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Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis.
Kristensen, G, Berg, KD, Toft, BG, Stroomberg, HV, Nolley, R, Brooks, JD, Brasso, K, Roder, MA
Journal of clinical pathology. 2019;(10):696-704
Abstract
AIMS: Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP). METHODS The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP. RESULTS Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5). CONCLUSIONS Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.
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Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet.
Zhu, C, Wong, M, Li, Q, Sawrey-Kubicek, L, Beals, E, Rhodes, CH, Sacchi, R, Lebrilla, CB, Zivkovic, AM
Journal of proteome research. 2019;(11):3977-3984
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Abstract
Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery.
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The effects of exercise and milk-fat globule membrane (MFGM) on walking parameters in community-dwelling elderly Japanese women with declines in walking ability: A randomized placebo controlled trial.
Kim, H, Won, CW, Kim, M, Kojima, N, Fujino, K, Osuka, Y, Hosoi, E, Suzuki, T
Archives of gerontology and geriatrics. 2019;:106-113
Abstract
OBJECTIVE To investigate the effects of exercise and milk fat globule membrane (MFGM) supplementation on walking ability and walking parameters in community-dwelling elderly Japanese women with declined walking ability. METHODS A randomized placebo controlled trial was performed on 126 elderly community-dwelling women over 79 years old. Participants were randomly assigned to one of four three-month interventions: exercise and MFGM (Ex + MFGM), exercise and placebo (Ex + P), MFGM, and placebo interventions. The exercise intervention group performed one-hour progressive exercise classes twice a week. The MFGM supplementation included ingesting 1 g of MFGM per day. Medical history, physical function measurements included grip strength, knee extension strength, walking speed, as well as walking parameters, and blood components were analyzed. RESULTS Significant group × time interactions were observed in usual walking speed, stride, and foot progression angle between the groups. Walking speed improved in both exercise groups (P < 0.001). Similarly, stride significantly increased in the exercise groups compared to the MFGM and placebo groups (P < 0.001). Foot progression angle decreased in the exercise groups (P = 0.023) but not in MFGM or placebo groups. Participants with decreased or unchanged walking speed had significantly lower knee extension strength at baseline (P = 0.016), and a higher prevalence of knee OA (P = 0.033, P = 0.010, respectively). CONCLUSION The exercise interventions alone or combined with nutrition were effective in improving walking speed as well as other walking parameters. Improvement in stride and foot progression angle may have contributed to the increase in walking speed. However, augmented effects of MFGM with exercise could not be confirmed.
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A novel noninvasive appendicitis score with a urine biomarker.
Yap, TL, Fan, JD, Chen, Y, Ho, MF, Choo, CS, Allen, J, Low, Y, Jacobsen, AS, Nah, SA
Journal of pediatric surgery. 2019;(1):91-96
Abstract
PURPOSE The aim of our study was to develop an appendicitis score incorporating a urine biomarker, Leucine rich alpha-2-glycoprotein (LRG), for evaluation of children with abdominal pain. METHODS From January to August 2017 we prospectively enrolled children aged 4-16 years old admitted for suspected appendicitis. Urine samples for LRG analysis were obtained preoperatively and quantified by enzyme-linked immunosorbent assay (ELISA) after correction for patient hydration status. The diagnosis of appendicitis was based on operative findings and histology. Logistic regression was used to identify prospective predictors. RESULTS A total of 148 patients were recruited, of which 42(28.4%) were confirmed appendicitis. Our Appendicitis Urinary Biomarker (AuB) model incorporated urine LRG with 3 clinical predictors: 'constant pain', 'right iliac fossa tenderness', 'pain on percussion'. Area under the ROC curve for AuB was 0.82 versus 0.78 for the Pediatric Appendicitis Score (PAS) on the same cohort of patients. A model-calculated risk score of <0.15 is interpreted as low risk of appendicitis. Sensitivity for the AuB at this cutoff was 97.6%, specificity 37.7%, negative predictive value 97.6%, positive predictive value 38.3%, and negative likelihood ratio 0.06. CONCLUSION The noninvasive AuB score appears promising as a diagnostic tool for excluding appendicitis in children without the need for blood sampling. TYPE OF STUDY Study of diagnostic test. LEVEL OF EVIDENCE Level III.
