Biomarker InsightsPub Date : 2025-09-23eCollection Date: 2025-01-01DOI: 10.1177/11772719251378813
Jianhua Wang, Andrew Hoover, Justin H Townsend, Zohar Yehoshua, Kirill Stremousov, Juan Pablo de Rivero Vaccari, Hong Jiang
{"title":"Blood Based Vascular Marker Responses to Ocufolin<sup>®</sup> in Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms.","authors":"Jianhua Wang, Andrew Hoover, Justin H Townsend, Zohar Yehoshua, Kirill Stremousov, Juan Pablo de Rivero Vaccari, Hong Jiang","doi":"10.1177/11772719251378813","DOIUrl":"10.1177/11772719251378813","url":null,"abstract":"<p><strong>Background: </strong>Patients with inborn errors of metabolism related to Methylenetetrahydrofolate reductase (<i>MTHFR</i>) gene variants are at an increased risk for microvascular complications resulting from diabetic retinopathy. Early intervention with targeted nutritional support, particularly folate supplementation, may help stabilize metabolic function and slow the progression of diseases such as diabetes and hypertension, especially before irreversible structural damage occurs.</p><p><strong>Objectives: </strong>To assess the effects of the folate supplement Ocufolin<sup>®</sup> on serum markers in patients with Type 2 diabetes (T2D) and mild diabetic retinopathy (MDR).</p><p><strong>Design: </strong>Prospective Cohort Study.</p><p><strong>Methods: </strong>Ten patients with both MDR and <i>MTHFR</i> polymorphisms (<i>C677T or A1298C</i>) were enrolled in the present study and received Ocufolin<sup>®</sup> to address errors in folate methylation metabolism. Patients were excluded if they had a history of other ocular or systemic diseases. Serum biomarkers associated with clinical chemistry (homocysteine, high-sensitivity C-reactive protein [hs-CRP], myeloperoxidase [MPO], fasting insulin, triglycerides, total cholesterol, high density lipoprotein [HDL], low density lipoprotein [LDL], Oxidized-LDL [Ox-LDL], vascular endothelial growth factor [VEGF], D-Dimer, hemoglobin A1c [HbA1c] and glutathione) were measured pre-and post-intervention.</p><p><strong>Result: </strong>Treatment with Ocufolin<sup>®</sup> resulted in a 23% decrease in serum homocysteine (<i>P</i> = .005), an 18% decrease in hsCRP, a 13% decrease in fasting insulin, a 15% increase in D-Dimer (<i>P</i> = .03) and a 47% decrease in VEGF (<i>P</i> = .04). Additionally, there was a 9% increase in glutathione, a 2% increase in MPO, a 6% reduction in triglycerides, a 3% increase in total cholesterol, a 4% increase in HDL, a 4% increase in LDL, an 8% increase in Ox-LDL. HbA1c did not change.</p><p><strong>Conclusion: </strong>Normalizing folate metabolism through Ocufolin<sup>®</sup> significantly improved key blood-based biomarkers in patients with diabetic retinopathy. These metabolic improvements may underlie enhanced retinal perfusion and reduced oxidative stress, suggesting potential adjunctive therapeutic benefits for managing vascular retinopathies in this population.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251378813"},"PeriodicalIF":2.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2025-09-11eCollection Date: 2025-01-01DOI: 10.1177/11772719251361306
Elizabeth Lyster Andersen, Magnar Gangås Solberg, Steve Enger, Sophia Onarheim, Mona Olufsen, Trygve Berge, Sissel Åkra, Maiken Kojen Kleveland, Ingrid Elisabeth Christophersen, Sara Reinvik Ulimoen, Ingebjørg Seljeflot, Arnljot Tveit
{"title":"Circulating Biomarkers and Recurrence of Persistent Atrial Fibrillation After Electrical Cardioversion.","authors":"Elizabeth Lyster Andersen, Magnar Gangås Solberg, Steve Enger, Sophia Onarheim, Mona Olufsen, Trygve Berge, Sissel Åkra, Maiken Kojen Kleveland, Ingrid Elisabeth Christophersen, Sara Reinvik Ulimoen, Ingebjørg Seljeflot, Arnljot Tveit","doi":"10.1177/11772719251361306","DOIUrl":"10.1177/11772719251361306","url":null,"abstract":"<p><strong>Background: </strong>Rhythm control therapy is recommended for individuals with symptomatic atrial fibrillation (AF) to reduce symptoms and improve quality of life. Electrical cardioversion (ECV) is used to restore sinus rhythm (SR), but AF recurrence is common.