{"title":"Single-Cell Profiling Identifies CLEC5A+ Macrophages as Key Drivers of Thoracic Aortic Aneurysm Via CCL5-Mediated M1 Polarization.","authors":"Xiangyu Li, Chunguang Guo, Mingyao Luo, Chang Shu","doi":"10.1002/jcla.70200","DOIUrl":"https://doi.org/10.1002/jcla.70200","url":null,"abstract":"<p><strong>Background: </strong>Thoracic aortic aneurysm (TAA) is a life-threatening disease with limited therapeutic options, largely due to an incomplete understanding of its pathogenic mechanisms. Inflammation and immune dysregulation are central to TAA progression, yet the specific pathogenic cell subsets and signaling pathways remain unclear.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was performed on aortic tissues from four healthy individuals and four TAA patients. Key immune cell populations were identified through clustering, macrophage subsetting, and M1/M2 polarization scoring. Machine learning (Random Forest and Boruta) across multiple bulk RNA-seq cohorts was used to identify robust biomarkers. Cell-cell communication was analyzed using CellChat and NewCCI. Molecular docking of 2988 FDA-approved drugs was conducted to screen potential CLEC5A inhibitors, followed by cellular validation experiments.</p><p><strong>Results: </strong>A total of 105,541 cells were profiled, revealing significant alterations in macrophage, dendritic cell, and NK cell proportions in TAA. CLEC5A+ macrophages emerged as the predominant pathogenic subset, exhibiting the highest M1 polarization score. Machine learning consistently identified CLEC5A and SPP1 as stable diagnostic biomarkers across four cohorts (AUC > 0.7). Cell-cell communication revealed strong CCL5-CLEC5A signaling from T/NK cells to macrophages. Molecular docking identified Dioscin as a potential CLEC5A inhibitor. Cellular experiments showed that CCL5-induced M1 polarization was CLEC5A-dependent and could be effectively blocked by Dioscin.</p><p><strong>Conclusions: </strong>CLEC5A<sup>+</sup>M1-polarized macrophages are key pathogenic cells in TAA. CLEC5A serves as a robust biomarker, and targeting the CCL5-CLEC5A axis with Dioscin represents a promising therapeutic strategy.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70200"},"PeriodicalIF":2.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jana Stikarova, Leona Chrastinova, Kristyna Svobodova, Marek Havlicek, Jan Louzil, Eliska Ceznerova, Alzbeta Hlavackova, Ondrej Pastva, Pavla Pecherkova, Ingrid Hrachovinova, Ondrej Kucerka, Roman Kotlin, Petr Soukup, Peter Salaj, Martin Maly, Jiri Suttnar
{"title":"Measurement of Active Thrombin Bound to Circulating D-Dimers as a Sensitive Biomarker for Prothrombotic Conditions.","authors":"Jana Stikarova, Leona Chrastinova, Kristyna Svobodova, Marek Havlicek, Jan Louzil, Eliska Ceznerova, Alzbeta Hlavackova, Ondrej Pastva, Pavla Pecherkova, Ingrid Hrachovinova, Ondrej Kucerka, Roman Kotlin, Petr Soukup, Peter Salaj, Martin Maly, Jiri Suttnar","doi":"10.1002/jcla.70224","DOIUrl":"https://doi.org/10.1002/jcla.70224","url":null,"abstract":"<p><strong>Background: </strong>Thrombin activity plays a crucial role in hemostasis, and it is tightly regulated by a system of activators and inhibitors. Active, unregulated thrombin may initiate clotting without previous vessel injury, causing thrombosis. Thrombin bound to fibrin participates in fibrinogen transformation, while its inhibition by the naturally occurring heparin-antithrombin complex is impeded. Bound thrombin activity has been detected on fibrin degradation products.</p><p><strong>Methods: </strong>D-dimers were isolated using a commercial ELISA kit. Mass spectrometry was used to confirm the presence of thrombin on captured D-dimers. D-dimer-bound thrombin activity was evaluated using specific substrate and inhibitors: hirudin-PPACK and heparin-antithrombin. Groups of 72 patients and 159 controls were analyzed.</p><p><strong>Results: </strong>The activity of thrombin was assessed utilizing our system, demonstrating stability throughout the procedures. The thrombin concentration during fibrin polymerization was reflected in the thrombin activity levels detected on D-dimers. Analysis of patient plasma samples indicated the feasibility of detecting low levels of active thrombin. Significant differences in D-dimer-bound thrombin activity were observed between subjects with chronic (controls) and acute conditions (patients).</p><p><strong>Conclusions: </strong>We present a proof-of-concept method for the evaluation of thrombin activity on circulating D-dimers that may aid in the diagnosis of thrombotic events and the monitoring of anticoagulant therapy.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70224"},"PeriodicalIF":2.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaohan Liu, Lei Huang, Junzhu Wang, Yixuan Guo, Hongli Shen, Xianghong Zhao, Lanzhu Yue, Zhaoyun Liu, Rong Fu
