Retinol-binding Protein 4 Levels Research Articles

MiR-24-3p regulation of retinol binding protein 4 in trophoblast biofunction and preeclampsia.

Preeclampsia (PE) is a pregnancy-related disease and is the leading cause of overall maternal mortality and morbidity. Our previous studies have shown that the serum and placental levels of retinol-binding protein 4 (RBP4) in PE are reduced. Our previous bioinformatics analysis predicted that RBP4 is a target of the microRNA miRNA-24-3p. In this study, our database analysis also indicated that RBP4 is a miR-24-3p target. Compared with that of the normal placenta, the expression level of RBP4 in human PE placenta was significantly reduced, and miR-24-3p was highly expressed. In HTR-8/SVneo cells, transfection of exogenous miR-24-3p reduced RBP4 expression. A dual-luciferase reporter assay validated RBP4 as a direct target of miR-24-3p, indicating that it directly binds to the 3'-untranslated region of RBP4. This binding was reversed by a mutation in the microRNA-binding site. Transwell invasion experiments and CCK8 assay showed that inhibitory effect of miR-24-3p reduced RBP4 mediated HTR-8/SVneo cell invasion and proliferation. These data provide a new overarching perspective on the physiological role played by miR-24-3p in regulating RBP4 during trophoblast dysfunction and PE development.

Correlation of Blood Glucose and Pancreatic Islet Function with Serum Retinol-Binding Protein 4, Serum Cystatin C, and Human New Satiety Molecule Protein-1 in Pregnant Women with Gestational Diabetes Mellitus.

Objective To investigate the correlation of blood glucose and islet function with serum retinol-binding protein 4, serum cystatin C, and nesfatin-1 levels in women with gestational diabetes mellitus. Methods Between June 2018 and June 2020, 70 patients with gestational diabetes mellitus were included in a study group and 70 healthy pregnant women were recruited into a healthy group. Alterations in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), fasting serum insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), serum retinol-binding protein 4 (RBP4), serum cystatin C (CysC), and nesfatin-1 of all eligible participants were analyzed, and the occurrence of complications was recorded. Correlation analysis of serum RBP4, serum CysC, and nesfatin-1 levels with blood glucose and islet function in women with gestational diabetes mellitus was performed. Results Gestational diabetes mellitus was associated with significantly higher levels of FPG, HbA1c, and HOMA-IR and lower levels of FINS (6.58 ± 1.41, 9.24 ± 1.09, 3.21 ± 2.03, 8.23 ± 2.21) versus a healthy condition (5.23 ± 0.85, 7.61 ± 0.67, 2.42 ± 1.14, 10.54 ± 2.15) (P < 0.05). Women with gestational diabetes mellitus showed significantly higher levels of serum RBP4, serum CysC, and nesfatin-1 (62.45 ± 7.86, 1.95 ± 0.59, 2.65 ± 0.49) versus healthy pregnant women (45.48 ± 6.15, 1.03 ± 0.67, 1.42 ± 0.62) (P < 0.05). With serum RBP4, serum CysC, and nesfatin-1 as dependent variables, univariate correlation analysis showed that serum RBP4, serum CysC, and nesfatin-1 levels were positively correlated with FPG and HbA1c levels and HOMA-IR, and negatively correlated with FINS in women with gestational diabetes mellitus (P < 0.05). Gestational diabetes mellitus resulted in a significantly higher incidence of preterm delivery, cesarean section, excess amniotic fluid, and premature rupture of membranes versus a healthy status (P < 0.05). Conclusion Glucose metabolism and islet function in women with gestational diabetes are significantly correlated with serum RBP4, serum CysC, and nesfatin-1 levels, which shows great potential for the prevention and treatment of gestational diabetes mellitus and perinatal complications.