</p><p><strong>Objective: </strong>We aimed to investigate if a selection of circulating biomarkers can predict rhythm outcomes in individuals with persistent AF treated with ECV.</p><p><strong>Design: </strong>This was an observational cohort study.</p><p><strong>Methods: </strong>We included 200 individuals aged ⩾ 18 years referred for ECV of AF from November 2017 to March 2022. We obtained blood samples 0 to 6 weeks before ECV. Plasminogen activator inhibitor type 1 (PAI-1) activity, soluble suppression of tumorigenicity 2 (sST2), galectin-3 (GAL-3), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), growth differentiation factor-15, (GDF-15), transforming growth factor-β-1 (TGF-β1), and fibroblast growth factor-23 (FGF-23) were analyzed by ELISA methods. The participants recorded thumb ECGs twice daily for 28 days after the ECV to detect AF recurrence.</p><p><strong>Results: </strong>A total of 188 individuals were eligible for the analyses. Twenty-four participants converted spontaneously to SR before ECV. Among the cardioverted, 74 maintained SR, whereas 90 experienced AF recurrence before hospital discharge (n = 15) or during the follow-up period of 28 days (n = 75). TIMP-1 was significantly higher in those with AF recurrence than in those who maintained SR, but overlapping distributions suggest limited predictive ability. PAI-1 activity, sST2, GAL-3, IL-6, MMP-9, GDF-15, TGF-β1, and FGF-23 did not differ among the participants who had ECV.</p><p><strong>Conclusion: </strong>TIMP-1 was higher in participants with recurrence of AF after ECV, but its predictive ability was limited. None of the other biomarkers were associated with AF recurrence. We do not recommend using these biomarkers for candidate selection for ECV of persistent AF.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251361306"},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pre-treatment Circulating Tumor Cell Associated White Blood Cell Clusters Independently Predict Poor Survival in Patients with Extensive-disease Small Cell Lung Cancer.","authors":"Ying Wang, Minghang Zhang, Cen Chen, Yanxia Liu, Yuan Gao, Hongxia Li, Baohua Lu, Mingming Hu, Hongmei Zhang, Peter Ping Lin, Zhanliang Ren, Tongmei Zhang, Shaofa Xu","doi":"10.1177/11772719251338620","DOIUrl":"10.1177/11772719251338620","url":null,"abstract":"<p><strong>Background: </strong>Patients with extensive disease (ED)-small cell lung cancer (SCLC) commonly suffer a more inferior prognosis than those with limited disease (LD)-SCLC.</p><p><strong>Objectives: </strong>This study aims to investigate the heterogeneity and prognostic significance of various aneuploid circulating tumor cells (CTCs) subtypes and CTC-associated white blood cell (CTC-WBC) clusters in patients with LD-and ED-SCLC respectively.</p><p><strong>Design: </strong>This prospective, non-interventional, single-center study included 48 patients with LD-SCLC and 47 patients with ED-SCLC.</p><p><strong>Methods: </strong>A total of 95 SCLC patients were prospectively enrolled and serial blood samples were obtained before chemotherapy administration (t<sub>0</sub>) and after 2 cycles of chemotherapy (t<sub>1</sub>). Comprehensive in situ co-detection of CTCs and CTC-WBC clusters were performed in all enrolled patients.</p><p><strong>Results: </strong>The analysis revealed no significant difference in CTCs quantity between LD-SCLC and ED-SCLC patients (<i>P</i> = .610). However, significant morphologic heterogeneity in CTCs, including cell size and chromosome 8 (Chr8) ploidy in CTCs was observed between the 2 groups (<i>P</i> < .001 and <i>P</i> < .001). Patients with post-therapeutic small cell CTCs ⩾ 2/6 ml or triploid CTCs ⩾ 2/6 ml exhibited reduced overall survival (OS) compared to those with small cell CTCs < 2/6 ml or triploid CTCs < 2/6 ml in the ED-SCLC (<i>P</i> = .011 and <i>P</i> = .018). Additionally, the positive detection of post-therapeutic tetraploid CTCs was associated with inferior survival in both LD-and ED-SCLC (<i>P</i> = .041 and <i>P</i> = .049). The presence of CTC-WBC clusters at baseline and after treatment significantly correlated with inferior OS in ED-SCLC (<i>P</i> = .016 and <i>P</i> = .028) but not in LD-SCLC (<i>P</i> = .355 and <i>P</i> = .621). Multivariate analysis identified brain metastasis and pre-treatment CTC-WBC clusters as independent prognostic factors for OS in ED-SCLC patients (<i>P</i> = .004 and <i>P</i> = .013).</p><p><strong>Conclusion: </strong>Ideal biomarkers should be more specific for survival prediction in patients with different disease stages. Pre-treatment CTC-WBC clusters can independently predict inferior OS in ED-SCLC but not LD-SCLC.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251338620"},"PeriodicalIF":2.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2025-07-27eCollection Date: 2025-01-01DOI: 10.1177/11772719251355038
