Clinica Chimica Acta最新文献

{"title":"Advances in Immunoassays for detection of pancreatitis biomarkers","authors":"Suresh Kumar Srinivasamurthy ,&nbsp;Piyush Mittal ,&nbsp;Shakir Saleem ,&nbsp;K.Benod Kumar ,&nbsp;Kavita Goyal ,&nbsp;Mohit Rana ,&nbsp;Haider Ali ,&nbsp;Sachin Kumar Singh ,&nbsp;Poonam Negi ,&nbsp;Parteek Prasher ,&nbsp;Mohamed Jaber ,&nbsp;Gaurav Gupta","doi":"10.1016/j.cca.2025.120492","DOIUrl":"10.1016/j.cca.2025.120492","url":null,"abstract":"<div><div>Pancreatitis is a predominant cause of gastrointestinal morbidity. However, the early and accurate detection of biomarkers, which is essential for guiding risk stratification and therapeutic decision-making, is constrained by the sensitivity and throughput limitations of conventional assays. This review critically examines advances in immunoassay technologies, including high-sensitivity lipase and amylase ELISAs, chemiluminescence and time-resolved fluorescence formats, label-free plasmonic sensors, digital single-molecule platforms, and multiplex bead-based and microarray systems, as applied to pancreatitis biomarker quantitation. This study synthesizes data on classical enzymatic markers, such as lipase and amylase, established proteins, including C-reactive protein and trypsinogen activation peptide, and emerging molecular targets, such as cytokines, DAMPs, and microRNAs. The focus is on evaluating analytical performance metrics, including sensitivity, specificity, dynamic range, precision, and robustness, along with preanalytical factors and clinical applications. These components are analyzed in relation to early diagnosis, assessment of severity, and evaluation of therapeutic response. Current challenges in assay standardization, head-to-head validation, and preanalytical variability are highlighted, and the potential of microfluidic “lab-on-a-chip” and point-of-care platforms is explored. This review effectively integrates advanced immunoassay modalities with the performance of pancreatitis-specific biomarkers, thereby uniquely linking technological innovation to clinical applicability. This study aims to offer a prioritized roadmap for the development and implementation of standardized multiplexed assays in personalized pancreatitis diagnostics.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"578 ","pages":"Article 120492"},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667314","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":"99 Chinese ASS1 carriers: Genetics, metabolism, and citrulline levels","authors":"Ziyan Cen ,&nbsp;Chao Zhang ,&nbsp;Pingping Ge ,&nbsp;Peiyao Wang ,&nbsp;Zhenzhen Hu ,&nbsp;Lingwei Hu ,&nbsp;Benqing Wu ,&nbsp;Xinwen Huang","doi":"10.1016/j.cca.2025.120491","DOIUrl":"10.1016/j.cca.2025.120491","url":null,"abstract":"<div><div>Citrullinemia type I is an autosomal recessive disorder caused by mutations in the ASS1 gene, whereas ASS1 mutation carriers typically have a mutation in only one allele. While carriers are usually asymptomatic, they often show mildly elevated plasma citrulline levels. This study aims to investigate the relationship between the genetic background of ASS1 carriers and plasma citrulline levels, as well as the potential mechanisms behind the elevation. The study analyzed 99 ASS1 mutation carriers identified through neonatal screening. Clinical and genetic data were collected, including plasma citrulline levels at initial and follow-up screenings. This is the first large-scale analysis of the relationship between ASS1 mutations and plasma citrulline levels in carriers. Twenty-eight distinct variants were identified, with c.1087C &gt; T (p.R363W) being the most common. Plasma citrulline levels in carriers were elevated, showing a rising then falling pattern over first six months, with a peak of 65.84 µmol/L during re-screening. Levels gradually declined thereafter and stabilized around 49.92 μmol/L, but consistently remained above the normal reference range. A citrulline threshold of 62.04 µmol/L effectively differentiated ASS1 carriers from Citrullinemia type I patients (AUC = 0.984). Elevated plasma citrulline levels are often seen in mutations affecting the monomer–monomer interface, though other mechanisms may be involved. This study identified 62.04 µmol/L as a reference threshold at the time of newborn screening to distinguish ASS1 carriers from Citrullinemia type I patients, observed a dynamic pattern of citrulline levels over the first six months in carriers, and suggested a potential role for dominant-negative effects in the underlying mechanism.