Diagnostic value of retinol-binding protein 4 in diabetic nephropathy: a systematic review and meta-analysis.

Objective: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN. Methods: We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated. Results: Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71-0.80] and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test. Conclusion: Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.

Development of a time-resolved immunochromatographic test strip for rapid and quantitative determination of retinol-binding protein 4 in urine.

Urine retinol-binding protein 4 (RBP4) has recently been reported as a novel earlier biomarker of chronic kidney disease (CKD) which is a global public health problem with high morbidity and mortality. Accurate and rapid detection of urine RBP4 is essential for early monitor of impaired kidney function and prevention of CKD progression. In the present study, we developed a time-resolved fluorescence immunochromatographic test strip (TRFIS) for the quantitative and rapid detection of urine RBP4. This TRFIS possessed excellent linearity ranging from 0.024 to 12.50 ng/mL for the detection of urine RBP4, and displayed a good linearity (Y = 239,581 × X + 617,238, R2 = 0.9902), with the lowest visual detection limit of 0.049 ng/mL. This TRFIS allows for quantitative detection of urine RBP4 within 15 min and shows high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 8%, respectively. Additionally, this TRFIS was applied to detect RBP4 in the urine samples from healthy donors and patients with CKD, and the results of TRFIS could efficiently discern the patients with CKD from the healthy donors. The developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range, and is suitable for rapid and quantitative determination of urine RBP4.

A candidate panel of eight urinary proteins shows potential of early diagnosis and risk assessment for diabetic kidney disease in type 1 diabetes.

Diabetic kidney disease (DKD) poses a significant health challenge for individuals with diabetes. At its initial stages, DKD often presents asymptomatically, and the standard for non-invasive diagnosis, the albumin-creatinine ratio (ACR), employs discrete categorizations (normal, microalbuminuria, macroalbuminuria) with limitations in sensitivity and specificity across diverse population cohorts. Single biomarker reliance further restricts the predictive value in clinical settings. Given the escalating prevalence of diabetes, our study uses proteomic technologies to identify novel urinary proteins as supplementary DKD biomarkers. A total of 158 T1D subjects provided urine samples, with 28 (15 DKD; 13 non-DKD) used in the discovery stage and 131 (45 DKD; 40 pDKD; 46 non-DKD) used in the confirmation. We identified eight proteins (A1BG, AMBP, AZGP1, BTD, RBP4, ORM2, GM2A, and PGCP), all of which demonstrated excellent area-under-the-curve (AUC) values (0.959 to 0.995) in distinguishing DKD from non-DKD. Furthermore, this multi-marker panel successfully segregated the most ambiguous group (microalbuminuria) into three distinct clusters, with 80% of subjects aligning either as DKD or non-DKD. The remaining 20% exhibited continued uncertainty. Overall, the use of these candidate urinary proteins allowed for the better classification of DKD and offered potential for significant improvements in the early identification of DKD in T1D populations.

Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with the risk of COVID-19 remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of retinol, retinol binding protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein 1 (CRABP1) with COVID-19 in European population. METHODS: The outcome utilized the summary statistics of COVID-19 from the COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the causal relationship between exposure and outcome. Sensitivity analyses were performed to ensure the validity of the results. RESULTS: The MR estimates showed that retinol was associated with lower COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53-0.90, P: 0.0065), whereas the associations between retinol and COVID-19 hospitalization or severity were not significant. RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% CI: 0.72-0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 hospitalization (OR: 1.10, 95% CI: 1.01-1.18, P: 0.0199). CRABP1 was association with lower COVID-19 susceptibility (OR: 0.95, 95% CI: 0.91-0.99, P: 0.0290) using the IVW. CONCLUSIONS: We found evidence of possible causal association of retinol, RBP4, RDH16 and CRABP1 with the susceptibility, hospitalization and severity of COVID-19. Our study defines that retinol is significantly associated with lower COVID-19 susceptibility, which provides a reference for the prevention of COVID-19 with vitamin A supplementation.

Retinol-binding protein 4 (RBP4) circulating levels and gestational diabetes mellitus: a systematic review and meta-analysis.