RETRACTED ARTICLE: The impact of vitamin A supplementation on thyroid function and insulin sensitivity: implication of deiodinases and phosphoenolpyruvate carboxykinase in male Wistar rats

PurposeVitamin A is an essential nutrient with vital biological functions. The present study investigated the effect of different doses of vitamin A palmitate at different time intervals on thyroid hormones and glycemic markers.MethodsMale rats were administrated vitamin A palmitate at different doses (0, 0.7, 1.5, 3, 6, and 12 mg/kg, oral) and samples were collected at different time intervals of 2, 4, and 6 weeks. The levels of vitamin A, thyroid hormones (T3, T4, and TSH), deiodinases (Dio1 and Dio3), glycemic markers (blood insulin and fasting glucose levels, HOMA IR and HOMA β), retinol-binding protein 4 (RBP4) and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were measured.ResultsThe findings demonstrated that long-term supplementation with high doses of vitamin A palmitate resulted in hypothyroidism (lower T3 and T4 levels and elevated TSH levels) as well as upregulation of Dio1 and Dio3 expression levels. This effect was associated with elevated glucose and insulin levels, enhanced HOMA IR, and decreased HOMA B index. In addition, prolonged vitamin A supplementation significantly increased RBP4 levels that upregulated the expression of PEPCK.ConclusionHigh doses of vitamin A supplementation increased the risk of hypothyroidism, modulated insulin sensitivity, and over a long period, increased the incidence of type 2 diabetes mellitus associated with oxidative stress and hepatitis.

Tracking Prostate Carcinogenesis over Time through Urine Proteome Profiling in an Animal Model: An Exploratory Approach.

Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer.

Associaton of Retinol Binding Protein 4 (RBP4) Levels With Hyperuricemia: A Cross-Sectional Study in a Chinese Population

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<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).ConclusionsRBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors.

Serum retinol binding protein-4 and the risk of hypothyroidism in Egyptian diabetic patients with cardiovascular manifestations

Retinol binding protein-4 (RBP4) levels have been associated with patients of type 2 diabetes (T2DM) including insulin resistance (IR), dyslipidemia, and cardiovascular disease (CVD). The present study examined the relationship between serum levels of RBP4 and the risk factors related to hypothyroidism (Hypo) and CVD in diabetic Egyptian patients. A total of 96 subjects were recruited and divided into 8 groups. Subjects were assessed for different biochemical parameters. In addition, serum levels of RBP4 were measured using specific immunoassays. There was a highly statistically significant difference in fasting blood glucose (FBG) and hemoglobin A1C (HbA1c) between the different patient groups and the control group. Thyroid stimulating hormone (TSH) concentration in the (T2DM+Hyp) group was considerably higher than in the other groups. There were statistically significant variations in TSH levels between all groups and controls. The mean RBP4 value in Group5 (T2DM+Hyp+CVD) was significantly higher than in the other groups. In (T2DM+Hypo+CVD) group, the receiver operating characteristic (ROC) curve revealed that RBP4 had a higher area under curve (AUC), making it a powerful discriminator of those diseases.

Reduced Vitamin A RBP Levels in Hospitalized COVID-19 Patients

ObjectivesVitamin A plays a key role in the regulation of the innate and acquired immune system. Vitamin A plays an important role in the fetal development of lung tissue and in the repair of infection-related damage. Reduced vitamin A levels have been described in the context of acute infections. In addition to an increased requirement, an increased excretion during inflammation is discussed. In this prospective, multicenter cohort study (University Hospital Münster, Hospital Steinfurt), vitamin A plasma levels were compared in critically to convalescent COVID-19 patients. For the first time, unbound free vitamin A, retinol-binding protein (RBP) and total vitamin A were differentiated. MethodsThe vitamin A levels of hospitalized COVID-19 patients with critical illness course (n = 20) were compared with COVID-19 patients with blood sampling in convalescence (n = 20). In addition to the determination of total vitamin A, the determination of unbound vitamin A and RBD was performed. ResultsIn the critically ill COVID-19 patients in the acute phase of the disease, significantly lower levels of total vitamin A (total, p < 0.01) and RBD itself (p < 0.01) were detected compared to the patients with blood sampling in convalescence. In both groups, only a very small amount of unbound vitamin A was present. ConclusionsDuring the acute phase of disease in COVID-19 patients, both total vitamin A and RBD-bound levels are significantly decreased. These results support previous data on vitamin A deficiency in the setting of acute infections. Further work is needed to investigate the impact on COVID-19 disease progression. Funding SourcesNo funding.

