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Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism in cryptochrome proteins to signalling pathways in cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate proteins showing binding to cryptochrome type 4a. So far, only the interaction of the cone specific G-protein transducin α-subunit was investigated in more detail. In the present study, we compare the binding features of the G-protein α-subunit with those of another candidate from the yeast-two-hybrid screen, cellular retinol binding protein. Purified recombinant European robin retinol binding protein bound retinol with high affinity, displaying an EC50 of less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance and a Förster resonance transfer analysis to test for interactions between retinol binding protein and cryptochrome 4a. In the absence of retinol, we observed no robust binding events, which contrasts the strong interaction we observed between cryptochrome 4a and the G-protein α-subunit. We conclude that retinol binding protein is unlikely to be involved in the primary magnetosensory signalling cascade. [ABSTRACT FROM AUTHOR]

Abstract Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism in cryptochrome proteins to signalling pathways in cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate proteins showing binding to cryptochrome type 4a. So far, only the interaction of the cone specific G-protein transducin α-subunit was investigated in more detail. In the present study, we compare the binding features of the G-protein α-subunit with those of another candidate from the yeast-two-hybrid screen, cellular retinol binding protein. Purified recombinant European robin retinol binding protein bound retinol with high affinity, displaying an EC50 of less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance and a Förster resonance transfer analysis to test for interactions between retinol binding protein and cryptochrome 4a. In the absence of retinol, we observed no robust binding events, which contrasts the strong interaction we observed between cryptochrome 4a and the G-protein α-subunit. We conclude that retinol binding protein is unlikely to be involved in the primary magnetosensory signalling cascade.

Background: Cardiometabolic disorders, notably primary hypertension and type 2 diabetes, present substantial global health challenges. The intricate interplay between metabolic and cardiovascular pathways has prompted extensive research into molecular mechanisms linking these conditions. The adipokine Retinol Binding Protein 4 (RBP4), initially recognized for retinol transport, has emerged as a potential biomarker in the network of metabolic and cardiovascular dysfunction. Recent studies implicate RBP4 in insulin resistance and its complications, including hypertension. This study explores RBP4 dynamics in patients with primary hypertension and type 2 diabetes, aiming to contribute valuable insights into diagnostic and therapeutic advancements in managing these interconnected disorders. Methods: This cross-sectional study, conducted over 2 years in a tertiary healthcare centre of North India, aimed to investigate the serum concentration of Retinol Binding Protein 4 (RBP4) in 119 participants diagnosed with primary hypertension and type 2 diabetes. Ethical guidelines were strictly followed, and comprehensive clinical assessments, including blood pressure measurements, were performed. RBP4 levels were quantified using an ELISA kit, alongside markers of insulin resistance. Statistical analyses, involving t-tests and correlation assessments, sought to unravel potential associations between RBP4, insulin resistance, and blood pressure parameters using SPSS 20.0. Results: The study comprised 61 healthy control (HC) participants and 58 individuals diagnosed with both essential hypertension and type 2 diabetes (EH+T2D). EH+T2D participants were on average older (45.71 ± 9.29 years vs. 40.34 ± 9.47 years, P = 0.002). Dyslipidemia prevalence was markedly higher in EH+T2D (72.4% vs. 11.4%, P < 0.0001), accompanied by disrupted lipid profiles. Serum RBP4 concentration was significantly elevated in EH+T2D (49.17 ± 19.37 mg/L, P < 0.0001), suggesting its potential role in the shared pathophysiology of primary hypertension and type 2 diabetes. Pearson’s correlation analysis revealed associations between RBP4 levels, metabolic, and cardiovascular parameters, underscoring its potential as a link between these conditions. Conclusion: Elevated serum RBP4 levels suggest its potential as a novel biomarker in the shared pathophysiology of primary hypertension and type 2 diabetes. The correlation analysis highlights the intricate interplay between metabolic, lipid, and cardiovascular parameters, emphasizing the need for holistic interventions.

Retinol binding protein (RBP) is used as a proxy for retinol in population-based assessments of vitamin A deficiency (VAD) for cost-effectiveness and feasibility. When the cut-off of < 0·7 μmol/l for retinol is applied to RBP to define VAD, an equivalence of the two biomarkers is assumed. Evidence suggests that the relationship between retinol and RBP is not 1:1, particularly in populations with a high burden of infection or inflammation. The goal of this analysis was to longitudinally evaluate the retinol:RBP ratio over 1 month of follow-up among fifty-two individuals exposed to norovirus (n 26 infected, n 26 uninfected), test whether inflammation (measured as α -1-acid glycoprotein (AGP) and C-reactive protein (CRP)) affects retinol, RBP and the ratio between the two and assess whether adjusting vitamin A biomarkers for AGP or CRP improves the equivalence of retinol and RBP. We found that the median molar ratio between retinol and RBP was the same among infected (0·68) and uninfected (0·68) individuals. AGP was associated with the ratio and RBP individually, controlling for CRP, and CRP was associated with both retinol and RBP individually, controlling for AGP over 1 month of follow-up. Adjusting for inflammation led to a slight increase in the ratio among infected individuals (0·71) but remained significantly different from the expected value of one. These findings highlight the need for updated recommendations from the WHO on a cut-off value for RBP and an appropriate method for measuring and adjusting for inflammation when using RBP in population assessments of VAD. [ABSTRACT FROM AUTHOR]

Retinol binding protein (RBP) is associated with an increased risk of insulin resistance, metabolic syndrome, atherosclerosis and hypertension. This study aimed to evaluate serum RBP levels in patients with acute pancreatitis (AP). The study included 1,871 AP patients, including 1,411 with mild AP (MAP), 244 with moderately severe AP (MSAP), and 186 with severe AP (SAP). Retrospective analysis was conducted on RBP concentrations and other clinical data of AP patients. AP patients were subgrouped by RBP level into low RBP (LRBP), normal RBP (NRBP), and high RBP (HRBP) groups. The LRBP group showed a significantly higher proportion of SAP patients than NRBP and HRBP groups. Additionally, the LRBP group had the highest BISAP and CTSI scores among the three groups; WBC and CRP levels in the NRBP group were significantly lower than those in the LRBP and HRBP groups. RBP was better at predicting acute necrotic collection (ANC) than other local complications, with an area under the curve (AUC) of 0.821. RBP was also an independent risk factor for acute lung injury (ALI) and ANC in AP patients. The AUC of RBP for predicting ALI was 0.829, with 30.45 mg/L as the optimal cutoff value, and the sensitivity and specificity were 59.70% and 96.50%, respectively. The AUC of RBP for predicting ANC was 0.821, with 28.35 mg/L as the optimal cutoff value, and the sensitivity and specificity were 61.20% and 95.50%, respectively. Serum RBP had predictive value for AP severity, local and systemic complications. [ABSTRACT FROM AUTHOR]