Background: Gestational diabetes mellitus (GDM) is a prevalent condition where diabetes is diagnosed during pregnancy, affecting both maternal and fetal outcomes. Retinol-binding protein 4 (RBP4) is a circulating adipokine which belongs to the lipocalin family and acts as a specific carrier protein that delivers retinol (vitamin A) from the liver to the peripheral tissues. Growing data indicate that circulating RBP4 levels may positively correlate with GDM. Thus, this systematic review and meta-analysis aimed to investigate the potential relationship between circulating RBP4 levels and GDM when measured at various stages of pregnancy. Methods: MEDLINE, CINAHL, EMCARE, EMBASE, Scopus, and Web of Science databases were searched to identify studies comparing pregnant women with and without GDM, whose circulating RBP4 levels were measured in at least one pregnancy trimester. Findings were reported using standardized mean difference (SMD) and random-effects models were used to account for variability among studies. Furthermore, the risk of bias was assessed using the RoBANS tool. Results: Out of the 34 studies identified, 32 were included in the meta-analysis (seven with circulating RBP4 levels measured in the first trimester, 19 at 24-28 weeks, and 14 at >28 weeks of pregnancy). RBP4 levels were statistically higher in the GDM group than in controls when measured during all these pregnancy stages, with the noted RBP4 SMD being 0.322 in the first trimester (95% CI: 0.126-0.517; p < 0.001; 946 GDM cases vs. 1701 non-GDM controls); 0.628 at 24-28 weeks of gestation (95% CI: 0.290-0.966; p < 0.001; 1776 GDM cases vs. 1942 controls); and 0.875 at >28 weeks of gestation (95% CI: 0.252-1.498; p = 0.006; 870 GDM cases vs. 1942 non-GDM controls). Significant study heterogeneity was noted for all three pregnancy timepoints. Conclusion: The present findings indicate consistently higher circulating RBP4 levels in GDM cases compared to non-GDM controls, suggesting the potential relevance of RBP4 as a biomarker for GDM. However, the documented substantial study heterogeneity, alongside imprecision in effect estimates, underscores the need for further research and standardization of measurement methods to elucidate whether RBP4 can be utilized in clinical practice as a potential GDM biomarker. Systematic review registration: PROSPERO (CRD42022340097: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340097).

Adipokines in depressed women with and without adverse childhood experiences.

BACKGROUND: Adverse childhood experiences (ACE) elevate the risk of both major depressive disorder (MDD) and metabolic diseases. The underlying pathophysiology might include alterations of adipokine levels as a consequence of ACE. In this study, we used a full-factorial design to investigate the levels of select adipokines in women with ACE-only (n = 23), MDD-only (n = 27), ACE+MDD (n = 25) and healthy controls (HC, n = 29) to identify metabolic makers associated with vulnerability and resilience of developing MDD after ACE exposure. METHODS: Serum levels of adiponectin, leptin, adiponectin-to-leptin (A/L) ratio, and retinol binding protein 4 (RBP4) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin levels did not differ between groups. Individuals with vs. without MDD showed higher leptin serum concentrations. As predicted, A/L ratio indicated lower values in individuals with vs. without ACE. RBP4 showed a more nuanced pattern with reduced levels in the ACE-only and MDD-only groups compared to HC. Furthermore, the ACE-only group showed lower RBP4 concentrations compared to ACE+MDD. These results were not accounted by BMI or medication status. CONCLUSION: Our results do not support the utility of adiponectin and leptin as predictors of vulnerability or resilience of developing MDD after ACE. In contrast, RBP4 might play a role in resilience towards the development of MDD following ACE. Further research on this more recently discovered adipokine seems warranted.

Assessing the Impact of Bariatric Surgery on Retinol-Binding Protein 4 (RBP4): A Systematic Review and Meta-Analysis.

This study aimed to analyze changes in retinol-binding protein 4 (RBP4) levels before and after bariatric surgery in obese individuals. Bariatric surgery is a safe and effective treatment for morbid obesity, impacting molecules like RBP4. A systematic review and meta-analysis of 12 relevant studies were conducted, utilizing databases such as PubMed, Cochrane Central, Web of Science, and Scopus. Significant differences in RBP4, glucose, and BMI levels pre- and post-surgery were observed. Meta-regression analysis explored associations with age, pre-BMI, triglycerides, glucose, and post-insulin levels. Findings suggest RBP4 may improve insulin sensitivity after bariatric surgery, warranting further investigation as a potential pharmacotherapeutic target. These results highlight the importance of understanding RBP4's role in the context of bariatric surgery and its implications for improving metabolic health in obese individuals.

Genetic influences on circulating retinol and its relationship to human health.

Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.

