Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
Platelet-derived extracellular vesicles as neurodegenerative disease biomarkers.
Alqahtani SM, Afzal M, Afzal O … +3 more , Alabbas A, Phalak P, Goyal K
Clin Chim Acta · 2026 Jun · PMID 42229706 · Publisher ↗
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are increasingly prevalent worldwide and have not yet been adequately diagnosed, especially because they re...
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are increasingly prevalent worldwide and have not yet been adequately diagnosed, especially because they require minimally invasive, non-invasive techniques. Although established blood-based biomarkers, such as plasma p-tau217, neurofilament light chain (NfL), and GFAP, have shown clinical utility, limitations in sensitivity and scalability remain. Platelets, anucleate cytoplasmic fragments originating from megakaryocytes, are the primary producers of extracellular vesicles in the peripheral blood. These vesicles contain disease-specific cargo, including amyloid-β, α-synuclein, tau, disease-associated glycoproteins, and microRNAs (miRNAs) derived from platelets. Recent findings suggest that the cargo of platelet-derived extracellular vesicles (pEVs) may be associated with neurodegenerative changes linked to disease severity. However, validation through a prospective multicenter study is necessary. A systematic narrative review was performed by searching the PubMed, Scopus, and Web of Science databases with the keywords "platelet-derived extracellular vesicles," "platelet microvesicles," "neurodegeneration," and "biomarkers" (inception through April 2026). This review discusses the biogenesis of pEV, their composition in relation to blood markers, and their pathomechanistic roles, such as platelet-mediated blood-brain barrier disruption, neuroinflammation, and misfolded protein seeding. The diagnostic evidence of pEV-associated cargo in neurodegenerative diseases is critically evaluated and contextualized with current blood markers. Key preanalytical considerations, including the selection of anticoagulants, isolation procedures, storage conditions, and the number of freeze-thaw cycles, as well as analytical considerations, such as flow cytometric calibration, single-vesicle resolution, and multiplexed platforms, are examined for their applicability in clinical laboratory settings. The emphasis is on reporting according to the MISEV and the harmonization between laboratories. The limitations of this study are the small heterogeneous cohorts, lack of preanalytical handling standardization, ex vivo platelet activation artifact, and lack of external validation.
Usefulness of PPi levels to interpret variants of unknown significance and incomplete penetrant alleles in the ABCC6 gene.
Van Wynsberghe J, De Zaeytijd J, Verschuere S … +4 more , Van Gils M, De Backer T, Hemelsoet D, Vanakker O
Clin Chim Acta · 2026 Jun · PMID 42229705 · Publisher ↗
Pseudoxanthoma elasticum is usually caused by biallelic pathogenic variants in ABCC6, leading to reduced ATP transport and decreased levels of circulating calcification inhibitor inorganic pyrophosphate. Variants of unkn...
Pseudoxanthoma elasticum is usually caused by biallelic pathogenic variants in ABCC6, leading to reduced ATP transport and decreased levels of circulating calcification inhibitor inorganic pyrophosphate. Variants of unknown significance and incomplete penetrant variants complicate genetic counseling. This study assessed whether plasma pyrophosphate levels can aid in interpreting their pathogenicity or penetrance. Blood samples were collected from 90 patients, 139 carriers, and 31 healthy volunteers. Demographic, clinical, imaging, and biochemical data were collected. ABCC6 variants were classified according to Sherloc guidelines into (likely) pathogenic, variant of unknown significance, or variant with incomplete penetrance. The latter two were further classified as 'Likely causal' or 'No arguments for causality'. Participants were grouped accordingly for comparative analysis of plasma pyrophosphate levels. Plasma pyrophosphate levels were significantly decreased in patients compared to carriers and controls. However, large variability persisted within cohorts and individual families. No differences in plasma pyrophosphate levels were observed between the variant types. In carriers, no significant differences were observed between presumed penetrant versus non-penetrant variants or between presumed causal versus non-causal variants of unknown significance. Although pyrophosphate levels are reduced in patients, ABCC6 variant classification does not affect pyrophosphate levels. Our results show that plasma pyrophosphate levels have no added value for interpreting causality of variants of unknown significance or penetrance of incomplete penetrant alleles in ABCC6.
Plasma autoantibodies as novel risk markers for stroke: A nested case-control study of the JPHC study.
Yamagishi K, Hiwasa T, Sun W … +27 more , Sata M, Yamaji T, Iwasaki M, Inoue M, Sawada N, Yoshida Y, Kubota M, Matsutani T, Higuchi Y, Li SY, Zhang BS, Machida T, Goto KI, Ohno M, Nishi E, Wang H, Kudo T, Doi H, Tomiyoshi G, Nakamura R, Muraki I, Kokubo Y, Saito I, Yatsuya H, Iso H, Tsugane S, JPHC Study Group
Clin Chim Acta · 2026 Jun · PMID 42225204 · Publisher ↗
BACKGROUND AND AIMS: Recent reports have shown the development of autoantibodies in patients with atherosclerosis. The purpose of this study is to examine whether these autoantibodies are associated with the risk of inci...
