ABSTRACT
BACKGROUND: Visceral fat accumulation and obesity-induced chronic inflammation have been proposed as early markers for multiple disease states, especially in women. Nevertheless, the potential impact of fat distribution on α1-acid glycoprotein(AGP), a marker of inflammation, remains unclear. This research was conducted to investigate the relationships among obesity, fat distribution, and AGP levels. METHODS: A cross-sectional observational study was performed using blood samples from adult females recruited through the National Health and Nutrition Examination Survey from 2015 to 2018. Serum levels of AGP were measured using the Tina-quant α-1-Acid Glycoprotein Gen.2 assay. Based on the fat distribution data obtained from dual-energy X-ray absorptiometry assessments, body mass index (BMI), total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral percent fat (VPF), subcutaneous percent fat (SPF), visceral fat/subcutaneous fat ratio (VSR) were used as dependent variables. To investigate the link between fat distribution and AGP, multivariate linear regression analysis was utilized. Furthermore, a sensitivity analysis was also performed. RESULTS: The present study included 2,295 participants. After adjusting for covariates, BMI, TPF, APF, GPF, VPF, and SPF were found to be positively correlated with AGP levels (BMI: ß = 23.65 95%CI:20.90-26.40; TPF: ß = 25.91 95%CI:23.02-28.80; APF: ß = 25.21 95%CI:22.49-27.93; GPF: ß = 19.65 95%CI:16.96-22.34; VPF: ß = 12.49 95%CI:9.08-15.90; SPF: ß = 5.69, 95%CI:2.89-8.49; AGR: ß = 21.14 95%CI:18.16-24.12; VSR: ß = 9.35 95%CI:6.11-12.59, all P < 0.0001). All the above indicators exhibited a positive dose-response relationship with AGP. In terms of fat distribution, both AGR and VSR showed positive associations with AGP (P for trend < 0.0001). In particular, when compared to individuals in tertile 1 of AGR, participants in tertiles 2 and 3 had 13.42 mg/dL (95% CI 10.66-16.18) and 21.14 mg/dL (95% CI 18.16-24.12) higher AGP levels, respectively. Participants in the highest tertile of VSR were more likely to exhibit a 9.35 mg/dL increase in AGP compared to those in the lowest tertile (95% CI 6.11-12.59). CONCLUSIONS: Overall, this study revealed a positive dose-dependent relationship between fat proportion/distribution and AGP levels in women. These findings suggest that physicians can associate abnormal serum AGP and obesity with allow timely interventions.
Subject(s)
Body Mass Index , Intra-Abdominal Fat , Orosomucoid , Humans , Female , Orosomucoid/metabolism , Orosomucoid/analysis , Adult , Middle Aged , Cross-Sectional Studies , United States/epidemiology , Intra-Abdominal Fat/metabolism , Obesity/blood , Absorptiometry, Photon , Body Fat Distribution , Nutrition SurveysABSTRACT
There is an urgent need for new high-quality markers for the early detection of hepatocellular carcinoma (HCC). Åström et al. suggested that S2-bound α1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated the predictive advantage of S2-bound AGP in the early detection of HCC. In a retrospective case-control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (n = 93), we measured S2-bound AGP using the HepaCheC® ELISA kit (Glycobond AB, Linköping, SE) at the start of treatment, end of treatment and follow-up (maximum: 78 months). Patients were retrospectively propensity score matched (1:2). Thirty-one patients chronically infected with HCV developed HCC after a sustained virological response, while 62 did not. In addition, samples of patients with chronic hepatitis B virus infection, metabolic dysfunction-associated steatotic liver disease and HCC of different etiologies were analysed. S2-bound AGP elevation in HCC patients was confirmed. However, we did not observe a predictive advantage of S2-bound AGP for the early detection of HCC during treatment and follow-up. Interestingly, S2-bound AGP levels correlated with aspartate aminotransferase (ρ = .56, p = 9.5×10-15) and liver elastography (ρ = .67, p = 2.2×10-16). Of note, S2-bound AGP decreased in patients chronically infected with HCV after treatment-induced HCV clearance. Fucosylated S2-bound AGP levels were elevated in patients with chronic HCV and HCC. The potential role of S2-bound AGP as a novel tumour marker requires further investigation.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Orosomucoid , Humans , Carcinoma, Hepatocellular/virology , Hepatitis C, Chronic/complications , Male , Female , Middle Aged , Orosomucoid/metabolism , Orosomucoid/analysis , Retrospective Studies , Liver Neoplasms/virology , Case-Control Studies , Aged , Adult , Biomarkers/blood , Antiviral Agents/therapeutic use , Biomarkers, Tumor/metabolism , Early Detection of Cancer/methods , HepacivirusABSTRACT
