Retinol-binding Protein Research Articles

Role of specific nutritional biomarkers in predicting post-operative complications among patients undergoing elective abdominal surgery.

Nutritional biomarkers like serum prealbumin, transferrin, retinol-binding protein (RBP), C-reactive protein (CRP), leptin, and insulin-like growth factor 1 (IGF1) have the inherent ability to diagnose undernutrition objectively before it is clinically manifested. The primary objective of the study was to evaluate the diagnostic efficacy of the specific nutritional biomarkers in predicting post-operative complications. A prospective cohort study was conducted in the department of surgery and included all patients aged 18 years and above who underwent elective abdominal surgery. Demographic details and clinical and surgical details were documented from the case records. Nutritional biomarker assay was done at admission. The post-operative complications occurring until discharge were graded using the Clavien-Dindo classification. The diagnostic accuracy of the specific nutritional biomarkers in predicting post-operative complications was assessed. A total of 320 patients were included in the study. Of these, 126 (39.38%) developed post-operative complications. Major complications accounted for 19.05% of the complications, while 80.95% were minor complications. Patients with blood prealbumin level less than 17.287 mg/dL had a higher incidence of complications (p < 0.001). Serum transferrin levels less than 168.04 mg/dL and IGF1 levels less than < 44.51 ng/ml showed increased incidence of complications (p < 0.001). The AUC was found to be the highest for serum IGF1 with 0.7782. Sensitivity was equally high for IGF1 and serum transferrin, with 76.98% for the former and 76.19% for the latter. Specific nutritional biomarkers, like serum prealbumin and transferrin, were efficient in predicting postoperative complications of patients before undergoing elective abdominal surgeries even after adjusting for confounders. This can facilitate preoperative corrective measures to lower the overall postoperative complications.

Assessment of Circulating Retinol Binding Protein-4 Levels in Patients with Compound Heterozygosity for Hb S and β-Thalassemia

Background: Retinol Binding Protein-4 (RBP-4) is a member of the lipocalin family of proteins and the major transport protein of the hydrophobic molecule retinol, also known as vitamin A, in the circulation. Expression of RBP4 is highest in the liver, where most of the body's vitamin A reserves are stored as retinyl esters. For the mobilization of vitamin A from the liver, retinyl esters are hydrolyzed to retinol, which then binds to RBP-4 in the hepatocyte. After associating with transthyretin (TTR), the retinol/RBP-4/TTR complex is released into the bloodstream and delivers retinol to tissues via binding to specific membrane receptors. While, after its dissociation from TTR and retinol release, retinol-free apo-RBP4 in the circulation is filtrated by the kidney. More than 99% of that is reabsorbed by the proximal renal tubule, which renders urinary RBP-4 a highly sensitive marker for tubular dysfunction. We and other have shown previously that the patients with Sickle Cell Disease (SCD) have deficiencies or suboptimal levels of vitamin A, while recently (Br J Haematol. 2023;doi:10.1111/bjh.18862) higher urine RBP-4 in patients with SCD especially in those with persistent albuminuria but without an association of urine RBP-4 levels with estimated glomerular filtration rate (eGFR). In this context, we aimed to investigate the potential clinical significance of circulating plasma RBP-4 levels and its association with disease features in Caucasian patients with compound heterozygosity for HbS and β-thalassemia (HbS/β thal). Patients and Methods: Ninety Caucasian adult patients with HbS/β thal at steady phase were included in the study, while 22 apparently healthy individuals of similar age and gender served as controls. None of the patients was diabetic and has received any transfusions at least 6-monthes before enrollment in the study. RBP-4 concentration was measured with an immunoturbidimetric assay applied in an automated chemistry analyzer, along with hematologic, and series of blood chemistry parameters reflecting renal, cardiac and endothelial dysfunction. eGFR values were calculated using the CKD-EPI (Cystatin C and/or Creatinine equations). Results: We found that: a) Plasma RBP-4 levels were significantly lower in patients with HbS/β thal compared to controls, 30.5±2.7mg/L (Confidence Intervals (CI): 28.8;32.2mg/mL) vs 36.3±3.6mg/L (CI: 32.7;39.9mg/mL), p&amp;lt;0.003. The patients with β + genotypehave higher RBP-4 levels than those with β 0 genotype (p&amp;lt;0.05), whereas patients treated with hydroxycarbamide(50/90) are more likely to express higher RBP-4 levels, p-trend=0.06; b) RBP-4 levels in patients with HbS/β thal correlated positively with their age, body mass index (BMI) and Hb levels (r=0.264, p=0.012; r=0.334, p=0.001 and r=0.209, p&amp;lt;0.05, respectively; c) RBP-4 levels in patients with HbS/β thal correlated with total bilirubin, total cholesterol, triglycerides and uric acid (r=-0.452, p&amp;lt;0.001; r=0.395, p=0.004; r=0.292, p=0.015 and r=0.435, p&amp;lt;0.001, respectively); d) RBP-4 levels in patients with HbS/β thal correlated negatively with eGFR values rho=-0.360, p=0.003 and hs-CRP concentrations r=-0.309, p=0.004 and e) No correlations were found between RBP-4 levels with markers of cardiac and endothelial dysfunction such as High Sensitivity Troponin T, Growth Differentiation Factor-15, von Willebrand factor antigen, Α Disintegrin and Metalloproteinase with Thrombospondin Type 1 Motif 13 antigen and P-Selectin, as well as with number of vaso-occlusive crisis and mean pulmonary arterial pressure in the patients. Conclusions: These findings demonstrate a multifactorial role of RBP-4 in patients with HbS/β thal as the circulating levels of the protein correlate significantly with markers of erythropoiesis, inflammation and renal function. It is unclear of this study if RBP-4 has any specific functions in patients with HbS/β thal. However, RBP-4 should be more investigated in order to determine its clinical significance and in the case of sickle cell nephropathy both plasma and urine measurements should be considered.

