Plasma Retinol Binding Protein 4 as a Biomarker for Detecting Progressive Stroke and Prediction of Early Prognosis in Patients with Acute Ischemic Stroke

Aim and purpose: Progressive stroke (PS) lacks effective treatment measures and leads to serious disability or death. Retinol binding protein 4 (RBP4) could be closely associated with acute ischemic stroke(AIS). We aimed to explore plasma RBP4 as a biomarker for detecting the progression in patients with AIS. Methods: Participants of this retrospective study were 234 patients with AIS within the 48 h onset of disease. The primary endpoint was to ascertain if there was PS through the National Institute of Health stroke scale (NIHSS), early prognosis was confirmed through the modified Rankin scale score (mRS) at discharge or 14 days after the onset of stroke, and determine the significance of demographic characteristics and clinical data . Results: In this study, 43 of 234 patients demonstrated PS. . The level of plasma RBP4 in patients with progressive stroke was significantly lower (29 mg/L, 22.60－40.38 mg/L) than that without progression (38.70 mg/L, 27.28－46.40 mg/L, P = 0.003). In patients with lower plasma RBP4, he proportion of patients with progression (c2 = 9.63, P = 0.008) and with mRS scores ≥2 (c2 = 6.73, P = 0.035) were significantly higher Multivariate logistic regression analysis showed that a lower RBP4 level on admission was an independent risk factor for progressive stroke during hospitalization with an OR value of 2.70 (P = 0.03, 95% CI: 1.12－6.52). Conclusion: A low plasma RBP4 level on admission could be an independent risk factor of PS during hospitalization.

Metabolomic Profiles of Plasma Retinol-Associated Dyslipidemia in Men and Women

Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population.Methods: We included 250 participants aged 20–80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex.Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status.Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).

Does the Amount of Stable Isotope Dose Influence Retinol Kinetic Responses and Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method in Theoretical Children and Adults?

Background To minimize both cost and perturbations to the vitamin A system, investigators limit the amount of stable isotope administered when estimating vitamin A total body stores (TBS) by retinol isotope dilution (RID). Objectives We hypothesized that reasonable increases in the mass of stable isotope administered to theoretical subjects would have only transient impacts on vitamin A kinetics and minimal effects on RID-predicted TBS. Methods We adapted previously-used theoretical subjects (3 children, 3 adults) with low, moderate, or high assigned TBS and applied compartmental analysis to solve a steady state model for tracer and tracee using assigned values for retinol kinetic parameters and plasma retinol. To follow retinol trafficking when increasing amounts of stable isotope were administered [1.39-7 (children) and 2.8-14 µmol retinol (adults)], we added assumptions to an established compartmental model so that plasma retinol homeostasis was maintained. Using model-simulated data, we plotted retinol kinetics versus time and applied the RID equation TBS = FaS/SAp [Fa, fraction of dose in stores; S, retinol specific activity (SA) in plasma/SA in stores; SAp, SA in plasma] to calculate vitamin A stores. Results The model predicted that increasing the stable isotope dose caused transient early increases in hepatocyte total retinol; increases in plasma tracer were accompanied by decreases in tracee to maintain plasma retinol homeostasis. Despite changes in kinetic responses, RID accurately predicted assigned TBS (98-105%) at all loads for all theoretical subjects from 1-28 d postdosing. Conclusions Results indicate that, compared with doses of 1.4–3.5 µmol used in recent RID field studies, doubling the stable isotope dose should not affect accuracy of TBS predictions, thus allowing for experiments of longer duration when including a super-subject design (Ford et al., J Nutr 2020;150:411–8) and/or studying retinol kinetics.