BACKGROUND AND AIMS: Recent reports have shown the development of autoantibodies in patients with atherosclerosis. The purpose of this study is to examine whether these autoantibodies are associated with the risk of incident stroke in community-based population. METHODS: We performed a nested case-control study within the Japan Public Health Center-based Prospective Study involving 32,527 Japanese individuals aged 40-69 years at baseline (1990-1993). Incident stroke was followed up until the end of 2007. We identified 38 novel autoantibody biomarkers for atherosclerosis, and the plasma levels of these autoantibodies were measured by use of amplified luminescent proximity homogeneous assay-linked immunosorbent assay methods in 371 stroke cases (203 ischemic and 168 hemorrhagic) and 371 age-, sex-, and community-matched controls. Conditional odds ratios of total, ischemic, and hemorrhagic strokes according to quartiles of each autoantibody were calculated after adjustment for major cardiovascular risk factors. RESULTS: Of the 38 the novel autoantibodies, the levels of anti-DIDO1 peptide, anti-LIMA1 peptide, anti-SH3BP5 peptide, anti-FOXJ2 peptide, anti-KIF20B protein, anti-DIDO1 protein, anti-TPM3 protein, anti-COPE protein, anti-MMP1 protein and anti-IFI16 peptide autoantibodies were significantly associated with the risk of total stroke (odds ratios of the highest versus lowest quartile ≥1.63) after adjustment for major cardiovascular risk factors. The association was generally similar but weakly observed for ischemic stroke but not for hemorrhagic stroke. CONCLUSIONS: These novel autoantibodies have the potential to predict future stroke incidence.
Calreticulin mutations in essential thrombocythemia and primary myelofibrosis.
Bhat AA, Fuloria S, Thapa R … +7 more , Agnihotri S, Ansari MT, Narain K, Biswas A, Biswas S, Bhatia S, Fuloria NK
Clin Chim Acta · 2026 Jun · PMID 42225203 · Publisher ↗
Mutations in calreticulin have been identified as driver mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) and are especially important for diagnostics and prognosis in primary myelofibrosis and essentia...
Mutations in calreticulin have been identified as driver mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) and are especially important for diagnostics and prognosis in primary myelofibrosis and essential thrombocythemia. The vast majority of pathogenic variants are insertions or deletions in exon 9 that result in a mutant C-terminal sequence that activates the signaling of the thrombopoietin receptor, which in turn promotes megakaryocytic proliferation. This review examines the potential clinical utility of calreticulin mutations as laboratory biomarkers in essential thrombocythemia (ET) and primary myelofibrosis (PMF). It emphasizes their role in confirming clonality in JAK2/MPL-unmutated cases, distinguishing a clonal myeloproliferative disease from reactive thrombocytosis, clarifying the molecular interpretation, and guiding molecular diagnostic workflows. Special focus is placed on practical laboratory challenges, such as choosing assays, detecting rare and non-canonical variants in exon 9, analytical sensitivity, molecular reporting, and the integration of bone marrow morphology, cytogenetics, co-mutations, and next-generation sequencing. Overall, clinical information gained from calreticulin testing is greatest when it is used in an integrated clinicopathologic and molecular testing context rather than as a standalone test. To make calreticulin mutations more effectively used for diagnosis or prognosis in routine hematology practice, we need standardization of testing, harmonization of reporting, and prospective validation of risk-models based on both the subtypes and the burden of the mutation.
Machine learning models for reducing false positives in Fluorometric newborn screening of phenylketonuria: Development, validation, and clinical application.
Gao Y, Duan G, Zhang W … +7 more , Zhan Z, Huang F, Zhong L, Xie S, Yu W, Wu B, Liu W
Clin Chim Acta · 2026 Jun · PMID 42225202 · Publisher ↗
BACKGROUND: Fluorometric newborn screening for phenylketonuria (PKU) is widely used but plagued by high false positives (FPs), leading to unnecessary follow-ups and parental anxiety. Machine learning (ML) models may opti...
BACKGROUND: Fluorometric newborn screening for phenylketonuria (PKU) is widely used but plagued by high false positives (FPs), leading to unnecessary follow-ups and parental anxiety. Machine learning (ML) models may optimize screening efficiency by reducing FPs while preserving sensitivity. METHODS: A retrospective study used fluorometric PKU screening data from 493,652 neonates (2022-2024) at Shenzhen Maternity and Child Healthcare Hospital. The cohort included 70,342 concurrent tandem mass spectrometry (MS/MS) tests, with 711 screen-positive cases selected for internal validation. A 1:2 propensity score matching (PSM) cohort (n = 120, 40 confirmed PKU cases and 80 false-positive cases) was constructed to validate model robustness. An temporal cohort comprised 539 screen-positive cases from 154,721 neonates screened in 2021. Key predictors were selected via least absolute shrinkage and selection operator (LASSO) regression. Four ML models (logistic regression, extreme gradient boosting (XGBoost), support vector machine (SVM), random forest) were trained and evaluated based on sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). RESULTS: LASSO regression identified three predictors: fluorometric phenylalanine (Phe) concentration, gestational age, and birth weight. Logistic regression performed best, achieving an AUC of 0.873 (95% CI: 0.780-0.958) in internal validation and 0.955 in the test cohort. Temporal validation confirmed strong performance, with an AUC of 0.927 and 100% sensitivity in both test and temporal cohorts. In the PSM test subset, the model yielded an AUROC of 0.813 and a PPV of 0.538. A freely accessible web-based prediction tool was developed and deployed. CONCLUSION: Using only three routine clinical variables, our logistic regression model effectively stratified PKU risk in screen-positive newborns, significantly reducing FPs without sacrificing sensitivity. This offers a cost-effective tool for optimizing fluorometry-based newborn screening workflows.
