitative analysis of NPYto bridge the gap between basic research and clinical practice.
Electrochemical biosensors for MLKL-related necroptosis biomarkers in lung cancer: From bench to clinical laboratory.
Kazmi I, Alzarea SI, Shahwan M … +7 more , Thakur P, Rathore V, Hajarnavis AM, Uniyal P, Maji C, Almujri SS, Almalki WH
Clin Chim Acta · 2026 Jul · PMID 42019750 · Publisher ↗
Lung cancer continues to be a leading cause of cancer-related mortality globally, necessitating the development of enhanced biomarkers for early detection and ongoing disease monitoring in clinical practice. Current diag...
Lung cancer continues to be a leading cause of cancer-related mortality globally, necessitating the development of enhanced biomarkers for early detection and ongoing disease monitoring in clinical practice. Current diagnostic methodologies predominantly rely on imaging and tissue biopsy, which may not sufficiently capture the dynamic molecular alterations occurring during disease progression. Necroptosis is an inflammatory form of regulated cell death that is pathologically relevant in lung cancer. Mixed lineage kinase domain-like protein (MLKL) and its phosphorylated form (pMLKL) have become molecular executors and targets of biomarker clinical applications. In contrast to the available reviews that cover biosensor technologies and regulated cell death in general, this review is uniquely focused on MLKL-centric necroptosis biology and electrochemical biosensing as an analysis gap in clinical laboratory applications. Electrochemical biosensors have emerged as promising analytical platforms for the rapid and sensitive detection of disease-associated targets in complex biological samples. This review critically analyzes recent developments in MLKLs- and pMLKL-related necroptosis biomarkers and electrochemical biosensing approaches for their detection in clinically relevant specimens, such as serum, plasma, and bronchoalveolar lavage fluid (BALF). The focus is on the design of electrode interfaces, biorecognition components such as antibodies, aptamers, and molecularly imprinted polymers, and signal amplification methods. The limitations of traditional techniques such as ELISA, immunohistochemistry, and PCR are critically analyzed when compared to biosensor techniques. An informatics framework bridging laboratory research and clinical applications is proposed, focusing on AI-assisted informatics for the integration of a multimodal MLKL biomarker panel. This study underscores the potential of electrochemical biosensing as a distinctive approach for developing MLKL-specific necroptosis diagnostics in lung cancer.
Labile Hemoglobin A (LHbA): From analytical interference to clinically valuable biomarker.
Wang K, Han W
Clin Chim Acta · 2026 Jul · PMID 42019749 · Publisher ↗
Labile hemoglobin A (LHbA), the reversible Schiff base intermediate formed during early hemoglobin glycation, has long been regarded solely as an analytical interference requiring elimination for accurate HbA measurement...
Labile hemoglobin A (LHbA), the reversible Schiff base intermediate formed during early hemoglobin glycation, has long been regarded solely as an analytical interference requiring elimination for accurate HbA measurement. This review synthesizes research from 2016 to 2024, examining the biochemical foundations, measurement methodologies, and emerging clinical applications of LHbA. Unlike stable HbA, which reflects average glycemia over 2-3 months, LHbA correlates with glycemic levels over hours to days, thereby bridging a critical information gap in diabetes assessment. Recent studies demonstrate the value of LHbA in detecting acute glycemic excursions, screening for hemoglobin variants, identifying preanalytical errors, and providing insights into the "glycation gap" through the LHbA/HbA ratio. Mathematical modeling has elucidated the kinetic relationships among glucose, LHbA, and stable HbA, enabling quantitative predictions of LHbA behavior under various clinical scenarios. The LHbA/HbA ratio has emerged as a particularly versatile parameter, with values outside the reference range identifying approximately 15% of samples in which HbA may not reflect expected glycemia. We argue that LHbA, long dismissed as mere interference, deserves recognition as a clinically valuable parameter that, when interpreted alongside established glycemic markers, can enhance precision diabetes care. However, standardization efforts and prospective outcome studies remain essential before widespread clinical adoption.
Evaluation and clinical application of an accurate isotope dilution liquid chromatography-tandem mass spectrometry method for serum glycocholic acid.
Jin Z, Ou Y, Zong M … +8 more , Ye Z, Li Z, Zhang S, Sun H, Fan X, Luo X, Jiang L, Ju Y
Clin Chim Acta · 2026 Jul · PMID 42019748 · Publisher ↗
OBJECTIVES: Glycocholic acid (GCA) is an important identified biomarker for various hepatobiliary diseases. Accurate measurement of GCA is essential for diagnosis and treatment of hepatobiliary diseases. Our aim was to d...