Synthesis, X-Ray Structure, Hirshfeld Surface Analysis, DFT Calculations, and Molecular Docking Studies of Nickel(II) Complex with Thiosemicarbazone Derivative

This article presents both experimental and computational study of a new Ni(II) complex, namely, bis{2-(2-trifluoromethylbenzylidene)hydrazine-1-carbothioamido-κ2N2, S}nickel(II) (abbreviate as NiL2). The complex was synthesized and well characterized using various spectroscopic methods. The single X-ray crystallographic study revealed a distorted square planar geometry around Ni(II) metal ion centre in which the angles deviated from ideal 90° with a maximum value of 6.57° occupied by nitrogen and sulphur donor atoms. The theoretical bond lengths and angles for the NiL2 complex were obtained by using the B3LYP level of density function theory (DFT) with LANL2DZ/6-311G (d, p) basis sets. These results showed very good agreement with the experimental X-ray values. The electrophilicity index (ω = 50.233 eV) shows that the NiL2 complex is a very strong electrophile. In addition, strong F⋯H/H⋯F interactions with 28.5% of the total Hirshfeld surface analyses in NiL2 were obtained indicating that the complex could bind with protein effectively. Furthermore, the new NiL2 complex was docked with plasma retinol-binding protein 4 (RBP4) (PDB id: 5NU7), which implied that the NiL2 complex bound to Tyrosine 133 and Aspartate 102 amino acids via N-H intermolecular hydrogen bonds.

Retinol-binding protein, retinol, and modified-relative-dose response in Ugandan children aged 12–23 months and their non-pregnant caregivers

Retinol-binding protein (RBP), retinol, and modified-relative-dose response (MRDR) are used to assess vitamin A status. We describe vitamin A status in Ugandan children and women using dried blood spot (DBS) RBP, serum RBP, plasma retinol, and MRDR and compare DBS-RBP, serum RBP, and plasma retinol. Blood was collected from 39 children aged 12–23 months and 28 non-pregnant mothers aged 15–49 years as a subsample from a survey in Amuria district, Uganda, in 2016. DBS RBP was assessed using a commercial enzyme immunoassay kit, serum RBP using an in-house sandwich enzyme-linked immunosorbent assay, and plasma retinol/MRDR test using high-performance liquid chromatography. We examined (a) median concentration or value (Q1, Q3); (b) R2 between DBS-RBP, serum RBP, and plasma retinol; and (c) Bland-Altman plots. Median (Q1, Q3) for children and mothers, respectively, were as follows: DBS-RBP 1.15 µmol/L (0.97, 1.42) and 1.73 (1.52, 1.96), serum RBP 0.95 µmol/L (0.78, 1.18) and 1.47 µmol/L (1.30, 1.79), plasma retinol 0.82 µmol/L (0.67, 0.99) and 1.33 µmol/L (1.22, 1.58), and MRDR 0.025 (0.014, 0.042) and 0.014 (0.009, 0.019). DBS RBP-serum RBP R2 was 0.09 for both children and mothers. The mean biases were −0.19 µmol/L (95% limits of agreement [LOA] 0.62, −0.99) for children and −0.01 µmol/L (95% LOA −1.11, −1.31) for mothers. DBS RBP-plasma retinol R2 was 0.11 for children and 0.13 for mothers. Mean biases were 0.33 µmol/L (95% LOA −0.37, 1.03) for children, and 0.29 µmol/L (95% LOA −0.69, 1.27) for mothers. Serum RBP-plasma retinol R2 was 0.75 for children and 0.55 for mothers, with mean biases of 0.13 µmol/L (95% LOA −0.23, 0.49) for children and 0.18 µmol/L (95% LOA −0.61, 0.96) for mothers. Results varied by indicator and matrix. The serum RBP-retinol R2 for children was moderate (0.75), but poor for other comparisons. Understanding the relationships among vitamin A indicators across contexts and population groups is needed.

