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Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis.
Mondello, S, Sorinola, A, Czeiter, E, Vámos, Z, Amrein, K, Synnot, A, Donoghue, E, Sándor, J, Wang, KKW, Diaz-Arrastia, R, et al
Journal of neurotrauma. 2021;(8):1086-1106
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Abstract
Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE®, Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.
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Unraveling the Roles of Vascular Proteins Using Proteomics.
Liu, Y, Lin, T, Valencia, MV, Zhang, C, Lv, Z
Molecules (Basel, Switzerland). 2021;(3)
Abstract
Vascular bundles play important roles in transporting nutrients, growth signals, amino acids, and proteins between aerial and underground tissues. In order to understand these sophisticated processes, a comprehensive analysis of the roles of the components located in the vascular tissues is required. A great deal of data has been obtained from proteomic analyses of vascular tissues in plants, which mainly aim to identify the proteins moving through the vascular tissues. Here, different aspects of the phloem and xylem proteins are reviewed, including their collection methods, and their main biological roles in growth, and biotic and abiotic stress responses. The study of vascular proteomics shows great potential to contribute to our understanding of the biological mechanisms related to development and defense in plants.
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Impact of Preoperative Total Proteins and Glycated Hemoglobin on Recurrences after Early Colorectal Cancer.
Castro, MJ, Jiménez, JM, López, M, Cao, MJ, Santos-Torres, J, López, A, Moreno, A, Ruiz-Tovar, J
Nutrients. 2021;(2)
Abstract
BACKGROUND The outcome of colorectal cancer is mostly based on TNM classification. There are several factors determining that patients with the same tumoral stage present different outcomes. The nutritional status has been related to the immunological response and may affect the oncologic results. The purpose of this study was to determine if preoperative nutritional parameters may predict the oncologic outcome in patients with early colorectal cancer. METHODS A prospective observational study of patients undergoing elective surgery for colorectal cancer was performed with stage I. Preoperative nutritional assessment included glycemic and lipid profiles, total proteins, and albumin levels. These parameters were correlated with tumoral recurrence during a follow-up of at least 24 months. RESULTS During the period of study, 744 patients were operated on and 228 (30.6%) followed the inclusion criteria for this study. Recurrence rate was 5.7% (13 patients). Patients with hypoproteinemia showed a 7.8-fold greater risk of recurrence during the first 24 months after surgery [OR 7.8 (CI95% 1.3-48), p = 0.012]. Patients with glycated hemoglobin levels (HbA1c) > 6.2% showed a 2.3 increased risk of recurrence [OR 2.3 (CI95% 1.1-4.7; p = 0.01]. CONCLUSIONS Preoperative values of total proteins and HbA1c correlate with the recurrence rate in early colorectal cancer.
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Protein profiles in plasma: Development from infancy to 5 years of age.
Mikus, M, Järnbert-Pettersson, H, Johansson, C, Nilsson, P, Scheynius, A, Alm, J
Proteomics. Clinical applications. 2021;(4):e2000038
Abstract
PURPOSE Little is known about the longitudinal development of different plasma protein levels during early childhood and particularly in relation to lifestyle factors. This study aimed to monitor the plasma proteome early in life and the influence of different lifestyles. EXPERIMENTAL DESIGN A multiplex bead-based immunoassay was used to analyze plasma levels of 97 proteins in 280 blood samples longitudinally collected in children at 6, 12, 24, and 60 months of age living in families with an anthroposophic (n = 15), partly anthroposophic (n = 27), or non-anthroposophic (n = 28) lifestyle. RESULTS A total of 68 proteins (70%) showed significantly altered plasma levels between 6 months and 5 years of age. In lifestyle stratified analysis, 59 of 97 (61%) proteins were altered over time within one or more of the three lifestyle groups. Nearly half of these proteins (28 out of 59) changed irrespective of lifestyle. The temporal changes represented four longitudinal trends of the plasma proteins during development, also following stratification of lifestyle. CONCLUSIONS AND CLINICAL RELEVANCE Our findings contribute to understand the development of the plasma proteome under the influence of lifestyle exposures in early childhood.
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A fully joint Bayesian quantitative trait locus mapping of human protein abundance in plasma.