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"578 ","pages":"Article 120491"},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667313","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":"Validation of free light chain reference intervals and their association with age and eGFR","authors":"Junyi Wu ,&nbsp;Xiaowen Zheng ,&nbsp;Yilin Ge ,&nbsp;Li Mu ,&nbsp;Siyu Chen ,&nbsp;Ke Chen ,&nbsp;Jiashu Yang ,&nbsp;Hui Yuan","doi":"10.1016/j.cca.2025.120494","DOIUrl":"10.1016/j.cca.2025.120494","url":null,"abstract":"<div><h3>Objectives</h3><div>To establish reference intervals (RIs) for serum free κ and λ light chains and the κ/λ ratio (FLCR) in healthy adults in China, and to evaluate the influence of age and estimated glomerular filtration rate (eGFR)</div></div><div><h3>Methods</h3><div>A total of 549 healthy adults with eGFR &gt; 90 mL/min/1.73 m² were enrolled. FLCs were measured using nephelometric assays (Goldsite Diagnostics). RIs of κ-FLC and λ-FLC were calculated based on the 2.5th to 97.5th percentiles(95 % interval),and FLCR was calculated on 100 % of this cohort. Additional subgroup analyses included individuals with reduced eGFR(60–89 mL/min/1.73 m²)to assess the association between renal function and FLC concentrations. Spearman correlation and regression analyses were used to assess relationships between FLCs, FLCR, age, and eGFR.</div></div><div><h3>Results</h3><div>This study RIs were determined: κ-FLC 4.27–35.05 mg/L, λ-FLC 12.61–34.09 mg/L, FLCR 0.15–1.58. All FLC parameters were inversely correlated with eGFR(p &lt; 0.001) and increased with age(p &lt; 0.001)</div></div><div><h3>Conclusions</h3><div>RIs derived from other assays or cohorts may not be directly applicable to all settings. The influence of age and renal function in clinical practice, FLC results should be interpreted in combination with relevant clinical and laboratory information.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"578 ","pages":"Article 120494"},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665966","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":"Fingernail analysis in diagnosis and management of diabetes mellitus","authors":"Jiani Fan ,&nbsp;Jiabao Cai ,&nbsp;Shengguang Chen","doi":"10.1016/j.cca.2025.120490","DOIUrl":"10.1016/j.cca.2025.120490","url":null,"abstract":"<div><div>This systematic review elucidates the role of fingernail analysis in the diagnosis and management of diabetes mellitus (DM) and its complications. It combines multidisciplinary insights to highlight the potential of non-invasive diabetes assessment, long-term glucose monitoring, and early detection of complications. Covers a wide range of techniques, including spectroscopy and imaging methods such as near-infrared spectroscopy (NIR), Raman spectroscopy (RS), laser-induced breakdown spectroscopy (LIBS), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), as well as microscopy and elemental analysis techniques such as dermoscopy, nail fold video capillaroscopy (NVC), inductively coupled plasma mass spectrometry (ICP-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS), Nail biochemical analysis and Doppler ultrasound imaging were also included. Special emphasis is placed on glycemic biomarkers such as N-acetyl-DL-leucine enantiomers, carboxymethyl lysine (CML), and advanced glycation end-products (AGEs), which demonstrate robust diagnostic utility. Meta-analytical data indicate that these multimodal approaches yield Area Under the Curve (AUC) values of 0.78 e (CML), and advanced glycation end-products (AGEs), which demonstrate robust diagnostic utility. Meta-analytical data indicate that these multimodal approaches yield Area Under the Curve (AUC) values of from 0.78 to 0.88, underscoring their clinical potential for high sensitivity and specificity discrimination between diabetic and healthy populations Notwithstanding, challenges persist, including instrumentation costs, environmental interferences, and operator expertise requirements. Future directions prioritize elucidating the molecular mechanisms underlying nail-diabetes associations, innovating minimally invasive analytical platforms, and conducting multicenter validation trials to bridge the translational gap.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"578 ","pages":"Article 120490"},"PeriodicalIF":3.