Background: Retinol Binding Protein 4 (RBP4) is a transport protein responsible for carrying vitamin A (retinol) from the liver to peripheral tissues. Visfatin, also known as Nicotinamide Phosphoribosyl Transferase (NAMPT), is an adipokine involved in glucose metabolism and has pro-inflammatory properties. Our core hypothesis suggests a potential link between thyroid diseases and distinct serum level of RBP4 and visfatin. The study aims to discern any significant differences in these protein levels between individuals with thyroid disorders and healthy control. Methods: Conducted as a case-control study at multiple centers in Baghdad, Iraq from November 2022 to May 2023, this research assessed 150 serum samples across five groups: Hyperthyroidism, Hypothyroidism, Thyroid cancer, Thyroid Goiter, and healthy controls. Parameters included BMI, Serum RBP4 and Visfatin., and thyroid hormones (T3, T4, TSH). Assessment utilized ELISA kits and Tosoh AIA 360 Analyzer. Results: Significant differences in serum RBP4 and Visfatin levels were discovered across thyroid conditions and between genders. Elevated RBP4 levels were predominantly seen in Hypothyroidism, Thyroid Cancer, and Thyroid Goiter cases, while Visfatin levels were notably higher in hypothyroid patients. Additionally, varying BMI levels across thyroid conditions were observed, promoting further investigation. Conclusion: The results corroborate our hypothesis, suggesting that RBP4 and Visfatin could be potential markers for thyroid dysfunction. However, the complexity and hormone-specific interactions necessitate caution in their diagnostic application. Future studies should explore the diagnostic and prognostic value of these adipokines for specific thyroid conditions and further examine variables affecting BMIA. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Introduction: Iron and vitamin A deficiency are two very prevalent and easily preventable nutrient deficiencies. This study was conducted to assess vitamin A status in patients with iron deficiency anemia and to further study the correlation of vitamin A status with biochemical markers of iron deficiency. Materials and Method: Eighty patients with iron deficiency anemia were enrolled and investigated for a complete blood count, an iron profile, liver, and kidney function tests and plasma retinol binding protein levels. The mean age of patients was 31.14 ± 11.33 years, with a range of 16 to 62 years. Results: Mean hemoglobin was 7.19 ± 2.1 g/dL. Serum iron, ferritin, and transferrin saturation were low in all patients, while total iron binding capacity (TIBC) was elevated in only 74 patients (94.81%). Nineteen patients (23.8%) had vitamin A deficiency, with a mean retinol binding protein (RBP) 0.53 ± 0.13 µmol/L. Vitamin A deficient patients had a mean hemoglobin of 6.8±2.14 gm/dL, mean corpuscular volume (MCV) 71.35 ± 8.86 fL, a mean corpuscular hemoglobin (MCH) 19.43±4.36 pg, mean corpuscular hemoglobin concentration (MCHC) 25.44±4.92 gm/dL, serum iron of 28.21 ± 9.73 mcg/dL, serum ferritin 13.04 ± 12.41 ng/mL, transferrin saturation 6.81 ± 3.07%, and TIBC 427.85 ± 78.57 mcg/dL. Among vitamin A deficient patients, RBP had positive correlation with serum iron and transferrin saturation; while, simultaneously showing negative correlation with serum ferritin and TIBC. Conclusion: Vitamin A deficiency affects iron metabolism, causing abnormal iron trapping and systemic iron deficiency, thus worsening the clinical profile of iron deficiency anemia. This study guides us to screen iron deficiency anemia patients for the concomitant vitamin A deficiency for efficient treatment of such patients.

Abstract Background We aimed to explore the predictive value of retinol binding protein (RBP) for outcomes of hip fractures. Methods Patients with hip fractures who underwent hip surgeries between December 2017 and February 2021 and met the inclusion criteria were analyzed. Propensity score matching was used to reduce the bias of co-factors and ROC curves based on matched populations were created to determine the optimal cutoff point of RBP. The outcomes between patients with low levels of RBP and high levels of RBP were compared. Results Four hundred eighty patients were enrolled in this study and 69 patients died within one year. After a 1:1 PSM, patients with more than 1-year survival had significantly higher RBP (p = 0.013) than those who died within one year, as well as patients divided by 6-months survival (p = 0.012). Logistics analysis showed that low RBP may be an independent risk factor for 3-month survival, 6-month survival, 1-year survival, and 3-month free walking ability. Conclusion RBP may be associated with the survival and 3-month walking abilities of patients with hip fractures.

Previous studies have indicated that exposure to a single toxic metal can cause renal tubular damage, while evidence about the effects of multimetal exposure on renal tubular damage is relatively limited. We aimed to evaluate the relationships of multimetal coexposure with renal tubular damage in adults in heavy metal-polluted rural regions of China. A cross-sectional study of 1918 adults in China's heavy metal-contaminated rural regions was conducted. Inductively coupled plasma–mass spectrometry (ICP–MS) was used to measure the plasma levels of 18 metals in participants, and immune turbidimetry was used to measure sensitive biological indicators, reflecting renal tubular damage (including retinol-binding protein and β2-microglobulin). Least absolute shrinkage and selection operator (LASSO) penalized regression analysis, logistic and linear regression analysis, restricted cubic spline (RCS) regression analysis and the Bayesian kernel machine regression (BKMR) method were used to explore associations of multimetal coexposure with renal tubular damage risk or renal tubular damage indicators. Plasma selenium, cadmium, arsenic, and iron were identified as the main plasma metals associated with renal tubular damage risk after dimensionality reduction. Multimetal regression models showed that selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators. Multimetal RCS analyses additionally revealed a non-linear relationship of selenium with renal tubular damage risk. The BKMR models showed that the metal mixtures were positively associated with biological indicators of renal tubular damage when the metal mixtures were above the 50th percentile of concentration. Our findings indicated that natural exposure to high levels of multimetal mixtures increases the risk of renal tubular damage. Under the conditions of multimetal exposure, selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators. [ABSTRACT FROM AUTHOR]

Abstract: Emergent therapeutic strategies that merge robust anti-cancer effects with antioxidant attributes are imperative for addressing lung cancer, a prevalent and often fatal ailment. This presentation explores the potential application of Ginkgo biloba silver nanoparticles (GB-AgNPs) and bilobtin as a viable avenue to impede the advancement of lung cancer while concurrently furnishing antioxidative benefits. In the current study, a total of 30 samples were examined from each of the three distinct groups: control, small cell lung cancer, and adenocarcinoma lung cancer. The results of the study indicate that the application of GB-AgNPs and bilobetein led to a significant reduction in elevated protein carbonyl and retinol binding protein (RBP) levels. This suggests that these interventions have the potential to effectively counteract crucial molecular markers linked to the onset and advancement of lung cancer. These findings open up a new and innovative pathway for the development of targeted therapeutic approaches for lung cancer, utilizing natural compounds as potential treatment agents.

BackgroundPsoriasis vulgaris is a chronic skin disease which is related to cardiovascular and metabolic diseases. In the pathogenesis of these diseases, adipokines, including retinol binding protein-4 (RBP-4), play crucial roles. Studies have also shown that RBP-4 might be a meaningful factor in psoriasis however, relying on the analysis of a single study have some drawbacks.ObjectiveTo evaluate the association between RBP-4 and psoriasis vulgaris more comprehensively.MethodsSix databases were searched to obtain relevant publications. The selection of the included studies was based on a criteria. The standardized mean difference (SMD) was used for analysis. A value of p < 0.05 was defined as significance.ResultsSeven studies were included, with 271 cases and 235 controls. In the comparison between patients and controls, the merged data suggested that levels of RBP-4 were significantly higher in patients (SMD = 0.61, 95%CI: 0.14, 1.07, p 0.05). Subgroup analysis was conducted based on the therapy method. Patients with systematic treatment showed a significant decrease of BRP-4 level after the treatment (SMD = −0.64, 95%CI: −1.26, −0.03, p