CircRNAs as central regulators of Immunometabolic crosstalk in hepatocellular carcinoma.
Sulaiman SH, Omer RA, Barzani HAH … +6 more , Muhammad HY, Qader AB, Muhammad EH, Muhammad DK, Ahmad SW, Ali HS
Clin Chim Acta · 2026 May · PMID 42219103 · Publisher ↗
Hepatocellular carcinoma (HCC) is distinguished by profound metabolic reprogramming and a highly immunosuppressive tumor microenvironment, two hallmarks that cooperatively drive tumor progression and therapeutic resistan...
Hepatocellular carcinoma (HCC) is distinguished by profound metabolic reprogramming and a highly immunosuppressive tumor microenvironment, two hallmarks that cooperatively drive tumor progression and therapeutic resistance. While metabolic rewiring and immune escape have traditionally been studied as parallel processes, the molecular regulators that integrate these pathways remain incompletely defined. Circular RNAs (circRNAs) are a type of covalently closed non-coding RNAs with exceptionally stable and regulatory versatility, and have recently emerged as critical modulators of both cancer metabolism and immune signaling. However, their coordinated role at the intersection of metabolism and immunology in HCC has not been systematically synthesized. This review provides a comprehensive, mechanistic framework that positions circRNAs as central regulators of immunometabolic crosstalk in HCC. We summarize how circRNAs modulate glycolysis, lipid remodeling, glutamine metabolism, and redox balance while simultaneously regulating immune checkpoint pathways, macrophage polarization, T-cell depletion, and NK-cell dysfunction. We further discuss exosomal circRNAs as mediators of tumor-immune communication and remodeling of the tumor microenvironment, linking metabolic stress responses to adaptive immune suppression. Importantly, we highlight circRNA-driven immunometabolic circuits as contributors to resistance against immune checkpoint inhibitors and metabolic therapies. By integrating metabolic, immune, and translational perspectives, this review identifies key knowledge gaps, including context-dependent circRNA functions, challenges in detection standardization, and the need for multi-omic stratification strategies. We propose that targeting circRNA-mediated immunometabolic networks represents a promising frontier for precision therapy in HCC.
Analytical performance evaluation and the 99th percentile reference limit study of a rapid whole blood high-sensitivity cardiac troponin T assay.
Yue Y, Xiang J, Fu W … +2 more , Shi J, Zhang R
Clin Chim Acta · 2026 May · PMID 42219102 · Publisher ↗
BACKGROUND: This study aimed to comprehensively evaluate the analytical performance of a novel rapid whole blood hs-cTnT assay and establish 99th percentile upper reference limit (URL) for healthy individuals. METHODS: T...
BACKGROUND: This study aimed to comprehensively evaluate the analytical performance of a novel rapid whole blood hs-cTnT assay and establish 99th percentile upper reference limit (URL) for healthy individuals. METHODS: The imprecision, limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity, comparability and whole blood-plasma equivalence were evaluated according to the Clinical and Laboratory Standards Institute guidelines. The sex-specific 99th percentile URL was established via nonparametric analysis of healthy volunteers. RESULTS: The within-run CVs were 2.3% at low concentration 5.7 ng/L, 1.8% at high concentration 13.9 ng/L and 1.8% at high concentration 137.0 ng/L; between-run CVs were 1.0%, 1.3% and 1.8%, respectively. LoB and LoD were 0.7 and 1.2 ng/L, respectively, and LoQ for whole blood samples was 2.8 ng/L at 10% CV. The results met the requirements of linearity and the correlation coefficient was 0.999. Comparability analysis against the Roche® showed good agreement with R = 0.995. Whole blood-plasma equivalence was a mean ratio of 0.944 (95% limits of agreement ratio: 0.929 to 0.958), with a correlation coefficient R of 0.961. The 99th percentile URL for whole blood samples was 16.8 ng/L for males, 8.9 ng/L for females, and 15.2 ng/L for total. The hs-cTnT detection rate of all observed healthy individuals from LoD to 99th was 97.6%, and 95.3% for the males, 100% for the females. CONCLUSIONS: The rapid whole blood high-sensitivity cardiac troponin T (hs-cTnT) assay demonstrated robust analytical performance. Its sex-stratified and age-stratified 99th percentile URLs provided preliminary support for its potential clinical utility in the rapid exclusion of the diagnosis of acute myocardial infarction (AMI) in emergency settings.
A pilot study on the application of Oxford Nanopore PromethION sequencing with adaptive sampling for DMPK repeat expansion sizing in myotonic dystrophy type 1.