OBJECTIVES: Glycocholic acid (GCA) is an important identified biomarker for various hepatobiliary diseases. Accurate measurement of GCA is essential for diagnosis and treatment of hepatobiliary diseases. Our aim was to develop and validate a high accuracy method for the quantification of GCA in serum. METHODS: An isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS) method has been developed and validated. The assay validation was performed, including imprecision, trueness, matrix effects, linearity, interference, and carry-over, etc. Furthermore, the developed method was applied to comparison with three latex-enhanced immunoturbidimetric assays and for external quality assessment (EQA) of clinical systems. RESULTS: Excellent linearity coefficients (R = 0.9998) were obtained in the range from 0.063 to 49.53 μg/g. The limit of detection and limit of quantification were 0.1 ng/mL and 2.3 ng/mL, respectively. The total imprecisions were below 2.33% for low, medium, and high concentration samples. Good recoveries were achieved at three spiked levels (98.94% - 101.80%), and a relative expanded uncertainty was < 3% (k = 2). No interference, matrix effects, or carry-over were observed. Significant bias across routine GCA assays obtained by immunoassays and ID-LC/MS/MS method highlighted the urgency of standardization for the measurement of GCA. CONCLUSIONS: This study successfully established an accurate quantitative method for detecting serum GCA using ID-LC/MS/MS. The method could serve as an accurate reference baseline for routine methods and can be used for value assignment for reference materials. It could support EQA management for GCA testing and promote GCA standardization.
ISG15 as a novel serum biomarker for breast Cancer: Diagnostic and prognostic significance, clinical laboratory applications, and multi-biomarker integration strategies.
Rahman S, Al-Zharani M, Afzal M … +7 more , Alfakeeh S, Al-Blwi NS, Sindi MM, Al-Osaimi MM, Moafa AE, Alghazali SA, Al-Abbasi FA
Clin Chim Acta · 2026 Jul · PMID 42019747 · Publisher ↗
The clinical management of breast cancer depends on circulating biomarkers, which aid in the early detection of breast cancer, stratification of prognosis, and monitoring of therapy efficacy. However, existing serum mark...
The clinical management of breast cancer depends on circulating biomarkers, which aid in the early detection of breast cancer, stratification of prognosis, and monitoring of therapy efficacy. However, existing serum markers, such as CA15-3, carcinoembryonic antigen, and circulating HER2 extracellular domain, have poor sensitivity in the early stages of the disease and incomplete specificity when used as individual tests. ISG15 (interferon stimulated gene 15) is a ubiquitin like modifier, which is released into the blood at the time of immune activation, has now become an easy-to-measurable circulating protein indicating tumor associated immune signaling and disease progression. This review critically assesses the relevance of serum ISG15 in the diagnosis and prognosis of breast cancer in the context of clinical chemistry and laboratory medicine. It should be mentioned that direct evidence of breast cancer serum is not abundant; most evidence is extrapolated to other forms of cancer or tissue-based research. Analytical studies have provided evidence that ISG15 can be detected in serum but have also emphasized that pre-analytical variables, assay platforms, analytical sensitivity, and inter-study heterogeneity have a strong effect on the measured concentrations. Moreover, ISG15 can be increased in non-malignant infections and inflammatory diseases, which should be considered when interpreting clinical measurements. Existing evidence indicates that ISG15 will probably not be able to replace well-known tumor markers but might have an additive clinical value when included in multiplexing biomarkers and risk algorithms. The enactment of ISG15 in clinical laboratory practices entails standardized assays, clearly defined decision limits, rigorous quality management, and prospective validation across diverse patient groups. Overall, serum ISG15 is a biologically feasible and analytically measurable candidate biomarker that meets the translational clinical chemistry objectives; however, its clinical implementation requires assay harmonization, outer validation, and incremental validation over the existing laboratory tests.
Electrochemical microRNA biosensors for gallbladder cancer: Translational perspectives for clinical chemistry and point-of-care diagnostics.
Goyal A, Hajarnavis AM, Jakhmola V … +5 more , Shahwan M, Lakshmi T, Vijayan MP, Almujri SS, Almalki WH
Clin Chim Acta · 2026 Jul · PMID 42019746 · Publisher ↗
Gallbladder cancer is a biliary malignancy characterized by a high mortality rate, primarily due to the limitations of current serum biomarkers and imaging techniques in detecting the disease at an early stage. Circulati...
