| 1. |
- Camporesi, Elena, et al.
(författare)
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Fluid Biomarkers for Synaptic Dysfunction and Loss
- 2020
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Ingår i: Biomarker Insights. - : SAGE Publications. - 1177-2719. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer's disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and alpha-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.
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| 2. |
- Gu, HF
(författare)
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Biomarkers of adiponectin: plasma protein variation and genomic DNA polymorphisms
- 2009
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Ingår i: Biomarker insights. - : SAGE Publications. - 1177-2719. ; 4, s. 123-33
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin is secreted by white adipose tissue and exists as the most abundant adipokine in the human plasma. Recent research has indicated that plasma adiponectin levels are inversely correlated with body mass index (BMI) and insulin resistance. Reduction of plasma adiponectin levels is commonly observed in the patients with type 2 diabetes (T2D) and/or in those who are obese in comparison with healthy control individuals. The adiponectin ( AdipoQ) gene has a moderate linkage disequilibrium (LD), but two small LD blocks are observed, respectively, in the promoter region and the boundary of exon 2-intron 2. Genetic association studies have demonstrated that single nucleotide polymorphisms (SNPs) +45G15G(T/G) in exon 2 and +276G/T in intron 2 of the AdipoQ gene confer the risk susceptibility to the development of T2D, obesity and diabetic nephropathy (DN). The SNPs in the promoter region, including –11426A/G, –11377C/G and –11391G/A, are found to be associated with T2Dand DN. Recent research has indicated that the promoter polymorphisms interfere with the AdipoQ promoter activity. The haplotypes constructed by the promoter polymorphisms and SNP +276G/T in intron 2 are associated with circulating adiponectin levels. This review summarises genetic and pathophysiological relevancies of adiponectin and discusses about the biomarkers of adiponectin plasma protein variation and genomic DNA polymorphisms.
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| 3. |
- Gu, HF, et al.
(författare)
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The Common FTO Genetic Polymorphism rs9939609 is Associated with Increased BMI in Type 1 Diabetes but not with Diabetic Nephropathy
- 2010
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Ingår i: Biomarker insights. - : SAGE Publications. - 1177-2719. ; 5, s. 29-32
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Tidskriftsartikel (refereegranskat)abstract
- The fat mass and obesity associated (FTO) gene has an important genetic effect on body mass index (BMI) and risk of obesity, and obesity contributes to the progression of renal diseases, including diabetic nephropathy. We thus conducted a genetic association study to evaluate whether the FTO gene confers the risk susceptibility to the development of diabetic nephropathy. Genotyping experiments of the common FTO polymorphism, rs9939609, in 1170 type 1 diabetes patients with (n = 597) or without diabetic nephropathy (n = 573) were performed with TaqMan allelic discrimination. All subjects are of European descent and selected from the Genetics of Kidney Diseases in Diabetes (GoKinD) study. The frequency of T allele of this polymorphism was 0.414 in the studied population. There was no allelic association of this polymorphism with diabetic nephropathy. But, the risk susceptibility of A allele conferring to the increased BMI among type 1 diabetes patients was observed. The subjects carrying with AA genotype had higher BMI compared to the carriers with TA and/or TT genotype(s) ( P ≥ 0.019). The present study provides evidence that the common FTO genetic polymorphism, rs9939609, is associated with increased BMI in type 1 diabetes but not with diabetic nephropathy.
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| 4. |
- Gustafsson, Anna, et al.
(författare)
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Detection of suPAR in the saliva of healthy young adults : comparison with plasma levels
- 2011
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Ingår i: Biomarker Insights. - : Libertas Academica. - 1177-2719. ; 2011:6, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- The soluble urokinase plasminogen activator receptor (suPAR) has been detected in blood, plasma, serum, urine, ovarian cystic fluid, and cerebrospinal fluid. Elevated suPAR levels in plasma have been associated with negative outcomes in various diseases, such as bacteremia, sepsis, SIRS, cardiovascular disease, cancer, and tuberculosis. The primary aim of this study was to investigate whether suPAR can be detected in saliva from healthy individuals and thus, if saliva suPAR can be related to plasma suPAR, CRP, BMI, or gender. Blood and unstimulated whole saliva was collected from 20 healthy individuals (10 female and 10 male, median age of 28 years; range 21–41). CRP and suPAR were measured with ELISA in saliva and serum/plasma. suPAR was detected in all saliva samples in the 5.2–28.1 ng/mL range, with a median value of 17.1 ng/mL. Saliva suPAR was significantly higher (P , 0.001) but not correlated to plasma suPAR in healthy young adults with normal plasma suPAR levels. suPAR and CRP levels were correlated in blood but not in saliva. No correlation was found between BMI, age, or gender and suPAR in saliva.
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| 5. |
- Gustafsson, Anna, et al.
(författare)
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Effects of Acute Exercise on Circulating Soluble Form of the Urokinase Receptor in Patients With Major Depressive Disorder
- 2017
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Ingår i: Biomarker Insights. - : Sage Publications. - 1177-2719. ; 12, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD) have increased plasma levels of the soluble form of the urokinase receptor (suPAR), a marker for low-grade inflammation. The aim of this study was to test the hypothesis that acute exercise would induce inflammatory response characterized by increased suPAR and elucidate whether patients with MDD display altered levels of suPAR in response to acute exercise. A total of 17 patients with MDD and 17 controls were subjected to an exercise challenge. Plasma suPAR (P-suPAR) was analyzed before, during, and after exercise. There was a significantly higher baseline P-suPAR in the patients with MDD, and the dynamic changes of P-suPAR during the exercise were significantly lower in the patients with MDD, compared with the controls. This study supports the hypothesis that an activation of systemic inflammatory processes, measured as elevated P-suPAR, is involved in the pathophysiology of depression. The study concludes that P-suPAR is influenced by acute exercise, most likely due to release from activated neutrophils.