Distribution of injected fat-soluble vitamins in plasma and tissues of nursery pigs

Objective: The objective of this experiment was to investigate the effects of fat-soluble vitamin injection on plasma and tissue vitamin status in nursery pigs.Methods: A total of 16 pigs (initial body weight: 7.15±1.1 kg) were allotted to 2 treatments at d 7 post-weaning. Pigs were fed a corn-soybean meal-based basal diet with no supplemental vitamin A and i.m. injected with 300,000 IU of retinyl palmitate, 900 IU of d-α-tocopherol and 30,000 IU of vitamin D₃ with control pigs having no vitamin injection. Blood (d 0, 3, 7, and 14 post-injection) and tissue samples (liver, brain, heart, lung, and muscle; d 7 and 14 post-injection) were collected from pigs. Retinyl palmitate, retinol, and α-tocopherol concentrations were analyzed in plasma and tissues, while plasma was assayed for 25-hydroxycholecalciferol (25-OHD₃).Results: Plasma retinol and 25-OHD₃ concentrations increased by the vitamin injection from d 3 to 14 post-injection (p<0.05) whereas plasma retinyl palmitate was detected only in the vitamin treatment at d 3 and 7 post-injection (115.51 and 4.97 μg/mL, respectively). Liver retinol, retinyl palmitate, and retinol+retinyl palmitate concentrations increased by retinyl palmitate injection at d 7 and 14 post-injection (p<0.05) whereas those were not detected in the other tissues. The d-α-tocopherol injection increased α-tocopherol concentrations in plasma at d 3 and 7 post-injection (p<0.05) and in liver, heart (p<0.10), and muscle (p<0.05) at d 7 post-injection.Conclusion: Fat-soluble vitamin injection increased plasma status of α-tocopherol, retinol, retinyl palmitate and 25-OHD₃. As plasma levels decreased post-injection, vitamin A level in liver and vitamin E level in muscle, heart and liver increased. The α-tocopherol found in plasma after injection was distributed to various tissues but retinyl palmitate only to the liver.

Changes in Retinol Binding Protein 4 Level in Undernourished Children After a Nutrition Intervention Are Positively Associated With Mother’s Weight but Negatively With Mother’s Height, Intake of Whole Milk, and Markers of Systemic Inflammation: Results From a Community-Based Intervention Study

Background: The changes of plasma retinol binding protein 4 (RBP4) level after a nutrition intervention can indicate the metabolic changes associated with the delivered intervention. Objective: We investigated the changes in plasma RBP4 level among 12- to 18-month-old children after a nutrition intervention and measured its association with subcutaneous adiposity, maternal characteristics, and inflammation. Methods: Data of 520 undernourished children (250 of them had length-for-age Z score [LAZ] <−1 to −2 and 270 had LAZ score <−2) were collected from the Bangladesh Environmental Enteric Dysfunction study conducted in Dhaka, Bangladesh. Multivariable linear regression and generalized estimation equations (GEE) modeling techniques were used to measure the association. Results: At baseline, median RBP4 level was 19.9 mg/L (interquartile range [IQR]: 7.96), and at the end of the intervention, it was 20.6 mg/L (IQR: 9.06). Percentage changes in plasma RBP4 level were not significantly associated ( P > .05) with the percentage changes in child’s height, weight, and subcutaneous adiposity. But maternal height (regression coefficient, β = −1.62, P = .002) and milk intake (β = −0.05, P = .01) were negatively and maternal weight was positively associated (β = 0.56, P = .03) with the changes in RBP4 levels. The GEE models revealed negative association of RBP4 levels with C-reactive protein (CRP; β = −0.14, P < .05) and α-1-acid glycoprotein (AGP; β = −0.03, P < .05). Conclusion: Children, whose mothers were taller, experienced less increase in plasma RBP4 level and, children, whose mother had a higher weight, experienced more increase in the RBP4 level from baseline. We have also found that CRP and AGP levels and intake of whole milk were negatively associated with the plasma RBP4 level.