H Stephen Injeyan, Julita A Teodorczyk-Injeyan, Sheilah Hogg-Johnson, Shadi Rashed, Joyce Lee, Glen Harris
{"title":"Salivary Biomarkers of Inflammation in Patients With Chronic Non-Specific Low Back Pain.","authors":"H Stephen Injeyan, Julita A Teodorczyk-Injeyan, Sheilah Hogg-Johnson, Shadi Rashed, Joyce Lee, Glen Harris","doi":"10.1177/11772719251355038","DOIUrl":"10.1177/11772719251355038","url":null,"abstract":"<p><strong>Background: </strong>Chronic non-specific low back pain (CNSLBP) is a debilitating condition with unclear underlying mechanisms. The presence of systemic biomarkers associated with inflammation in nonspecific low back pain (NSLBP) has been inconsistently reported primarily through invasive blood sampling.</p><p><strong>Objective: </strong>This study evaluates the use of saliva as an alternative medium for assessing inflammatory biomarker levels in patients with CNSLBP.</p><p><strong>Design: </strong>Prospective cross-sectional pilot study.</p><p><strong>Methods: </strong>Twenty-five patients with CNSLBP and 25 age and sex matched asymptomatic participants were selected according to specific inclusion and exclusion criteria. The primary outcome was determination of the levels of inflammatory biomarkers in unstimulated saliva samples of CNSLBP patients relative to controls using Luminex™ 200 technology. Secondary outcomes were pain, disability and anxiety/stress levels of participants.</p><p><strong>Results: </strong>In CNSLBP patients, 9 biomarkers interferon γ (IFNγ), interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-13, IL-12p40, IL-12p70, and tumor necrosis factor α (TNFα) were comparable to controls (<i>P</i> = .25-.94). However, 4 pro-inflammatory mediators were significantly elevated, exhibiting medium to large effect sizes: IL-1β (<i>P</i> = .028, Cohen's <i>d</i> = 1.62), IL-6 (<i>P</i> = .001, <i>d</i> = 1.0), IL-8 (<i>P</i> = .002, <i>d</i> = 0.86), and MCP-1 (<i>P</i> = .001, <i>d</i> = 0.77). Additionally, IL-1Ra levels were significantly higher, though with a small effect size (<i>P</i> = .03, <i>d</i> = 0.43). A significant correlation (<i>P</i> = .02) was observed between VAS pain scores and MCP-1 levels.</p><p><strong>Conclusion: </strong>Saliva represents a viable medium for assessing key inflammatory biomarkers in patients with chronic non-specific low back pain (CNSLBP). Elevated levels of proinflammatory cytokines, IL-1, IL-6, IL-8, and the nociceptive chemokine MCP-1 were observed in comparison to asymptomatic controls, with MCP-1 showing a positive correlation with self-reported pain intensity. Future studies utilizing unstimulated saliva samples may further investigate changes in inflammatory biomarker levels to monitor treatment outcomes.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251355038"},"PeriodicalIF":2.6,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2025-07-13eCollection Date: 2025-01-01DOI: 10.1177/11772719251324322
Chiara Barisione, Jorge Miguel Mena Vera, Caterina Ivaldo, Silvia Ortona, Pier Francesco Ferrari, Paola Visconti, Michele Paudice, Martina Bastianon, Caterina Melani, Gaddiel Mozzetta, Valerio Vellone, Giovanni Pratesi, Domenico Palombo