Lau NKC, Tong TTY, Chong YK … +1 more , Ching CK
Clin Chim Acta · 2026 May · PMID 42214742 · Publisher ↗
Myotonic dystrophy type 1 (DM1) is caused by a CTG repeat expansion in the DMPK gene, but conventional polymerase chain reaction and Southern blot-based workflows provide limited resolution for large expansions and somat...
Myotonic dystrophy type 1 (DM1) is caused by a CTG repeat expansion in the DMPK gene, but conventional polymerase chain reaction and Southern blot-based workflows provide limited resolution for large expansions and somatic mosaicism. This pilot study evaluated Oxford Nanopore PromethION sequencing with adaptive sampling for DMPK repeat expansion sizing. Fifteen samples, including Coriell reference materials, European Molecular Genetics Quality Network external quality assessment materials, and clinical samples, were sequenced across seven adaptive-sampling runs using native barcoding. DMPK repeat-spanning reads were aligned to the reference genome and summarized at read level. Sequencing runs generated a median of 38.9 gigabases of data and 56.2 million reads, with median DMPK repeat-locus coverage of 49×. Reducing multiplexing to two samples per flow cell improved median expanded-allele coverage. Normal allele sizing was concordant across reference, external quality assessment, and clinical samples, and expanded-allele estimates in reference materials and selected clinical samples were consistent with prior orthogonal results. Single-molecule reads also provided repeat-size distributions consistent with intra-sample variability. However, expanded-allele coverage remained variable, and low-read observations limited confidence for some samples. These findings support adaptive-sampling PromethION sequencing as a feasible pilot approach for DMPK repeat expansion sizing, while indicating that improved coverage and larger clinical validation are needed before routine diagnostic implementation.
Shifts in bacterial pathogen and resistance spectra of adult respiratory tract infections before vs. after the COVID-19 pandemic: A 7-year retrospective data analysis.
Li Y, Ge J, Yang M … +2 more , Li Y, Zhao X
Clin Chim Acta · 2026 May · PMID 42214741 · Publisher ↗
OBJECTIVE: To assess the impact of the COVID-19 pandemic on the distribution and antimicrobial resistance (AMR) patterns of common bacterial pathogens isolated from respiratory specimens in adults. METHODS: We analyzed 4...
OBJECTIVE: To assess the impact of the COVID-19 pandemic on the distribution and antimicrobial resistance (AMR) patterns of common bacterial pathogens isolated from respiratory specimens in adults. METHODS: We analyzed 49,260 adult respiratory tract specimens collected between 2018 and 2024, dividing them into pre-pandemic (2018-2019), pandemic (2020-2022), and post-pandemic (2023-2024) periods. We focused on shifts in seasonal patterns, the relative abundance of five key pathogens (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus), and changes in their antimicrobial susceptibility profiles. RESULTS: The overall pathogen positivity rate dropped from 18.60% pre-pandemic to 14.34% during the pandemic, with only a partial recovery to 15.99% afterwards. Seasonal variation was attenuated, particularly with suppressed summer rates. K. pneumoniae solidified its position as the dominant pathogen, increasing from 27.33% to 41.16% of isolates. The pandemic period saw a transient surge in A. baumannii (14.70%), which later declined. More critically, we observed a clear "rebound effect" in AMR: resistance rates to several key antimicrobials fell temporarily during the pandemic but subsequently rose to meet or exceed pre-pandemic baselines. Carbapenem resistance in A. baumannii and P. aeruginosa remained critically high (>60%). CONCLUSION: Our data indicate that the pandemic's disruptive effects on respiratory pathogen ecology were temporary. The post-pandemic era is characterized by a consolidating dominance of K. pneumoniae, persistently high carbapenem resistance in non-fermenters, and a rebound in resistance rates for many drugs. These trends reinforce the need for continuous local surveillance and rigorous antimicrobial stewardship.
Echinococcus multilocularis serine protease inhibitor 1 (EmSPI-1): a highly effective serodiagnostic antigen for alveolar echinococcosis.
Tian M, Li J, Wu C … +11 more , Yan M, Bao J, Qi W, Fan H, Wang Z, Wang W, Liu X, Ding J, Zhang Y, Wang X, Zhang W
Clin Chim Acta · 2026 May · PMID 42191022 · Publisher ↗
BACKGROUND: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is a lethal zoonotic disease. Population screening for early diagnosis is crucial for effective treatment, and novel diagnostic antigens ar...