Ruffieux, H, Carayol, J, Popescu, R, Harper, ME, Dent, R, Saris, WHM, Astrup, A, Hager, J, Davison, AC, Valsesia, A
PLoS computational biology. 2020;(6):e1007882
Abstract
Molecular quantitative trait locus (QTL) analyses are increasingly popular to explore the genetic architecture of complex traits, but existing studies do not leverage shared regulatory patterns and suffer from a large multiplicity burden, which hampers the detection of weak signals such as trans associations. Here, we present a fully multivariate proteomic QTL (pQTL) analysis performed with our recently proposed Bayesian method LOCUS on data from two clinical cohorts, with plasma protein levels quantified by mass-spectrometry and aptamer-based assays. Our two-stage study identifies 136 pQTL associations in the first cohort, of which >80% replicate in the second independent cohort and have significant enrichment with functional genomic elements and disease risk loci. Moreover, 78% of the pQTLs whose protein abundance was quantified by both proteomic techniques are confirmed across assays. Our thorough comparisons with standard univariate QTL mapping on (1) these data and (2) synthetic data emulating the real data show how LOCUS borrows strength across correlated protein levels and markers on a genome-wide scale to effectively increase statistical power. Notably, 15% of the pQTLs uncovered by LOCUS would be missed by the univariate approach, including several trans and pleiotropic hits with successful independent validation. Finally, the analysis of extensive clinical data from the two cohorts indicates that the genetically-driven proteins identified by LOCUS are enriched in associations with low-grade inflammation, insulin resistance and dyslipidemia and might therefore act as endophenotypes for metabolic diseases. While considerations on the clinical role of the pQTLs are beyond the scope of our work, these findings generate useful hypotheses to be explored in future research; all results are accessible online from our searchable database. Thanks to its efficient variational Bayes implementation, LOCUS can analyze jointly thousands of traits and millions of markers. Its applicability goes beyond pQTL studies, opening new perspectives for large-scale genome-wide association and QTL analyses. Diet, Obesity and Genes (DiOGenes) trial registration number: NCT00390637.
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Altered Mineral Metabolism and Disequilibrium Between Calcification Promoters and Inhibitors in Chronic Hemodialysis Patients.
Wang, CL, Lin, KP, Hsu, GW, Liu, KL, Guo, CH
Biological trace element research. 2020;(1):14-22
Abstract
Patients undergoing long-term hemodialysis (HD) are known to have abnormal blood concentrations of antioxidant minerals; concurrent oxidative stress can contribute to increased vascular calcification. This study aims to evaluate the associations between circulating antioxidant minerals and clinical biomarkers of vascular calcification in HD patients. Blood biochemical parameters, antioxidant minerals (selenium (Se), zinc (Zn), copper (Cu), and magnesium (Mg)), and several promoters and inhibitors of calcification (matrix Gla protein (MGP), fibroblast growth factor-23 (FGF-23), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitors of metalloproteinase (TIMP-1 and -2)) were determined in HD patients (n = 62) and age- and sex-matched healthy individuals (n = 30). Compared with healthy subjects, HD patients had significantly lower plasma concentrations of Se and Zn, increased Cu and Mg, and higher levels of oxidative stress and inflammatory markers (Cu/Zn ratios, malondialdehyde (MDA), advanced glycation end products (AGEs), and C-reactive protein (CRP)). We observed that HD patients had significantly lower concentrations of MGP and higher levels of FGF-23, MMP-2 and -9, TIMP-1 and -2, and MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios. We also observed significant relationships between the concentrations of these minerals and calcification biomarkers in HD patients. These results suggest that changes in the homeostasis of antioxidant minerals (Se, Zn, Cu, and Mg) may contribute to the effects of oxidative stress and inflammatory status, thereby participating in the mechanism for accelerated vascular calcification in patients undergoing long-term HD.
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The acid and neutral fractions of pectins isolated from ripe and overripe papayas differentially affect galectin-3 inhibition and colon cancer cell growth.
Pedrosa, LF, Lopes, RG, Fabi, JP
International journal of biological macromolecules. 2020;:2681-2690
Abstract
The water-soluble fractions of pectin extracted from the pulp of ripe papayas have already been found to exert positive effects on cancer cell cultures. However, the mechanisms that lead to these beneficial effects and the pectin characteristics that exert these effects are still not well understood. Characteristics such as molecular size, monosaccharide composition and structural conformation are known as polysaccharide factors that can cause alterations in cellular response. During fruit ripening, a major polysaccharide solubilization, depolymerization, and chemical modification occur. The aims of this work are to fractionate the pectin extracted from the pulp of papayas at two stages of ripening (fourth and ninth day after harvesting) into uronic and neutral fractions and to test them for the inhibition of human recombinant galectin-3 and the inhibition of colon cancer cell growth. The structures of the fractions were chemically characterized, and the uronic fraction extracted from the fourth day after harvesting presented the best biological effects across different concentrations in both galectin-3 inhibition and viability assays. The results obtained may help to establish a relationship between the chemical structures of papaya pectins and the positive in vitro biological effects, such as inhibiting cancer cell growth.
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Serum proteome assessment in nonalcoholic fatty liver disease in children: a preliminary study.