Objective: To study Analysis of the Expression and significance of Urea nitrogen (BUN) and RBP in serum of children with glomerulonephritis. Methods: 75 cases of children with glomerulonephritis admitted to our hospital from January 2018 to January2021 were selected as the subjects of this study, and 55 cases of children with glomerulonephritis who underwent physical examination in our hospital during the same period were selected as the control group. The changes of serum BUN and RBP levels and their diagnostic value were analyzed. Results: The serum BUN and RBP levels of experimental group (15.52 ±1.51 mmol/L, 97.87±21.28 mg/L) were significantly higher than those of control group (5.07±0.97 mmol/L, 42.17±10.25 mg/L), and the differences were significant (P<0.05). The serum BUN and RBP levels of severe glomerulonephritis (19.01±1.20 mmol/L, 118.83±21.24 mg/L) were significantly higher than those of mild glomerulonephritis (11.56±1.07mmol/L, 71.24±19.87) Mg/L), moderate glomerulonephritis (14.89±1.12mmol/L, 95.75±22.13 mg/L), the difference was significant (P<0.05); The serum BUN and RBP levels in children with moderate glomerulonephritis (14.89 ±1.12 mmol/L, 95.75 ±22.13 mg/L) were significantly higher than those in children with mild glomerulonephritis (11.56 ±1.07mmol/L, 71.24±19.87 mg/L), and the differences were significant (P<0.05). The AUC of GLOMERulonephritis diagnosed by BUN was 0.866, 95%CI was 0.807-0.926, and the cut-off value was 8.45 mmol/L. The AUC of RBP in diagnosing glomerulonephritis was0.957, 95%CI was 0.927-0.987, and truncation value was 57.29 mg/L. The AUC and 95%CI for the diagnosis of glomerulonephritis were0.991 and 0.980-1.000, respectively. There were significant differences in the area under the curve between single detection and combined detection (Z=4.11, 2.150, P<0.05). The specificity and accuracy of combined detection were 93.41% and 94.15%, respectively. Conclusion: There is a close relationship between the expression of serum BUN and RBP and the severity of the disease in children with glomerulonephritis. [ABSTRACT FROM AUTHOR]

Introduction: Iron and vitamin A deficiency are two very prevalent and easily preventable nutrient deficiencies. This study was conducted to assess vitamin A status in patients with iron deficiency anemia and to further study the correlation of vitamin A status with biochemical markers of iron deficiency. Materials and Method: Eighty patients with iron deficiency anemia were enrolled and investigated for a complete blood count, an iron profile, liver, and kidney function tests and plasma retinol binding protein levels. The mean age of patients was 31.14 ± 11.33 years, with a range of 16 to 62 years. Results: Mean hemoglobin was 7.19 ± 2.1 g/dL. Serum iron, ferritin, and transferrin saturation were low in all patients, while total iron binding capacity (TIBC) was elevated in only 74 patients (94.81%). Nineteen patients (23.8%) had vitamin A deficiency, with a mean retinol binding protein (RBP) 0.53 ± 0.13mmol/L. Vitamin A deficient patients had a mean hemoglobin of 6.8±2.14 gm/dL, mean corpuscular volume (MCV) 71.35 ± 8.86 fL, a mean corpuscular hemoglobin (MCH) 19.43±4.36 pg, mean corpuscular hemoglobin concentration (MCHC) 25.44±4.92 gm/dL, serum iron of 28.21 ± 9.73 mcg/dL, serum ferritin 13.04 ± 12.41 ng/ mL, transferrin saturation 6.81 ± 3.07%, and TIBC 427.85 ± 78.57 mcg/dL. Among vitamin A deficient patients, RBP had positive correlation with serum iron and transferrin saturation; while, simultaneously showing negative correlation with serum ferritin and TIBC. Conclusion: Vitamin A deficiency affects iron metabolism, causing abnormal iron trapping and systemic iron deficiency, thus worsening the clinical profile of iron deficiency anemia. This study guides us to screen iron deficiency anemia patients for the concomitant vitamin A deficiency for efficient treatment of such patients. [ABSTRACT FROM AUTHOR]

Purpose: To report a unique case of Dent Disease presenting with nyctalopia associated with vitamin A deficiency and abnormal electroretinogram findings without prior systemic symptomatology. Observations: A 16-year-old male presented with a several month history of nyctalopia and peripheral vision deficits. Central visual acuity, anterior and posterior segment examinations, and macular optical coherence tomography were unremarkable. Electroretinogram (ERG) testing revealed a rod-cone dystrophic pattern, with further workup demonstrating serum vitamin A deficiency (VAD). Laboratory evaluation revealed renal dysfunction and proteinuria with a significantly elevated urinary retinol-binding protein (RBP). Kidney biopsy showed glomerular and tubular disease.Genetic screening for inherited renal disease was performed identifying a hemizygous pathogenic variant c.2152C>T (p.Arg718*) in the Chloride Voltage-Gated Channel 5 (CLCN5) gene, confirming the diagnosis of X-linked Dent Disease. Following vitamin A supplementation, our patient reported resolution of nyctalopia and reversal of abnormal ERG findings were demonstrated. Conclusions and Importance: To our knowledge, this is the first case in the literature describing Dent disease solely presenting with ophthalmic symptoms of nyctalopia and abnormal electroretinogram findings that later reversed with vitamin A repletion. This case stresses the importance for clinicians to consider renal tubular disorders in the differential for VAD.

The stoichiometry of a ligand binding reaction to a protein is given by a parameter (n). The value of this parameter may indicate the presence of protein monomer or dimers in the binding complex. Members of the lipocalin superfamily show variation in the stoichiometry of binding to ligands. In some cases the stoichiometry parameter (n) has been variously reported for the same protein as mono- and multimerization of the complex. Prime examples include retinol binding protein, β lactoglobulin and tear lipocalin, also called lipocalin-1(LCN1). Recent work demonstrated the stoichiometric ratio for ceramide:tear lipocalin varied (range n = 0.3-0.75) by several different methods. The structure of ceramide raises the intriguing possibility of a lipocalin dimer complex with each lipocalin molecule attached to one of the two alkyl chains of ceramide. The stoichiometry of the ceramide-tear lipocalin binding complex was explored in detail using size exclusion chromatography and time resolved fluorescence anisotropy. Both methods showed consistent results that tear lipocalin remains monomeric when bound to ceramide. Delipidation experiments suggest the most likely explanation is that the low 'n' values result from prior occupancy of the binding sites by native ligands. Lipocalins such as tear lipocalin that have numerous binding partners are particularly prone to an underestimated apparent stoichiometry parameter.

Background: We aimed to explore the predictive value of retinol binding protein (RBP) for outcomes of hip fractures. Methods: Patients with hip fractures who underwent hip surgeries between December 2017 and February 2021 and met the inclusion criteria were analyzed. Propensity score matching was used to reduce the bias of co-factors and ROC curves based on matched populations were created to determine the optimal cutoff point of RBP. The outcomes between patients with low levels of RBP and high levels of RBP were compared. Results: Four hundred eighty patients were enrolled in this study and 69 patients died within one year. After a 1:1 PSM, patients with more than 1-year survival had significantly higher RBP (p = 0.013) than those who died within one year, as well as patients divided by 6-months survival (p = 0.012). Logistics analysis showed that low RBP may be an independent risk factor for 3-month survival, 6-month survival, 1-year survival, and 3-month free walking ability. Conclusion: RBP may be associated with the survival and 3-month walking abilities of patients with hip fractures. [ABSTRACT FROM AUTHOR]

Purpose of Review: Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial delay between initial symptoms and diagnosis. With the recent emergence of various targeted therapies proven to reduce morbidity and mortality, there is an imperative to diagnose subclinical disease. Biomarkers may be well-suited for this role. Recent Findings: Conventional markers of heart failure, such as natriuretic peptides and cardiac troponins, and estimated glomerular filtration rate are associated with risk in ATTR-CM. Circulating transthyretin (TTR) levels parallel TTR kinetic stability, correlate with disease severity, and may serve as indirect markers of ATTR-CM disease activity and response to targeted treatment. There is also growing evidence for the correlation of TTR to retinol-binding protein 4, a biomarker which independently associates with this disease. The rate-limiting step for ATTR pathogenesis is dissociation of the TTR homotetramer, which may be quantified using subunit exchange to allow for early risk assessment, prognostication, and assessment of treatment response. The protein species that result from the dissociation and misfolding of TTR are known as nonnative transthyretin (NNTTR). NNTTR is quantifiable via peptide probes and is a specific biomarker whose reduction is positively correlated with improvement in neuropathic ATTR amyloidosis. Neurofilament light chain (NfL) is released into the blood after axonal damage and correlates with neuropathic ATTR amyloidosis, but its clinical use in ATTR-CM is uncertain. Summary: Conventional markers of heart failure, transthyretin, retinol-binding protein 4, transthyretin kinetic stability, nonnative transthyretin, peptide probes, and neurofilament light chain have potential as biomarkers to enable early, subclinical diagnosis in patients with transthyretin cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