BACKGROUND: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is a lethal zoonotic disease. Population screening for early diagnosis is crucial for effective treatment, and novel diagnostic antigens are needed for diagnostic purposes. METHODS: E. multilocularis serine protease inhibitor 1 (EmSPI-1) was cloned and expressed in Escherichia coli. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to assess gene expression at different life-cycle stages of the tapeworm. The diagnostic potential of recombinant EmSPI-1 (rEmSPI-1) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting using sera from patients with AE and individuals with other infectious diseases, and healthy controls. RESULTS: Soluble recombinant EmSPI-1 (rEmSPI-1) was successfully expressed in E. coli cultured at 15 °C. Protein sequence alignment and structural analysis demonstrated 100% identity between EmSPI-1 and EgSPI-1 (EGR_03125), both containing conserved serpin domains with α-helices and a reactive center loop. Stage expression results demonstrated that EmSPI-1 was highly expressed in the germinal layer (GL) of the cyst, pepsin-treated protoscoleces (PSCs) and adult worms (AW). Notably, rEmSPI-1 induced a dominant IgG4 antibody response in sera from AE patients. A diagnostic assay using ELISA showed 90.37% sensitivity (122/135) and 96.24% specificity among 638 non-AE serum samples. Receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.942 (95% CI: 0.921-0.963) for differentiating AE patients from healthy controls, and an AUC of 0.971 for distinguishing AE from non-AE infectious samples. For WHO-IWGE early-stage AE (P1N0M0 + P2N1M0 + P2N1M1, n = 15), rEmSPI-1 showed a sensitivity of 80.0% (12/15). The P1N0M0 subgroup (n = 4) showed a sensitivity of 25.0% for rEmSPI-1 and 0% for rEm18. CONCLUSIONS: EmSPI-1 is highly expressed in the AW, GL, and PSCs of E. multilocularis and serves as a serodiagnostic biomarker for detecting IgG4 antibodies in the sera of AE patients, with 90.37% sensitivity and 96.24% of specificity.
Iridium(III)-based luminescent biosensors for cancer biomarker detection: From molecular design to clinical translation.
Khan NH, Godara A, Afzal M … +7 more , Mishra A, Patel PKN, S RJ, Arora V, Rathore V, Goyal K, Jakhmola V
Clin Chim Acta · 2026 May · PMID 42184864 · Publisher ↗
Cyclometalated iridium (III) [Ir(III)] complexes are a new generation of octahedral d transition metal-based emissive species that exhibit characteristics that overcome important analytical constraints that are present w...
Cyclometalated iridium (III) [Ir(III)] complexes are a new generation of octahedral d transition metal-based emissive species that exhibit characteristics that overcome important analytical constraints that are present within existing clinical oncology immunoassay systems. This review evaluates Ir(III) luminescent biosensors for the detection of cancer biomarkers, considering their applications in clinical chemistry and diagnostic laboratory medicine. The d6 electronic configuration of iridium facilitates efficient spin-orbit coupled intersystem crossing to the low-lying triplet metal-to-ligand charge transfer excited states. Consequently, this property can be utilized to suppress autofluorescence in time-gated detection formats. The ligand system can be modified systematically and the emission wavelengths (450-800 nm) can be adjusted to avoid spectral overlaps with hemoglobin absorption interference in blood-based samples. In complex biological matrices, with co-reactant mediated electrode reaction, ECL signals are generated without any external photoexcited species to induce background signal, which significantly reduces background signal. Tumor markers in serum, circulating nucleic acids, and exosomal biomarkers at attomol/L and fmol/L concentrations can be detected using MOF/COF scaffold-doped luminophores, self-enhanced intramolecular ECL reagents, and nanomaterial-amplified detection cascades. Translation barriers, such as endogenous matrix interference, manufacturing reproducibility, cytotoxicity and biocompatibility of Ir(III) complexes, compliance with ISO 15189, and IVD regulatory considerations through the FDA and European IVDR 2017/746 frameworks, are highly evaluated. It critically evaluates the reported analytical performance against established clinical immunoassay benchmarks (e.g., Roche Elecsys, Abbott Architect) based on the CLSI validation and ISO metrology standards. Additionally, it outlines a translational roadmap with defined technological readiness milestones for implementing these biosensors in clinical laboratories, particularly in precision oncology.
Harnessing exosomes for biomarker development and therapy in hepatitis virus infection.
Zafarjanovna KM, Abbasovna AL, Muhammadovich TH … +10 more , Uktam I, Go'zal Ubaydullayevna N, Azamatovna NM, Nodira N, Sardor K, Matkurbanov TA, Jabborov ABO, Xasanov I, Xusanov S, Muydinov FF
Clin Chim Acta · 2026 May · PMID 42177969 · Publisher ↗
Exosomes, a specialized subclass of extracellular vesicles, have emerged as critical mediators in the pathogenesis of viral hepatitis. Hepatotropic viruses hijack host exosomal biogenesis pathways to facilitate immune ev...
Exosomes, a specialized subclass of extracellular vesicles, have emerged as critical mediators in the pathogenesis of viral hepatitis. Hepatotropic viruses hijack host exosomal biogenesis pathways to facilitate immune evasion, promote viral dissemination, and drive chronic inflammation and hepatic fibrosis. Paradoxically, these same vesicles offer unprecedented opportunities for noninvasive disease monitoring and targeted therapeutic intervention. This narrative review synthesizes current evidence on the dual role of exosomes in hepatitis virus infection, evaluating their evolution from pathogenic vectors to clinical tools for liquid biopsy diagnostics and engineered antiviral delivery. We examined how exosomal cargo, including microRNAs, proteins, and viral nucleic acids, enables precise stratification of liver disease stages, real-time treatment monitoring, and early detection of hepatocellular carcinoma. Furthermore, we explore advanced bioengineering strategies, such as endogenous cargo loading, surface functionalization, and the targeted delivery of CRISPR/Cas9 complexes and RNA-based therapeutics, which position engineered exosomes as next-generation precision nanomedicines. Despite compelling preclinical data, clinical translation remains constrained by significant bottlenecks, including scalable good manufacturing practice (GMP) production, the lack of standardized isolation and characterization protocols, and evolving regulatory pathways. Bridging the gap between laboratory innovation and bedside application will require coordinated advancements in manufacturing technology, global standardization initiatives, and rigorous clinical validation. Successfully overcoming these hurdles could establish exosome-based platforms as transformative tools for achieving functional cures and improving long-term outcomes in patients with viral hepatitis.