OBJECTIVE: To assess diet quality and its association with body and biochemical parameters in patients who underwent Roux-en-Y gastric bypass (RYGB). METHODS: Prospective observational study with individuals of both sexes subjected to RYGB. Body composition, biochemical parameters, and diet quality were assessed before and six months after RYGB. Diet quality was assessed by the Healthy Eating Index (HEI). Data were analyzed by the paired t-test or Wilcoxon signed-rank test, with a significance level of 5%. Spearman's correlation and simple linear regression were performed between variables. RESULTS: The final sample included 34 patients. Their diet was classified as poor before and 6 mo after RYGB. BMI, fat mass, fat-free mass, waist perimeter, serum total protein, transthyretin, alpha-1-acid glycoprotein, and C-reactive protein decreased significantly (P < 0.05). Variations in the HEI score and caloric intake were associated with serum albumin and transthyretin (P < 0.05). CONCLUSION: Poor diet quality was present before and six months after RYGB, and the study data suggest that poor diet quality is associated to a risk of loss of lean body mass and visceral protein six months after RYGB.
Subject(s)
Body Composition , Diet , Gastric Bypass , Nutritional Status , Prealbumin , Humans , Male , Female , Prospective Studies , Adult , Prealbumin/analysis , Prealbumin/metabolism , Middle Aged , Diet/methods , Diet/statistics & numerical data , Dietary Proteins/administration & dosage , Body Mass Index , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Obesity, Morbid/surgery , Obesity, Morbid/blood , Serum Albumin/analysis , Serum Albumin/metabolism , Energy Intake , Orosomucoid/analysis , Orosomucoid/metabolism , Diet, Healthy/statistics & numerical data , Diet, Healthy/methodsABSTRACT
OBJECTIVE: This study aimed to investigate the expression of acute phase proteins and plasma cytokines in cats with various tumor types and varying metastatic statuses. ANIMALS: 5 clinically healthy cats and 22 cats with neoplastic disease that underwent CT imaging before treatment were enrolled. Patients were grouped based on their tumor types and metastatic status. METHODS: Blood samples were collected from all cats for general blood analyses before they underwent CT imaging. The remaining plasma sample was frozen for subsequent alpha 1-acid glycoprotein (AGP), serum amyloid A (SAA), and feline cytokine panel measurements. These results were compared with those of healthy cats as well as between metastatic status and tumor types. RESULTS: Only 4 cats (18%) exhibited elevated SAA levels, whereas 16 (73%) showed elevated AGP levels. AGP was significantly increased in cats with tumors (P = .016), while SAA was not. Only IL-8 showed a significant difference (P = .002) between cats with primary tumors and those with radiologically suspected tumor metastasis. CLINICAL RELEVANCE: While AGP is a more prominent biomarker than SAA in cats with tumors, a significant elevation of AGP and SAA levels in association with metastasis and specific tumor types could not be identified. Alternatively, further investigation is warranted to evaluate the potential significance of IL-8 in tumor progression and metastasis.
Subject(s)
Cat Diseases , Neoplasms , Humans , Cats , Animals , Orosomucoid/analysis , Orosomucoid/metabolism , Interleukin-8 , Serum Amyloid A Protein/analysis , Serum Amyloid A Protein/metabolism , Biomarkers , Neoplasms/veterinaryABSTRACT
OBJECTIVES: The aim of this study was to evaluate performance of a feline-specific ELISA for the measurement of alpha-1-acid glycoprotein (AGP) and to establish a reference interval (RI). METHODS: Surplus serum samples with low (~200 µg/ml), medium (~450 µg/ml) and high (~745 and 930 µg/ml) AGP concentrations were used to assess the intra- and inter-assay coefficients of variation (CVs). The quality goal for bioanalytical method validation was a CV of <20%. Linearity was assessed by serial dilution of a sample with a high AGP concentration. Spike recovery was evaluated by mixing samples with low, medium and high AGP concentrations at different ratios. To establish the RI, residual serum samples from 51 healthy adult cats that were presented for health examinations or blood donation between August 2020 and June 2021 were included. RESULTS: The intra-assay CV was 8.5%, 4.3% and 4.0%, and the inter-assay CV was 18.8%, 15.5% and 11.5% for serum samples with low, medium and high AGP concentrations, respectively. Excellent linearity (R2 = 0.98) was demonstrated for AGP concentrations ranging between 251.6 and 954.4 µg/ml. Average recovery was 95.0-99.7%. The right-sided RI for AGP was 328 µg/ml (90% confidence interval 300-354). Age had a statistically significant impact (increasing values with older age, P = 0.0026), but sex did not (P = 0.44), on AGP concentrations. CONCLUSIONS AND RELEVANCE: The ELISA was accurate and showed acceptable precision with the modification of dilution used in this study. AGP concentrations in this population appeared to increase with increasing age.