Healthy pediatric immune responses depend on adequate vitamin A and D levels. Relationships between solar ultraviolet B (UVB) radiation and vitamin D are well understood, while relationships between sunlight, vitamin A, and its serum escort, retinol binding protein (RBP), are not. A pediatric clinical study enrolled 2–8-year-old children at various times between September 2016 and March 2017, inclusive, in Memphis, Tennessee. A serum sample from each child was then assayed to examine the influence of season on vitamin levels. We found that RBP and RBP/retinol molar ratios decreased in winter months and RBP/retinol ratios correlated positively with the average daily sunlight hours per month. A food frequency questionnaire given to parents/guardians indicated a shift in dietary intake from plant-based foods to animal-based foods by children between winter and spring months. This translated to higher retinol and zinc (integral to RBP–transthyretin–retinol complexes) in the spring, perhaps explaining the seasonal influence on RBP/retinol. RBP and retinol were associated positively with IgG/IgM and IgA/IgM ratios. RBP and retinol, but not 25(OH)D, also correlated positively with influenza virus-specific antibodies. Retinol correlated negatively, while 25(OH)D correlated positively, with certain serum cytokine/chemokine levels. Significant differences in 25(OH)D, immunoglobulin ratios, and cytokines/chemokines were observed between black and white children. In sum, seasonal changes in dietary foods rich in retinol and zinc may have influenced RBP levels, which in turn influenced innate and adaptive immune responses. Results encourage routine monitoring and reporting of season, RBP, and vitamin levels in future clinical studies, as seasons may affect sunlight exposures, diet, vitamin levels, and immune protection against infectious disease. [ABSTRACT FROM AUTHOR]

Background: There are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia. Purpose: This study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model. Methods: We conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria. Results: Serum RBP4 level had a highly significant association with hyperuricemia (P <0.001). After adjusting for potential confounders, logistic regression indicated that the risk of hyperuricemia was highest in the highest RBP4 quartile (odds ratio: 7.9, 95% confidence interval [CI]: 4.18–14.84, compared to the lowest quartile). The area under the receiver operating characteristic (ROC) curve (AUC) for RBP4 was 0.749 (95% CI: 0.725–0.774, P <0.001), which was higher than that for all the other predictors assessed. The optimum model for predicting hyperuricemia in the general population consisted of RBP4, sex (male), body mass index, serum creatinine, high-sensitivity C-reactive protein, fasting blood glucose, insulin, and alcohol consumption. The AUC was 0.804 (95% CI: 0.782–0.826, P <0.001). Conclusions: RBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors. [ABSTRACT FROM AUTHOR]

BackgroundThere are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia.PurposeThis study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model.MethodsWe conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria.ResultsSerum RBP4 level had a highly significant association with hyperuricemia (P

Vitamin A is distributed within the body to support chromophore synthesis in the eyes and retinoid signaling in most other tissues. Two pathways exist for the delivery of vitamin A: the extrinsic pathway transports dietary vitamin A in lipoproteins from intestinal enterocytes to tissues, while the intrinsic pathway distributes vitamin A from hepatic stores bound to serum retinol binding protein (RBP). Previously, the intestine-specific homeodomain transcription factor (ISX) and the RBP receptor STRA6 were identified as gatekeepers of these pathways; however, it is not clear how mutations in the corresponding genes affect retinoid homeostasis. Here, we used a genetic dissection approach in mice to examine the contributions of these proteins in select tissues. We observed that ISX deficiency increased utilization of both preformed and provitamin A. We found that increased storage of retinoids in peripheral tissues of ISX-deficient mice was dependent on STRA6 and induced by retinoid signaling. In addition, double-mutant mice exhibited a partial rescue of the Stra6 mutant ocular phenotype. This rescue came at the expense of a massive accumulation of vitamin A in other tissues, demonstrating that vitamin A is randomly distributed when present in excessive amounts. Remarkably, provitamin A supplementation of mutant mice induced the expression of the RBP receptor 2 in the liver and was accompanied by increased hepatic retinyl ester stores. Taken together, these findings indicate dynamic crosstalk between the delivery pathways for this essential nutrient and suggest that hepatic reuptake of vitamin A takes place when excessive amounts circulate in the blood.

Background and Purpose : Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH. Method : We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels. Results : Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047). Conclusion : Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease. [ABSTRACT FROM AUTHOR]

The measurement of plasma concentrations of retinol binding protein is a component of nutritional assessment in neonatal intensive care. However, serial testing in newborns is hampered by the limited amount of blood that can be sampled. Limitations are most severe with preterm infants, for whom close monitoring may be most important. We developed an assay to quantify retinol binding protein using trypsin digestion and liquid chromatography-tandem mass spectrometry, which requires a serum or plasma volume of 5 µl. Additionally, we validated the method according to current recommendations and performed comparison with a standard nephelometry platform in clinical use. The assay demonstrated linearity from below 1 mg/dL (0.48 µM) to more than 20 mg/dL (9.7 µM), and an imprecision of 11.8% at 0.43 mg/dL (0.21 µM). The distribution of results observed with the new method was different when compared with nephelometry. Liquid chromatography-tandem mass spectrometry facilitated testing a smaller sample volume, thereby increasing the ability to monitor key nutritional markers in premature infants. The differences in results compared with a commercially-available nephelometric assay revealed questionable results for lower concentrations by immunoassay. [ABSTRACT FROM AUTHOR]

Khalid Siddiqui,1 Salini Scaria Joy,1 Teena Puthiyaparampil George,1 Muhammad Mujammami,1– 3 Assim A Alfadda1,3,4 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 4Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Khalid SiddiquiStrategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh 11411, Kingdom of Saudi ArabiaTel +966 114724179 ext.1340Email ksiddiqui@ksu.edu.saBackground: Analyzing urinary biomarkers may provide better insight into pathophysiological mechanisms of diabetic kidney diseases. The study aimed to analyze the pattern of selected excreted urinary biomarkers and its correlation with albuminuria and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.Methods: A total of 185 patients with type 2 diabetes were categorized according to KDIGO guideline based on albuminuria and eGFR. The urinary markers (transferrin, KIM-1, RBP, MCP-1 and NGAL) were measured by ELISA.Results: The urinary markers were associated with eGFR (total protein/Cr, p=0.001; RBP/Cr, p=0.007; MCP-1/Cr, p=0.023; NGAL/Cr, p=0.011) and albuminuria (total protein/Cr, p< 0.001; transferrin, p< 0.001; RBP/Cr, p< 0.001; MCP-1/Cr, p< 0.001; NGAL/Cr, p=0.002).Conclusion: The urinary marker levels (total protein, RBP, MCP-1, and NGAL) are elevated with severity of kidney damage and expressed more in progressive renal impairment.Keywords: diabetic kidney disease, urinary markers, albuminuria, transferrin, kidney injury molecule-1, retinol-binding protein, monocyte chemoattractant protein-1, neutrophil gelatinase-associated lipocalin

Background and Purpose: Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH.Method: We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels.Results: Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047).Conclusion: Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease.