Identification of potential crucial genes and therapeutic targets for epilepsy.

BACKGROUND: Epilepsy, a central neurological disorder, has a complex genetic architecture. There is some evidence suggesting that genetic factors play a role in both the occurrence of epilepsy and its treatment. However, the genetic determinants of epilepsy are largely unknown. This study aimed to identify potential therapeutic targets for epilepsy. METHODS: Differentially expressed genes (DEGs) were extracted from the expression profiles of GSE44031 and GSE1834. Gene co-expression analysis was used to confirm the regulatory relationship between newly discovered epilepsy candidate genes and known epilepsy genes. Expression quantitative trait loci analysis was conducted to determine if epilepsy risk single-nucleotide polymorphisms regulate DEGs' expression in human brain tissue. Finally, protein-protein interaction analysis and drug-gene interaction analysis were performed to assess the role of DEGs in epilepsy treatment. RESULTS: The study found that the protein tyrosine phosphatase receptor-type O gene (PTPRO) and the growth arrest and DNA damage inducible alpha gene (GADD45A) were significantly upregulated in epileptic rats compared to controls in both datasets. Gene co-expression analysis revealed that PTPRO was co-expressed with RBP4, NDN, PAK3, FOXG1, IDS, and IDS, and GADD45A was co-expressed with LRRK2 in human brain tissue. Expression quantitative trait loci analysis suggested that epilepsy risk single-nucleotide polymorphisms could be responsible for the altered PTPRO and GADD45A expression in human brain tissue. Moreover, the protein encoded by GADD45A had a direct interaction with approved antiepileptic drug targets, and GADD45A interacts with genistein and cisplatin. CONCLUSIONS: The results of this study highlight PTPRO and GADD45A as potential genes for the diagnosis and treatment of epilepsy.

Adipose Signals Regulating Distal Organ Health and Disease.

Excessive adiposity in obesity is a significant risk factor for development of type 2 diabetes (T2D), nonalcoholic fatty liver disease, and other cardiometabolic diseases. An unhealthy expansion of adipose tissue (AT) results in reduced adipogenesis, increased adipocyte hypertrophy, adipocyte hypoxia, chronic low-grade inflammation, increased macrophage infiltration, and insulin resistance. This ultimately culminates in AT dysfunction characterized by decreased secretion of antidiabetic adipokines such as adiponectin and adipsin and increased secretion of proinflammatory prodiabetic adipokines including RBP4 and resistin. This imbalance in adipokine secretion alters the physiological state of AT communication with target organs including pancreatic ß-cells, heart, and liver. In the pancreatic ß-cells, adipokines are known to have a direct effect on insulin secretion, gene expression, cell death, and/or dedifferentiation. For instance, impaired secretion of adipsin, which promotes insulin secretion and ß-cell identity, results in ß-cell failure and T2D, thus presenting a potential druggable target to improve and/or preserve ß-cell function. The cardiac tissue is affected by both the classic white AT-secreted adipokines and the newly recognized brown AT (BAT)-secreted BATokines or lipokines that alter lipid deposition and ventricular function. In the liver, adipokines affect hepatic gluconeogenesis, lipid accumulation, and insulin sensitivity, underscoring the importance of adipose-liver communication in the pathogenesis of nonalcoholic fatty liver disease. In this perspective, we outline what is currently known about the effects of individual adipokines on pancreatic ß-cells, liver, and the heart.

The association between retinol-binding protein 4 and risk of type 2 diabetes: A systematic review and meta-analysis.

Retinol-binding protein 4 (RBP4) was controversially associated with type 2 diabetes mellitus (T2DM). This meta-analysis aimed at evaluating the association between RBP4 level and T2DM risk. MEDLINE and EMBASE were searched to identify relevant studies up to 3 December 2022. Random effects model was used to pool multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias was estimated by Funnel plot and Egger's test, it was considered to be significant when P < 0.05. Eight studies including 8087 participants were finally included. Compared to those with the lowest level, subjects with the highest level of RBP4 have a higher risk of T2DM (OR = 1.47, 95% CI: 1.16-1.78, P < 0.001, I2 = 86.9%). No publication bias among the included studies was found (t = 0.94, P = 0.377). This meta-analysis indicated that high RBP4 level was associated with increasing risk of T2DM.