Gallbladder cancer is a biliary malignancy characterized by a high mortality rate, primarily due to the limitations of current serum biomarkers and imaging techniques in detecting the disease at an early stage. Circulating microRNAs (miRNAs) in serum, plasma, and bile are stable, less invasive biomarkers that are indicative of the biology of gallbladder cancer and have the potential for diagnostics through liquid biopsy. This review critically evaluates miRNA-based electrochemical biosensors that have been developed to detect gallbladder cancer, including their analytical performance, sensitivity, specificity, and detection limits in clinically relevant matrices, preanalytical variables, and analytical and clinical validation in clinical laboratories. We provide a brief overview of the relevant miRNA signatures in disease, their specificity to gallbladder cancer over other malignancies and inflammatory responses, comment on the approaches to transduction and nanomaterial-engineered interfaces in the detection of sensitive miRNAs in human biofluids, and critique the performance of biosensors in relation to the conventional molecular procedures, such as RT-qPCR and droplet digital PCR (ddPCR). In routine applications, particular emphasis is placed on specificity, detection limits in clinically relevant matrices, robustness, and sources of both analytical and biological variability. This encompasses the complex composition of bile, which includes bile salts, proteins, and pH changes that can pose challenges such as electrode fouling. We also describe how these biosensors are integrated into central laboratories and point-of-care procedures to diagnose, differentiate between malignant and inflammatory biliary lesions, assess risks, and treat gallbladder cancer. The review provides a conceptual framework of translation that reinforces the purpose and reasoning behind the implementation of electrochemical biosensors in clinical oncology by bridging miRNA pathobiology with miRNA electrochemical biosensors assay engineering and laboratory medicine issues to guide the design and implementation of miRNA electrochemical biosensors as a clinical diagnostic tool.
Trimethyllysine as a potential biomarker for heart failure.
Lei Y, Fang Q, Wu Q … +7 more , Xiong G, Jiang J, Wu Y, Chen L, Ouyang D, Li Z, Li X
Clin Chim Acta · 2026 Jul · PMID 42019745 · Publisher ↗
Trimethyllysine (TML), a methylated amino acid involved in carnitine biosynthesis, has been linked to cardiovascular disease. This cross-sectional study assessed the association between plasma TML and heart failure (HF),...
Trimethyllysine (TML), a methylated amino acid involved in carnitine biosynthesis, has been linked to cardiovascular disease. This cross-sectional study assessed the association between plasma TML and heart failure (HF), and its potential as a diagnostic biomarker. We enrolled 104 participants (65 stable HF patients and 39 non-HF controls) and quantified plasma TML using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results showed that plasma TML levels were significantly higher in the HF group and correlated with various clinical parameters: positively with alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA), and left ventricular end-diastolic diameter (LVEDD), and negatively with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDLC), estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF). After adjusting for age, sex, BMI, smoking, alcohol, comorbidities, and traditional clinical factors, higher TML levels remained independently associated with HF (T3 vs. T1: adjusted odds ratio 5.41, 95% confidence interval 1.08-27.15, P = 0.040). Elevated TML was cross-sectionally associated with renal dysfunction in HF patients (odds ratio 32.12, 95% confidence interval 2.59-398.13, P = 0.007). The receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.673 (95% CI 0.570-0.776) for TML in distinguishing HF. In conclusion, elevated plasma TML is independently associated with HF and may indicate renal dysfunction in HF patients, supporting its potential as a clinically relevant biomarker for HF evaluation.
Letter to the editor regarding: "Heat-resistant cryoglobulin investigated through dynamic cryoaggregation assay and mass spectrometry". Clinica Chimica acta 586(2026) 120935.
Wang L, Xu X, Zhou H … +2 more , Zhang F, Li H
Clin Chim Acta · 2026 Jul · PMID 42014013 · Publisher ↗
Abstract loading — click title to view on PubMed.
Cuproptosis-related circulating non-coding RNAs as diagnostic and prognostic biomarkers in oncology.
Afzal O, Afzal M, Goud P … +5 more , Vijayan MP, Altharawi A, Alamri MA, Alossaimi MA, Altamimi ASA
Clin Chim Acta · 2026 Jul · PMID 42014012 · Publisher ↗
Cuproptosis is a recently described copper-dependent form of regulated cell death linked to mitochondrial metabolic stress and is emerging as a biologically relevant pathway in cancer. Circulating noncoding RNAs (ncRNAs)...