Background: Cardiometabolic disorders, notably primary hypertension and type 2 diabetes, present substantial global health challenges. The intricate interplay between metabolic and cardiovascular pathways has prompted extensive research into molecular mechanisms linking these conditions. The adipokine Retinol Binding Protein 4 (RBP4), initially recognized for retinol transport, has emerged as a potential biomarker in the network of metabolic and cardiovascular dysfunction. Recent studies implicate RBP4 in insulin resistance and its complications, including hypertension. This study explores RBP4 dynamics in patients with primary hypertension and type 2 diabetes, aiming to contribute valuable insights into diagnostic and therapeutic advancements in managing these interconnected disorders., Methods: This cross-sectional study, conducted over 2 years in a tertiary healthcare centre of North India, aimed to investigate the serum concentration of Retinol Binding Protein 4 (RBP4) in 119 participants diagnosed with primary hypertension and type 2 diabetes. Ethical guidelines were strictly followed, and comprehensive clinical assessments, including blood pressure measurements, were performed. RBP4 levels were quantified using an ELISA kit, alongside markers of insulin resistance. Statistical analyses, involving t-tests and correlation assessments, sought to unravel potential associations between RBP4, insulin resistance, and blood pressure parameters using SPSS 20.0., Results: The study comprised 61 healthy control (HC) participants and 58 individuals diagnosed with both essential hypertension and type 2 diabetes (EH+T2D). EH+T2D participants were on average older (45.71 ± 9.29 years vs. 40.34 ± 9.47 years, P = 0.002). Dyslipidemia prevalence was markedly higher in EH+T2D (72.4% vs. 11.4%, P < 0.0001), accompanied by disrupted lipid profiles. Serum RBP4 concentration was significantly elevated in EH+T2D (49.17 ± 19.37 mg/L, P < 0.0001), suggesting its potential role in the shared pathophysiology of primary hypertension and type 2 diabetes. Pearson's correlation analysis revealed associations between RBP4 levels, metabolic, and cardiovascular parameters, underscoring its potential as a link between these conditions., Conclusion: Elevated serum RBP4 levels suggest its potential as a novel biomarker in the shared pathophysiology of primary hypertension and type 2 diabetes. The correlation analysis highlights the intricate interplay between metabolic, lipid, and cardiovascular parameters, emphasizing the need for holistic interventions., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

The article presents the discussion on Idiopathic membranous nephropathy being a common primary glomerular disease. Topics include characterized by the deposition of immune complexes under the epithelial cells of the glomerular basement membrane and diffuse thickening of the basement membrane; and searching for markers of renal tubulointerstitial damage having great clinical value for early identification of renal injury.

Objective: To study the relationship between urinary neurite guidance factor 1 (Netrin-1), kidney injury molecule-1 (KIM-1) and retinol binding protein (RBP) levels and early renal injury in hypertensive disorder complicating pregnancy (HDCP). Methods: A total of 80 patients with HDCP who were admitted to our hospital from February 2017 to February 2020 were included in this study. According to the severity of HDCP, the patients were divided into gestational hypertension group with 22 cases, mild preeclampsia group with 32 cases and severe preeclampsia group with 26 cases. Another 40 cases of normal pregnant women who received regular pregnancy and childbirth tests in our hospital during the same period were randomly selected as the normal pregnancy group. The urinary Netrin-1, Kim-1 and RBP levels in each group were detected and compared. In addition, patients with HDCP were divided into renal function injury group with 42 cases and renal function normal group with 38 cases according to the occurrence of early renal injury. The urinary Netrin-1, Kim-1, RBP and renal function indexes levels were compared between the two groups, and the correlation analysis was carried out. The influencing factors of early renal injury in HDCP were analyzed by Logistic regression. Results: The urinary Netrin-1 levels in normal pregnancy group, gestational hypertension group, mild preeclampsia group and severe preeclampsia group showed a gradually decreasing trend, while the urinary Kim-1 and RBP levels showed a gradually increasing trend, there were statistically significant differences in the pairwise comparison between multiple groups of data (all P＜0.05). The urinary Netrin-1 level in renal function injury group was lower than that in renal function normal group, while the urinary Kim-1, RBP, blood urea nitrogen and serum creatinine and 24 h Urinary albumin excretion (UAE) levels in renal function injury group were significantly higher than those in renal function normal group (all P<0.05). According to Pearson correlation analysis, urinary Netrin-1 level was negatively correlated with blood urea nitrogen and serum creatinine, UAE in early renal injury in HDCP, while Kim-1, RBP levels were positively correlated with blood urea nitrogen and serum creatinine, UAE (all P<0.05). Logistic regression analysis showed that urinary Netrin-1 was a protective factor for early renal injury in HDCP, while Kim-1 and RBP were risk factors for early renal injury in HDCP (all P<0.05). Conclusion: With the decrease of urinary Netrin-1 level and the increase of Kim-1 and RBP levels, the risk of early renal injury in HDCP is higher, detection of urinary Netrin-1, Kim-1, RBP levels may be helpful to evaluate the severity of HDCP and renal function damage. [ABSTRACT FROM AUTHOR]

Objective:To study the relationship between urinary neurite guidance factor 1 (Netrin-1), kidney injury molecule-1 (KIM-1) and retinol binding protein (RBP) levels and early renal injury in hypertensive disorder complicating pregnancy (HDCP). Methods: A total of 80 patients with HDCP who were admitted to our hospital from February 2017 to February 2020 were included in this study. According to the severity of HDCP, the patients were divided into gestational hypertension group with 22 cases, mild preeclampsia group with 32 cases and severe preeclampsia group with 26 cases. Another 40 cases of normal pregnant women who received regular pregnancy and childbirth tests in our hospital during the same period were randomly selected as the normal pregnancy group. The urinary Netrin-1, Kim-1 and RBP levels in each group were detected and compared. In addition, patients with HDCP were divided into renal function injury group with 42 cases and renal function normal group with 38 cases according to the occurrence of early renal injury. The urinary Netrin-1, Kim-1, RBP and renal function indexes levels were compared between the two groups, and the correlation analysis was carried out. The influencing factors of early renal injury in HDCP were analyzed by Logistic regression. Results: The urinary Netrin-1 levels in normal pregnancy group, gestational hypertension group, mild preeclampsia group and severe preeclampsia group showed a gradually decreasing trend, while the urinary Kim-1 and RBP levels showed a gradually increasing trend, there were statistically significant differences in the pairwise comparison between multiple groups of data (all P＜0.05). The urinary Netrin-1 level in renal function injury group was lower than that in renal function normal group, while the urinary Kim-1, RBP, blood urea nitrogen and serum creatinine and 24 h Urinary albumin excretion (UAE) levels in renal function injury group were significantly higher than those in renal function normal group (all P<0.05). According to Pearson correlation analysis, urinary Netrin-1 level was negatively correlated with blood urea nitrogen and serum creatinine, UAE in early renal injury in HDCP, while Kim-1, RBP levels were positively correlated with blood urea nitrogen and serum creatinine, UAE (all P<0.05). Logistic regression analysis showed that urinary Netrin-1 was a protective factor for early renal injury in HDCP, while Kim-1 and RBP were risk factors for early renal injury in HDCP (all P<0.05). Conclusions: With the decrease of urinary Netrin-1 level and the increase of Kim-1 and RBP levels, the risk of early renal injury in HDCP is higher, detection of urinary Netrin-1, Kim-1, RBP levels may be helpful to evaluate the severity of HDCP and renal function damage. [ABSTRACT FROM AUTHOR]

Healthy pediatric immune responses depend on adequate vitamin A and D levels. Relationships between solar ultraviolet B (UVB) radiation and vitamin D are well understood, while relationships between sunlight, vitamin A, and its serum escort, retinol binding protein (RBP), are not. A pediatric clinical study enrolled 2–8-year-old children at various times between September 2016 and March 2017, inclusive, in Memphis, Tennessee. A serum sample from each child was then assayed to examine the influence of season on vitamin levels. We found that RBP and RBP/retinol molar ratios decreased in winter months and RBP/retinol ratios correlated positively with the average daily sunlight hours per month. A food frequency questionnaire given to parents/guardians indicated a shift in dietary intake from plant-based foods to animal-based foods by children between winter and spring months. This translated to higher retinol and zinc (integral to RBP–transthyretin–retinol complexes) in the spring, perhaps explaining the seasonal influence on RBP/retinol. RBP and retinol were associated positively with IgG/IgM and IgA/IgM ratios. RBP and retinol, but not 25(OH)D, also correlated positively with influenza virus-specific antibodies. Retinol correlated negatively, while 25(OH)D correlated positively, with certain serum cytokine/chemokine levels. Significant differences in 25(OH)D, immunoglobulin ratios, and cytokines/chemokines were observed between black and white children. In sum, seasonal changes in dietary foods rich in retinol and zinc may have influenced RBP levels, which in turn influenced innate and adaptive immune responses. Results encourage routine monitoring and reporting of season, RBP, and vitamin levels in future clinical studies, as seasons may affect sunlight exposures, diet, vitamin levels, and immune protection against infectious disease.