Extended Nutritional Monitoring in Patients Undergoing Intensive Chemotherapy for Acute Myeloid Leukemia

Background Fit patients (pts) with acute myeloid leukemia (AML) are conventionally administered repeated cycles of intensive chemotherapy, often followed by allogeneic hematopoietic stem cell transplant. AML pts need to be long hospitalized in a protected setting, they are often prescribed a neutropenic diet and chemotherapy-induced gastro-intestinal toxicity is common. As a result, malnutrition is frequently observed, it sensibly reduces the quality of life and has the potential to undermine eligibility for intensive treatment, increase treatment-related toxicity, and ultimately reduce survival. Aims Aim of this study was to systematically assess the nutritional status of fit pts undergoing treatment for AML and to explore early predictors and associations with known nutritional risk scores and relevant clinical outcomes. Methods Nutritional Risk Screening 2002 (NRS) score was calculated for each patient at time of diagnosis (a score of 3 or more is considered high). Then, nutritional monitoring included standard anthropometric measurements (body weight, BW; body mass index, BMI) and a bioelectrical impedance analysis (BIA) performed by a registered dietitian to assess fat-free mass, body cell mass (BCM, the metabolically active component of body mass), fat mass and the phase angle. Variations in nutritional parameters between admission and day 7 (end of CHT, called “dif7”) or between admission and day 14 (called “dif14”) were calculated and tested for correlation with variations of the same parameter at discharge from the same cycle (called “dif30”) or at discharge after the first consolidation (called “dif60”). Results Up to now, 26 pts with newly diagnosed AML (median age 55y, range 21-74) were prospectively monitored during a total of 61 cycles of intensive chemotherapy (35 induction cycles, 26 consolidation cycles). Median NRS score at enrolment was 3 (range 2-6). Median follow up for surviving pts is 300 days. We observed a significant reduction in fat-free mass and body cell mass during induction cycles. Similar trends, although not significant, were observed for consolidation cycles as well. These trends were observed irrespectively of baseline NRS, disease response, or whether admission was complicated by a fever lasting more or less than 7 days. A high NRS score was only associated with a greater fat mass loss between diagnosis and discharge after first consolidation (FM dif60), but the score failed to predict any meaningful nutritional parameter variation. For fat-free mass, body cell mass and the phase angle (but not for BW or BMI), dif7 correlated with dif30 for induction and consolidation cycles. For body cell mass and the phase angle, both dif7 and dif14 also correlated with dif60. Only variations in body cell mass at day 7 (BCM dif7) correlated with cumulative weight loss at discharge after the first consolidation cycle (BW dif60). Reduction in BW, BMI and fat mass at day 7, and of phase angle at day 14, were associated with extended length of stay for consolidation chemotherapy cycles only. Conclusions In this study, pts intensively treated for AML suffered a significant reduction in the metabolically active component of body mass during admission for induction chemotherapy and, cumulatively, during the first two treatment cycles. Bioelectrical impedance analysis performed as early as seven days from admission could already reveal the first signals of nutritional deterioration: body cell mass loss between day 0 and day 7 correlated with both cumulative body cell mass loss and cumulative body weight loss after two cycles of chemotherapy. Notably, a commonly used nutritional risk screening tool failed to predict the risk of malnutrition in our cohort of patients. “NUTRIAMO” is a prospective, observational trial currently starting at our institution, where pts intensively treated for AML are monitored via known nutritional assessment tools, new biochemical markers (e.g., prealbumin and retinol-binding protein) and microbiome analysis and variations. Our aim is to find more sensitive nutritional triggers to activate earlier and more effective support measures (e.g., oral nutritional supplements, diet variations, psychological support) and ultimately improve AML patients' quality of life and survival beyond the cure of their disease.