Interplay of retinol binding protein 4 with obesity and associated chronic alterations (Review).

Obesity is a multifactorial disease, defined as excessive fat deposition in adipose tissue. Adipose tissue is responsible for the production and secretion of numerous adipokines that induce metabolic disorders. Retinol-binding protein 4 (RBP4) is an adipokine that transports vitamin A or retinol in the blood. High levels of RBP4 are associated with development of metabolic disease, including obesity, insulin resistance (IR), metabolic syndrome, and type 2 diabetes (T2D). The present review summarizes the role of RBP4 in obesity and associated chronic alterations. Excessive synthesis of RBP4 contributes to inflammatory characteristic of obesity by activation of immune cells and release of proinflammatory cytokines, such as TNFα and ILs, via the Toll-like receptor/JNK pathway. The retinol-RBP4 complex inhibits insulin signaling directly in adipocytes by activating Janus kinase 2 (JAK2)/STAT5/suppressor of cytokine signaling 3 signaling. This mechanism is retinol-dependent and requires vitamin A receptor stimulation by retinoic acid 6 (STRA6). In muscle, RBP4 is associated with increased serine 307 phosphorylation of insulin receptor substrate-1, which decreases its affinity to PI3K and promotes IR. In the liver, RBP4 increases hepatic expression of phosphoenolpyruvate carboxykinase, which increases production of glucose. Elevated serum RBP4 levels are associated with β-cell dysfunction in T2D via the STRA6/JAK2/STAT1/insulin gene enhancer protein 1 pathway. By contrast, RBP4 induces endothelial inflammation via the NF-κB/nicotinamide adenine dinucleotide phosphate oxidase pathway independently of retinol and STRA6, which stimulates expression of proinflammatory molecules, such as vascular cell adhesion molecule 1, E-selectin, intercellular adhesion molecule 1, monocyte chemoattractant protein 1 and TNFα. RBP4 promotes oxidative stress by decreasing endothelial mitochondrial function; overall, it may serve as a useful biomarker in the diagnosis of obesity and prognosis of associated disease, as well as a potential therapeutic target for treatment of these diseases.

Retinol-binding protein-4 and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common as the global economy grows and living standards improve. Timely and effective preventions and treatments for NAFLD are urgently needed. Retinol-binding protein-4 (RBP4), the protein that transports retinol through the circulation, was found to be positively related to diabetes, obesity, cardiovascular disease, and other metabolic diseases. Observational studies on the association between serum RBP4 level and the prevalence of NAFLD found contradictory results. Some of the underlying mechanisms responsible for this association have been revealed, and the possible clinical implications of treating NAFLD by targeting RBP4 have been demonstrated. Future studies should focus on the predictive value of RBP4 on NAFLD development and its potential as a therapeutic target in NAFLD.

Sexual Dimorphism in the Association of Serum Retinol-Binding Protein-4 With Long-Term Dynamic Metabolic Profiles in Non-Diabetes.

ObjectivesWe aimed to investigate the association of circulating retinol-binding protein-4 (RBP4) levels with long-term cardiometabolic risk profiles and whether sex disparity mattered.MethodsWe included 784 non-diabetic participants aged 40 years and above from a well-defined community-based cohort at baseline in 2005 and they were invited to attend the on-site follow-up examination for two consecutive times with 3-year intervals in 2008 and 2011, respectively. Serum RBP4 was measured at baseline, and the anthropometry and biochemical measurements were performed at each visit. Generalized estimating equation models were used to assess the association of serum RBP4 levels with the dynamic changes in adiposity and glucolipid profile.ResultsBased on all the baseline and the 3- and 6-year follow-up data, baseline serum RBP4 levels (each 1-unit of log10RBP4) were significantly associated with waist circumference [β=3.12, 95% confidence interval (CI) (0.77, 5.47), P=0.01], fasting, and 2-h post-loading glucose [β=0.26 (0.05, 0.47), P=0.02, and 1.70 (1.29, 2.12), P< 0.0001], serum triglycerides [β=0.75, 95% CI (0.54, 0.96), P< 0.0001], total cholesterol [β=0.47, 95% CI [0.23 0.70], P<0.0001), and marginally with body mass index (β=0.97, 95% CI (0.02, 1.93), P=0.046], in total participants, after adjusting potential confounders. The association of RBP4 with 2-h post-loading glucose was stronger in women than that in men [β=1.99, 95% CI (1.49, 2.50) vs. 0.61 (-0.14, 1.36), P for interaction=0.001]. The analysis of change in Z-score of cardiometabolic profiles corresponding to each 1-unit increment in log10RBP4 showed consistent results.ConclusionsHigher RBP4 levels are associated with longitudinal increase in adiposity and deteriorated glucolipid profile defined by repeated measurements. The associations differ in sex regarding to the 2-h post-loading glucose.