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Circulating zinc-α2-glycoprotein is reduced in women with polycystic ovary syndrome, but can be increased by exenatide or metformin treatment.
Zheng, S, Liu, E, Zhang, Y, Long, T, Liu, X, Gong, Y, Mai, T, Shen, H, Chen, H, Lin, R, et al
Endocrine journal. 2019;(6):555-562
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Abstract
The study was to investigate circulating zinc-α2-glycoprotein (ZAG) concentrations in women with PCOS, and changes in ZAG levels after exenatide or metformin treatment. One hundred eighty-two women with polycystic ovary syndrome (PCOS) who met the 2003 Rotterdam diagnostic criteria and 150 controls without PCOS were recruited. We partitioned women with PCOS into groups according to body mass index or blood glucose concentrations, determined serum ZAG, anthropometric parameters, metabolic and endocrine indicators, and inflammatory markers, and statistically analyzed the results. Eighty-two overweight/obese subjects of the recruited women with PCOS were then randomly assigned to groups administered either 12 weeks of exenatide injection (10 μg b.i.d.) or oral metformin (1,000 mg b.i.d.). Circulating ZAG levels were determined after 12 weeks of treatment. The results showed that circulating ZAG was significantly lower in PCOS women than in healthy women (p < 0.01). Overweight/obese women and those with higher blood glucose levels had lower circulating ZAG. After 12 weeks of exenatide or metformin treatment, there were significant increases (p < 0.01) in circulating ZAG in both treatment groups (the exenatide baseline level was 46.54 ± 2.38 ng/mL vs. 56.41 ± 2.02 ng/mL after treatment, p < 0.01; metformin baseline was 47.81 ± 2.14 ng/mL vs. 55.67 ± 2.01 ng/mL after treatment, p < 0.01), however there was no statistical difference between the 2 treatments (p > 0.05). Circulating ZAG is closely related to PCOS and could be an important adipokine involved in the occurrence and development of PCOS. ZAG might possibly be applicable as a new observational indicator in the treatment of PCOS.
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A positive impact on the serum lipid profile and cytokines after the consumption of a plant sterol-enriched beverage with a milk fat globule membrane: a clinical study.
Alvarez-Sala, A, Blanco-Morales, V, Cilla, A, Silvestre, RÁ, Hernández-Álvarez, E, Granado-Lorencio, F, Barberá, R, Garcia-Llatas, G
Food & function. 2018;(10):5209-5219
Abstract
The hypocholesterolemic effect and the modification of serum biomarkers of a dietary plant sterol (PS) intake, cholesterol precursors and cytokines after the consumption of milk-based fruit beverages with a milk fat globule membrane were evaluated by a randomized, double-blind, crossover, multiple dose bioavailability study. Postmenopausal women (n = 38) consumed daily 250 mL of a beverage with or without 2 g of PS added during 6 weeks in each of the study periods. With the intake of the PS-added beverage, significant decreases (mg dL-1) in serum total cholesterol (pre-treatment: 220.0 ± 27.8 vs. post-treatment: 212.9 ± 25.8; p < 0.05) and LDL-cholesterol (129.4 ± 28.5 vs. 121.7 ± 24.4; p < 0.05) were detected. The cholesterol precursor lathosterol (11.2%), markers of the dietary PS intake (campesterol 43.1% and β-sitosterol 32.5%), and anti-inflammatory IL-10 cytokine (22.5%) increased significantly, with a concomitant significant reduction in pro-inflammatory IL-1β (6.7%). No variations in HDL-cholesterol, other sterols (desmosterol and stigmasterol) or cytokines (IL-6, IL-8, IL-12p70 and TNF-α) were detected. These results indicated that this kind of PS-enriched milk-based fruit beverage is suitable during the period of clinical intervention, and its consumption may be an adequate way to improve PS functionality since a significant reduction in cholesterol levels has been observed. Therefore, the intake of this beverage could contribute to reduce the risk of cardiovascular disease also obtaining a beneficial effect on the serum inflammatory status in postmenopausal women.