Małecki, P, Tracz, J, Łuczak, M, Figlerowicz, M, Mazur-Melewska, K, Służewski, W, Mania, A
Expert review of proteomics. 2020;(7-8):623-632
Abstract
OBJECTIVES Nonalcoholic fatty disease (NAFLD) affects 3-10% of the pediatric population, making it the most common chronic liver disease among children. The aim of the study is to identify potential biomarkers enabling the diagnosis of NAFLD and monitoring the course of the disease. METHODS Proteome analysis was performed in a group of 30 patients (19 boys and 11 girls) in total, of whom 16 children had previously diagnosed NAFLD based on the abdominal ultrasound after excluding other diseases of this organ. RESULTS A total of 297 proteins have been identified. Thirty-seven proteins (responsible for inflammation, stress response, and regulation of this process) differentiating both experimental groups were identified. Up-regulated proteins included afamin, retinol-binding protein-4, complement components, and hemopexin; while serum protease inhibitors, clusterin, immunoglobulin chains, and vitamin D binding protein were found in the down-regulated group. The correlation between selected proteins and indicators of noninvasive assessment of liver fibrosis (APRI, FIB-4) as well as differences between the serum proteome of patients with normal weight, overweight, and obesity were also assessed. CONCLUSION The plasma protein profile is significantly altered in nonalcoholic liver disease in children and may prove to be a valuable source of biomarkers to evaluate the extent of liver disease.
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Serum and follicular fluid levels of sirtuin 1, sirtuin 6, and resveratrol in women undergoing in vitro fertilization: an observational, clinical study.
Bódis, J, Sulyok, E, Kőszegi, T, Gödöny, K, Prémusz, V, Várnagy, Á
The Journal of international medical research. 2019;(2):772-782
Abstract
OBJECTIVE This observational, clinical study was designed to assess the role of sirtuin 1 (SIRT1), sirtuin 6 (SIRT6), and resveratrol in in vitro fertilization (IVF). METHODS Paired serum and follicular fluid (FF) samples were obtained from 30 consecutive patients (age: 36.43 ± 4.17 years, body mass index: 22.90 ± 2.05 kg/m2, duration of infertility: 5.10 ± 2.80 years) who received IVF treatment. SIRT1, SIRT6, and resveratrol levels were measured by enzyme-linked immunosorbent assay. RESULTS Ovarian hyperstimulation resulted in significantly higher serum SIRT1 levels in pregnant women (8 patients) compared with non-pregnant women (22 patients). SIRT6 levels remained unchanged after ovarian hyperstimulation, but were significantly lower in pregnant women compared with non-pregnant women before and after hyperstimulation. Both SIRTs were detected in FF, but they appeared to be independent of their serum levels. After correction for confounders, FF SIRT6 levels were positively related to mature oocytes (F = 6.609), whereas serum SIRT1 and SIRT6 levels were related to clinical pregnancy (F = 10.008, F = 5.268, respectively). CONCLUSIONS Our study shows that SIRT1 and SIRT6, but not resveratrol, are involved in human reproduction and they may have a role in oocyte maturation and clinical pregnancy in IVF.
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Vegetarian-Based Dietary Patterns and their Relation with Inflammatory and Immune Biomarkers: A Systematic Review and Meta-Analysis.
Craddock, JC, Neale, EP, Peoples, GE, Probst, YC
Advances in nutrition (Bethesda, Md.). 2019;(3):433-451
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Abstract
Dietary patterns with substantial proportions of energy from plant sources have been associated with favorable biomarkers of low-grade inflammation. Less is known of the relation between vegetarian-based dietary patterns and markers of inflammation and immune status. This systematic review and meta-analysis aimed to determine the relation between vegetarian-based dietary patterns and inflammatory and immune markers (C-reactive protein, tumour necrosis factor α, fibrinogen, natural killer cells, leukocytes, lymphocytes, thrombocytes, interleukins, and immunoglobulins). PubMed, Medline, and Cochrane scientific databases were searched to identify relevant studies. Random effects meta-analyses were conducted to assess the weighted mean differences (WMDs) for each outcome variable between vegetarian and non-vegetarian groups. Thirty observational and 10 intervention studies were included in the review. Pooled effects of vegetarian-based dietary patterns were associated with significantly lower concentrations of CRP (WMD: -0.61 mg/L; 95% CI: -0.91, -0.32 mg/L; P = 0.0001), fibrinogen (WMD: -0.22 g/L; 95% CI: -0.41, -0.04 mg/L; P = 0.02), and total leukocyte (WMD: -0.62 × 10(3)/μL; 95% CI -1.13 × 10(3), -0.10 × 10(3)/μL; P = 0.02) compared with those following non-vegetarian dietary patterns in observational studies. Insufficient data were identified for a meta-analysis of intervention studies. This study provides evidence that vegetarian-based dietary patterns are associated with lowered serum C-reactive protein, fibrinogen, and total leukocyte concentrations. Future research should focus on large-scale intervention trials, contrasting differences in inflammation and immune status and function between vegetarian and non-vegetarian-based populations.