Increased RBP4 and Asprosin Are Novel Contributors in Inflammation Process of Periodontitis in Obese Rats.

There is a significant comorbidity between obesity and periodontitis, while adipokines are pivotal in the immunoinflammatory process, which may play a role in this special relationship. We aimed to assess the effect of adipokines as mediators in the progression of periodontitis in obese Sprague Dawley rats. Rats were divided into four groups: normal body weight with and without periodontitis and obesity with and without periodontitis. Experimental obesity and periodontitis were induced by a high-fat diet or ligaturing, and the effect was measured using metabolic and micro-computed tomography analysis and histological staining. Compared with the other three groups, the group of periodontitis with obesity (OP) had the heaviest alveolar bone absorption, the largest increase in osteoclasts, the utmost inflammatory cell infiltration and the highest expressions of pro-inflammatory cytokines and nuclear factor-kappa B ligand (RANKL); meanwhile, its expression of the osteogenesis-related gene was the lowest among the four groups. The expressions of leptin, visfatin, resistin, retinol-binding protein 4 (RBP4) and asprosin were upregulated, while adiponectin was decreased significantly in OP. The strong positive associations between the periodontal or circulating levels of RBP4 (or asprosin) and the degree of alveolar resorption in experimental periodontitis and obese rats were revealed. The upregulated expression of inflammation biomarkers, the corresponding degradation in connective tissue and the generation of osteoclasts in periodontitis were activated and exacerbated in obesity. The elevated level of RBP4/asprosin may contribute to a more severe periodontal inflammatory state in obese rats.

PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice.

Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as "forever chemicals" due to their ubiquitous contamination and their persistence in the environment, wildlife, and humans. Numerous studies have demonstrated that PFAS exposure adversely affects multiple bodily functions, including liver metabolism and gonadal function. It is unclear, however, how the disruption of hepatic fatty acid metabolism affects testicular function. In this study, male mice were administered 0.3 and 3 μg/g body weight of PFOS for 21 days. Our data showed that PFOS exposure caused hepatic steatosis, as evidenced by significant increases in triglyceride levels, expression of ATP-citrate lyase, and fatty acid synthase, as well as fasting insulin levels. PFOS perturbed the expression levels of hepatokines, of which fibroblast growth factor-21 (Fgf-21), leukocyte cell-derived chemotaxin-2 (Lect-2), and retinol-binding protein-4 (Rbp-4) were significantly reduced, whereas angiopoietin-like 4 (Angptl4) was noticeably increased. While Rbp-4 and Fgf-21 are known to contribute to spermatogenesis and testosterone synthesis. In PFOS-exposed groups, testicular ATP, and testosterone decreased significantly with a significant increase in the expression of peroxisome proliferator-activated receptor-coactivator 1α. Mass spectrophotometry imaging revealed the localization of PFOS in testes, along with significant increases in fatty acid metabolites. These included arachidonic acid, dihomo-α-linolenic acid, dihomo-γ-linolenic acid, oxidized ceramide, diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, which are associated with inflammation and post-testicular causes of infertility. This study revealed potential links between PFOS-elicited changes in hepatic metabolism and their impacts on testicular biology. This study provides insights into alternative targets elicited by PFOS that can be used to develop diagnostic and therapeutic strategies for improving testicular dysfunction.

Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach.

Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach. Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers. Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only. MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.