Harnessing extracellular vesicles for gastric cancer management: Biomarker discovery and therapeutic strategies.
Oriquat G, Mutee AF, Kubaev A … +4 more , Tillyayeva Z, Salih RM, Jaber MA, Hussen S
Clin Chim Acta · 2026 May · PMID 42177968 · Publisher ↗
Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication in gastric cancer (GC), functioning as both pathogenic drivers and promising therapeutic tools. Tumor-derived EVs (TEVs) activ...
Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication in gastric cancer (GC), functioning as both pathogenic drivers and promising therapeutic tools. Tumor-derived EVs (TEVs) actively remodel the tumor microenvironment by promoting immune evasion, metastasis, angiogenesis, and therapy resistance, largely through the transfer of oncogenic proteins and non-coding RNAs such as miR-21 and circSMARCC1. In contrast, EVs from mesenchymal stromal cells and immune cells offer opportunities for innovative therapeutic strategies, including targeted drug delivery, immune modulation, and gene-silencing approaches such as anti-PD-L1 small interfering RNA (siRNA) delivery. EVs also hold substantial promise as non-invasive biomarkers, with exosomal ncRNAs, proteins, and DNA methylation signatures demonstrating superior diagnostic and prognostic performance compared to traditional serum markers. Despite these advances, challenges persist in standardizing EV isolation, scaling manufacturing, ensuring quality control, and navigating regulatory pathways. This narrative review synthesizes current insights into the dualistic roles of EVs in GC pathogenesis, diagnostics, and therapeutics, highlighting their transformative potential while underscoring the critical barriers that must be addressed to enable clinical translation. As EV-based technologies evolve, they offer a compelling foundation for precision oncology and integrated theranostic strategies in gastric cancer management.
Electrochemical biosensors for rapid detection of antibiotic-resistant bacteria.
Ardah MT, Jameel RK, Shakhmurova G … +5 more , Rizaev J, Alaal MA, Panigrahi R, Tailor NK, Singh R
Clin Chim Acta · 2026 May · PMID 42177967 · Publisher ↗
The increasing threat of antibiotic-resistant bacteria (ARB) necessitates rapid and accurate diagnostic tools to guide effective treatment strategies. Traditional culture-based methods are time-consuming, delaying crucia...
The increasing threat of antibiotic-resistant bacteria (ARB) necessitates rapid and accurate diagnostic tools to guide effective treatment strategies. Traditional culture-based methods are time-consuming, delaying crucial interventions and potentially contributing to the spread of resistance. Electrochemical biosensors offer a promising alternative, providing high sensitivity, specificity, and rapid detection capabilities suitable for point-of-care applications. These platforms leverage biorecognition elements, advanced electrode materials, and the electrochemical detection of microbial products or genetic material to identify ARB. Recent advancements include the integration of microfluidics and lab-on-a-chip systems for high-throughput antimicrobial susceptibility testing, significantly improving diagnostic speed and precision. This review critically examines the latest developments in electrochemical biosensing for ARB detection, highlighting key strategies such as DNA probe-based sensors and the use of nanomaterials to increase performance. It also addresses persistent challenges, including sensor reproducibility and cost-effectiveness, and explores future directions aimed at improving the clinical applicability and accessibility of these vital diagnostic technologies in the fight against antimicrobial resistance worldwide.
Circulating CHI3L1/YKL-40 in lung cancer: Biomarker potential, analytical challenges, and clinical translation prospects.
Omer AB, Saleem S, Khan R … +2 more , Venkatesh R, Goyal K
Clin Chim Acta · 2026 May · PMID 42177966 · Publisher ↗
Lung cancer is the leading cause of cancer-related mortality worldwide, primarily due to inadequate early detection, which consequently leads to poor overall survival rates. Current serum tumor markers, including carcino...