{"title":"The Genoa Vascular Biobank: A Today Resource for Future Perspectives in Vascular Research.","authors":"Chiara Barisione, Jorge Miguel Mena Vera, Caterina Ivaldo, Silvia Ortona, Pier Francesco Ferrari, Paola Visconti, Michele Paudice, Martina Bastianon, Caterina Melani, Gaddiel Mozzetta, Valerio Vellone, Giovanni Pratesi, Domenico Palombo","doi":"10.1177/11772719251324322","DOIUrl":"10.1177/11772719251324322","url":null,"abstract":"<p><strong>Background: </strong>Biological knowledge and patient care have been significantly improved by the emergence of big data analysis and -omics sciences, requiring high quality standards for biospecimen and data collection. Biobanks are complex and dynamic units designated to fulfill these needs.</p><p><strong>Objectives: </strong>The Genoa Vascular Biobank (GTB-VD) is a collaborative network between the IRCCS Ospedale Policlinico San Martino (Centre of Biological Resources), and the University of Genoa (Vascular and Endovascular Surgery Unit; Anatomic Pathology Unit; Laboratory of Clinical and Experimental Vascular Biology). This work describes workflow, ethic and governance requirements, demographic and clinical characteristics of subjects enrolled in the GTB-VD, and the volume of open or endovascular surgical interventions.</p><p><strong>Design: </strong>The GTB-VD recruits patients undergoing surgical repair for carotid artery stenosis (CS) and abdominal aortic aneurysm (AAA), enrolled on the basis of selection criteria and subdivided for pathology and type of intervention, upon informed consent.</p><p><strong>Methods: </strong>Biospecimens comprise serum, plasma, whole blood, peripheral blood mononuclear cells, and urine (from AAA only), stored at -80°C; lesions from open surgeries are frozen and formalin fixed paraffin embedded. Samples are associated with donor's clinical data through pseudonymization to prevent patient identification. Data accuracy and sample quality are ensured by harmonized standard operative procedures.</p><p><strong>Results: </strong>From 2018 to the end of 2023, 442 CS (distinguished into severe-asymptomatic or symptomatic, displaying a ratio of 5:1) and 214 AAA have been collected. CS is more frequently associated with diabetes and peripheral artery diseases, AAA with pulmonary history, and renal function impairment. Open surgery is more used for CS and endovascular for AAA.</p><p><strong>Conclusion: </strong>The GTB-VD, as organized, represents an \"<i>unicum</i>\" in our Country; it supports studies to identify molecular targets and biomarkers associated with specific arteriopathy, for developing secondary prevention strategies and minimally invasive, in situ therapies. Collaborative studies and sample sharing are welcome.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251324322"},"PeriodicalIF":3.4,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Comprehensive Description of the Roadmap to Identify and Validate a Myelin Biomarker.","authors":"Giovanna Capodivento, Davide Visigalli, Andrea Armirotti, Chiara Demichelis, Marinella Carpo, Roberto Fancellu, Erika Schirinzi, Daniele Severi, Diego Franciotta, Fiore Manganelli, Gabriele Siciliano, Alessandro Beronio, Elisabetta Capello, Paola Lanteri, Eduardo Nobile-Orazio, Angelo Schenone, Luana Benedetti, Lucilla Nobbio","doi":"10.1177/11772719251349605","DOIUrl":"10.1177/11772719251349605","url":null,"abstract":"<p><strong>Background: </strong>Demyelination and remyelination are major issues for scientists dealing with myelin disorders in both clinical and research fields. Despite that, rapid, reliable and convenient tools to monitor myelin changes still lack both in central and peripheral nervous system. Given that myelin is enriched in specific lipids and proteins, it is reasonable they could represent eligible candidates as structural damage biomarkers for this characteristic membrane. Among them, we focused on sphingomyelin (SM) due to the enrichment in myelin and because it is easily measurable in different biological matrices.</p><p><strong>Objective: </strong>Depicting the roadmap to identify and validate SM dosage as a myelin biomarker useful for pre-clinical and clinical practice.</p><p><strong>Design: </strong>This study adheres to STROBE guidelines for observational cross-sectional studies on human patients and to ARRIVE guidelines for animal models.</p><p><strong>Method: </strong>Following the recommendations of the Society for CSF Analysis and Clinical Neurochemistry, we describe the stepwise process to validate SM as a myelin biomarker, starting from the optimization of the fluorescence-based assay and analytical validation in experimental models until clinical and pathological validation in biological fluids of neurological patients.