A comparative study on indicators of vitamin A status and risk factors for sensitivity and specificity of the methods to detect vitamin A deficiency

BackgroundSerum retinol (SR) and retinol-binding protein (RBP) are commonly used indicators, but they are affected by infections and inflammation. This study aimed to assess the sensitivity and specificity of VA indicators to detect vitamin A deficiency (VAD) in 36–59-month-old children living in a rural area in Burkina Faso.MethodsIn a community-based study, two cross-sectional surveys were carried out from November 2016 to September 2017 in the health district of Dandé in Burkina Faso. The surveys included 115 children 36–59 months old. Indicators of VA and inflammation assessed in all children included SR, RBP and total liver VA reserves (TLR) estimated by retinol isotope dilution, and inflammation markers (C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP)). We calculated the sensitivity, specificity, positive and negative predictive values. In addition, the effects of inflammation, helminth infection, and season on sensitivity and specificity were assessed.ResultsThe prevalence of VAD assessed by SR (< 0.7 µmol/L), RBP (< 0.7 µmol/L), and TLR (< 0.1 µmol/g liver) were, respectively, 30.9%, 33.3%, and 0%. Compared to TLR, the specificity, positive predictive value, and negative predictive value of SR were 71.1%, 0%, and 100%, and of RBP, were 68.9%, 0%, and 100%, respectively. The sensitivity was indeterminable for SR and RBP. The specificity of SR and RBP was lower during the dry season. Elevated CRP (> 5.0 mg/L) and AGP (> 1.0 g/L) were detected in 1.9% and 28.6% of children, respectively. The adjustment of VA indicators for inflammation improved SR’s specificity to 75.9% and decreased RBP’s specificity to 67.8%.ConclusionNo cases of VAD were identified by TLR. However, (inflammation-adjusted) SR and RBP had varying accuracy in the estimation of VAD.Trial registrationThe study was registered, retrospectively, on 22 March 2018 as a clinical trial with the Pan African Clinical Trials Registry under the number Cochrane South Africa; PACTR201803002999356.

RETRACTED: Analysis of the association between serum levels of 25(OH)D, retinol binding protein, and Cyclooxygenase-2 and the disease severity in patients with diabetic foot ulcers.

Diabetic foot ulcers (DFUs) pose significant clinical challenges, representing severe complications in diabetes mellitus patients and contributing to non-traumatic amputations. Identifying reliable biomarkers can optimize early diagnosis and improve therapeutic outcomes. This study focused on evaluating the association between serum levels of 25-hydroxyvitamin D [25-(OH)D], Serum Retinol Binding Protein (RBP), and Cyclooxygenase-2 (COX-2) in elderly DFU patients. A retrospective study involving 240 participants, from March 2020 to March 2023. The participants were segmented into three cohorts: 80 with DFUs, 80 diabetic patients without DFUs, and 80 healthy controls. Serum concentrations of the three biomarkers were assayed using methods like enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and an automated biochemistry analyser. Comparisons were made both between groups and within the DFU group based on disease severity. Statistical analysis revealed significant differences in biomarker levels across the groups (p < 0.05). COX-2 and RBP concentrations were highest in the DFU group, followed by the non-DFU diabetic group, and lowest in the control group. Conversely, 25(OH)D levels were highest in the control group, followed by the non-DFU diabetic group, and lowest in the DFU group. Within the DFU group, RBP and COX-2 levels increased with disease severity, while 25(OH)D levels decreased. These variations were especially pronounced in patients with the most severe Wagner grading. A significant positive correlation was observed between disease severity and levels of RBP (r = 0.651, p < 0.05) and COX-2 (r = 0.356, p < 0.05). Conversely, a significant negative correlation was identified between disease severity and 25(OH)D levels (r = -0.658, p < 0.05). Assessing 25(OH)D, RBP, and COX-2 serum levels offers a promising tool for evaluating the severity and progression of DFUs. Monitoring these biomarkers can enrich our understanding of the metabolic and inflammatory pathways of the disease and potentially refine therapeutic strategies.

Experimental study on the therapeutic effect and mechanism of erlotinib on non-proliferative diabetic retinopathy

Experimental study on the therapeutic effect and mechanism of erlotinib on non-proliferative diabetic retinopathy

Regulation of circulating thyroid hormone levels by hypothalamic tanycytes and hypophysial pars tuberalis-specific cells and their morphological and gene- and protein-expression changes under different photoperiods.