{"title":"Exportin 1 Inhibitor Combined With Venetoclax Induces Apoptosis in Myelodysplastic Syndrome by Mitochondria-Induced Apoptosis Pathway.","authors":"Xiaohan Liu, Lei Huang, Junzhu Wang, Yixuan Guo, Hongli Shen, Xianghong Zhao, Lanzhu Yue, Zhaoyun Liu, Rong Fu","doi":"10.1002/jcla.70229","DOIUrl":"https://doi.org/10.1002/jcla.70229","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies that pose a serious health threat. Current therapies include symptomatic treatments for low-risk and hypomethylating agents for high-risk MDS. However, many patients develop resistance to hypomethylating drugs. (Exportin 1) XPO1 inhibition has shown efficacy in inducing tumor cell death by blocking the nuclear export of oncogenes; nevertheless, the role of XPO1 inhibition in MDS remains unexplored.</p><p><strong>Methods: </strong>We investigated the role of XPO1 in the pathogenesis of MDS by analyzing XPO1 expression in MDS patients with different risk stratification and healthy controls in the GEO database, and evaluated the effects of the XPO1 inhibitor Selinexor on the proliferation and apoptosis of MDS cells and its mechanism by CCK-8, EdU, flow cytometry, and immunofluorescence. The effects of Selinexor on the proliferation and apoptosis of MDS cells, its mechanism, and its synergistic effect with Bcl-2 inhibitor Venetoclax were evaluated.</p><p><strong>Results: </strong>We found that XPO1 may have an important role in the development of MDS, and Selinexor induced apoptosis and inhibited the proliferation of MDS cells by inhibiting the nuclear export of p53. Drug combination index assays showed that Selinexor was able to synergize with Venetoclax. The combination of the two resulted in the inhibition of XPO1, which could increase ROS levels in MDS cells and activate mitochondria-mediated apoptotic pathways in cells after inducing elevated MOMP.</p><p><strong>Conclusion: </strong>Our study found that inhibition of XPO1 is a promising modality in the treatment of MDS, especially when combined with Venetoclax, which could be a potential target for MDS therapy.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70229"},"PeriodicalIF":2.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Flow Cytometric Profiling Reveals Platelet Dysfunction and Impaired Immune Communication in Acute and Chronic Cerebrovascular Disease\".","authors":"","doi":"10.1002/jcla.70246","DOIUrl":"https://doi.org/10.1002/jcla.70246","url":null,"abstract":"","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70246"},"PeriodicalIF":2.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Interpretation of Platelet Activation Marker sCLEC-2 in Antiphospholipid Syndrome.","authors":"Risa Kaneshige, Yukari Motoki, Kiyoshi Ichihara, Junzo Nojima","doi":"10.1002/jcla.70230","DOIUrl":"https://doi.org/10.1002/jcla.70230","url":null,"abstract":"<p><strong>Background: </strong>Soluble C-type lectin-like receptor 2 (sCLEC-2) has emerged as a biomarker of platelet activation and thrombus formation. Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis and pregnancy complications, driven in part by platelet activation. However, the clinical utility of sCLEC-2 and the sCLEC-2/D-dimer ratio in APS remains unclear.</p><p><strong>Methods: </strong>Plasma samples from 19 patients with primary APS, 30 with SLE-associated APS, 10 with SLE without APS, 40 with other collagen diseases, and 40 healthy controls (n = 139) were analyzed. Plasma sCLEC-2 levels and D-dimer levels were quantified by immunoassay. Antiphospholipid antibodies (anti-cardiolipin antibodies and anti-β<sub>2</sub>-glycoprotein I antibodies IgG/IgM) were measured by ELISA kits. Group comparisons and correlations were evaluated.