Human cord plasma proteomic analysis reveals sexually dimorphic proteins associated with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is associated with increased risk of cardiometabolic disease later in life and has been shown to affect female and male offspring differently, but the mechanisms remain unclear. The purpose of this study was to identify proteomic differences and metabolic risk markers in IUGR male and female neonates when compared to appropriate for gestational age (AGA) babies that will provide a better understanding of IUGR pathogenesis and its associated risks. Our results revealed alterations in IUGR cord plasma proteomes with most of the differentially abundant proteins implicated in peroxisome pathways. This effect was evident in females but not in males. Furthermore, we observed that catalase activity, a peroxisomal enzyme, was significantly increased in females (p < 0.05) but unchanged in males. Finally, we identified risk proteins associated with obesity, type-2 diabetes, and glucose intolerance such as EGF containing fibulin extracellular matrix protein 1 (EFEMP1), proprotein convertase subtilisin/kexin type 9 (PCSK9) and transforming growth factor beta receptor 3 (TGFBR3) proteins unique to females while coagulation factor IX (C9) and retinol binding protein 4 (RBP4) are unique in males. In conclusion, IUGR may display sexual dimorphism which may be associated with differences in lifelong risk for cardiometabolic disease between males and females.

Comparison of test performance of two commonly used multiplex assays to measure micronutrient and inflammatory markers in serum: results from a survey among pregnant women in South Africa.

The combined sandwich-ELISA (s-ELISA; VitMin Lab, Germany) and the Quansys Q-Plex™ Human Micronutrient Array (7-Plex) are multiplex serum assays that are used to assess population micronutrient status in low-income countries. We aimed to compare the agreement of five analytes, α-1-acid glycoprotein (AGP), C-reactive protein (CRP), ferritin, retinol-binding protein 4 (RBP4) and soluble transferrin receptor (sTfR) as measured by the 7-Plex and the s-ELISA. Serum samples were collected between March 2016 and December 2017. Pregnant women (n 249) were recruited at primary healthcare clinics in Johannesburg, and serum samples were collected between March 2016 and December 2017. Agreement between continuous measurements was assessed by Bland-Altman plots and concordance measures. Agreement in classifications of deficiency or inflammation was assessed by Cohen's kappa. Strong correlations (r > 0·80) were observed between the 7-Plex and s-ELISA for CRP and ferritin. Except for CRP, the 7-Plex assay gave consistently higher measurements than the s-ELISA. With the exception of CRP (Lin's ρ = 0·92), there was poor agreement between the two assays, with Lin's ρ < 0·90. Discrepancies of test results difference between methods increased as the serum concentrations rose. Cohen's kappa for all the five analytes was < 0·81 and ranged from slight agreement (vitamin A deficiency) to substantial (inflammation and Fe deficiency) agreement. The 7-Plex 1.0 is a research and or surveillance tool with potential for use in low-resource laboratories but cannot be used interchangeably with the s-ELISA. Further optimising and validation is required to establish its interchangeability with other validated methods.

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

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

A novel multiplex biomarker panel for profiling human acute and chronic kidney disease.

Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5-73.0) and median CKD/ESKD age was 65.0 (IQR 50.0-71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and ß2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease.

Evaluation of adipokines concentrations in plasma, peritoneal, and endometrioma fluids in women operated on for ovarian endometriosis.

Introduction: Some studies indicate the role of selected adipokines in the development of endometriosis. However, a comprehensive assessment of plasma, peritoneal, and endometrioma fluids adipokines concentrations in women with ovarian endometriosis has not yet been performed. Therefore, this study aimed to analyze plasma, peritoneal, and endometrioma fluids selected adipokines concentrations in women operated on for ovarian endometriosis. Materials and methods: A cross-sectional cohort study involved 56 women operated on for ovarian endometriosis. Body mass, height, and waist circumference were measured, and BMI was calculated. Plasma, peritoneal, and endometrioma fluids adiponectin, leptin, omentin resistin, RBP4, and visfatin/NAMPT were determined by ELISA. Results: The highest plasma levels of adiponectin, leptin, omentin, and RBP4 than in the endometrioma and peritoneal fluids were found, while levels of resistin and visfatin/NAMPT were significantly higher in endometrioma fluid than in plasma and peritoneal fluid. In addition, levels of visfatin/NAMPT were significantly higher in peritoneal fluid than in plasma. There were also positive correlations between leptin, RBP4, and adiponectin levels in endometrioma and peritoneal fluids (ρ = 0.28; p < 0.05; ρ = 0.31; p < 0.05; ρ= 0.32; p < 0.05, respectively). There were no associations between adipokines levels in plasma, endometrioma, and peritoneal fluids and endometriosis stage. Conclusion: Our results show that visfatin/NAMPT and resistin may be locally secreted in endometrioma related to inflammation regardless of the stage of endometriosis.