Thyroid hormone in the hypothalamus acts as a key determinant of seasonal transitions. Thyroid hormone-levels in the brain are mainly regulated by the hypothalamic tanycytes and pituitary pars tuberalis (PT)-specific cells. TSHβ produced by the PT-specific cells stimulates Dio2 expression and decreases Dio3 expression of the tanycytes. Both tanycytes and PT-specific cells in photosensitive animals exhibit remarkable changes of morphological appearance and expressions of genes and proteins under different photoperiods. Long photoperiods induce increased gene- and protein-expressions and active features. Short photoperiods cause the decreased gene- and protein-expressions and inactive features. In the PT, expressions of TSHβ, common α-subunit of glycoprotein hormones (α-GSU), and MT1 receptor of melatonin receptors and eyes absent 3 change under different photoperiods. Diurnal rhythms of α-GSU mRNA expression are observed in the PT of Djungarian hamsters. Hes1, Nkx2.1, and LIM homeodomain gene 2 (Lhx2) are involved in the differentiation of PT. In the hypothalamic tanycytes, expressions of Dio2, Dio3, vimentin, serine/threonine kinase 33, GPR50, Nestin, Retinoid signaling genes (retinaldehyde dehydrogenase 1, cellular retinol binding protein 1, and Stra6), monocarboxylate transporter 8, and neural cell adhesion molecule change under different photoperiods. Rax, Lhx2, Nfia/b/x, and fibroblast growth factor 10 are involved in the differentiation of tanycytes.

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment

BackgroundSeveral studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. ObjectiveTo determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). MethodsIn this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. ResultsThe serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. ConclusionsOur study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

An in vitro model for vitamin A transport across the human blood–brain barrier

Vitamin A, supplied by the diet, is critical for brain health, but little is known about its delivery across the blood–brain barrier (BBB). Brain microvascular endothelial-like cells (BMECs) differentiated from human-derived induced pluripotent stem cells (iPSCs) form a tight barrier that recapitulates many of the properties of the human BBB. We paired iPSC-derived BMECs with recombinant vitamin A serum transport proteins, retinol-binding protein (RBP), and transthyretin (TTR), to create an in vitro model for the study of vitamin A (retinol) delivery across the human BBB. iPSC-derived BMECs display a strong barrier phenotype, express key vitamin A metabolism markers, and can be used for quantitative modeling of retinol accumulation and permeation. Manipulation of retinol, RBP, and TTR concentrations, and the use of mutant RBP and TTR, yielded novel insights into the patterns of retinol accumulation in, and permeation across, the BBB. The results described herein provide a platform for deeper exploration of the regulatory mechanisms of retinol trafficking to the human brain.

An in vitro model for vitamin A transport across the human blood-brain barrier.

Vitamin A, supplied by the diet, is critical for brain health, but little is known about its delivery across the blood-brain barrier (BBB). Brain microvascular endothelial-like cells (BMECs) differentiated from human-derived induced pluripotent stem cells (iPSCs) form a tight barrier that recapitulates many of the properties of the human BBB. We paired iPSC-derived BMECs with recombinant vitamin A serum transport proteins, retinol-binding protein (RBP), and transthyretin (TTR), to create an in vitro model for the study of vitamin A (retinol) delivery across the human BBB. iPSC-derived BMECs display a strong barrier phenotype, express key vitamin A metabolism markers, and can be used for quantitative modeling of retinol accumulation and permeation. Manipulation of retinol, RBP, and TTR concentrations, and the use of mutant RBP and TTR, yielded novel insights into the patterns of retinol accumulation in, and permeation across, the BBB. The results described herein provide a platform for deeper exploration of the regulatory mechanisms of retinol trafficking to the human brain.

Adipokines and Their Role in Heart Failure: A Literature Review.