Present in the small intestine, cellular retinol binding protein 2 (CRBP2) plays an important role in the uptake, transport, and metabolism of dietary retinoids. However, the recent discovery of the interactions of CRBP2 with 2-arachidonoylglycerol and other monoacylglycerols (MAGs) suggests the broader involvement of this protein in lipid metabolism and signaling. To better understand the physiological role of CRBP2, we determined its protein-lipid interactome using a fluorescence-based retinol replacement assay adapted for a high-throughput screening format. By examining chemical libraries of bioactive lipids, we provided evidence for the selective interaction of CRBP2 with a subset of nonretinoid ligands with the highest affinity for sn-1 and sn-2 MAGs that contain polyunsaturated C18-C20 acyl chains. We also elucidated the structure-affinity relationship for nonretinoid ligands of this protein. We further dissect the molecular basis for this ligand's specificity by analyzing high-resolution crystal structures of CRBP2 in complex with selected derivatives of MAGs. Finally, we identify T51 and V62 as key amino acids that enable the broadening of ligand selectivity to MAGs in CRBP2 as compared with retinoid-specific CRBP1. Thus, our study provides the molecular framework for understanding the lipid selectivity and diverse functions of CRBPs in controlling lipid homeostasis.

Objective: To explore the diagnostic value of retinol binding protein (RBP), C-reactive protein (CRP) and urine microalbumin (UMA) for ischemic cerebrovascular disease (ICD) in patients with chronic kidney disease (CKD)., Methods: In this study, a total of 118 patients with CKD were selected and grouped into two groups: a group of patients who were complicated with ICD (CKD+ICD group, n=58), and a group of patients with CKD only (CKD group, n=60). Then, the patients in the CKD+ICD group were further classified into a good prognosis group and a bad prognosis group according their modified Rankin scale score at sixth months after discharge. Serum RBP, CRP and urine UMA levels were compared between the CKD group and CKD+ICD group. The diagnostic efficiency of serum RBP, CRP and urine UMA levels for ICD in patients with CKD was analyzed. The receiver operating characteristic (ROC) curve was used to assess their prognostic performance. Logistic regression analysis was used to evaluate the risk factors for poor prognosis of patients with CKD and ICD., Results: The levels of RBP, CRP, and UMA in the CKD+ICD group were significantly higher than those in the CKD group (all P<0.05). RBP demonstrated the highest diagnostic accuracy and sensitivity for ICD in CKD patients, while CRP and UMA exhibited equivalent specificity, surpassing that of RBP. ROC curves showed that the areas under the curve (AUCs) of RBP and CRP were significantly greater than that of UMA (P<0.05) and there was no significant difference for AUCs between RBP and CRP. In addition, the levels of RBP, CRP and UMA in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). Logistic regression analysis showed that RBP, CRP and UMA were independent risk factors for the poor prognosis of patients with CKD and ICD (Odds ratios =2.507, 3.677 and 1.919, respectively; all P<0.05)., Conclusion: The assessment of RBP, CRP and UMA is recommended for diagnosis of ICD in CKD patients. RBP, CRP and UMA are independent risk factors for poor prognosis of CKD patients with ICD., Competing Interests: None., (AJTR Copyright © 2024.)

Objective: Transformation of white into brown fat (“browning”) reduces obesity in many preclinical models and holds great promise as a therapeutic concept in metabolic disease. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue; however, the physiologic importance of systemic retinoid transport for adipose tissue browning and adaptive thermogenesis is unknown. Methods: We performed cold exposure studies in mice and humans and used a genetic model of defective vitamin A transport, the retinol binding protein deficient (Rbp−/-) mouse, to study the effects of cooling on systemic vitamin A and the relevance of intact retinoid transport on cold-induced adipose tissue browning. Results: We show that cold stimulation in mice and humans leads to an increase in circulating retinol and its plasma transporter, Rbp. In Rbp−/- mice, thermogenic programming of adipocytes and oxidative mitochondrial function are dramatically impaired in subcutaneous white fat, which renders Rbp−/- mice more cold-sensitive. In contrast, retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In humans, cold-mediated retinol increase is associated with a shift in oxidative substrate metabolism suggestive of higher lipid utilisation. Conclusions: Systemic vitamin A levels are regulated by cold exposure in mice and humans, and intact retinoid transport is essential for cold-induced adipose tissue browning and adaptive thermogenesis.

