يعرض 1 - 10 نتائج من 82 نتيجة بحث عن '"(1"', وقت الاستعلام: 0.81s تنقيح النتائج
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    المصدر: Clinica Chimica Acta. 494(July):79-93

    الوصف: Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders. © 2019 The Authors

  2. 2

    المصدر: Clinica Chimica Acta. 503:197-202

    الوصف: Background Ankylosing spondylitis (AS) is an autoimmune disease with high disability rate, and it is sometimes difficult to distinguish from generalized osteoarthritis (GOA). Deoxyribonuclease 1-like 3 (DNASE1L3) was associated with a variety of autoimmune diseases. However, the serum DNASE1L3 level in AS and GOA remain unreported. Herein, this study was designed to gauge serum DNASE1L3 level in patients with AS and GOA, and to discern the utility of serum DNASE1L3 as a biomarker for assessing the severity of patients with AS. Methods The study population consisted of 60 patients with AS, 60 patients with GOA and 60 control subjects. Serum DNASE1L3 levels were measured using enzyme-linked immunosorbent assay (ELISA) assay. Disease activity were assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. Results Our data showed that serum DNASE1L3 levels were significantly higher in patients with AS than that of the healthy controls and patients with GOA. Serum DNASE1L3 levels in patients with AS were positively correlated with BASDAI scores, C3 and C-reactive protein (CRP). Furthermore, serum DNASE1L3 showed higher discriminatory accuracy in the diagnosis of AS from GOA (AUC = 0.851, sensitivity = 78.33% and specificity = 81.67%). Conclusions Elevated Serum DNASE1L3 levels in patients with AS were significantly associated with the clinic features and disease activity. DNASE1L3 could be a serum biomarker with a positive diagnostic value in patients with AS, and which could be used as a differential diagnostic indicator for GOA and AS.

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    المصدر: Clinica Chimica Acta. 500:54-58

    الوصف: Oxidized low-density lipoprotein (ox-LDL) and its receptor, lectin-like ox-LDL receptor-1 (LOX-1) are involved in the pathogenesis of atherosclerosis. Expression of LOX-1 was substantially raised in the basilar arterial wall of subarachnoid hemorrhage (SAH) rabbits. We ascertained the relationship between serum soluble LOX-1 concentrations and functional outcome after human aneurysmal SAH.We enrolled 94 aneurysmal SAH patients and 94 healthy controls. Serum soluble TOX-1 concentrations were quantified using commercial enzyme-linked immunosorbent assay kit. A poor outcome was defined as Glasgow outcome scale score of 1-3.Median values of serum soluble LOX-1 in stroke patients were significantly higher than those in controls (1.5 vs. 0.4 ng/ml, P 0.001). Thirty patients (31.9%) had a poor outcome at 6 months after stroke. Serum soluble LOX-1 was a strong predictor of poor outcome (OR 5.20, 95% CI 1.25-22.04). Serum soluble LOX-1 concentrations exhibited a significant discriminatory capability (area under curve 0.811, 95% confidence interval 0.717-0.884). The predictive powers of World Federation of Neurological Surgeons grade, Hunt-Hess grade, modified Fisher grade, and serum soluble LOX-1 concentrations were comparable (all P 0.05).Serum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.

  4. 4

    المصدر: Clinica Chimica Acta. 487:145-152

    الوصف: Background ST2, a receptor of interleukin-33, is involved in inflammation. We discerned the relationship between serum soluble ST2 (sST2) concentrations, inflammation, severity and prognosis following traumatic brain injury (TBI). Methods We measured serum sST2, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl-terminal hydrolase L1 concentrations in 106 healthy controls and 106 severe TBI patients. We recorded long-term prognosis (i.e., 6-month mortality and functional outcome) and in-hospital major adverse events, including in-hospital mortality, acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction. Results sST2 concentrations were significantly higher in patients than in controls and were significantly correlated with Glasgow coma scale (GCS) score and the preceding biomarkers concentrations. Serum sST2 was an independent prognostic predictor and its predictive ability significantly exceeded those of serum interleukin-6, tumor necrosis factor-alpha and C-reactive protein concentrations and was similar to those of GCS scores and serum concentrations of other remaining biomarkers. Moreover, sST2 concentrations significantly improved predictive ability of GCS score. Conclusion Increased serum sST2 concentrations are significantly related to inflammation, severity and prognosis, substantialized ST2 as a potential prognostic biomarker for TBI.

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    المصدر: Clinica Chimica Acta. 485:158-165

    الوصف: Background TEA domain transcription factor (TEAD) has an oncogenic role in hepatocellular carcinoma (HCC). However, whether a membrane protein can serve not only as a tumor marker that reflects TEAD function but also as a therapeutic target that stimulates tumorigenesis in HCC remains unknown. Methods Tissue NRP1 was measured using immunohistochemistry. Cell viability, colony formation and caspase3/7 activity were assessed using MTT, soft agar and caspase 3/7 Glo assays, respectively. Serum NRP1 was examined using ELISA and Western blotting. Results NRP1 expression was up-regulated by TEAD. We also identified a conserved TEAD-binding motif in the NRP1 promoters, which was essential for the TEAD-NRP1 interaction. NRP1 was upregulated in HCC tissues and cell lines, and knockdown of NRP1 inhibited the transformative phenotypes of HCC cells. Notably, the concentrations of serum NRP1 in the HCC patients were much higher than those of hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer and lung cancer patients. Moreover, serum NRP1 was significantly associated with AFP, γ-GT, Alb, bile acid, ALT, AST, ALP and pre-Alb. The area under the receiver operating characteristic curve (AUC-ROC) for serum NRP1 was 0.971, presenting better diagnostic performance compared to AFP. Conclusions NRP1 is a novel tumor marker in HCC.