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666084","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":"Construction of a machine learning-based screening model for IgD myeloma","authors":"Manli Zhou ,&nbsp;Sisi Feng","doi":"10.1016/j.cca.2025.120488","DOIUrl":"10.1016/j.cca.2025.120488","url":null,"abstract":"<div><h3>Objective</h3><div>Immunoglobulin D (IgD) myeloma is a rare subtype of multiple myeloma (MM), comprising approximately 1 %–2 % of all MM cases. Owing to the diminished levels of IgD in serum, IgD MM manifests as subtle M protein spikes in routine serum electrophoresis, rendering it susceptible to misdiagnosis and underdiagnosis. The objective of this study was to develop a machine learning (ML) model utilizing readily available complete blood count and biochemical test data for the purpose of screening IgD MM.</div></div><div><h3>Methods</h3><div>This study encompassed clinical data from 83 newly diagnosed IgD MM patients and 166 non-IgD MM patients, decision tree, random forest, support vector machine (SVM), stochastic gradient descent (SGD), and adaptive boosting (AdaBoost) algorithms were employed for model construction. The predictive performance of the ML models was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve analysis, and decision curve analysis.</div></div><div><h3>Results</h3><div>The random forest-based screening model demonstrated superior performance, incorporating seven key features: LDH, albumin, creatinine, Ca, β2 microglobulin, age and Hb. It achieved an AUC of 0.954 (95 % CI 0.930–0.977), with a sensitivity of 0.958, specificity of 0.747, positive predictive value of 88.3 % and negative predictive value of 89.9 %. Furthermore, this model has been evaluated in the validation cohort.</div></div><div><h3>Conclusions</h3><div>The model constructed based on the random forest algorithm demonstrates potential in screening IgD MM patients, particularly when routine IgD immunotyping testing is not conducted in clinical practice. This can assist clinicians in early diagnosis and personalized treatment strategies, thereby optimizing the utilization of medical resources.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"577 ","pages":"Article 120488"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633801","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":"Hemodialysis and minerals in end stage renal disease","authors":"Elcy Tufenkjy,&nbsp;Raghda Lahdo","doi":"10.1016/j.cca.2025.120485","DOIUrl":"10.1016/j.cca.2025.120485","url":null,"abstract":"<div><h3>Background-aim</h3><div>Hemodialysis is the most common reliable therapy of renal replacement in Kidney Disease, especially, the end stage renal disease (ESRD), characterized with the complete loss of kidney function, including excretion of wastes and fluids, control of blood acid-base and mineral concentrations. During hemodialysis, kidney roles are restored, by the balance of substances between the dialysis fluid and patients’ blood. However, it may cause serious disturbances of some minerals concentrations in patients’ blood, like (Zn, Cu, Mg, etc.), if hemodialysis conditions weren’t suitable. This review will discuss this major problem that may lead to life threatening complications in ESRD patients, like: cancer, cardiovascular disease, and worsening of kidney function.</div></div><div><h3>Methods</h3><div>A literature review was done, comparing the results of several previous studies published in international scientific journals, about mineral disturbances in ESRD patients undergoing hemodialysis, among different countries in the world. In all mentioned studies blood samples were taken from patients pre and post dialysis, measuring minerals by atomic absorption spectroscopy.</div></div><div><h3>Results</h3><div>The included studies obtained conflicting results, as some of them showed an increase in some minerals levels in post dialysis patients compared to pre dialysis, like (Zn, Cr), while other studies revealed a decrease in minerals post dialysis, like Mg, whereas, others found no significant differences between pre and post dialysis, like (Cu, Se). This contradiction may be due to the country of the study, environmental pollution, nutritional conditions, as well as, the conditions of hemodialysis, such as the composition of dialysis fluid, which is affected by the source of its water, and its content of minerals. The type of used dialysis membrane and its surface area also have effect on the movement of minerals through it, between the blood and the dialysis fluid.</div></div><div><h3>Conclusion</h3><div>In order to avoid the disturbances in serum minerals concentrations in ESRD patients, they should be regularly measured pre and post dialysis, doing the appropriate therapeutic procedures, in addition to best controlling of hemodialysis conditions, especially, the mineral content of hemodialysis fluid, in order to keep their balance in patients’ blood.