Subject(s)
Orosomucoid , Cats , Animals , Orosomucoid/analysis , Enzyme-Linked Immunosorbent Assay/veterinary , Enzyme-Linked Immunosorbent Assay/methods , CatalaseABSTRACT
BACKGROUND: Vitamin A (VA) assessment is important for targeting public health programs. Retinol isotope dilution (RID) is a sensitive method to estimate total body VA stores (TBSs) and total liver reserves (TLRs), but the impact of subclinical inflammation on RID is unclear. OBJECTIVE: We determined the association between TBSs and TLRs, estimated by RID, and inflammation among preschool children without clinical infection in Burkina Faso, Cameroon, Ethiopia, South Africa, and Tanzania. METHODS: Five studies (n = 532; 47.9 ± 8.3 mo; 49.0% male) included 13C-RID and measurement of inflammation markers, CRP, and α1-acid glycoprotein (AGP). Spearman correlations were used to evaluate TBSs and TLRs with inflammation biomarkers. Wilcoxon and Kruskal-Wallis tests were used to compare TBSs and TLRs by inflammation categories [normal vs. elevated CRP (>5 mg/L) or AGP (>1 g/L)] and inflammation stage [reference, incubation (elevated CRP), early convalescence (elevated CRP and AGP), and late convalescence (elevated AGP)]. RESULTS: Complete data were available for 439 children. Median (Q1, Q3) TLRs ranged from 0.12 (0.07, 0.18) µmol/g in Ethiopia to 1.10 (0.88, 1.38) µmol/g in South Africa. Elevated CRP ranged from 4% in Burkina Faso to 42% in Cameroon, and elevated AGP from 20% in Tanzania to 58% in Cameroon. Pooled analysis (excluding Cameroon) showed a negative correlation between TBSs and AGP (ρ = -0.131, P = 0.01). Children with elevated AGP had higher probability of having lower TBSs (probability = 0.61, P = 0.002). TBSs differed among infection stages (P = 0.020). Correlations between TLRs and CRP or AGP were not significant. CONCLUSIONS: No indication of systematic bias in RID-estimated TLRs was found due to subclinical inflammation among preschool children. The inverse relationship between TBSs and AGP may reflect decreased stores after infection or an effect of inflammation on isotope partitioning. Further research should investigate potential confounding variables to improve TBS-estimate validity.
Subject(s)
Vitamin A Deficiency , Vitamin A , Humans , Male , Child, Preschool , Female , Convalescence , Inflammation , Biomarkers , Liver/chemistry , Isotopes , South Africa , Orosomucoid/analysisABSTRACT
The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) research group was formed over a decade ago to improve the interpretation of micronutrient biomarkers in settings with inflammation. The BRINDA inflammation adjustment method uses regression correction to adjust for the confounding effects of inflammation on select micronutrient biomarkers and has provided important insights to micronutrient research, policy, and programming. However, users may face challenges when applying the BRINDA inflammation adjustment methods to their own data due to varying guidance on the adjustment approach for different biomarkers and the need to develop statistical programming to conduct these analyses. This may result in lost opportunities to have results of micronutrient data readily available during critical decision-making periods. Our research objectives are to 1) provide an all-in-one summary of the BRINDA method in adjusting multiple micronutrient biomarkers for inflammation, 2) evaluate whether malaria as a binary variable should be included in the BRINDA inflammation adjustment method, and 3) present standardized and user-friendly BRINDA adjustment R package and SAS macro. This paper serves as a practical guidebook for the BRINDA inflammation adjustment approach and aids users to use the BRINDA R package and SAS to streamline their analyses.