High prevalence of malnutrition and vitamin A deficiency among schoolchildren of rural areas in Malaysia using a multi-school assessment approach.

Childhood malnutrition is known as a public health concern globally. The present study aims to assess the anthropometry and blood biochemical status of rural primary schoolchildren in Malaysia. A total of 776 children (7-11 years old) from ten rural primary schools from five states were included in this study. Nutritional outcomes were assessed based on sex, age group and school categories among the children (median age: 9 years (P25:8, P75:10)). The overall prevalence of malnutrition was 53·4 %. Vitamin A deficiency (VAD) was recorded at 20·6 and 39·8 % based on retinol and retinol-binding protein (RBP) levels, respectively. Anaemia, iron deficiency (ID), iron-deficiency anaemia (IDA) and elevated inflammation were found at 14·9, 17·9, 9·1 and 11·5 %, respectively. Malnutrition, VAD, anaemia, ID, IDA and elevated inflammation were more prevalent among Orang Asli (OA) schoolchildren compared with Non-Orang Asli schoolchildren. Higher occurrences of VAD and anaemia were also found among children aged <10 years. Retinol, RBP, α-carotene, ferritin and haemoglobin levels were lower among undernourished children. Besides, overweight/obese children exhibited a higher level of high-sensitivity C-reactive protein. Multivariate analysis demonstrated that OA school children (adjusted OR (AOR): 6·1; 95 % CI 4·1, 9·0) and IDA (AOR: 3·6; 95 % CI 1·9, 6·6) were associated with stunting among this population. The present study revealed that malnutrition, micronutrient deficiencies and anaemia are prevalent among rural primary schoolchildren in Malaysia, especially those from OA schools and younger age children (<10 years). Hence, more appropriate and targeted measures are needed to improve the nutritional status of these children.

Circulating levels of WISP-1 (Wnt1-inducible signaling pathway protein 1) and other selected adipokines in children with inflammatory bowel disease.

Wnt1 inducible protein-1 signaling pathway (WISP-1) is a relatively new adipokine involved in many cellular processes, including epithelial mucosa healing. The aim of the study was to compare circulating levels of WISP-1 and other selected adipokines [adiponectin, resistin and retinol-binding protein 4 (RBP-4)] in children with inflammatory bowel disease (IBD) with healthy controls and to investigate possible differences between Crohn's disease patients. (CD) or ulcerative colitis (UC). The study was performed as a case-control study. In addition to adipokines, anthropometric, lipid parameters, markers of inflammation or disease activity were evaluated in all participants. Compared to healthy controls (n=20), significantly lower levels of adiponectin and higher levels of resistin and WISP-1 were found in patients with IBD (n=58). Elevation of WISP-1 was detected only in the CD group (n=31). There were no differences in RBP-4 levels between the groups. Adiponectin, WISP-1 and RBP-4 were independently associated with body mass index only, resistin levels were associated with C-reactive protein levels and leukocyte counts. Adverse adipokines production reflects presence of dysfunctional fat tissue in IBD patients. Higher levels of WISP-1 in CD compared to patients with UC may indicate a specific role for mesenteric adipose tissue in WISP-1 production.

Comparative Evaluation of Chiglitazar and Sitagliptin on the Levels of Retinol-Binding Protein 4 and Its Correlation With Insulin Resistance in Patients With Type 2 Diabetes.