Objective: To analyze the clinical values of serum Cys C, retinol binding protein and urinary mAlb in diagnosis of glomerulonephritis. Methods: 42 patients with glomerulonephritis in our hospital from December 2017 to December 2018 were selected as the observation group, and 39 healthy subjects were selected as the control group. The levels of serum Cystatin C (Cys-C), retinol binding protein (RBP) and Microalbumin (mALB) in the two groups were observed. The level of renal function indexes in the observation group with different prognosis. The levels of serum Cys C, RBP and urinary malab in the two groups with different prognosis were observed. Results: The levels of serum Cys C, RBP and urinary mALB in the observation group were significantly higher than those in the control group[（2.73±0.72）mg/L vs（0.85±0.21）mg/L,（104.72±21.36）mg/L vs（37.69±8.91）mg/L,（39.51±4.02）mg/L vs（7.08±1.26）mg/L]（P＜0.05）. There was no significant difference in CRF/CKD, 24-hour urinary protein and urea nitrogen levels in 10 patients between remission and no progress（P＞0.05）. Serum creatinine and urea nitrogen water were significantly higher than those in remission or no progress group[（105.76±12.37）μmol/L vs（92.09±11.01）μmol/L,（17.02±2.73）μmol/L vs（7.15±1.06）μmol/L]（P＜0.05）. The levels of serum Cys C, RBP and urinary mALB in CRF patients were significantly higher than those in remission or no progression patients[（3.91±0.56）mg/L vs（2.08±0.35）mg/L（, 182.36±31.23）mg/L vs（47.08±9.35）mg/L,（258.68±70.27）mg/L vs（16.03±3.24）mg/L] （P＜0.05）. The positive rates of serum Cys C, RBP and urinary mALB were 83.33%, 76.19% and 73.80%, respectively. The combined detection rate was 92.85%. The detection rate of combination was significantly higher than that of single index （P＜0.05). Conclusion: The combined detection of serum Cys C, retinol binding protein and urinary mALB has a high effective rate, which can be used to evaluate the filtration function and renal function damage in patients with glomerulonephritis, and to observe the prognosis of patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between the level of serum retinol binding protein (RBP), the ratio of neutrophils to lymphocytes (NLR), the endopentamerin 3 (PTX3) and the stability of carotid atherosclerotic plaque in patients with acute cerebral infarction (ACI). Methods: 300 patients with ACI who were admitted to our hospital from January 2017 to January 2019 were enrolled in this study. According to the results of carotid atherosclerotic plaque ultrasound, they were divided into stable plaque group (n=173) and unstable plaque group (n=127). Another 100 volunteers who had physical examination in the physical examination center of our hospital at the same time were selected as the control group. The RBP, NLR, PTX3 and blood lipid indexes of patients with ACI and control group were detected, and the statistical comparison between groups was made. Pearson test was used to analyze the correlation between RBP, NLR, PTX3 and blood lipid indexes in patients with ACI. Results: There was no significant difference in gender, age, body mass index (BMI), smoking history and drinking history among the three groups (P>0.05). The levels of RBP, NLR and PTX3 in stable plaque group and unstable plaque group were higher than those in control group, and the levels of the above indexes in unstable plaque group were higherthan those in stable plaque group (P<0.05). The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C) and fibrinogen (FIB) in stable plaque group and unstable plaque group were higher than those in the control group. The levels of the above indexes in the unstable plaque group were higher than those in the stable plaque group (P<0.05). According to Pearson test, the levels of RBP, NLR and PTX3 in patients with ACI were positively correlated with TC, TG, LDL-C and FIB(P<0.05). Conclusion: The levels of RBP, NLR and PTX3 are higher in patients with ACI, and they are closely related to the stability of carotid atherosclerotic plaque. It is preliminarily speculated that RBP, NLR and PTX3 may be involved in the formation of carotid atherosclerotic plaque, and then affect the occurrence and development of ACI disease. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value of Multi-Latex polygranular technique joint detection of kidney injury-related urinary microproteins in noninvasive diagnosis after renal transplantation. Methods Clinical data of 72 recipients undergoing renal transplantation were retrospectively analyzed. According to the level of serum creatinine (Scr), the recipients were divided into normal renal function group (group A, n=14), mild kidney injury (group B, n=37), and severe kidney injury group (group C, n=21). 20 healthy volunteers were selected as the healthy control group (HC group). The contents of urinary retinol binding protein (RBP), microalbumin (mAlb), IgG, transferrin (TRF), α1-microglobulin (MG), and β2-MG of subjects in each group were detected using the Multi-Latex polygranular technique. The correlation between urinary microproteins and Scr, blood urea nitrogen (BUN) was analyzed. The differences of urinary microproteins in each group were compared. And the diagnostic value of single and joint detection of urinary microproteins was evaluated. Results Six kinds of urinary microproteins in HC group and group A were significantly lower than those in group B and group C, and six kinds of urinary microproteins in group B were significantly lower than those in group C (all P<0.01). Six kinds of urinary microproteins in renal transplant recipients were positively correlated with BUN. RBP, mAlb, α1-MG, and β2-MG were positively correlated with Scr. The correlations were statistically significant (P<0.001-0.05). The diagnostic value of joint detection of urinary microproteins is better than the detection of single index, among which TRF+mAlb+RBP+α1-MG quadruple detection had the highest diagnostic value. Conclusions Six kinds of urinary microproteins can be used as specific indicators to reflect graft renal function. The polygranular technique can simultaneously detect its contents and achieve noninvasive diagnosis. The diagnosis based on TRF+mAlb+RBP+α1-MG quadruple detection is expected to further improve the noninvasive diagnosis system after renal transplantation. [ABSTRACT FROM AUTHOR]

Purpose of Review: Transthyretin amyloidosis is an increasingly recognized cause of restrictive cardiomyopathy related to amyloid fibril deposition in cardiac tissues. As treatment therapies have emerged for transthyretin amyloidosis (ATTR), so has interest in using biomarkers to identify disease prior to advanced presentation. Recent Findings: Lower levels of transthyretin and retinol binding protein-4 have been demonstrated in patients with pathogenic mutations of transthyretin either with or without clinical disease. Levels associate with the severity of mutations as well as response to treatment with transthyretin stabilizers or small interfering RNA molecules which silence transthyretin production. Transthyretin stability is the rate limiting step of amyloid fibril formation and directly measuring transthyretin kinetic stability has the potential to identify patients as risk as well as therapeutic response to treatment regardless of pathogenic or wild-type genetics. In addition, non-antibody protein-based peptide probes have been developed that directedly measure misfolded transthyretin oligomers due to transthyretin breakdown. Although promising, both TTR kinetic and protein peptide probes remain in early stages of clinical investigation. Summary: Transthyretin, retinol binding protein-4, transthyretin kinetic stability, and protein-based peptide probes have potential as biomarkers to facilitate an earlier ATTR diagnosis for patients with pathogenic transthyretin mutations. [ABSTRACT FROM AUTHOR]

The cardiovascular system facilitates body-wide distribution of oxygen, a vital process for the development and survival of virtually all vertebrates. However, the zebrafish, a vertebrate model organism, appears to form organs and survive mid-larval periods without a functional cardiovascular system. Despite such dispensability, it is the first organ to develop. Such enigma prompted us to hypothesize other cardiovascular functions that are important for developmental and/or physiological processes. Hence, systematic cellular ablations and functional perturbations were performed on the zebrafish cardiovascular system to gain comprehensive and body-wide understanding of such functions and to elucidate the underlying mechanisms. This approach identifies a set of organ-specific genes, each implicated for important functions. The study also unveils distinct cardiovascular mechanisms, each differentially regulating their expressions in organ-specific and oxygen-independent manners. Such mechanisms are mediated by organ-vessel interactions, circulation-dependent signals, and circulation-independent beating-heart-derived signals. A comprehensive and body-wide functional landscape of the cardiovascular system reported herein may provide clues as to why it is the first organ to develop. Furthermore, these data could serve as a resource for the study of organ development and function.

The extracellular protein, transthyretin is responsible for the transport of thyroxin and retinol binding protein complex to the various parts of the body. In addition to this transport function, transthyretin has also been involved in cardiovascular malfunctions, polyneuropathy, psychological disorders, obesity and diabetes, etc. Recent developments have evidenced that transthyretin has been associated with many other biological functions that are directly or indirectly associated with the oxidative stress, the common hallmark for many human diseases. In this review, we have attempted to address that transthyretin is associated with oxidative stress and could be an important biomarker. Potential future perspectives have also been discussed.

To analyze the relationship between serum cystatin C (CysC), retinol binding protein (RBP) and 茁2-microglobulin (茁2-MG) levels in patients with early chronic renal failure (CRF) and to explore their diagnostic value in the early CRF. 240 patients with early CRF who were admitted to the Second Affiliated Hospital of Xinjiang Medical University from August 2016 to October 2018 were selected as the study group, and 240 healthy persons who underwent physical examination in the same period served as control group. The levels of serum creatinine (Scr), CysC, RBP and 茁2-MG were compared between the two groups, the correlation of CysC, RBP and 茁2-MG and their diagnostic value for early CRF were analyzed. The serum levels of SCr, CysC, RBP, 茁2-MG and the positive rate in the study group were significantly higher than those in the control group, the difference was statistically significant (P<0.05). Pearson correlation analysis showed that serum CysC was positively correlated with RBP and 茁2-MG levels in CRF patients (r=0.532, 0.784, P=0.012, 0.000), and RBP was positively correlated with 茁2-MG levels (r=0.518, P=0.015). The specificity, sensitivity and accuracy of combined diagnosis of CysC, RBP and 茁2-MG were 98.75%, 88.33% and 93.54%, respectively. The serum levels of CysC, RBP and 茁2-MG in early CRF patients increased, and there was a certain correlation among the three indicators. The combined detection of CysC, RBP and 茁2-MG has high diagnostic value for early CRF diagnosis. [ABSTRACT FROM AUTHOR]