Subject(s)
Anemia, Iron-Deficiency , Anemia , Trace Elements , Humans , C-Reactive Protein/analysis , Micronutrients , Nutritional Status , Orosomucoid/analysis , Biomarkers , InflammationABSTRACT
BACKGROUND: Feline obstructive disease of the lower urinary tract (FLUTD) is a common pathologic condition of cats. It can be related to sterile inflammation, which leads to acute impairment of renal function and the accumulation of electrolytes and acid-base imbalance. Acute-phase proteins (APPs) are biomarkers of tissue damage from inflammation that assist in monitoring treatment and prognosis. OBJECTIVE: Monitoring the inflammatory processes of obstructive feline lower urinary tract disease through the determination of plasma fibrinogen concentrations and serum concentrations of the acute-phase proteins, serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP), and albumin. METHODOLOGY: Twenty-five male cats were included in this study. They were divided into two experimental groups: a control group (CG) and an obstruction group (OG). There were 8 healthy cats in the CG group and 17 cats with obstructive FLUTD in the OG group. APP measurements were conducted using ELISA kits. Samples were collected for APP analyses, serum biochemical assays, urinalyses, and urine protein: creatinine ratio calculations at diagnosis, before urethral clearance (H0), and 12 (H12), 24 (H24), and 48 (H48) hours after urethral clearance from cats in the OG group. Samples were collected once from cats in the CG group cats. RESULTS: At H0, we found positive correlations of SAA, AGP, and fibrinogen with urea and creatinine, and negative correlations of albumin with hematuria, SAA, and potassium. At H48, we found positive correlations between SAA and AGP, AGP and urea, fibrinogen and urea, fibrinogen and creatinine, fibrinogen and AGP, and fibrinogen and SAA. In addition, a negative correlation of albumin with urea and creatinine was observed. CONCLUSIONS: Serum amyloid A, AGP, fibrinogen, and albumin could be used as biomarkers of inflammatory processes in cats with obstructive FLUTD.
Subject(s)
Cat Diseases , Urologic Diseases , Acute-Phase Proteins/analysis , Animals , Biomarkers , Cat Diseases/diagnosis , Cats , Male , Orosomucoid/analysis , Orosomucoid/metabolism , Serum Amyloid A Protein/analysis , Urologic Diseases/veterinaryABSTRACT
INTRODUCTION: Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Research Design and Methods. Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women. Stepwise multivariate linear regression analyses were used to identify the most important determinants of orosomucoid. RESULTS: Orosomucoid was higher in women with positive (n = 57) compared to women with negative FHD and was associated positively with FHD (both p = 0.01). Orosomucoid also showed positive associations with fasting glucose (p < 0.001), free fatty acids (p = 0.001), and HbA1c (p = 0.007), whereas there was no association with fasting insulin and serum lipids. In addition, orosomucoid was associated inversely with adiponectin (p = 0.02) and positively with adipose tissue-insulin resistance index (AT-IR, the product of fasting insulin and free fatty acids; p = 0.001) but not with homeostasis model assessment-insulin resistance, leptin, and high-sensitivity C-reactive protein. In multivariate analyses, AT-IR (standardized ß, 0.22; p = 0.003), serum adiponectin (standardized ß, -0.163; p = 0.032), FHD+ (standardized ß, 0.178; p = 0.029), and HbA1c (standardized ß, 0.213; p = 0.005) emerged as independent determinants of orosomucoid and explained 15.2% of its variability. CONCLUSIONS: These results are the first to demonstrate that orosomucoid is associated not only with adipose tissue-insulin resistance and adiponectin but also with FHD.