</p><p><strong>Results: </strong>Using the upper limit of the 95% CI of healthy controls as a cutoff, sCLEC-2 positivity was observed in 100% of non-APS autoimmune disease patients, and 98.0% of APS patients. sCLEC-2, D-dimer, and the sCLEC-2/D-dimer ratio were significantly higher in non-APS and APS groups compared with controls (p < 0.001). A slight but significant difference in the sCLEC-2 and the ratio was observed between the non-APS and APS groups. However, no significant differences were found among APS subgroups stratified by thrombosis type. sCLEC-2 showed no correlation with any of four major antiphospholipid antibody titers.</p><p><strong>Conclusion: </strong>Although we observed raised sCLEC-2 and sCLEC-2/D-dimer ratio among APS and non-APS groups and modest differences between the two groups, clinical interpretation of the findings requires a prospective study evaluating dynamic changes of sCLEC-2 in the clinical course.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70230"},"PeriodicalIF":2.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune Imbalance in Sickle Cell Anemia: Flow Cytometric Insights Into Regulatory T Cells and Neutrophil Dynamics.","authors":"Rukiye Ölçüoğlu, Funda Tanrıkulu, Sevtap Kılınç, Eda Çakmak, Süheyl Asma, Can Boğa, Hakan Özdoğu, İlknur Pamuk","doi":"10.1002/jcla.70227","DOIUrl":"https://doi.org/10.1002/jcla.70227","url":null,"abstract":"<p><strong>Objective: </strong>To investigate immunophenotypic alterations in regulatory T cells (Tregs) and neutrophil dynamics in adult sickle cell anemia (SCA) patients during painful crises and steady state.</p><p><strong>Methods: </strong>Ninety-three participants were included: 17 SCA patients in painful crisis, 27 in steady state, and 49 healthy controls. Flow cytometry was used to assess CD3<sup>+</sup>CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs and related subsets. Hematological parameters were evaluated by complete blood counts. Statistical analyses included group comparisons, multiple regression, and ROC curve analysis.</p><p><strong>Results: </strong>SCA patients exhibited significant reductions in CD25<sup>+</sup> and CD4<sup>+</sup> T cell subsets, despite preserved FoxP3<sup>+</sup> Treg frequencies. White blood cell and neutrophil counts were elevated, especially during crisis. Neutrophil and lymphocyte percentages significantly predicted T cell subset levels. ROC analysis identified CD3<sup>+</sup> and CD4<sup>+</sup> percentages as strong classifiers of disease state.</p><p><strong>Conclusion: </strong>Despite numerical preservation of FoxP3<sup>+</sup> Tregs, SCA is marked by impaired T cell activation and sustained innate immune activation. These immune shifts may relate to but do not directly determine end-organ complications. Functional assays and longitudinal studies are needed to elucidate Treg competence, hydroxyurea effects, and age-related immune changes in SCA.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70227"},"PeriodicalIF":2.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chaoqiong Zhou, Ting Chen, Ying Huang, Huali Wang, Dahai He, Feng Wu, Yan Zhang, Lirui Kong
{"title":"Recent Advances in Thalassemia Research: A Comprehensive Assessment From Diagnostic Technologies to Clinical Treatment.","authors":"Chaoqiong Zhou, Ting Chen, Ying Huang, Huali Wang, Dahai He, Feng Wu, Yan Zhang, Lirui Kong","doi":"10.1002/jcla.70228","DOIUrl":"https://doi.org/10.1002/jcla.70228","url":null,"abstract":"<p><strong>Background: </strong>Thalassemia is a common hereditary blood disorder characterized by impaired globin synthesis, leading to anemia and a variety of related complications. With the rapid advances in genomics and molecular biology, remarkable progress has been made in this field in recent years, especially in the in-depth exploration of genetic mechanisms, the innovation of diagnostic techniques and the continuous update of therapeutic strategies. It is worth noting that with the emergence of new treatment strategies such as gene therapy and stem cell transplantation, offer new hope for patients. Despite significant progress, further research is needed to address the limitations of existing treatment methods and optimize long-term management for patients.</p><p><strong>Methods: </strong>This review introduces the epidemiology, pathogenic mechanisms, and related complications of thalassemia.</p><p><strong>Results: </strong>It also highlights innovations in the diagnosis of thalassemia (such as TGS and Genomics technologies) and treatment advancements (such as CRISPR/Cas9, HSCT, and Luspatercept) and their limitations, and explores why transformative tools have not been fully utilized in regions with high prevalence of thalassemia.