</p><p><strong>Results: </strong>SM dosage monitors myelination, demyelination, remyelination and even small myelin changes associated to myelin pathology and pharmacological treatments in experimental models. SM is detectable in human biological fluids and informative of myelin damage in the CSF of neurological patients. SM dosage identifies myelin breakdown in the CSF of patients affected by Guillain-Barrè Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), identifying disease activity, axonal from demyelinating variants, and avoiding misdiagnosis.</p><p><strong>Conclusion: </strong>SM dosage displayed extremely promising real-word performances being able to identify, monitor and stage myelin pathology. Given that it is simple, inexpensive and easily adaptable to routine use in any hospital setting, it might rapidly progress to the implementation and impact on clinical outcomes.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251349605"},"PeriodicalIF":3.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2025-06-30eCollection Date: 2025-01-01DOI: 10.1177/11772719251351687
Kehinde A Taiwo, Ibrahim O Ahmed, Muritala A Asafa, Olusola J Olarewaju, Oludolapo A Omoyiola, Olatokunbo O Oguns, Temilola O Owojuyigbe, Rahman A Bolarinwa
{"title":"Pro-Inflammatory Cytokines in Patients With Chronic Phase-Chronic Myeloid Leukaemia Treated With Imatinib: Any Role in the Monitoring of Treatment Response?","authors":"Kehinde A Taiwo, Ibrahim O Ahmed, Muritala A Asafa, Olusola J Olarewaju, Oludolapo A Omoyiola, Olatokunbo O Oguns, Temilola O Owojuyigbe, Rahman A Bolarinwa","doi":"10.1177/11772719251351687","DOIUrl":"10.1177/11772719251351687","url":null,"abstract":"<p><strong>Background: </strong>Cancers cause changes in the levels of inflammatory cytokines by inhibiting or promoting their production thus affecting the immune system. The measurement of serum levels of cytokines may be useful in assessing these immunological changes and invariably assessing cancer status.</p><p><strong>Objectives: </strong>To investigate the effect of imatinib mesylate (glivec<sup>®</sup>) on the serum levels of interleukins (IL-6 and IL-10), and C-reactive protein (CRP) in patients with chronic phase chronic myeloid leukaemia (CP-CML).</p><p><strong>Design: </strong>This prospective cohort study included 26 imatinib naïve CP-CML patients with no other co-morbidities and 26 age and sex-matched healthy controls.</p><p><strong>Method: </strong>Serum levels of interleukins (IL6 and 10) and CRP were determined using the ELISA method at recruitment for both patients and controls and repeated for the CML patients at 3 months into imatinib therapy.</p><p><strong>Results: </strong>The mean serum levels of IL-6 and CRP were significantly higher in CP-CML than in the controls at recruitment 439.83 ± 167.52 versus 39.62 ± 10.11 pg/ml, (<i>t</i> = 8.720 <i>P</i> ⩽ .0001), (8.45 ± 2.88 vs 2.86 ± 1.08 mg/l; <i>t</i> = 6.729 <i>P</i> ⩽ .0001) respectively. In contrast, the mean of the IL-10 in the controls (36.63 ± 12.43) was noticed to be significantly higher than the patients (22.88 ± 4.76 vs 36.63 ± 12.43 pg/ml; <i>t</i> = -3.851 <i>P</i> = .003). Interestingly, there was a significant drop in the serum levels of IL-6 (439.83 ± 167.52 vs 46.85 ± 14.48 pg/ml, (<i>t</i> = 8.055 <i>P</i> ⩽ .0001) and CRP (8.45 ± 2.88 mg/l vs 4.24 ± 1.57; <i>t</i> = 4.305 <i>P</i> = .0001) in the CML subjects 3 months into imatinib therapy. Only IL-10 had a non-significant drop in the CML subjects after 3 months of imatinib therapy. Method validation of these biomarkers was done using the Receiver operating characteristic (ROC) curve which revealed an area under the curve (AUC) of 1.000 for both IL-6 and CRP and 0.152 for IL-10.</p><p><strong>Conclusion: </strong>The study has concluded that treatment naïve CML is associated with a significant elevation of pro-inflammatory cytokines (IL-6 and CRP) and treatment with imatinib led to a significant decline in the serum levels of these markers suggesting that IL-6 and CRP could be useful as adjunct in the monitoring of CML treatment.