Subject(s)
Adiponectin/analysis , Diabetes Mellitus, Type 2/diagnosis , Insulin Resistance/physiology , Orosomucoid/analysis , Adiponectin/blood , Adipose Tissue/metabolism , Adipose Tissue/physiopathology , Adult , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Insulin/analysis , Insulin/biosynthesis , Insulin/blood , Japan/epidemiology , Male , Medical History Taking/methods , Medical History Taking/statistics & numerical data , Middle Aged , Orosomucoid/metabolismABSTRACT
The ever-increasing complexity of biological samples to be analysed by mass spectrometry has led to the necessity of sophisticated separation techniques, including multidimensional separation. Despite a high degree of orthogonality, the coupling of liquid chromatography (LC) and capillary zone electrophoresis (CZE) has not gained notable attention in research. Here, we present a heart-cut nanoLC-CZE-ESI-MS platform to analyse intact proteins. NanoLC and CZE-MS are coupled using a four-port valve with an internal nanoliter loop. NanoLC and CZE-MS conditions were optimised independently to find ideal conditions for the combined setup. The valve setup enables an ideal transfer efficiency between the dimensions while maintaining good separation conditions in both dimensions. Due to the higher loadability, the nanoLC-CZE-MS setup exhibits a 280-fold increased concentration sensitivity compared to CZE-MS. The platform was used to characterise intact human alpha-1-acid glycoprotein (AGP), an extremely heterogeneous N-glycosylated protein. With the nanoLC-CZE-MS approach, 368 glycoforms can be assigned at a concentration of 50 µg/mL as opposed to the assignment of only 186 glycoforms from 1 mg/mL by CZE-MS. Additionally, we demonstrate that glycosylation profiling is accessible for dried blood spot analysis (25 µg/mL AGP spiked), indicating the general applicability of our setup to biological matrices. The combination of high sensitivity and orthogonal selectivity in both dimensions makes the here-presented nanoLC-CZE-MS approach capable of detailed characterisation of intact proteins and their proteoforms from complex biological samples and in physiologically relevant concentrations.
Subject(s)
Chromatography, Liquid/methods , Electrophoresis, Capillary/methods , Mass Spectrometry/methods , Nanotechnology , Orosomucoid/analysis , Glycosylation , Humans , Limit of Detection , Reproducibility of ResultsABSTRACT
El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.
Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Orosomucoid/analysis , Biomarkers/blood , Lipocalins/analysis , Lipocalins/blood , Hyperaldosteronism/blood , Enzyme-Linked Immunosorbent Assay , Cross-Sectional Studies , Cohort Studies , Renin/analysis , Aldosterone/blood , Arterial Pressure , Hyperaldosteronism/diagnosis , Hypertension/diagnosisABSTRACT
Management of end-stage renal disease (ESRD) patients requires monitoring each of the components of malnutrition-inflammation-atherosclerosis (MIA) syndrome. Restrictive diet can negatively affect nutritional status and inflammation. An acute-phase protein-α1-acid glycoprotein (AGP), has been associated with energy metabolism in animal and human studies. The aim of our study was to look for a relationship between serum AGP concentrations, laboratory parameters, and nutrient intake in ESRD patients. The study included 59 patients treated with maintenance hemodialysis. A 24 h recall assessed dietary intake during four non-consecutive days-two days in the post-summer period, and two post-winter. Selected laboratory tests were performed: complete blood count, serum iron, total iron biding capacity (TIBC) and unsaturated iron biding capacity (UIBC), vitamin D, AGP, C-reactive protein (CRP), albumin, prealbumin, and phosphate-calcium metabolism markers (intact parathyroid hormone, calcium, phosphate). Recorded dietary intake was highly deficient. A majority of patients did not meet recommended daily requirements for energy, protein, fiber, iron, magnesium, folate, and vitamin D. AGP correlated positively with CRP (R = 0.66), platelets (R = 0.29), and negatively with iron (R = -0.27) and TIBC (R = -0.30). AGP correlated negatively with the dietary intake of plant protein (R = -0.40), potassium (R = -0.27), copper (R = -0.30), vitamin B6 (R = -0.27), and folates (R = -0.27), p < 0.05. However, in multiple regression adjusted for confounders, only CRP was significantly associated with AGP. Our results indicate that in hemodialyzed patients, serum AGP is weakly associated with dietary intake of several nutrients, including plant protein.
Subject(s)
Eating/physiology , Kidney Failure, Chronic/physiopathology , Malnutrition/blood , Orosomucoid/analysis , Renal Dialysis/adverse effects , Biomarkers/blood , C-Reactive Protein/analysis , Diet/adverse effects , Diet/statistics & numerical data , Diet Records , Female , Humans , Inflammation , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Malnutrition/etiology , Middle Aged , Nutritional Status , Orosomucoid/deficiency , Prospective Studies , Recommended Dietary Allowances , Regression AnalysisABSTRACT
Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo. Aim: To evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA. Subjects and Methods: A cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9. Results: PA and EH subjects have significantly higher SBP and DBP (p <0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p <0.05) than the CTL&EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p <0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 - 1.00], p <0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 - 1.00], p<0.001) to discriminate the PA condition from EH and controls. Conclusion: Serum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.