Lung cancer is the leading cause of cancer-related mortality worldwide, primarily due to inadequate early detection, which consequently leads to poor overall survival rates. Current serum tumor markers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (ProGRP), exhibit limitations in terms of sensitivity, specificity, and predictive value for immunotherapy. The secreted glycoprotein chitinase-3-like protein 1 (CHI3L1/YKL-40), detectable by ELISA in serum and plasma, is a biologically plausible, research-stage, and potentially clinically relevant circulating lung cancer marker. Two meta-analyses (n > 950 patients) validated that elevated serum CHI3L1 is an independent predictor of poor survival in non-small cell (HR = 2.23) and small cell (HR = 1.45) lung cancer. There is preliminary evidence that it can predict the response to immune checkpoint inhibitors; however, this needs to be validated in a prospective study. Elevated levels of CHI3L1 in chronic obstructive pulmonary disease (COPD) and other inflammatory disorders significantly contribute to false-positive results, necessitating the use of disease-specific reference intervals for correction. To establish CHI3L1 as a clinical biomarker, it is imperative to address key technical issues, including pre-analytical sample handling, variability across ELISA platforms, biological influences such as age and chronic obstructive pulmonary disease, and the CHI3L1 promoter single nucleotide polymorphism (SNP) (rs4950928). A translational framework is proposed, which involves the standardization of multi-analytical platforms, the conduct of multi-center prospective studies, and the attainment of regulatory approval as an in vitro diagnostic tool.
Advances in laboratory diagnostic studies of pheochromocytoma and paraganglioma.
Li C, Li L, Mu D … +4 more , Ma Y, Gao Y, Li Y, Cheng X
Clin Chim Acta · 2026 May · PMID 42176937 · Publisher ↗
Pheochromocytoma (PCC) and paraganglioma (PGL), collectively referred to as pheochromocytomas and paragangliomas (PPGLs), are rare neuroendocrine tumors characterized by marked genetic susceptibility and substantial biol...
Pheochromocytoma (PCC) and paraganglioma (PGL), collectively referred to as pheochromocytomas and paragangliomas (PPGLs), are rare neuroendocrine tumors characterized by marked genetic susceptibility and substantial biological heterogeneity. Given that all PPGLs are considered to have metastatic potential, early and accurate diagnosis is critical for optimizing therapeutic strategies and improving clinical outcomes. This review summarizes recent advances in the laboratory diagnosis of PPGL. For biochemical testing, plasma free metanephrines measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) are recommended by international guidelines as the preferred first-line screening biomarkers. However, strict control of preanalytical conditions, including patient posture, fasting status, and the standardization of laboratory reference intervals, is essential to ensure diagnostic accuracy. Molecular genetic testing covering more than 20 susceptibility genes, such as SDHx, VHL, and RET, enables molecular classification and risk stratification. Emerging biomarkers, including protein expression profiles, epigenetic alterations, immunohistochemical features, tumor microenvironment characteristics, and multiparametric prediction models, further expand the assessment of tumor aggressiveness and treatment-oriented decision making. In the future, laboratory-test driven integration of multiomics data and artificial intelligence assisted models may facilitate precise diagnosis, dynamic monitoring, and personalized management of PPGLs.
5'-tRF in serum is a specific tRNA-derived fragment biomarker for gastric cancer diagnosis.
Wang Y, Jiang C, Zhang Z … +4 more , Wu Y, Xin W, Shi A, Cong H
Clin Chim Acta · 2026 May · PMID 42176936 · Publisher ↗
BACKGROUND: Gastric cancer (GC) remains a significant global burden of cancer-related mortality, with current biomarkers exhibiting insufficient sensitivity and specificity for GC detection. This study investigated the p...
BACKGROUND: Gastric cancer (GC) remains a significant global burden of cancer-related mortality, with current biomarkers exhibiting insufficient sensitivity and specificity for GC detection. This study investigated the potential of transfer RNA-derived small RNAs (tsRNAs) as novel diagnostic biomarkers for GC. METHODS: The candidate biomarker 5'-tRF, initially identified through database screening, underwent rigorous validation procedures: including real-time quantitative PCR (RT-qPCR) for expression level detection, sequencing confirmation of sequence consistency, secondary structure computer modeling, and evaluation of its GC diagnostic efficacy based on discriminative power and electrophoresis experiments. RESULTS: The study found that 5'-tRF was significantly overexpressed in GC tissues, cells, and serum. Compared with healthy donors and gastritis patients, serum levels of 5'-tRF were significantly elevated in GC patients and markedly decreased postoperatively. Furthermore, high expression of 5'-tRF was associated with neural/lymphovascular invasion, high-grade histology, regional lymph node metastasis, and advanced TNM stage (all P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that 5'-tRF exhibited superior diagnostic accuracy for GC compared to existing clinical biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and carbohydrate antigen 199 (CA199), with significantly larger area under the curve (AUC) values. CONCLUSIONS: 5'-tRF is a promising biomarker for gastric cancer, with elevated serum levels reflecting tumor presence and aggressiveness. Its decrease after surgery and superior diagnostic accuracy over conventional markers support its potential use in non-invasive detection, postoperative monitoring, and risk stratification.
Urinary melatonin: A non-invasive breast cancer biomarker.
Khan A, Alhuthali HM, Alzahrani S … +5 more , Alrehaili AA, Alharthi NS, Singla N, Rehman ZU, Imran M
Clin Chim Acta · 2026 May · PMID 42176935 · Publisher ↗
Biomarkers of urinary melatonin represent an attractive non-invasive method for enhancing breast cancer diagnosis and follow-up, as they reflect combined circadian physiology in a readily accessible and repeatable urine...