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Dose of allergens in a peanut snack (Bamba) associated with prevention of peanut allergy.
Hindley, JP, Filep, S, Block, DS, King, EM, Chapman, MD
The Journal of allergy and clinical immunology. 2018;(2):780-782
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Arabidopsis pollen extensins LRX are required for cell wall integrity during pollen tube growth.
Sede, AR, Borassi, C, Wengier, DL, Mecchia, MA, Estevez, JM, Muschietti, JP
FEBS letters. 2018;(2):233-243
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Abstract
Proper cell wall assembly is crucial during pollen tube growth. Leucine-rich repeat extensins (LRXs) are extracellular glycoproteins which belong to the hydroxyproline-rich glycoprotein (HRGP) family. They contain a conserved N-terminal leucine-rich repeat (LRR) domain and a highly variable C-terminal extensin domain. Here, we characterized four LRX proteins (LRX8 through LRX11) from pollen of Arabidopsis thaliana. To investigate the role of LRX8-LRX11 in pollen germination and pollen tube growth, multiple T-DNA lrx mutants were obtained. The lrx mutants display abnormal pollen tubes with an irregular deposition of callose and pectin. They also show serious alterations in pollen germination and segregation ratio. Our results suggest that LRXs are involved in ensuring proper cell wall assembly during pollen tube growth.
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Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques.
Ereño-Orbea, J, Sicard, T, Cui, H, Akula, I, Julien, JP
Journal of visualized experiments : JoVE. 2018;(137)
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Abstract
Glycoproteins on the surface of cells play critical roles in cellular function, including signalling, adhesion and transport. On leukocytes, several of these glycoproteins possess immunoglobulin (Ig) folds and are central to immune recognition and regulation. Here, we present a platform for the design, expression and biophysical characterization of the extracellular domain of human B cell receptor CD22. We propose that these approaches are broadly applicable to the characterization of mammalian glycoprotein ectodomains containing Ig domains. Two suspension human embryonic kidney (HEK) cell lines, HEK293F and HEK293S, are used to express glycoproteins harbouring complex and high-mannose glycans, respectively. These recombinant glycoproteins with different glycoforms allow investigating the effect of glycan size and composition on ligand binding. We discuss protocols for studying the kinetics and thermodynamics of glycoprotein binding to biologically relevant ligands and therapeutic antibody candidates. Recombinant glycoproteins produced in HEK293S cells are amenable to crystallization due to glycan homogeneity, reduced flexibility and susceptibility to endoglycosidase H treatment. We present methods for soaking glycoprotein crystals with heavy atoms and small molecules for phase determination and analysis of ligand binding, respectively. The experimental protocols discussed here hold promise for the characterization of mammalian glycoproteins to give insight into their function and investigate the mechanism of action of therapeutics.
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Estimating the age of the p.Cys433Arg variant in the MYOC gene in patients with primary open-angle glaucoma.
Marques, AM, Ananina, G, Costa, VP, de Vasconcellos, JPC, de Melo, MB
PloS one. 2018;(11):e0207409
Abstract
The aim of this study was to estimate the age of the Cys433Arg (c.1297T>C, p.Cys433Arg) variant by comparing the genotypes of individuals affected and not affected by primary open angle glaucoma juvenile onset (JOAG). Our sample consisted of 35 JOAG-affected individuals from three families, 16 unrelated patients with the MYOC p.Cys433Arg variant and 16 unaffected individuals. Genomic DNA was amplified by PCR; nine short tandem repeats were genotyped through automated electrophoresis and three single nucleotide polymorphisms through Sanger sequencing. The determination of haplotypes was performed using Arlequin software and age estimation was performed using DMLE+ 2.3 and BDMC21 softwares. Four markers constituted the haplotypes associated with the p.Cys433Arg variant. The software DMLE+2.3 predicted an age of 43 generations for this variant with a 95% confidence interval ranging from 28 to 76 generations (560-1520 years) and BDMC21 predicted an age of 59 generations (1180 years) (95% CI: 40 to 100).