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    المصدر: Clinica Chimica Acta. 459:1-4

    الوصف: We evaluated the association between plasma levels of VWF, ADAMTS13 and d-Dimer, which consist on endothelial dysfunction and hypercoagulability biomarkers, and cystatin C with retinopathy in type 1 diabetic patients.Patients were classified according to presence (n=55) or absence (n=70) of retinopathy. Plasma levels of VWF, ADAMTS13, d-Dimer and cystatin C were evaluated by ELISA and ADAMTS13 activity was evaluated by FRET.Plasma levels of VWF (p=0.033), ADAMTS13 activity (p=0.014), d-Dimer (p=0.002) and cystatin C (p0.001) were elevated in diabetic patients with retinopathy compared to those without this complication. The multivariate logistic regression analysis showed that ADAMTS13 activity (p=0.031) d-Dimer (p=0.015) and cystatin C (p=0.001) remained associated with retinopathy after adjustment for age, diabetes duration, use of statin, use of ACEi or angiotensin antagonist, use of acetylsalicylic acid and glomerular filtration rate.ADAMTS13 activity, d-Dimer and cystatin C are associated with retinopathy in type 1 diabetic patients and are promising biomarkers for the diagnosis and monitoring of diabetic retinopathy.

  7. 7

    المصدر: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
    Universidade de São Paulo (USP)
    instacron:USP

    الوصف: Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 ( SLC2A1 ) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 – 0.80, p = 0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 – 0.70; p = 0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control.

  8. 8

    المصدر: Clinica Chimica Acta. 453:164-169

    الوصف: Caspase-1 induces the proinflammatory cytokines which appears to be a promising target in Th1-type inflammatory diseases, like psoriasis. We determined the effect of MTX on caspase-1, TNF-α and IL-18 in psoriasis patients.We recruited 45 control subjects and 58 psoriasis patients for this study. The patients were treated with 7.5mg of MTX per week for 12weeks. Folic acid was given at 5mg once daily except on the day of MTX for 12weeks. Blood samples and lesional skin biopsy were taken. Histological examination has been done. IL-18 and TNF-α levels were analyzed by using ELISA. Caspase-1 expression was analyzed by western blot and Real Time PCR.Histological examinations showed MTX decreased acanthosis in psoriasis skin. Plasma IL-18 level and serum TNF-α were increased in psoriasis and deduced significantly (P0.001) after MTX treatment. Protein and mRNA expression of caspase-1 in skin biopsy were higher in psoriasis and reduced significantly (P0.001) after MTX treatment.Decreasing inflammatory caspase and proinflammatory cytokines by MTX, inhibits the Th1 response in psoriasis. This shows the therapeutic effect of MTX in controlling the immunopathogenesis of psoriasis.

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    المصدر: Clinica Chimica Acta. 448:155-160

    الوصف: Background Thrombospondin-1 is a homotrimeric glycoprotein with well known functions in hemostasis and angiogenesis. Its expression was increased after experimental intracerebral hemorrhage. We determined whether increased plasma thrombospondin-1 concentrations are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). Methods Plasma thrombospondin-1 concentrations of 118 aSAH patients and 118 age- and gender-matched healthy controls were determined using enzyme-linked immunosorbent assay. Patients were followed up until death or completion of 6 months after aSAH. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1–3. Multivariate analyses of significant variables of univariate analyses were performed to determine independent risk factors for the clinical outcomes. Results Plasma thrombospondin-1 concentrations were significantly higher in aSAH patients than in healthy controls; plasma thrombospondin-1 concentrations were independently associated with clinical severity reflected by the World Federation of Neurological Surgeons score and Fisher score; thrombospondin-1 was identified as an independent predictor of 6-month mortality and 6-month unfavorable outcome; thrombospondin-1 had similar predictive performance compared with the World Federation of Neurological Surgeons score and Fisher score according to receiver operating characteristic curve analysis. Conclusion Higher plasma thrombospondin-1 concentrations are associated with clinical severity and long-term prognosis of aSAH patients.

  10. 10

    المساهمون: Vendittelli, F., Paolillo, C., Autilio, C., Lavieri, M. M., Silveri, S. L., Capizzi, R., Capoluongo, E.

    المصدر: Clinica Chimica Acta. 444:242-249

    الوصف: Background Malignant melanoma is the most malignant tumours of skin and mucous membranes mainly due to its aggressive biological behaviour and tendency to generate early metastases. Unfortunately, the mechanisms underlying the development, progression and the expression of an aggressive melanoma phenotype still remain largely unknown. Objectives The purpose of this study was to determine whether a multi-panel of molecular transcripts can be predictive for risk of recurrent disease in malignant melanoma patients. Results Peripheral blood was collected from 31 malignant melanoma patients in follow-up for melanoma and from 30 healthy volunteers randomly selected. Each specimen was examined by qRT-PCR analysis for the expression of six markers: PAX3d, TYR, MITFm, MCAM, TGFβ2 and ABCB5. Malignant melanoma patients expressed an important number of markers, with a median value of four markers. Only PAX3d displayed a trend in terms of differences when the levels of gene expression were made in function of Breslow index. Furthermore, PAX3d showed the best diagnostic capacity among the remaining residual markers or in combination with TGFβ2 and MTIF. Conclusions We demonstrated the usefulness of multimarker qRT-PCR to detect circulating melanoma cells in blood and to potentially assessing patient disease status or progression, especially when PAX3d was used in combination with MTIFm and TGFβ2.