Expression levels of retinol-binding protein (RBP) and albumin (Alb) in the kidney of patients with neonatal hydronephrosis were detected to explore whether RBP and Alb can be used as diagnostic indicators for neonatal hydronephrosis. Blood and urine samples from neonates with hydronephrosis in the obstetrics and gynaecology department of Hongqi Hospital Affiliated to Mudanjiang Medical University from January 2016 to January 2018, and healthy newborns were collected. RBP and Alb levels in neonates, and the expression of IL-12 in serum of the mothers were detected by ELISA. To establish the rat model, 30 male Sprague Dawley (SD) rats were randomly divided into two groups: sham operation group (n=15) and unilateral ureteral obstruction (UUO) (n=15). Expression of RBP and Alb protein was detected by western blot analysis. Another 30 female SD rats were randomly divided into the Sham and IL-12 knockdown groups. The Sham group was given NC treatment, while IL-12 knockdown group was given treatment with IL-12 knockdown adenovirus through tail vein injection. Results of ELISA showed that serum RBP and renal urinary Alb levels were higher in neonates with hydronephrosis compared with the control group (P=0.009 or P=0.013). Compared with the control group, levels of IL-12 were significantly lower in mother of neonatal hydronephrosis group (P=0.001). After the IL-12 knockdown treatment in pregnant rats, levels of RBP and Alb hydronephrosis-related indicators were significantly increased. The incidence of hydronephrosis in rats delivered via IL-12 knockdown pregnant rats was significantly higher than that of normal pregnant rats (P=0.001). The combination of RBP and Alb in the diagnosis of neonatal hydronephrosis has important clinical significance, and neonatal hydronephrosis is closely related to the level of IL-12 in mothers before birth. Our findings provide new ideas and theoretical basis for the diagnosis and prediction of neonatal hydronephrosis. [ABSTRACT FROM AUTHOR]

Abstract Introduction Idiopathic membranous nephropathy (IMN) is a primary glomerular disease and a major cause of adult nephrotic syndrome. Presently, little is known about the capabilities of the urine markers to reflect the severity of IMN. We aimed at establishing whether urinary N -acetyl-β-glucosaminidase (NAG), Retinol binding protein (RBP), Kidney injury molecule-1 (KIM-1) and Neutrophil gelatianse-associated lipocalin (NGAL) are related with renal parameters and the histological grades tubular injury. Methods The levels of urinary NAG, RBP, KIM-1 and NGAL were determined in 165 biopsy-proven patients and 64 healthy controls. Their levels were then compared between patients and healthy subjects, and between patients with and without nephrotic syndrome. Their linearity with renal parameters and associations with histological grades of renal tubular injury were also assessed. Results All biomarkers were significantly increased in patients (p <.001). However, no significant increase was observed between patients exhibiting moderate and severe grades tubular injury and those exhibiting mild histological grade. With exception of RBP, all biomarkers were higher in patients with nephrotic syndrome (p <.001) and significantly correlated with majority of renal parameters including proteinuria. Conclusion Our findings suggest that although urine markers of tubular injury are increased in IMN, they may not offer a reflection of histological grades. Highlights • Urine markers of tubular injury were increased in IMN. • The level of urine tubular markers failed to reflect histological grades of tubular injury. • Urinary RBP exhibited a weak relationship with parameters of renal function in IMN. [ABSTRACT FROM AUTHOR]

The extracellular protein, transthyretin is responsible for the transport of thyroxin and retinol binding protein complex to the various parts of the body. In addition to this transport function, transthyretin has also been involved in cardiovascular malfunctions, polyneuropathy, psychological disorders, obesity and diabetes, etc. Recent developments have evidenced that transthyretin has been associated with many other biological functions that are directly or indirectly associated with the oxidative stress, the common hallmark for many human diseases. In this review, we have attempted to address that transthyretin is associated with oxidative stress and could be an important biomarker. Potential future perspectives have also been discussed. [ABSTRACT FROM AUTHOR]

Introduction: The present study was designed to assess the validity and efficacy of urinary markers (NAG, RBP, transferrin, α1-microglobulin, and plasma homocysteine) as early predictors of microalbuminuria in diabetic nephropathy in children and adolescents with type-1 diabetes, and its relation with haemoglobin glycated (HbA1c), serum lipid profile, and blood pressure. Material and methods: This study is a follow-up study to the 2002 study by Salem et al. The present study included 35 type 1 diabetes mellitus (T1DM) children and adolescents recruited from regular attendees of the specialised Diabetology Clinic, Children's hospital, Ain Shams University, with previously measured urinary N-acetyl-β-glucosaminidase (13) or homocysteine (11) or transferrin (28) or α1-microglobulin (27) or retinol binding protein (13) as an early predictor of diabetic nephropathy in T1DM. Thirty-five patients with type 1 diabetes mellitus were enrolled, and 24 patients were normoalbuminuric at baseline. The patients were tested for markers other than urinary microalbumin, to predict diabetic nephropathy and early renal impairment in children and adolescents with type 1 diabetes mellitus. Results: Regarding the metabolic control between the studied groups, we found that there is significant difference in HbA1c between the microalbuminuric patients and the normoalbuminuric patients. According to the number of positive markers of diabetic nephropathy, the only parameter that was higher in patients with more than one elevated marker was mean systolic blood pressure. Although mean diabetic blood pressure was higher, it was not statistically significant. Regarding to the predictability of urinary markers, urinary N-acetyl-β-glucosaminidase is the most predictable marker with high sensitivity and specificity. The least sensitivity noticed was urinary RBP and the least specificity noticed was urinary α1-microglobulin. Conclusions: Regarding the predictability of urinary markers, urinary NAG is the most predictable marker with both high sensitivity and specificity, with a sensitivity of 60%, specificity 75%, positive predictive value 60%, negative predictive value 75%, and a diagnostic accuracy of 0.58%. Urinary RBP is another marker with low sensitivity but high specificity. Urinary α1-microglobulin is a valid marker with high sensitivity but low specificity. Contrary to previous markers, plasma homocysteine has high specificity but low sensitivity. [ABSTRACT FROM AUTHOR]

Latar belakang. Malnutrisi sering ditemukan pada pascabedah dan berhubungan dengan luaran yang tidak baik, seperti sepsis atau infeksi luka operasi. Retinol binding protein (RBP) merupakan parameter biokimia yang cukup reliabel untuk menilai malnutrisi. Tujuan. Mengetahui pengaruh malnutrisi berdasarkan penurunan RBP terhadap luaran pasien pascabedah Metode. Penelitian observasional analitik dilakukan di ICU Anak tiga rumah sakit yakni RS Cipto Mangunkusumo, RSUP Dr. Kariadi, dan RSUD Dr. Moewardi. Dilakukan pengukuran RBP, kortisol, CRP pada hari pertama dan kelima pascabedah. Luaran infeksi dinilai berdasarkan skor ASEPSIS. Analisis bivariat dilakukan terhadap beberapa faktor risiko dengan kejadian infeksi luka operasi dan sepsis. Analisis data menggunakan program SPSS versi 17.00. Hasil. Selama kurun waktu 6 bulan, 39 subjek memenuhi kriteria inklusi, tetapi 4 tidak melanjutkan penelitian. Penurunan kadar RBP hari kelima pascabedah 34,3% kasus. Penurunan RBP, CRP, usia 0,05 dan 95% IK masing-masing (0,35-54,4; 0,3 – 40,8;0,1-15,8; dan 0,97-1,6). Faktor lain-status nutrisi prabedah, lama pembedahan, kategori luka operasi dan kortisol-juga didapatkan hasil yang tidak signifikan. Penelitian ini tidak mendapatkan luaran sepsis. Kesimpulan. Terdapat risiko terjadi infeksi luka operasi 4,4 kali apabila kadar RBP menurun, 3,3 kali apabila CRP meningkat, 1,2 kali apabila usia

Background Urine protein loss is common in dogs with chronic kidney disease (CKD). Hypothesis/Objectives To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. Animals One hunderd and eighty dogs with naturally occurring kidney disease. Methods Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. Results Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex‐mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017). Conclusions and Clinical Importance Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.