Rapid and Sensitive Detection of Thrombospondin-2 Using Nanoparticle Sensors for Cancer Screening and PrognosisMohammadi, Mirjalili, Ikbal
et alMicromachines (Basel) (2025) 16 (3)
Abstract: Thrombospondin-2 (THBS2) is a prevailing prognostic biomarker implicated in different cancer types, such as deadly colorectal, pancreas, and triple-negative breast cancers. While the current methods for cancer-relevant protein detection, such as enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and immunohistochemistry, are feasible at advanced stages, they have shortcomings in sensitivity, specificity, and accessibility, particularly at low concentrations in complex biological fluids for early detection. Here, we propose and demonstrate a modular, in-solution assay design concept, Nanoparticle-Supported Rapid Electronic Detection (NasRED), as a versatile cancer screening and diagnostic platform. NasRED utilizes antibody-functionalized gold nanoparticles (AuNPs) to capture target proteins from a minute amount of sample (<10 µL) and achieve optimal performance with a short assay time by introducing active fluidic forces that act to promote biochemical reaction and accelerate signal transduction. This rapid (15 min) process serves to form AuNP clusters upon THBS2 binding and subsequently precipitate such clusters, resulting in color modulation of the test tubes that is dependent on the THBS2 concentration. Finally, a semiconductor-based, portable electronic device is used to digitize the optical signals for the sensitive detection of THBS2. High sensitivity (femtomolar level) and a large dynamic range (five orders of magnitude) are obtained to analyze THBS2 spiked in PBS, serum, whole blood, saliva, cerebrospinal fluids, and synovial fluids. High specificity is also preserved in differentiating THBS2 from other markers such as cancer antigen (CA) 19-9 and bovine serum albumin (BSA). This study highlights NasRED's potential to enhance cancer prognosis and screening by offering a cost-effective, accessible, and minimally invasive solution.
Plasma Proteins Associated with the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet and Incident DementiaYang, Bernard, Chen
et alJ Nutr (2025)
Abstract: The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet slows cognitive decline and protects brain health, but the mechanisms are poorly understood.We aimed to determine the plasma proteins associated with the MIND diet score and their ability to predict incident dementia in the Atherosclerosis Risk in Communities study.We analyzed 10,230 Black and White participants at visit 3 (1993-1995) with food frequency questionnaire and proteomics data and randomly divided them into discovery (n = 6,850) and replication (n = 3,380) samples. We examined associations between the MIND diet score and 4,955 proteins using multivariable linear regression and elastic net regression. C-statistics were calculated to assess if proteins improved prediction of high MIND diet adherence beyond participant characteristics. Cox proportional hazards models were used to assess associations between significant diet-related proteins and incident dementia over two decades. C-statistics assessed the ability of significant proteins to improve dementia prediction beyond known risk factors.Of 316 proteins associated with the MIND diet score in the discovery sample at a false discovery rate < 0.05, 62 were internally replicated. Of these, 21 proteins selected by the elastic net individually improved MIND diet score prediction. After a median follow-up of 21 years, there were 2,311 dementia cases. Five diet-related proteins, thrombospondin-2 (HR, 1.19; 95% CI, 1.11-1.29), protein ABHD14A (HR, 1.23; 95% CI, 1.11-1.37), structural maintenance of chromosomes protein 3 (HR, 1.19; 95% CI, 1.08-1.31), epidermal growth factor receptor (HR, 0.68; 95% CI, 0.53-0.86), and interleukin-12 subunit beta (HR, 1.14; 95% CI, 1.05-1.25) were significantly associated with incident dementia. All five proteins individually and together improved prediction of dementia risk.Using high-throughput proteomics, we identified candidate biomarkers of the MIND diet score and incident dementia, which are implicated in neural signaling, angiogenesis, and anti-inflammatory pathways.Copyright © 2025 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.
Pulmonary congestion on lung ultrasound in ambulatory patients with heart failure and preserved ejection fractionPlatz, McDowell, Gupta
et alJ Card Fail (2025)
Abstract: Early detection of pulmonary congestion among ambulatory patients with heart failure with preserved ejection fraction (HFpEF) is critical to optimize decongestive therapy prior to overt decompensation, yet traditional tools are insensitive.To examine the prevalence of B-lines, an ultrasound measure of pulmonary congestion, and their clinical and imaging correlates in patients with HFpEF.In a prospective, multi-site observational study, using a pocket ultrasound device, 8-zone lung ultrasound was performed in outpatients with HFpEF, left ventricular ejection fraction (LVEF) ≥45% and NYHA class II-IV. B-lines and cardiac structure and function from echocardiograms were quantified off-line in core laboratories, blinded to clinical findings.Among 415 participants (mean age 74 years, 52% women, 51% obese, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 744 pg/ml) B-lines were detectable in 78% of patients ranging from 0 to 36 (median 3 [interquartile range 1, 6]). There was a linear association between B-line count and log-transformed NT-proBNP (P<0.001). Among patients in the highest tertile of B-lines, 76% had no crackles on auscultation, and 50% did not have elevated NT-proBNP levels. A higher B-line count was associated with larger sizes of cardiac chambers, greater left ventricular mass, higher filling pressures (E/e'), tricuspid regurgitant velocity, and inferior vena cava size, and worse right ventricular systolic function (P trend < 0.05 for all), but not LVEF.Among ambulatory patients with HFpEF, lung ultrasound-detected B-lines were common, associated with NT-proBNP levels and clinically important echocardiographic features, and identified pulmonary congestion that was not always evident by auscultation.Copyright © 2025. Published by Elsevier Inc.
Thrombospondin-2 induces M2 macrophage polarization through fatty acid metabolism to drive lung adenocarcinoma proliferationWeng, Zhu
Anticancer Drugs (2025)
Abstract: Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as a tumor marker and is known to be overexpressed in LUAD. However, the specific role of THBS2 in M2 macrophage polarization within LUAD remains unclear. We conducted bioinformatics analyses to assess the clinical significance of THBS2 expression in LUAD, which was subsequently validated using quantitative PCR. We examined the relationship between THBS2 expression and M2 macrophage infiltration. A coculture system of LUAD cells and M0 macrophages was established to investigate the influence of THBS2 on macrophage infiltration and polarization through immunofluorescence and ELISA. We explored the impact of THBS2 on fatty acid metabolism (FAM) using oil red O staining and relevant kits and elucidated the role of THBS2 in regulating M2 macrophage polarization and LUAD proliferation through cell counting kit-8 (CCK-8) and colony formation assays. Western blot was employed to assess expression changes of Bax and Bcl-2. THBS2 was highly expressed in LUAD and was associated with poor prognosis in patients. In-vitro experiments demonstrated that silencing THBS2 significantly inhibited macrophage infiltration and polarization. THBS2 primarily activated FAM pathways, inducing M2 macrophage polarization and promoting LUAD cell proliferation. THBS2 enhanced LUAD proliferation by regulating FAM to induce M2 macrophage polarization. These findings provide a theoretical basis for targeting THBS2 as a novel therapeutic strategy in LUAD.Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.
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