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"577 ","pages":"Article 120485"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633325","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":"AI-powered liquid biopsy for early detection of gastrointestinal cancers","authors":"Md Sadique Hussain ,&nbsp;Mokhtar Rejili ,&nbsp;Amna Khan ,&nbsp;Saud O. Alshammari ,&nbsp;Ching Siang Tan ,&nbsp;Faouzi Haouala ,&nbsp;Sumel Ashique ,&nbsp;Qamar A. Alshammari","doi":"10.1016/j.cca.2025.120484","DOIUrl":"10.1016/j.cca.2025.120484","url":null,"abstract":"<div><div>Gastrointestinal cancers (GICs) are a leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis. Liquid biopsy has emerged as a promising non-invasive diagnostic tool, utilizing circulating tumor DNA (ctDNA), circulating tumor cells, exosomal RNA (exoRNA), and tumor-educated platelets for early cancer detection. Challenges, including data complexity, low biomarker abundance, and detection variability, require advanced computational solutions. Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has significantly improved the accuracy and clinical utility of liquid biopsy by enabling high-throughput biomarker discovery, multi-omics integration, and predictive modelling. AI-driven algorithms have enhanced ctDNA mutation profiling, methylation analysis, and fragmentomics, offering superior sensitivity and specificity for early GIC detection. Additionally, AI-based analysis of exoRNA and platelet-derived biomarkers provides novel insights into tumor progression and patient stratification. Despite these advances, key challenges remain, including data standardization, bias mitigation, and regulatory validation. The implementation of federated learning and ethical AI frameworks can further refine AI-powered liquid biopsy models, paving the way for precision oncology applications. This review highlights advances in AI-powered liquid biopsy for early GIC detection, emphasizing its potential and the need for validation, collaboration, and regulatory alignment for clinical adoption.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"577 ","pages":"Article 120484"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633803","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":"Blood collection tubes with protease inhibitors to prevent falsely high renin concentrations due to cryoactivation","authors":"Omer Ozcan ,&nbsp;Jacquelien J. Hillebrand ,&nbsp;Carla Beertsen ,&nbsp;Wendy P.J. den Elzen ,&nbsp;Annemieke C. Heijboer","doi":"10.1016/j.cca.2025.120486","DOIUrl":"10.1016/j.cca.2025.120486","url":null,"abstract":"<div><h3>Objectives</h3><div>Exposure of plasma samples to low temperatures (between −5 and + 4 °C) leads to conversion of prorenin to its open state, which is then converted to renin by plasma proteases. This process, known as cryoactivation, results in falsely elevated renin concentrations. This study examined the effects of storage temperature, protease inhibitors, and 2-hour incubation at 37 °C on renin cryoactivation.</div></div><div><h3>Methods</h3><div>Blood samples (n = 24) were collected in four types of tubes: K₂EDTA, aprotinin, trypsin inhibitor, and protease inhibitor cocktail. Renin concentrations (IDS-i10) were measured at baseline and after storage at + 4 °C (one week), −20 °C (two weeks), and −80 °C (two weeks). Samples stored at −20 °C were later incubated at 37 °C for two hours and reanalyzed. Aldosterone concentrations were measured (LC-MS/MS) and aldosterone to renin ratios (ARR) were calculated.</div></div><div><h3>Results</h3><div>Renin concentrations remained stable at −80 °C but increased significantly at + 4 °C (18–50 %) and −20 °C (61–500 %). ARR changes were minimal at −80 °C (−8 pmol/mU) but largest at −20 °C (−263 pmol/mU). Renin concentrations returned to baseline after a 2-hour incubation at 37 °C only in trypsin inhibitor and protease inhibitor cocktail tubes.</div></div><div><h3>Conclusions</h3><div>Our study shows more cryoactivation of renin in plasma aliquots stored at −20 °C compared to storage at + 4 °C. Cryoactivation of prorenin in trypsin inhibitor and protease inhibitor cocktail tubes was reversed by a 2-hours incubation at 37 °C, which may be an alternative procedure for laboratories that are not able to store renin samples in −80 °C freezers.