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251351687"},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Staphylococcus aureus</i>-derived Signature Protein(s) in Murine Vaginal Lavage Fluid: Investigating the Underlying factors of Infertility as a Consequence of Sperm Impairing Bacterium.","authors":"Ishwerpreet Kaur Jawanda, Thomson Soni, Seema Kumari, Vijay Prabha","doi":"10.1177/11772719251340518","DOIUrl":"10.1177/11772719251340518","url":null,"abstract":"<p><strong>Background: </strong>Bacterial infections are often an overlooked factor in female infertility. <i>Staphylococcus aureus</i> has been identified as the predominant vaginal pathogen in infertile women, with a prevalence of 57.33%. Previous studies showed that <i>S. aureus</i> induces infertility in mice by sperm impairment, suggesting its asymptomatic vaginal colonization creates a hostile environment for sperm. While sperm immobilization factor (SIF) from culture supernatant has been identified, its production within host's environment remained unexplored.</p><p><strong>Objective: </strong>To unveil <i>S. aureus</i>-derived signature protein(s) in vaginal lavage fluid (VLf).</p><p><strong>Design: </strong>Mass spectrometry combined with experimental studies.</p><p><strong>Methods: </strong>VLf was obtained from female mice administered either with sperm immobilizing <i>S. aureus</i> (test group) or PBS alone (control group) and analyzed using nano-LC-MS/MS, gel filtration chromatography, SDS-PAGE, functional assays, and in silico studies.</p><p><strong>Results: </strong>Nano-LC-MS/MS yielded 5 distinct bacterial proteins in test group and no bacterial protein in control. Elution profile of test VLf revealed a single peak and indicated 1 protein band (~36 kDa) using SDS-PAGE that aligned with GMP reductase. VLf-protein showed impairment of sperm motility and viability in concentration-dependent manner and disrupted sperm morphology. Binding studies using FITC-labeled VLf-protein depicted presence of green fluorescence over entire surface of mouse spermatozoa. These results were akin to SIF, already isolated and characterized in our laboratory, from culture supernatant of <i>S. aureus</i>, causing sperm impairment and hence, designated as vaginal lavage fluid-derived sperm immobilization factor (VLf-SIF). Through in silico analysis, superimposition of VLf-SIF and SIF, already known to show sequence homology to cysteine-tRNA ligase, revealed close structural alignment. Molecular docking analysis depicted energetically favorable binding between VLf-SIF and spermatozoa surface protein (Heat shock-related 70 kDa protein 2).</p><p><strong>Conclusion: </strong>This study provides novel evidence of sperm-impairing <i>S. aureus</i> signature proteins as key mediators of bacterial-induced infertility, paving way for diagnostic, and therapeutic advancements.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251340518"},"PeriodicalIF":3.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2025-05-24eCollection Date: 2025-01-01DOI: 10.1177/11772719251336274
Justine Demeuse, Alix Mackowiak, Elodie Grifnée, Philippe Massonnet, Loreen Huyghebaert, Thomas Dubrowski, Stéphanie Peeters, Caroline Le Goff, Etienne Cavalier
{"title":"Latest Advances in Structural Insights and Quantification Techniques for Type I Collagen Biomarkers: A path toward standardization?","authors":"Justine Demeuse, Alix Mackowiak, Elodie Grifnée, Philippe Massonnet, Loreen Huyghebaert, Thomas Dubrowski, Stéphanie Peeters, Caroline Le Goff, Etienne Cavalier","doi":"10.1177/11772719251336274","DOIUrl":"10.1177/11772719251336274","url":null,"abstract":"<p><p>With an aging population, the demand for sensitive and specific biomarkers to assess bone turnover has surged. Bone turnover involves 2 key processes: bone formation, during which Type I procollagen is cleaved into Type I collagen and subsequently mineralized into bone, and bone resorption, during which Type I collagen is demineralized and degraded into peptides by cathepsin K. To identify biomarkers that accurately reflect these processes, extensive efforts have been made to characterize the peptides generated during