Subject(s)
Extracellular Vesicles/metabolism , Hyperaldosteronism/diagnosis , MicroRNAs/urine , Orosomucoid/analysis , Adult , Biomarkers/analysis , Cross-Sectional Studies , Female , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/urine , Hypertension/blood , Hypertension/urine , Lipocalin-2/blood , Male , Middle AgedABSTRACT
OBJECTIVES: Numerous biomarkers have been shown to be associated with albuminuria. However, few of them are valuable separate predictors of albuminuria development. This study aimed to develop a model for predicting the short-term risk of new-onset albuminuria in normoalbuminuric patients with type 2 diabetes (T2D). METHODS: 213 patients with T2D who were normoalbuminuric at the baseline were enrolled in this study. Basal levels of clinical characteristics and renal biomarkers including urinary orosomucoid (alpha-1-acid-glycoprotein, UORM), neutrophil gelatinase-associated lipocalin, retinol-binding protein, alpha-1-microglobulin, transferrin, and albumin-to-creatinine ratio (ACR) were utilized to analyze the association with the short-term risk of new-onset albuminuria. RESULTS: 19.72% of normoalbuminuric subjects at baseline progressed to albuminuria over the 2-year follow-up period. Except for NGAL, the basal levels of the other five renal biomarkers were significantly associated with new-onset albuminuria risk in the univariate analysis. In the multivariate logistic regression analysis using Forward: LR method, a model incorporating UORM/Cr, ACR, and HbA1c was established. Comparatively, this model had a higher potential to predict new-onset albuminuria risk compared with the single use of renal markers. In the validation of this model performed by 5-fold cross-validation method, the accuracy of this model was 0.818 ± 0.008 in the training sets, 0.827 ± 0.062 in the test sets, indicating a good capability for assessing albuminuria risk. Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. CONCLUSION: The combined analysis of UORM/Cr, ACR and HbA1c may be of potential value for predicting the short-term risk of new-onset albuminuria in such patients.
Subject(s)
Albuminuria , Biomarkers , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Nomograms , Aged , Albuminuria/blood , Albuminuria/diagnosis , Albuminuria/etiology , Albuminuria/urine , Biomarkers/analysis , Biomarkers/blood , Biomarkers/urine , Creatinine/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/blood , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/etiology , Diabetic Nephropathies/urine , Female , Glycated Hemoglobin/analysis , Humans , Longitudinal Studies , Male , Middle Aged , Orosomucoid/analysis , Orosomucoid/urine , Predictive Value of Tests , Risk Assessment , Risk Factors , Serum Albumin/analysisABSTRACT
INTRODUCTION: Anemia is a public health problem worldwide and is most prevalent in preschool children, for whom it is the most frequent cause of nutritional deficits. In turn, iron deficiency is the main cause of anemia, affecting 43% of children globally. Previous studies in Cuba show rates of iron deficiency in preschool children between 38.6% and 57.6%, higher in infants (71.2% to 81.1%). WHO recommends using serum ferritin as an indicator of iron deficiency accompanied by acute (C-reactive protein) and chronic (a1-acid glycoprotein) inflammation biomarkers. OBJECTIVE: Assess how inflammation affects measuring and reporting of iron-deficiency anemia rates in Cuban preschool children. METHODS: Data were obtained from serum samples contained in the National Anemia and Iron Deficiency Survey, and included presumably healthy preschool Cuban children (aged 6-59 months). Serum samples were collected from 1375 children from randomly selected provinces in 4 regions of the country from 2014 through 2018. We examined the association between ferritin and two inflammatory biomarkers: C-reactive protein and a1-acid glycoprotein. Individual inflammation-adjusted ferritin concentrations were calculated using four approaches: 1) a higher ferritin cut-off point (⟨30 g/L); 2) exclusion of subjects showing inflammation (C-reactive protein ⟩5 mg/L or a1-acid glycoprotein ⟩1 g/L); 3) mathematical correction factor based on C-reactive protein or a1-acid glycoprotein; and 4) correction by regression with the method proposed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia Group. We estimated confidence intervals of differences between unadjusted prevalence and prevalence adjusted for inflammation by each method. RESULTS: The proportion of children with inflammation according to C-reactive protein concentrations >5 mg/L was lower (11.1%, 153/1375) than the proportion measured according to the concentrations of a1-acid glycoprotein, at >1 g/L (30.8%, 424/1375). The percentage of children with high concentrations of at least one of the aforementioned biomarkers was 32.7% (450/1375). Thus, each correction method increased the observed prevalence of iron deficiency compared to unadjusted estimates (23%, 316/1375). This increase was more pronounced when using the internal regression correction method (based only on C-reactive protein) or the method based on a higher cut-off point. Adjustment using all four methods changed estimated iron deficiency prevalence, increasing it from 0.1% to 8.8%, compared to unadjusted values. CONCLUSIONS: One-third of preschool children had biomarkers indicating elevated inflammation levels. Without adjusting for inflammation, iron deficiency prevalence was underestimated. The significant disparity between unadjusted and inflammation-adjusted ferritin when using some approaches highlights the importance of selecting the right approach for accurate, corrected measurement. The internal regression correction approach is appropriate for epidemiological studies because it takes into account inflammation severity. However, other models should be explored that account for inflammation and also provide better adjusted ferritin concentrations.