</p><p><strong>Conclusions: </strong>Unlike existing reviews that focus solely on either diagnostic or therapeutic aspects, this article integrates both perspectives with an emphasis on clinical accessibility. It aims to provide sustainable and equitable management guidance for clinicians, researchers, and policymakers involved in thalassemia care.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70228"},"PeriodicalIF":2.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RETRACTION: A-Kinase-Interacting Protein 1 Overexpression Correlates With Deteriorative Tumor Features and Worse Survival Profiles and Promotes Cell Proliferation but Represses Apoptosis in Non-Small-Cell Lung Cancer.","authors":"","doi":"10.1002/jcla.70235","DOIUrl":"https://doi.org/10.1002/jcla.70235","url":null,"abstract":"<p><strong>Retraction: </strong>H. Chen, S. Yan, L. Dong, X. Li, \"A-Kinase-Interacting Protein 1 Overexpression Correlates With Deteriorative Tumor Features and Worse Survival Profiles and Promotes Cell Proliferation but Represses Apoptosis in Non-Small-Cell Lung Cancer,\" Journal of Clinical and Laboratory Analysis 34, no. 2 (2019): e23061, https://doi.org/10.1002/jcla.23061. The above article, published online on 11 December 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Rong Fu; and Wiley Periodicals, LLC. The retraction has been agreed due to concerns raised by a third party, which identified compromised data and systematic issues in the published article. The authors and their institutes were unresponsive when these concerns were brought to their attention. Accordingly, the article is retracted as the editors have lost trust in the reliability of the data and the results presented.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70235"},"PeriodicalIF":2.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RETRACTION: Potentiality of Forkhead Box Q1 as a Biomarker for Monitoring Tumor Features and Predicting Prognosis in Non-Small Cell Lung Cancer.","authors":"","doi":"10.1002/jcla.70237","DOIUrl":"https://doi.org/10.1002/jcla.70237","url":null,"abstract":"<p><strong>Retraction: </strong>L. Li, B. Xu, H. Zhang, J. Wu, Q. Song, J. Yu, \"Potentiality of Forkhead Box Q1 as a Biomarker for Monitoring Tumor Features and Predicting Prognosis in Non-Small Cell Lung Cancer,\" Journal of Clinical and Laboratory Analysis 34, no. 1 (2019): e23031, https://doi.org/10.1002/jcla.23031. The above article, published online on 12 November 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Rong Fu; and Wiley Periodicals, LLC. The retraction has been agreed due to concerns raised by a third party, which identified compromised data and systematic issues in the published article. The authors and their institutes were unresponsive when these concerns were brought to their attention. Accordingly, the article is retracted as the editors have lost trust in the reliability of the data and the results presented.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70237"},"PeriodicalIF":2.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RETRACTION: Polo-Like Kinase 4 Correlates With Greater Tumor Size, Lymph Node Metastasis, and Confers Poor Survival in Non-Small Cell Lung Cancer.","authors":"","doi":"10.1002/jcla.70241","DOIUrl":"https://doi.org/10.1002/jcla.70241","url":null,"abstract":"<p><strong>Retraction: </strong>Q. Zhou, G. Fan, Y. Dong, \"Polo-Like Kinase 4 Correlates With Greater Tumor Size, Lymph Node Metastasis, and Confers Poor Survival in Non-Small Cell Lung Cancer,\" Journal of Clinical and Laboratory Analysis 34, no. 4 (2019): e23152, https://doi.org/10.1002/jcla.23152. The above article, published online on 25 December 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Rong Fu; and Wiley Periodicals, LLC. The retraction has been agreed due to concerns raised by a third party, which identified compromised data and systematic issues in the published article. The editors have lost trust in the reliability of the data and the results presented. The corresponding author confirmed scientific problems and requested retraction.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":" ","pages":"e70241"},"PeriodicalIF":2.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}