Nutritional Status Among School-Age Children of Bangladeshi Tea Garden Workers

Background: While considerable progress has been made in reducing undernutrition in Bangladesh, regional disparities are known to exist, and certain population subgroups may lag behind. Objective: To characterize nutritional status among school-age children in a historically marginalized population of Bangladesh. Methods: We conducted a cross-sectional assessment of children attending 14 nongovernmental organization-operated schools serving the tea estate population in Kulaura Upazila, Sylhet Division. We randomly selected 168 children from a population of 418 whose parents attended school-organized Parent–Teacher Association meetings. Parents provided consent and data on household food consumption in the past week, foods consumed by children in the past 24 hours, and household food insecurity. We drew venous blood from assenting children for the analysis of hemoglobin and plasma retinol, C-reactive protein, and α1-acid glycoprotein. Children were classified as stunted, underweight, or thin based on comparisons with the World Health Organization standards for height-for-age, weight-for-age, or body mass index-for-age, respectively. Results: Food insecurity was highly prevalent, with ∼85% of households affected. Roughly half of children had low dietary diversity. Prevalence estimates for stunting, underweight, and thinness were 32%, 50%, and 49%, respectively. Approximately 60% of children had a hemoglobin concentration <11 g/dL. The mean (±SD) plasma retinol concentration was 0.79 μmol/L (±0.23 μmol/L), with 34% deficient using a 0.70 μmol/L cutoff. Conclusions: A heightened focus on tracking progress in underserved populations and appropriately targeted programming will be critical as Bangladesh seeks to accelerate progress toward global development goals for nutrition.

Impact of Gastric Sleeve Surgery on Plasma Retinol Binding Protein 4 and Adipsin Levels in Healthy Male Population

Objectives: Bariatric surgery provides most substantial and sustainable weight loss measures in individuals with obesity. Caloric restriction is not only intervention, changes in hormonal secretions are also leading contributory mechanisms to reduce body weight and improve the glycaemic control. The aim of this study was to evaluate the impact of gastric sleeve surgery on plasma retinol binding protein 4 (RBP4) and adipsin levels among Saudi male obese population. Methods: This prospective study was conducted in the Departments of Physiology and Surgery, College of Medicine, King Saud University. Thirty-three obese (BMI>38.3) male patients age ranged from 25 to 50 years were recruited. RBP4 and adipsin levels were analyzed before and 6-12 months after gastric sleeve surgery by ELISA along with plasma glucose, insulin, HOMA-IR and lipid profile. Results: Circulating RBP4 levels were not significantly changed by bariatric surgery (4382.85±40.35 ng before, and 4393.28±33.13 ng after surgery, p=0.842), neither did adipsin (2949.68±46.86 pg before, and 2917.90±41.90 pg after surgery, p=0.535). Segregation of study participants into two age groups, 25-35 and 35-50 years of age, revealed that before surgery older age group (35-50) had higher RBP4 levels compared to younger group (25-35) (p=0.016). However, after surgery RBP4 levels were decreased in older group but not to a significant level (p=0.174). In younger age group after surgery, there was a near significant increase in RBP4 levels (p=0.052). There were no significant changes in RBP4 levels in both age groups after surgery (p=0.461). For adipsin, there were no significant differences before and after surgery in both age groups. Insulin, BMI and HOMA-IR index were decreased after surgery, however there was no correlation with RBP4 and adipsin levels. Conclusions: The present study findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in Saudi male obese population after gastric sleeve surgery. However, a decrease in RBP4 levels in older individuals after surgery needs further investigations to understand its effect on weight and glycemic control. doi: https://doi.org/10.12669/pjms.36.7.2329 How to cite this:Alshubrami S, Al-Regaiey K, Alfadda AA, Iqbal M. Impact of Gastric Sleeve Surgery on Plasma Retinol Binding Protein 4 and Adipsin Levels in Healthy Male Population. Pak J Med Sci. 2020;36(7):---------. doi: https://doi.org/10.12669/pjms.36.7.2329 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.