Biomarkers of urinary melatonin represent an attractive non-invasive method for enhancing breast cancer diagnosis and follow-up, as they reflect combined circadian physiology in a readily accessible and repeatable urine test. There has been a growing interest in this field, driven by the understanding that melatonin plays a role in regulating the endocrine system, influencing sleep patterns, managing circadian rhythms, affecting exposure to night-time light, and impacting the body's response to cancer and its treatment. The urinary analyte 6-sulfatoxymelatonin has become the most viable surrogate of systemic nocturnal melatonin secretion, due to its increased stability, higher concentration, and suitability for timed, overnight, first-morning, and 24-h urine collection paradigms. Epidemiological, case-control, and longitudinal studies indicate that changes in urinary melatonin levels may be linked to breast cancer risk, disease burden, treatment-associated circadian disruption, and survival-associated sleep impairment. This review aims to present a structured review of the biological foundation, measurement, pre-analytical and analytical determinants, and clinical evidence of urinary melatonin analysis in breast cancer. We compared parent melatonin and 6-sulfatoxymelatonin, assessed immunoassays and chromatographic systems, and discussed significant confounders, such as age, menopausal status, renal function, chronotype, light-at-night exposure, sleep behavior, diet, medications, and sample handling. We further refer to identify the weaknesses that at present clinical translation, such as pre-analytical variability, heterogeneity of assays, absence of reference intervals, and inadequate prospective validation. We believe that the most likely future use of urinary melatonin is as a biomarker component in circadian-informed strategies, where it supplements tumor-specific biomarkers by indicating host physiology, biological time, and treatment-associated circadian disruption.
Urinary N-glycoproteins from the PRM-SSS discrepancy: a novel diagnostic tool for tubular injury.
Zhu J, Li M, Lin T … +4 more , Li J, Jiang M, Liu Y, Zhao H
Clin Chim Acta · 2026 May · PMID 42176934 · Publisher ↗
BACKGROUND: Tubular injury is a key pathological feature driving the progression of both acute and chronic kidney disease. This study aimed to elucidate the mechanism underlying the discrepancy between two common urinary...
BACKGROUND: Tubular injury is a key pathological feature driving the progression of both acute and chronic kidney disease. This study aimed to elucidate the mechanism underlying the discrepancy between two common urinary total protein assays (the pyrogallol red-molybdate [PRM] and sulfosalicylic acid‑sodium sulfate [SSS] methods) and to evaluate its potential as a novel biomarker for tubular injury. METHODS: We analyzed 489 clinical urine samples using both assays. Proteins associated with the discrepancy were profiled by mass spectrometry and SDS-PAGE. To validate the role of glycosylation, detection of the native α1-microglobulin and uromodulin was assessed before and after PNGase F-mediated deglycosylation. Diagnostic performance was evaluated in patients categorized by the urinary albumin-to-protein ratio (uAPR). RESULTS: Despite a strong correlation between methods (r = 0.986), a systematic bias existed. Mass spectrometry demonstrated that the SSS method underestimates N-linked glycoproteins, which was reversible upon deglycosylation. In patients with proteinuria (150-2000 mg/L), the PRM-SSS discrepancy was significantly greater in those with tubular injury (uAPR≤0.4) versus glomerular injury (uAPR>0.4). The PRM-SSS discrepancy distinguished these groups with an area under the curve of 0.93, corresponding to a sensitivity of 84.8% and a specificity of 93.2%. CONCLUSION: The PRM-SSS discrepancy originates directly from differential detection of N-linked glycoproteins. Leveraging this inherent difference provides a cost-effective, readily available biomarker for tubular injury, suitable for large-scale screening and potentially enhancing early detection.
Atypical presentation of potter sequence associated with 46, XX testicular disorder of sex development.
Vinayak A, Vinesh K, Mahesheema A
Clin Chim Acta · 2026 May · PMID 42176933 · Publisher ↗
Prenatal diagnosis of congenital anomalies is primarily based on ultrasound assessment. This may be limited in settings with structural abnormalities and diagnoses that rely heavily on genetic testing. A 33-year-old whit...
Prenatal diagnosis of congenital anomalies is primarily based on ultrasound assessment. This may be limited in settings with structural abnormalities and diagnoses that rely heavily on genetic testing. A 33-year-old white woman, gravida 1, para 0, at 17 weeks of gestation, presented to the outpatient clinic the day after being involved in a motor vehicle collision, without any obstetric complaints. Upon physical examination, minimal tenderness was noted in the left lateral back. Serological markers were unremarkable. Ultrasound revealed an absence of fetal urinary bladder and bilateral renal agenesis, a finding consistent with Potter syndrome. Due to the severity of anomalies, the patient elected to terminate the pregnancy. Post-termination fetal examination suggests a male phenotype. The products of conception were collected and sent for karyotyping and microarray analysis, which revealed a normal female karyotype (46, XX). The case highlights a unique case of discordance between phenotypic and genotypic sex in the setting of congenital anomalies. It underscores the importance of confirmatory genetic testing and the integration of cytogenetics with prenatal imaging to help ensure accurate diagnosis when phenotypic findings alone may be unreliable.
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