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| 6. |
- Gustafsson, Anna, et al.
(författare)
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The Prognostic Value of suPAR Compared to Other Inflammatory Markers in Patients with Severe Sepsis
- 2012
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Ingår i: Biomarker Insights. - : Libertas Academica. - 1177-2719 .- 1177-2719. ; :7, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: It has been suggested that soluble urokinase plasminogen activator (suPAR) can be used as a marker of disease severity and risk of mortality in sepsis. The aim with the present study was to compare plasma levels of suPAR in patients with severe sepsis to control subjects and correlate it with the level of inflammatory activation, severity and mortality. Samples were collected from 27 sepsis patients at the intensive care unit (ICU), Lund, Sweden; 90-day mortalities were registered. The suPAR level was significantly elevated in sepsis patients compared to controls, but not significantly higher in nonsurvivors than survivors. Plasma levels of suPAR did correlate weakly with the SOFA score and myeloperoxidase (MPO) but not with CRP, PCT, IL-6 or IL-10 in patients with severe sepsis. The weak correlation between suPAR and other inflammatory markers might suggest that suPAR reflects general activation of the immune system rather than exerting inflammatory actions.
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| 7. |
- Stenman, Katarina, et al.
(författare)
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1H HRMAS NMR Derived Bio-markers Related to Tumor Grade, Tumor Cell Fraction, and Cell Proliferation in Prostate Tissue Samples
- 2011
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Ingår i: Biomarker Insights. - : Libertas Academica Ltd. - 1177-2719. ; 6, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- A high-resolution magic angle spinning NMR spectroscopic approach is presented for evaluating the occurrence, amount and aggressiveness of cancer in human prostate tissue samples. Using this technique, key metabolites in malignant and non-malignant samples (n = 149) were identified, and patterns of their relative abundance were analyzed by multivariate statistical methods. Ratios of various metabolites – including (glycerophophorylcholine + phosphorylcholine)/creatine, myo-inositol/scyllo-inositol, scyllo-inositol/creatine, choline/creatine, and citrate/creatine – correlated with: i) for non-malignant tissue samples, the distance to the nearest tumor and its Gleason score and; ii) the fraction of tumor cells present in the sample; and iii) tumor cell proliferation (Ki67 labelling index). This NMR-based approach allows the extraction of information that could be useful for developing novel diagnostic methods for prostate cancer.
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| 8. |
- Strawbridge, RJ, et al.
(författare)
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MUC1 as a Putative Prognostic Marker for Prostate Cancer
- 2008
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Ingår i: Biomarker insights. - : SAGE Publications. - 1177-2719. ; 3, s. 303-315
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Tidskriftsartikel (refereegranskat)abstract
- MUC1 is expressed on the apical surface of glandular epithelium. With functions including protection, adhesion and signaling, MUC1 has been implicated in prostate cancer. There are many splice variants, the best characterized of which are MUC1/1 and MUC1/2 which are determined by a SNP (rs4072037, 3506G>A). Blood DNA from the general population, BPH, sporadic and hereditary prostate cancer subjects were genotyped for the rs4072037 SNP. G allele frequencies were significantly reduced in hereditary prostate cancer (15%) compared to population, BPH or sporadic prostate cancer samples (27%, 39% and 26% respectively). In addition, the G allele was lost from 3 of 8 heterozygous sporadic prostate tumor samples compared to matched blood DNA. Bioinformatics analysis of MUC1 protein sequences provides insight into differences between the variants which may be functionally relevant. The literature indicates discrepancies between immunohistochemical studies, possibly due to the variety of MUC1 epitopes targeting diverse regions of the molecule. The contradictory findings in cell lines highlight the problem associated with inadequate experimental systems. This is the first report of genetic differences in MUC1 between blood and prostatic cancer tissue. This finding is important as proof of principle, given that many association studies focus on blood DNA rather than on the tumor DNA. As yet, potential functional differences between splice variants has been paid little attention. Antibodies which discriminate between the variants and standardization of methods would help to clarify whether there is a role for MUC1 as a prognostic marker.
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| 9. |
- Stålnacke, Britt-Marie, et al.
(författare)
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Repeatedly Heading a Soccer Ball Does Not Increase Serum Levels of S-100B, a Biochemical Marker of Brain Tissue Damage : an Experimental Study
- 2008
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Ingår i: Biomarker Insights. - : Sage Publications. - 1177-2719. ; 3, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the study was to analyse whether the controlled heading of soccer balls elicits increased serum concentrations of a biochemical marker of brain tissue damage S-100B.METHODS: Nineteen male soccer players were randomly divided into two groups, A and B. Group A headed a soccer ball falling from 18 m five times, while group B served as controls (no heading). Blood samples were taken before and 0.5 h, 2 h and 4 h after the heading for analysis of S-100B.RESULTS: No statistically significant (p > 0.05) increases in serum concentrations of S-100B were encountered in group A at 0.5 h (0.109 +/-0.024 mug/L), 2 h (0.098 +/- 0.026 mug/L), and 4 h (0.113 +/- 0.035 mug/L) when the blood samples obtained before and after the heading were compared (0.157 +/- 0.134 mug/L). No statistically significant difference was found when the serum concentrations of S-100B were compared between groups A and B either before or after heading.CONCLUSIONS: Heading a soccer ball dropped from a height of 18 m five times was not found to cause an increase in serum concentrations of S-100B, indicating that the impact was not sufficient to cause biochemically discernible damage of brain tissue.
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| 10. |
- Urbiola-Salvador, Victor, et al.
(författare)
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Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation
- 2024
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Ingår i: Biomarker Insights. - : Sage Publications. - 1177-2719. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers.Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages.Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
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