AimsWe evaluated the efficacy and significant changes in the levels of retinol-binding protein 4 (RBP-4) and insulin resistance in patients with type 2 diabetes mellitus (T2DM) treated with chiglitazar versus sitagliptin.MethodsEighty-one T2DM patients with haemoglobin A1c (HbA1c) level of 7.5%–10.0% were selected. Based on the study criteria, patients were randomly assigned to receive chiglitazar (32 mg), chiglitazar (48 mg), or sitagliptin (100 mg) orally for 24 weeks. Sociodemographic and anthropometric characteristics, lipid profiles, glucose profiles, and serum RBP-4 levels were determined at baseline and at the end of the therapy.ResultsAfter treatment for 24 weeks, significant changes in fasting blood glucose (FBG), fasting insulin (Fins), 2 h-blood glucose (2h-BG), the score values of insulin resistance/insulin secretion/β cell function (HOMA-IR, HOMA-IS, and HOMA-β), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), and RBP-4 levels were detected in patients with chiglitazar administration and sitagliptin administration. Changes in RBP-4 levels were positively correlated with changes in HOMA-IR and 2 h-BG in linear regression.ConclusionsChiglitazar showed a greater improvement in parameters of diabetes than sitagliptin, and changes in serum RBP-4 levels were associated with changes in insulin-sensitizing parameters.Clinical Trial Registration ClinicalTrials.gov, CT.gov identifier: NCT02173457.

The potential use of urinary transferrin, urinary adiponectin, urinary Retinol Binding Protein, and serum zinc alpha 2 glycoprotein levels as novel biomarkers for early diagnosis of diabetic nephropathy: A case-control study

Background and aimsThe level of albuminuria is used to evaluate diabetic nephropathy (DN). However, to detect or predict the early stages of DN, better biomarkers are needed. MethodsThis study is a case-control observational study. 80 Egyptians participated in the study: 60 patients with type 2 diabetes mellitus (T2DM) were divided into three groups (20 patients each), and 20 healthy subjects with matched age and gender were used as controls. Demographic and laboratory data were analyzed. An enzyme-linked immunosorbent assay was used to determine the levels of four biomarkers of DN; urinary adiponectin (ADP), urinary transferrin, serum Zinc Alpha 2 Glycoprotein (ZAG), and urinary Retinol Binding Protein (RBP). ResultsThe levels of DN biomarkers urinary ADP, transferrin, RBP, and serum, ZAG were significantly higher in patients with T2DM than in controls. The ROC curve of the validity of the simultaneous use of all four biomarkers in predicting albuminuria indicates a sensitivity of 90% and a specificity of 90%. The Area Under the Curve (AUC) was 0.948, the 95% confidence interval was 0.998–0.897, and the p-value was 0.001. ConclusionsIn patients with T2DM, urine adiponectin, transferrin, RBP, and serum ZAG concentration may be useful biomarkers in the early diagnosis of DN. A further longitudinal prospective study is required to explore the potential utility of these biomarkers.

Elevated Serum Retinol Binding Protein 4 is Associated with the Risk of Diabetic Cardiomyopathy.

Retinol binding protein 4 (RBP4), a biomarker for insulin resistance in type 2 diabetes (DM), is increased in heart failure. This case-control study aims to determine the association between serum RBP4 levels and diabetic cardiomyopathy (DCM). Demographic and clinical data were obtained from 245 DM patients and 102 non-diabetic controls. RBP4 levels were measured using ELISA. The association between RBP4 and DCM was evaluated using multivariate logistic regression and restricted cubic splines (RCS) in DM patients. We showed that serum RBP4 levels were higher in DCM patients than in DM patients without DCM or the controls. Multivariate analysis adjusted by age, gender, body mass index, diabetes duration, left ventricular ejection fraction, insulin treatment, triglycerides, low-density lipoprotein cholesterol, estimated glomerular filtration rate, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and log N-terminal proBNP showed a significant association between RBP4 and DCM (highest vs. lowest tertile OR 16.87, 95% CI: 6.58, 43.23, p 0.001). RCS displayed a positive linear correlation between RBP4 levels and the risk of DCM in diabetes (p = 0.004). Adding RBP4 to a basic risk model for DCM improved the reclassification (Net reclassification index: 87.86%, 95% CI: 64.4%, 111.32%, p 0.001). The positive association between serum RBP4 and DCM suggested the role of RBP4 as a potential diagnostic biomarker for distinguishing DCM in patients with DM.