both formation and resorption. Over the years, numerous biomarkers have been discovered for various disorders. However, despite their clinical utility, many of these markers lack specificity. This is due to factors such as the degradation of trimers into monomers, the coexistence of multiple peptide species arising from the unpredictable cleavage of Type I collagen/procollagen by cathepsin K and metalloproteinases, and the lack of assay standardization. Standardization is further hindered by the incomplete characterization of many of these peptides. For accurate assay development, a gold-standard technique like LC-MS/MS is essential, requiring full peptide characterization during method development. This review aims to present recent advances in the characterization of Type I collagen-derived peptides, providing a foundation for improved biomarker standardization and application in clinical practice.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251336274"},"PeriodicalIF":3.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomarker InsightsPub Date : 2025-05-21eCollection Date: 2025-01-01DOI: 10.1177/11772719251339955
Umaimah Zanif, Jaclyn Parks, Isabella Tai, Stephen Yip, Sindy Babinszky, Katy Milne, Peter Watson, Rachel A Murphy, Parveen Bhatti
{"title":"Pre-diagnostic Demographic, Lifestyle, and Health History Factors in Association with Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression in Colorectal Cancer Tissue.","authors":"Umaimah Zanif, Jaclyn Parks, Isabella Tai, Stephen Yip, Sindy Babinszky, Katy Milne, Peter Watson, Rachel A Murphy, Parveen Bhatti","doi":"10.1177/11772719251339955","DOIUrl":"10.1177/11772719251339955","url":null,"abstract":"<p><strong>Background: </strong>Demographic, health history, and lifestyle factors have been associated with prognosis of colorectal cancer (CRC), but mechanisms underlying these associations remain poorly understood. A compelling mechanism involves changes in expression of tumor markers that influence treatment outcomes, such as secreted protein acidic and rich in cysteine (SPARC), lower levels of which have previously been associated with poorer CRC prognosis.</p><p><strong>Objective: </strong>We explored the association of factors that have been previously associated with CRC prognosis with expression of SPARC in tumor tissues.</p><p><strong>Design: </strong>We conducted a prospective evaluation of 50 participants of a longitudinal cohort study that went on to develop CRC.</p><p><strong>Methods: </strong>Tumor and normal tissue cores were taken from formalin-fixed paraffin-embedded (FFPE) blocks of incident CRC cases and were used to create tissue microarrays (TMAs). Slides created from the TMAs were stained with SPARC antibodies and analyzed to calculate H-scores for both epithelial and non-epithelial components of tumor and normal tissues. H-scores were ln-transformed and analyzed in association with demographic, lifestyle, and health history factors assessed before cancer diagnosis using linear regression models.</p><p><strong>Results: </strong>In CRC tumor epithelium, smoking was associated with a 0.53-fold lower level of SPARC expression (<i>P</i> = .054). Higher income was associated with a 1.33-fold greater level of SPARC expression in tumor non-epithelial tissue (<i>P</i> = .041). Higher cancer stage was associated with a 0.74-fold lower level of non-epithelial tumor SPARC expression (<i>P</i> = .040). In the epithelial component of normal colorectal tissues, higher fruit consumption was associated with a 2.74-fold greater SPARC H-score (<i>P</i> = .002).</p><p><strong>Conclusions: </strong>The associations we observed for smoking, income, and cancer stage with SPARC in tumor tissue are consistent with previously established associations of these factors with CRC prognosis. Larger studies with prognostic data are needed, but our results suggest that differences in SPARC expression may contribute to previously observed impacts of various factors on CRC prognosis.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251339955"},"PeriodicalIF":3.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12099143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}