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"577 ","pages":"Article 120486"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633327","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":"Analysis of factors affecting laboratory alert level of trazodone based on therapeutic drug monitoring data","authors":"Jing Ding,&nbsp;Ying Chen,&nbsp;Yang Zhang,&nbsp;Suo zhang,&nbsp;Luyao Li,&nbsp;Huan Xing,&nbsp;Yuanyuan Zhai","doi":"10.1016/j.cca.2025.120487","DOIUrl":"10.1016/j.cca.2025.120487","url":null,"abstract":"<div><h3>Aims</h3><div>Previous studies have revealed the importance of therapeutic drug monitoring for personalized trazodone dosing. However, studies on risk factors related to trazodone plasma concentrations that exceed laboratory alert levels are lacking. This study aimed to identify the factors influencing the trazodone plasma concentration-to-dose (C/D) ratio in the Chinese population. Additionally, it attempted to comprehensively investigate the factors contributing to trazodone concentrations exceeding 1200 ng/mL.</div></div><div><h3>Methods</h3><div>A single-center, retrospective, cross-sectional study was conducted at Xi’an Mental Health Center in China, where data on Trazodone-treated patients between 2020 and 2023 were collected.</div></div><div><h3>Results</h3><div>The C/D ratios of trazodone were significantly influenced by age, the formulations of trazodone, and the concomitant use of fluvoxamine. Additionally, the results revealed that 21.67 % of patients receiving daily trazodone doses of 25–200 mg demonstrated plasma concentrations exceeding laboratory alert levels. A logistic regression analysis using a enter method determined patient older age [1.04 (95 CI: 1.01–1.07)], higher daily dose [1.04 (95 CI: 1.02–1.05)], higher total protein level [1.10 (95 CI: 1.02–1.19)] and concomitant use of fluvoxamine [7.99 (95 CI: 2.48–25.72)] as risk factors for surpassing laboratory alert levels in plasma concentrations.</div></div><div><h3>Conclusion</h3><div>In conclusion, this study provides important and valuable clinical results for future personalized trazodone administration.</div><div><strong>Keywords</strong> trazodone, therapeutic drug monitoring, laboratory alert level, related factors.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"577 ","pages":"Article 120487"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633326","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":"Identification of necroptotic biomarkers associated with immune microenvironment in sepsis based on the protein–protein interaction network and machine learning","authors":"Mengze Wu ,&nbsp;Zhao Zou ,&nbsp;Yuce Peng ,&nbsp;Suxin Luo","doi":"10.1016/j.cca.2025.120489","DOIUrl":"10.1016/j.cca.2025.120489","url":null,"abstract":"<div><h3>Background</h3><div>Necroptosis is inflammatorily sparked and closely associated with sepsis, but the crosstalk between necroptosis and inflammation in sepsis has rarely been studied in depth. This study is designed to reveal the role of necroptosis in the pathogenesis and development of sepsis by screening and validating hub necroptotic septic genes.</div></div><div><h3>Method</h3><div>We obtained datasets from the Gene Expression Omnibus (GEO) database. We screened differentially expressed genes (DEGs) and intersected them with necroptotic genes from the literature. Intersected genes were organized into one protein–protein interaction network (PPIN) and determined by machine learning algorithms as hub necroptotic DEGs (hub-NRDEGs). All hub-NRDEGs were examined for their septic change and diagnostic value and connected with septic changes in the immune microenvironment for their inflammatory roles. Experiments verified these genes using septic murine and cellular models.</div></div><div><h3>Results</h3><div>We obtained 4974 DEGs and concentrated on 336 necroptosis-related genes by the intersection. Experiencing the dual selection of PPIN and machine learning analysis, three hub-NRDEGs, CD40LG, TXN, and AIM2, were identified. Based on their transcriptomic profile, we classified septic samples into two groups, revealing their signalling discrepancy. They correlate with most immunocytes, and their abundance differentiates the immune infiltration widely. Experimental validation converged with the transcriptomic profile of three hub-NRDEGs in septic status.</div></div><div><h3>Conclusions</h3><div>One three-panel necroptotic signature for diagnosing sepsis was proposed. We initially screened the association between hub-NRDEGs and immunocytes, and we validated the expressional change of hub-NRDEGs in the experimental sepsis. Our necroptotic gene signature may contribute to the rapid diagnosis of sepsis.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"577 ","pages":"Article 120489"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633800","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}