Association Between Circulating Retinol-Binding Protein 4 and Adverse Cardiovascular Events in Stable Coronary Artery Disease.

BackgroundThe predictive role of retinol-binding protein 4 (RBP4) in the adverse prognosis of patients with stable coronary artery disease (CAD) has not been well-defined. We thus conducted this cohort study to investigate the association between circulating RBP4 level and major adverse cardiovascular events (MACEs) in Chinese patients with stable CAD.MethodsPatients with stable CAD and serum RBP4 concentration measurement at admission between July 2012 and January 2015 were included. The primary outcome in this study was incident MACEs, which included acute coronary syndrome, heart failure, stroke, peripheral vascular disease, and cardiovascular death. Cox proportional hazards regression was adopted to investigate the association between RBP4 and the incidence of MACEs.ResultsA total of 840 patients with stable CAD were analyzed. The mean age of patients was 61.2 ± 15.9 years, and 56.1% of them were men. After a median follow-up of 2.3 years, 129 MACEs were observed. Compared to participants exposed to the first quartile of serum RBP4 level, those in the second, the third, and the fourth quartiles had associated hazard ratios (HRs) of 2.38 [95% confidence interval (CI): 1.33–4.26], 2.35 (95% CI: 1.31–4.21), and 2.27 (95% CI: 1.28–4.04) after adjusted for confounders, respectively. Every 5 μg/ml increment in serum RBP4 concentration was associated with an adjusted HR of 1.13 (95% CI: 1.05–1.22) for the occurrence of MACEs. Subgroup analyses suggested no significant modifying effects of baseline characteristics for the association between RBP4 and MACEs in patients with stable CAD.ConclusionOur finding suggested that the higher circulating RBP4 level was significantly associated with an increased risk of MACEs in patients with stable CAD.

Urinary Proteomic Signature in Acute Decompensated Heart Failure: Advances into Molecular Pathophysiology.

Acute decompensated heart failure (ADHF) is a life-threatening clinical syndrome involving multi-organ function deterioration. ADHF results from multifaceted, dysregulated pathways that remain poorly understood. Better characterization of proteins associated with heart failure decompensation is needed to gain understanding of the disease pathophysiology and support a more accurate disease phenotyping. In this study, we used an untargeted mass spectrometry (MS) proteomic approach to identify the differential urine protein signature in ADHF patients and examine its pathophysiological link to disease evolution. Urine samples were collected at hospital admission and compared with a group of healthy subjects by two-dimensional electrophoresis coupled to MALDI-TOF/TOF mass spectrometry. A differential pattern of 26 proteins (>1.5-fold change, p < 0.005), mostly of hepatic origin, was identified. The top four biological pathways (p < 0.0001; in silico analysis) were associated to the differential ADHF proteome including retinol metabolism and transport, immune response/inflammation, extracellular matrix organization, and platelet degranulation. Transthyretin (TTR) was the protein most widely represented among them. Quantitative analysis by ELISA of TTR and its binding protein, retinol-binding protein 4 (RBP4), validated the proteomic results. ROC analysis evidenced that combining RBP4 and TTR urine levels highly discriminated ADHF patients with renal dysfunction (AUC: 0.826, p < 0.001) and significantly predicted poor disease evolution over 18-month follow-up. In conclusion, the MS proteomic approach enabled identification of a specific urine protein signature in ADHF at hospitalization, highlighting changes in hepatic proteins such as TTR and RBP4.

Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study.