Obesity is a major risk factor for heart failure (HF). The relationship between adipokines and HF has been implicated in many previous studies and reviews. However, this review article summarizes the basic role of major adipokines, such as apelin, adiponectin, chemerin, resistin, retinol-binding protein 4 (RBP4), vaspin, visfatin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, nesfatin-1, progranulin, leptin, omentin-1, lipocalin-2, and follistatin-like 1 (FSTL1), in the pathogenesis of HF. Apelin is reduced in patients with HF and upregulated following favorable left ventricular (LV) remodeling. Higher levels of adiponectin have been found in patients with HF compared to in control patients. Also, high plasma chemerin levels are linked to a higher risk of HF. Serum resistin is related to the severity of HF and associated with a high risk for adverse cardiac events. Evidence indicates that RBP4 can contribute to inflammation and damage heart muscle cells, potentially leading to HF. Vaspin might stop the progression of cardiac degeneration, fibrosis, and HF according to experiments on rats with experimental isoproterenol-induced chronic HF. The serum concentrations of visfatin are significantly lower in patients with systolic HF. Leptin levels were found to be correlated with low LV mass and myocardial stiffness, both of which are significant risk factors for the development of HF with preserved ejection fraction (HFpEF). Measuring serum omentin-1 levels appears to be a novel prognostic indicator for risk stratification in HF patients. Increased expression of neutrophil gelatinase-associated lipocalin in both systemic circulation and myocardium in clinical and experimental HF suggests that innate immune responses may contribute to the development of HF. FSTL1 was elevated in patients with HF with reduced ejection fraction and associated with an increase in the size of the left ventricle of the heart. However, other adipokines, such as plasminogen activator inhibitor-1, monocyte chemotactic protein-1, nesfatin-1, and progranulin, have not yet been studied for HF.

290 Vitamin A and Beta-Carotene Supplementation on Growth Performance, Immune System, and Mammary Gland Development in Finishing Pigs

Abstract A total of 224 finishing pigs were randomly assigned to split-sex pens (n = 4 pigs per pen). Each pen was assigned to one of four diets: control (7,656 IU vitamin A/kg), control diet supplemented with vitamin A (4.36 ppm; Rovimix A 1000, DSM, NJ, US), control diet supplemented with beta-carotene (163.28 ppm; Rovimix β-Carotene 10%, DSM, NJ, US), or control supplemented with oxidized beta-carotene (40 ppm; 10% active ingredient, Avivagen, Ottawa, ON, Canada). Pigs and feeder weights were recorded at the start of the study (d 0) and end of each phase (days 21, 42, and 63). A subset of gilts was randomly selected and a blood sample for vitamin A (retinol) analysis was collected on days 0, 18, 39, 60, and 63. The same gilts were vaccinated against Lawsonia intracellularis and porcine circovirus. Antibodies against each vaccination were measured on days 18, 39, and 60. At the end of the study, the subset of gilts was euthanized to obtain a liver sample for vitamin A (retinyl palmitate is converted to retinol for measurement) analysis and a jejunum sample to measure the mRNA abundance of genes involved in vitamin A metabolism (alcohol dehydrogenase class 1, lecithin retinol acyltransferase phosphatidylcholine-retinol O-acyltransferase, retinol binding protein, and beta-carotene oxygenase 1). Mammary tissue from the second and fourth right anterior mammary glands were collected to assess gland development via immunohistochemical staining for T cells, B cells, and macrophages (CD3, CD20, and IBA1, respectively) and DNA extraction. Vaccine antibodies measures, vitamin A analysis, and mammary immunohistochemical staining was completed at Iowa State University Veterinarian Diagnostic Laboratory (Ames, IA). Data were analyzed in SAS 9.4 (Statistical Analysis System, Cary, NC) via GLIMMIX procedure. Pen was the experimental unit and fixed effects were diet and time. Gilts were nested within pen when appropriate to account for more than one gilt per pen. Oxidized beta-carotene supplementation increased (P = 0.02) average daily gain across phases; however, there were no differences (P = 0.18) in the body weight of pigs. There was no effect (P &amp;gt; 0.05) of diet on plasma or hepatic retinol, IgG or IgM concentrations, immune cell presence, or DNA in mammary tissue. Supplemented vitamin A tended (P = 0.05) to increase the expression of retinol binding protein in the jejunum, but other genes were not affected (P &amp;gt; 0.05) by dietary treatments. A diet by time interaction (P = 0.04) was noted for circovirus sample-to-positive ratios and titer levels, where vitamin A supplementation had better vaccine responses at the end of the study. Thus, pigs supplemented with oxidized beta-carotene had an improved average daily gain over vitamin A supplemented pigs, but pigs supplemented with vitamin A appeared to have a more robust immune system.

Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients

Background The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. Methods Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. Results Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764–0.924). Conclusion Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.

Diagnostic value of α1-MG and URBP in early diabetic renal impairment.

Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define "diabetic kidney disease" or "diabetic nephropathy" precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD. Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30mg/g and eGFR≥90mL/min/1.73m2, n = 63) and DKD group (UACR>30mg/g or eGFR<90mL/min/1.73m2, n = 119) excluding other causes of chronic kidney disease. We further developed diagnostic models to improve the ability to predict the risk of developing DKD by screening potential risk factors using univariate and multivariate logistic regression analysis. Calibration plots and curve analysis were used to validate the model and clinical usefulness. Next, we screened patients with relatively normal estimated glomerular filtration rate (eGFR) (≥90mL/min/1.73m2) to investigate whether tubular injury markers could accurately predict the risk of DKD in patients with normal renal function. We defined the rate of GFR decline as a prognostic indicator of renal function in patients and collected the information of the re-hospitalized DKD patients to determine whether the relevant indicators had an impact on the renal prognosis. Results: The patients with DKD had higher levels of tubular injury markers than patients with DM. URBP, α1-MG, eGFR were statistically different in both univariate and multivariate logistic regression analyses and displayed great predictive power after modeling with an area under curve of 0.987. The calibration curve showed medium agreement. Decision curve showed it would add more net benefits for clinical decision. After adjusting eGFR and serum creatinine (Scr), URBP was demonstrated to be associated with early renal function impairment. Conclusion: Tubular injury markers play an important role in early diabetic renal function impairment.

Are variants of the RBP4 gene associated with serum retinol-binding protein 4 concentrations and carotid intima-media thickness values in women with obesity?

IntroductionSeveral studies showed the correlation of retinol-binding protein 4 (RBP4) with increased cardiovascular risk - including higher values of carotid intima-media thickness (cIMT) - particularly in individuals with obesity. ObjectivesOur study aimed to investigate the impact of rs10882273; rs3758538; rs3758539, and rs7094671 RBP4 gene variants on RBP4 serum concentrations as well as cIMT values (a marker of subclinical atherosclerosis) among female patients with obesity. Patients and methodsWe recruited 74 women with obesity and 24 women without obesity as a study and control group, respectively. The genotypic and allelic frequencies of RBP4 gene variants were evaluated for associations with serum RBP4 and cIMT. ResultsThe median serum RBP4 concentrations were 20.30 µg/mL and 19.80 µg/mL in the patients and control group, respectively (p = 0.740). No significant differences were seen in cIMT values between the two studied groups (0.60 [0.50–1.00] vs. 0.60 ± 0.10 in the patient and control group, respectively); however, the results were close to reaching significance (p = 0.071), similar as in observed association of the minor haplotype AA for rs7084671 and rs375839 with female obesity (p = 0.0559). The correlation analysis showed no significant differences between RBP4 gene variants with serum RBP4 and cIMT. ConclusionsAccording to our knowledge, this is the first study investigating the association between RBP4 gene variants and serum RBP4 and cIMT among Polish female patients with obesity. However, our results show that genetic variants rs10882273, rs3758538, rs3758539, and rs7094671 of the RBP4 gene are not associated with RBP4 serum concentrations or cIMT values among women with obesity.

Nutritional Status of Children with Newly Diagnosed Food Allergies.

Most published pediatric guidelines on food allergy highlight the importance of nutritional counseling and dietary adequacy to avoid either growth retardation or nutritional deficiencies. The aim of the study was an assessment of the nutritional status of children with IgE-mediated food allergies. 45 patients with newly diagnosed food allergy (FA) and 33 healthy controls were analyzed (aged 6 to 72 months, 60.2% boys). The nutritional status was assessed using anthropometric measurements (body weight and length) and serum laboratory tests. The results were analyzed with the Statistica 12 software (Tulsa, OK, USA). 82%, 40%, 8.8%, and 6.6% of the studied children demonstrated allergy to hen's egg, cow's milk, pork meat, and wheat/rye, respectively. Z-score BMI < -2SD was more often found in the FA subjects under 30 months of age than in the controls (p = 0.04). As many as 77.8% of the FA subjects and 78.8% of the controls were of normal height (hSDS: -0.23 ± 1.74 and -0.31 ± 1.49, respectively, p = 0.8). Retinol binding protein four serum concentration was significantly lower in the FA group (17.01 ± 3.84 mg/L) than in the controls (20.47 ± 4.87 mg/L, p < 0.001). No statistically significant differences were observed between the FA group and the controls (either in the younger or the older age group) (p > 0.05) for the serum concentrations of total protein, total cholesterol, thyroxin-binding prealbumin (TBPA), 25(OH)D, hemoglobin level or white blood cells. In patients under 30 months of age, one of the symptoms of food allergy may be body weight deficiency, while short stature is less common at the time of diagnosis.

Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRacand ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDPand alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic,dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children.