Cuproptosis is a recently described copper-dependent form of regulated cell death linked to mitochondrial metabolic stress and is emerging as a biologically relevant pathway in cancer. Circulating noncoding RNAs (ncRNAs), such as microRNAs, long noncoding RNAs and circular RNAs, can be quantified in body fluids and are potential liquid biopsy markers in laboratory medicine. This review evaluates the diagnostic and prognostic utility of cuproptosis-related circulating ncRNAs across human malignancies, with an emphasis on their relevance to clinical chemistry and diagnostic laboratory medicine. We synthesize current evidence linking these circulating ncRNAs to key regulators of cuproptosis, tumor stage, treatment response, and survival outcomes. We further examine their potential roles in early detection, differential diagnosis, risk stratification, and longitudinal disease monitoring, including their value relative to conventional tumor markers. The review highlights laboratory factors affecting clinical implementation, including specimen matrix selection (serum, plasma, and extracellular vesicle-associated fractions), preanalytical variability, normalization strategies, and cross-platform analytical validation. We also discuss how multimodal diagnostic models, artificial intelligence, and data-driven analytical frameworks may improve biomarker interpretation and support standardization. Overall, translating cuproptosis-related ncRNA signatures into routine diagnostic laboratory practice will require analytically validated workflows, standardized reporting, and prospective clinical validation. This review provides a laboratory medicine-focused framework for understanding the opportunities and current limitations of cuproptosis-related circulating ncRNAs as emerging biomarkers in oncology.
Emerging biomarkers for early detection of colorectal cancer.
Qannita RA, Zenati RA, Abuhelwa AY … +8 more , Alqudah MAY, Aleidi SM, El-Huneidi W, Abu-Gharbieh E, AlShareef ZM, Alzoubi KH, Bustanji Y, Semreen MH
Clin Chim Acta · 2026 Jul · PMID 42009160 · Publisher ↗
The worldwide impact of colorectal cancer (CRC) as a primary cause of cancer-related morbidity and mortality demonstrates the urgent need for better early detection methods and personalized treatment approaches. While co...
The worldwide impact of colorectal cancer (CRC) as a primary cause of cancer-related morbidity and mortality demonstrates the urgent need for better early detection methods and personalized treatment approaches. While colonoscopy and fecal tests have contributed to reduced mortality rates from CRC, they encounter important limitations stemming from their invasive procedures and insufficient sensitivity plus patient adherence issues. Consequently, the latest progress in molecular biology and omics technologies has enabled researchers to identify new biomarkers which present effective solutions for early detection and risk assessment while monitoring treatment efficacy. Therefore, this review explores new developments in CRC biomarker research through the lens of emerging liquid biopsy methods like circulating tumor DNA (ctDNA) and microRNAs (miRNAs) as well as genomic, epigenomic, gut microbiome, metabolomic, and proteomic markers. The usage of biomarker-based methods demonstrates transformative potential for CRC treatment by boosting survival rates and lessening global impact through precision medicine development in oncology.
Metal exposure in heart disease.
Hocher B
Clin Chim Acta · 2026 Jul · PMID 42001927 · Publisher ↗
Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. In addition to classical risk factors, environmental exposures to toxic metals have been increasingly associated with cardiovascu...
Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. In addition to classical risk factors, environmental exposures to toxic metals have been increasingly associated with cardiovascular risk in epidemiological studies. This narrative review summarizes current PubMed-indexed literature on the association of lead, cadmium, arsenic, mercury, and chromium with CHD, with emphasis on epidemiological evidence, mechanistic studies, and clinical implications. Literature was selected to cover major human observational studies, relevant experimental data, and translational reports addressing exposure pathways, biomarkers, vascular mechanisms, and prevention. Available epidemiological evidence suggests that chronic exposure to lead, cadmium, and arsenic is associated with higher risks of hypertension, atherosclerotic cardiovascular disease, and cardiovascular mortality, whereas the evidence for mercury and chromium is more heterogeneous and context-dependent. Mechanistic evidence, derived mainly from experimental and translational studies, indicates that these metals can promote oxidative stress, inflammation, endothelial dysfunction, disturbed lipid handling, mitochondrial injury, and, in some cases, epigenetic remodeling, thereby contributing to atherogenesis and plaque progression. However, the strength of evidence differs across metals and mechanisms, and causal interpretation remains strongest where experimental plausibility and human data converge. Clinically, heavy metal exposure should be considered in selected patients with CHD, particularly those with atypical risk profiles, relevant environmental or occupational exposure histories, or unexplained disease progression despite optimal standard management. Whole blood and urine measurements remain the preferred biomarkers in most settings, whereas hair analysis requires cautious interpretation. Prevention focuses on exposure reduction through water and food safety, emission control, smoking cessation, and targeted public health measures. Overall, toxic metals represent a plausible and likely underrecognized contributor to cardiovascular disease that deserves greater integration into cardiovascular prevention and environmental health research.