ContextObservational studies have suggested associations between adipokines and cardiovascular disease (CVD), but the roles of certain adipokines remain controversial, and these associations have not yet been ascertained causally.ObjectiveTo investigate whether circulating adipokines causally affect the risk of CVD using 2-sample Mendelian randomization (MR).MethodsIndependent genetic variants strongly associated with adiponectin, resistin, chemerin, and retinol binding protein 4 (RBP4) were selected from public genome-wide association studies. Summary-level statistics for CVD, including coronary artery disease (CAD), myocardial infarction, atrial fibrillation (AF), heart failure (HF), and stroke and its subtypes were collected. The inverse-variance weighted and Wald ratio methods were used for the MR estimates. The MR pleiotropy residual sum and outlier, weighted median, MR-Egger, leave-one-out analysis, MR Steiger, and colocalization analyses were used in the sensitivity analysis.ResultsGenetically predicted resistin levels were positively associated with AF risk (odds ratio [OR] 1.09; 95% confidence interval [CI], 1.04-1.13; P = 4.1 × 10-5), which was attenuated to null after adjusting for blood pressure. We observed suggestive associations between higher genetically predicted chemerin levels and an increased risk of CAD (OR 1.27; 95% CI, 1.01-1.60; P = 0.040), higher genetically predicted RBP4 levels and an increased risk of HF (OR 1.14; 95% CI, 1.02-1.27; P = 0.024). There was no causal association between genetically predicted adiponectin levels and CVD risk.ConclusionsOur findings reveal the causal association between resistin and AF, probably acting through blood pressure, and suggest potential causal associations between chemerin and CAD, RBP4, and HF.

Clinical study on the minimally invasive percutaneous nephrolithotomy treatment of upper urinary calculi.

BACKGROUNDUpper urinary tract stones are very common in my country, with an incidence of 1% to 5% in the North and an even higher incidence of 5% to 10% in the south. The incidence rate in the south is higher than that in the north, mainly due to the water quality, climate and eating habits of the region. From the perspective of sex, incidence is more likely in males than females. In the high-incidence population, young adults are most prone to stones. Men in the age range of 25 to 40 years are more likely to have stones.AIMTo observe the therapeutic effect of minimally invasive percutaneous nephrolithotomy (mPCNL) on upper urinary tract stones and its influence on the renal function of patients.METHODSPatients with upper urinary tract stones who were treated in our hospital from February 2017 to March 2018 were selected as research subjects and were divided into the PCNL group and the mPCNL group according to the random number table method. The general conditions of the two groups of patients were observed during the perioperative period, and the differences in stone clearance, pain, renal function indicators and complication rates were compared between the two groups to determine which were statistically significant (P < 0.05).RESULTSThe operation time of the mPCNL group was longer than that of the PCNL group (t = -34.392, P < 0.001), and the intraoperative blood loss of the mPCNL group was more than that of the PCNL group (t = 34.090, P < 0.001). There was no difference in renal function indices between the two groups of patients before treatment, and there was no difference in the levels of serum creatinine, β2 microglobulin or retinol binding protein in the mPCNL group after treatment. The visual analog scale score of patients in the mPCNL group was lower than that of the PCNL group (t = 12.191, P < 0.001), and there was no significant difference in the stone clearance rate between the two groups (χ2 value = 1.013, P = 0.314). There was no significant difference in the incidence of urine extravasation, dyspnea and peripheral organ damage between the two groups (χ2 value = 1.053, P = 0.305). At 1 mo after treatment and 3 mo after treatment, the quality of life of the mPCNL group was lower than that of the PCNL group, and the Qmax level of the mPCNL group was higher than that of the PCNL group.CONCLUSIONmPCNL has a good therapeutic effect on upper urinary tract stones, with a high stone clearance rate without causing kidney damage or increasing the incidence of complications, and thus has good application value.

Urinary Retinol-Binding Protein 4 is Associated With Renal Function and Rapid Renal Function Decline in Kidney Transplant Recipients

Urinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs). A total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m2/year or initiation of dialysis, and 19 (38%) were included in rapid renal function decline group. Urinary RBP4/creatinine was inversely correlated with allograft function (r=-0.54, P < .001 with eGFR, and r=0.49, P < .001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P=.017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P=.005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P=.010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P < .001) for rapid renal function decline. Urinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.