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Identification of a Novel Proteoform of Prostate Specific Antigen (SNP-L132I) in Clinical Samples by Multiple Reaction Monitoring.

Prostate specific antigen (PSA) is a well-established tumor marker, which is frequently employed as model biomarker to develop and evaluate emerging quantitative proteomics techniques, partially due to wide access to commercialized immunoassays serving as "gold standard". We designed a multiple reaction monitoring (MRM) assay to detect PSA proteoforms in clinical samples (n=72), utilizing specific

Improved porous silicon microarray based prostate specific antigen immunoassay by optimized surface density of the capture antibody

Enriching the surface density of immobilized capture antibodies enhances the detection signal of antibody sandwich microarrays. In this study, we improved the detection sensitivity of our previously developed P-Si (porous silicon) antibody microarray by optimizing concentrations of the capturing antibody. We investigated immunoassays using a P-Si microarray at three different capture antibody (PSA

A fast and scalable kymograph alignment algorithm for nanochannel-based optical DNA mappings.

Optical mapping by direct visualization of individual DNA molecules, stretched in nanochannels with sequence-specific fluorescent labeling, represents a promising tool for disease diagnostics and genomics. An important challenge for this technique is thermal motion of the DNA as it undergoes imaging; this blurs fluorescent patterns along the DNA and results in information loss. Correcting for this

Evaluation of Multiple Risk-Associated Single Nucleotide Polymorphisms Versus Prostate-Specific Antigen at Baseline to Predict Prostate Cancer in Unscreened Men

Background: Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear. Objective: Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men. Design, setting, an

Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients

Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the

miR-34c is down regulated in prostate cancer and exerts tumor suppressive functions.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in prostate cancer (p = 0.0005) by performing qRT-PCR on 49 TURPs from prosta

Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53

Validation of plasma proneurotensin as a novel biomarker for the prediction of incident breast cancer.

Background: High fasting plasma proneurotensin concentration was associated with the development of breast cancer in the Malmö Diet and Cancer Study (MDCS). Here we aimed at replicating the initial finding in an independent second cohort. Methods: The Malmö Preventive Project (MPP) is a population study and comprised 18 240 subjects when examined 2002-2006. Of women without history of breast cance

Galiellalactone is a Direct Inhibitor of STAT3 in Prostate Cancer Cells.

The transcription factor STAT3 is constitutively active in several malignancies including castration-resistant prostate cancer and has been identified as a promising therapeutic target. The fungal metabolite galiellalactone, a STAT3 signaling inhibitor, inhibits the growth, both in vitro and in vivo, of prostate cancer cells expressing active STAT3 and induces apoptosis of prostate cancer stem cel

Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes

Prediction of incident macrovascular events (iMEs) in individuals with type 2 diabetes (T2D) remains suboptimal. We aim to discover blood-based epigenetic biomarkers predicting iMEs in 752 newly diagnosed individuals with T2D, among whom 102 developed iMEs during follow-up. 461 DNA methylation sites, e.g., near ARID3A, GATA5, HDAC4, IRS2, and TMEM51, associate with iMEs. Using cross-validation, a

A genome-wide association study of imaging-defined atherosclerosis

Imaging-defined atherosclerosis represents an intermediate phenotype of atherosclerotic cardiovascular disease (ASCVD). Genome-wide association studies (GWAS) on directly measured coronary plaques using coronary computed tomography angiography (CCTA) are scarce. In the so far largest population-based cohort with CCTA data, we performed a GWAS on coronary plaque burden as determined by the segment

Atrial Fibrillation, Venous Thromboembolism, and Risk of Pulmonary Hypertension : A Swedish Nationwide Register Study

BACKGROUND: Atrial fibrillation (AF) is suggested to be associated with venous thromboembolism (VTE) and might thereby play a role in the development of chronic thromboembolic pulmonary hypertension (PH). By elevating left-sided filling pressure and promoting atrial myopathy, AF may also play a role in the development of postcapillary PH. We aimed to investigate the association between AF, with or

Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies

BACKGROUND: Melanoma, the deadliest form of skin cancer, exhibits resistance to conventional therapies, particularly in advanced and metastatic stages. Mitochondrial pathways, including oxidative phosphorylation and mitochondrial translation, have emerged as critical drivers of melanoma progression and therapy resistance. This study investigates the mitochondrial proteome in melanoma to uncover no

Low levels of soluble neuropilin-1 were associated with depression in adults with newly diagnosed type 2 diabetes

Aims: To explore the association between soluble neuropilin-1 (sNRP-1) and depression in patients with newly diagnosed type 2 diabetes (T2D). Materials and Methods: Multicentre, cross-sectional study including adults with serologically confirmed newly diagnosed T2D. Included variables: sex, sNPR-1 (low sNRP-1 was defined as <226 ng/mL), psychometrically assessed depression and anxiety, antidepress

Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pa