The association between ceramide levels and hepatic steatosis severity in metabolic dysfunction-associated fatty liver disease.
Yang R, Xu J, Zhao F … +6 more , Sun X, Li Y, Zhang Y, Peng H, Ding L, Guo B
Clin Chim Acta · 2026 Jul · PMID 42001926 · Publisher ↗
BACKGROUND AND AIMS: Ceramides (Cers) have been linked to various metabolic disorders, but the relationship between ceramide levels and hepatic steatosis in patients with metabolic dysfunction-associated fatty liver dise...
BACKGROUND AND AIMS: Ceramides (Cers) have been linked to various metabolic disorders, but the relationship between ceramide levels and hepatic steatosis in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. This study investigates the association between ceramide levels and hepatic steatosis, including its severity, in MAFLD patients. METHODS: A cross-sectional study was conducted with 344 participants, including 249 MAFLD patients and 95 healthy controls. Five ceramides were measured using LC-MS/MS. Binary logistic regression was applied to compare ceramide levels in patients with and without hepatic steatosis, while ordinal logistic regression assessed the relationship between ceramide levels and the severity of hepatic steatosis. Heatmap analysis visualized the associations between clinical indicators and ceramide levels. RESULTS: Ceramide levels were significantly higher in MAFLD patients with hepatic steatosis compared to those without. Ceramide 20:0 in the third quartile was positively associated with hepatic steatosis risk (OR = 5.08, 95% CI = 1.53-16.80). Additionally, ceramide 18:0 in the fourth quartile showed a positive correlation with the severity of hepatic steatosis (OR = 2.85, 95% CI = 1.12-7.26). Heatmap analysis revealed positive correlations between hepatic fat attenuation index, ceramides, and clinical parameters, except for HDLC, which showed a negative correlation. CONCLUSIONS: Elevated ceramide levels are a significant risk factor for hepatic steatosis and its severity in MAFLD patients. Monitoring ceramide levels may provide valuable insights for preventing liver disease progression and related complications.
Circulating metabolic and inflammatory biomarkers in MINOCA: pathophysiologic mechanisms and clinical implications.
Abdu FA, Hu H, Lu P
Clin Chim Acta · 2026 Jul · PMID 42001925 · Publisher ↗
Metabolic dysregulation and systemic inflammation are key contributors to the development of myocardial infarction with non-obstructive coronary arteries (MINOCA). MINOCA accounts for 5-15% of all acute myocardial infarc...
Metabolic dysregulation and systemic inflammation are key contributors to the development of myocardial infarction with non-obstructive coronary arteries (MINOCA). MINOCA accounts for 5-15% of all acute myocardial infarctions, with a prognosis comparable to obstructive coronary artery disease. Despite its clinical significance, current risk assessment and management remain inadequate, as traditional methods focused on epicardial obstruction overlook the systemic disturbances underlying MINOCA. This gap has driven interest in circulating biomarkers reflecting the mechanisms of microvascular dysfunction and myocardial injury. We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library from inception to May 2025, reviewing mechanistic and clinical studies on metabolic and inflammatory biomarkers in MINOCA. Evidence indicates that insulin resistance, hyperglycemia, dyslipidemia, thyroid dysfunction, hyperuricemia, renal impairment, hepatic dysfunction, and elevated inflammatory biomarkers independently contribute to endothelial dysfunction, coronary microvascular impairment, and vasomotor disturbances. These disruptions independently predict adverse cardiovascular outcomes. Specific metabolic biomarkers with demonstrated prognostic value include the stress hyperglycemia ratio, triglyceride-glucose index, atherogenic index of plasma, remnant cholesterol, lipoprotein(a), free triiodothyronine-to-free thyroxine ratio, serum uric acid, total bilirubin, fibrinogen-to-albumin ratio, and estimated glomerular filtration rate, while key inflammatory biomarkers include C-reactive protein, systemic inflammation response index, white blood cell count to mean platelet volume ratio, systemic immune-inflammation index, perivascular fat attenuation index, and interleukin-6. These findings are synthesized into a unified cardiometabolic-immune framework linking biomarker profiles to underlying pathophysiological mechanisms. We highlight the need for prospective multicenter validation, standardized protocols, and randomized trials targeting metabolic-inflammatory pathways to develop personalized management strategies for this underrecognized population.
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