Subject(s)
Anemia, Iron-Deficiency , Anemia, Iron-Deficiency/diagnosis , Anemia, Iron-Deficiency/epidemiology , Biomarkers , Child, Preschool , Cuba/epidemiology , Humans , Infant , Inflammation/epidemiology , Iron , Nutritional Status , Orosomucoid/analysis , PrevalenceABSTRACT
Separations based on combinations of 2.1 mm I.D. high-performance affinity microcolumns and capillary electrophoresis were developed and used to characterize the glycoforms of an intact glycoprotein. Human alpha1-acid glycoprotein (AGP) was used as a model analyte due to its heterogeneous glycosylation resulting from variations in its degree of branching, fucosylation, and number of sialic acids. Three separation formats were examined based on microcolumns that contained the lectins concanavalin A (Con A) or Aleuria aurantia lectin (AAL). These microcolumns were used with one another or in combination with capillary electrophoresis. N-Glycan analysis of the non-retained and retained AGP fractions was carried out by using PNGase F digestion and nanoflow electrospray ionization mass spectrometry. Con A microcolumns were found to selectively enrich AGP that contained bi-antennary N-glycans, while AAL microcolumns retained AGP with fucose-containing N-glycans. Results from these separation methods indicated that fucosylation of the N-linked glycans was more abundant when a high degree of branching was present in AGP. Sialic acid residues were more abundant when higher degrees of branching and more fucose residues were present in AGP. The separation and analysis methods that were developed could be used with relatively small amounts of AGP and can be adapted for use with other intact glycoproteins.
Subject(s)
Chromatography, Affinity/methods , Electrophoresis, Capillary/methods , Lectins/metabolism , Orosomucoid , Glycoproteins/analysis , Glycoproteins/chemistry , Glycoproteins/isolation & purification , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/metabolism , Lectins/chemistry , N-Acetylneuraminic Acid/chemistry , Orosomucoid/analysis , Orosomucoid/chemistry , Orosomucoid/isolation & purification , Polysaccharides/chemistryABSTRACT
BACKGROUND: Crush syndrome (CS) is the most common cause of deaths following earthquakes and other disasters. The pathogenesis of CS has yet to be fully elucidated. Thus, clinical choice of ideal drug treatments for CS remains deficient. METHODS AND RESULTS: In this study, we first evaluated the relation between extrusion force and the severities of CS. Rats were exposed to different extrusion forces: 1 kg, 3 kg, 5 kg, and 8âkg, respectively. Survival rates, crushed muscle tissue edema, serum biochemical parameters, and histopathological staining were used to assess severity. Our results showed that there were no statistical differences in survival rate or changes in thigh circumference among the different extrusion forces groups. However, serum levels of potassium, creatine kinase, blood urea nitrogen, creatinine, and myoglobin were elevated at 12- and 24-h post-decompression in 5 kg and 8âkg groups, compared with 1 kg and 3âkg groups. Histopathological staining demonstrated that the degree of organ damage to kidney, muscle, and lung tissues correlated with increasing extrusion force. We next analyzed changes in serum protein profiles in 3 kg or 5âkg extrusion pressure groups. A total of 76 proteins (20 upregulated, 56 downregulated) were found to be altered at all three time points (0, 12, and 72âh) post-decompression, compared with the control group. Three common upregulated proteins alpha-1-acid glycoprotein (α1-AGP), neutrophil gelatinase-associated lipocalin (NGAL), and Haptoglobin were selected for validation of increased expression. α1-AGP was explored as a treatment for CS-induced acute kidney injury (AKI). Intraperitoneal injection of α1-AGP protected kidneys from CS-induced AKI by regulating TNF-α and IL-6 production, attenuating neutrophil recruitment, and reducing renal cell apoptosis. CONCLUSION: Our findings demonstrated that the severity of crush injury is causally related to extrusion pressure and increase in blood serum markers. Our identification of the biomarker and treatment candidate, α1-AGP, suggests its implication in predicting the severity of CS and its use as a mediator of CS-induced AKI, respectively.
Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Orosomucoid/analysis , Acute Kidney Injury/etiology , Animals , Biomarkers/blood , Crush Syndrome/complications , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Severity of Illness IndexABSTRACT
Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.
Subject(s)
Acute Coronary Syndrome/blood , Blood Proteins/analysis , Proteome , Proteomics , Acute Coronary Syndrome/diagnosis , Aged , Biomarkers/blood , Case-Control Studies , Complement C5/analysis , Female , Gelsolin/blood , Glycoproteins/blood , Humans , Male , Middle Aged , Orosomucoid/analysis , Predictive Value of Tests , Reproducibility of Results , Tandem Mass Spectrometry , Vitronectin/bloodABSTRACT
The Clearum dialyzer, built by Medtronic, became commercially available in several European countries in 2020, but there are still no reports of in vivo data. The aim of this study was to evaluate the efficacy and risk of hypoalbuminemia of this dialyzer compared with previously evaluated hemodialysis (HD), expanded hemodialysis (HDx), and postdilution hemodiafiltration (HDF) treatments. A prospective study was carried out in 15 patients. Each patient underwent seven dialysis sessions: FX80 Cordiax in HD, Clearum HS17 in HD, Phylther 17-SD in HDx, Theranova 400 in HDx, Phylther 17-G in postdilution HDF, Clearum HS17 in postdilution HDF, and FX80 Cordiax in postdilution HDF. The reduction ratios of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. Comparison of dialysis techniques revealed no differences between small molecules, but HDx and HDF were significantly higher than HD with medium and large molecular weights. The Clearum dialyzer in HDF obtained similar results to FX80 Cordiax in HDF, was slightly superior to Phylther 17-G in HDF, and was statistically superior to both dialyzers in HDx. Albumin losses with the Clearum dialyzer were among the lowest, both in HD and HDF treatments. The highest global removal score (GRS) values were obtained with the helixone and Clearum dialyzers in HDF, with similar results both in HD and HDF. In addition, the GRS values with HDx treatments were statistically significantly higher than those with HD. The new Clearum dialyzer has excellent behavior and tolerance in HD and HDF. Its adequate permeability has been proven with its maximal performance in HDF, which could represent an upgrade versus its predecessor polyphenylene dialyzers.
Subject(s)
Hemodiafiltration/instrumentation , Kidney Failure, Chronic/therapy , Renal Dialysis/instrumentation , Aged , Aged, 80 and over , Alpha-Globulins/analysis , Creatinine/blood , Female , Hemodiafiltration/methods , Humans , Male , Middle Aged , Myoglobin/blood , Orosomucoid/analysis , Patient Safety , Prolactin/blood , Prospective Studies , Renal Dialysis/methods , Treatment Outcome , Urea/blood , beta 2-Microglobulin/bloodABSTRACT
BACKGROUND: This study aimed to identify differentially expressed proteins in the serum of advanced non-small cell lung cancer (NSCLC) patients responding to carboplatin (CAR) plus paclitaxel (PTX) chemotherapy compared to non-responders. MATERIALS AND METHODS: Serum from 8 responders and 6 non-responders was subjected to proteomic analysis by label-free liquid chromatography tandem mass spectrometry and validated by western blotting. CAR/PTX-resistant human H1792 and A549 cells were used for evaluating gene expression. RESULTS: Fifty-two proteins were differentially expressed between responders and non-responders. Alpha 1 antitrypsin antibody, alpha 1 acid glycoprotein (A1AG1), afamin, protein S100-A9 and immunoglobulin heavy constant gamma 3 (IGHG3) were validated. IGHG3 was elevated (p=0.037) while A1AG1 was reduced (p=0.003) in responders as compared to non-responders. Gene expression of IGHG3 and ORM1 in resistant cells showed consistent results with the proteomics profiles. CONCLUSION: Serum expression levels of IGHG3 and A1AG1 proteins may be useful to recruit an NSCLC subpopulation that can benefit from CAR plus PTX standard therapy.