[Construction of a fecal protein Luminex liquid chip detection system for early diagnosis of colorectal tumors].

OBJECTIVE: To construct a stool-based human protein diagnostic system using the Luminex liquid chip system for early diagnosis of colorectal tumors. METHODS: From January, 2021 to January, 2023, 70 patients with colorectal cancer (CRC), 42 patients with colorectal adenoma (CRA), and 38 healthy individuals were recruited from our hospital for detecting fecal protein levels of matrix metalloproteinase-9 (MMP-9), retinol-binding protein 4 (RBP4), chitinase-3-like protein 1 (CHI3L1), and complement component 3a (C3a) using Luminex liquid chip technology and serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) using chemiluminescence assay. Receiver-operating characteristic (ROC) curve analysis was used for assessing the diagnostic efficacy of the combination of MMP-9, RBP4, CHI3L1 and C3a and the combination of CEA and CA19-9 for colorectal tumors. RESULTS: The fecal contents of MMP-9, RBP4, CHI3L1, and C3a were significantly higher in CRC patients than in healthy individuals (P < 0.05). Fecal MMP-9 and CHI3L1 levels were significantly higher in CRC than in CRA patients (P < 0.05), but RBP4 and C3a levels did not differ significantly (P>0.05). CRC patients had significantly higher serum CEA and CA19-9 levels than healthy individuals and CRA patients (P < 0.05), but the differences were not significant between the latter two groups (P>0.05). ROC analysis showed that the sensitivity and specificity of the combination of MMP-9, RBP4, CHI3L1, and C3a was 91.4% and 100.0%, for diagnosing CRC, 81.0% and 89.5% for diagnosing CRA, and 83.9% and 97.4% for a combined diagnosis of CRC and CRA, respectively. Z-test analysis indicated that fecal MMP-9, RBP4, CHI3L1, and C3a contents had a greater diagnostic efficacy than serum tumor markers CEA and CA19-9 for a combined diagnosis of colorectal tumors (P < 0.05). CONCLUSION: The Luminex liquid chip detection system for detecting decal RBP4, MMP-9, CHI3L1, and C3a provides an effective means for early diagnosis of colorectal tumors with a greater diagnostic efficacy than serum CEA and CA19-9 levels.

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.

Astaxanthin Supplementation Augments the Benefits of CrossFit Workouts on Semaphorin 3C and Other Adipokines in Males with Obesity.

Regular physical activity and the use of nutritional supplements, including antioxidants, are recognized as efficacious approaches for the prevention and mitigation of obesity-related complications. This study investigated the effects of 12 weeks of CrossFit training combined with astaxanthin (ASX) supplementation on some plasma adipokines in males with obesity. Sixty-eight males with obesity (BMI: 33.6 ± 1.4 kg·m-2) were randomly assigned into four groups: the control group (CG; n = 11), ASX supplementation group (SG; n = 11), CrossFit group (TG; n = 11), and training plus supplement group (TSG; n = 11). Participants underwent 12 weeks of supplementation with ASX or placebo (20 mg/day capsule daily), CrossFit training, or a combination of both interventions. Plasma levels of semaphorin 3C (SEMA3C), apelin, chemerin, omentin1, visfatin, resistin, adiponectin, leptin, vaspin, and RBP4 were measured 72 h before the first training session and after the last training session. The plasma levels of all measured adipokines were significantly altered in SG, TG, and TSG groups (p < 0.05). The reduction of resistin was significantly higher in TSG than in SG (p < 0.05). The plasma levels of omentin1 were significantly higher in both training groups of TG and TSG than SG (p < 0.05), although such a meaningful difference was not observed between both training groups (p > 0.05). Significant differences were found in the reductions of plasma levels of vaspin, visfatin, apelin, RBP4, chemerin, and SEMA3C between the SG and TSG groups (p < 0.05). The study found that a 12-week intervention using ASX supplementation and CrossFit exercises resulted in significant improvements in several adipokines among male individuals with obesity. Notably, the combined approach of supplementation and training had the most pronounced results. The findings presented in this study indicate that the supplementation of ASX and participation in CrossFit exercise have the potential to be effective therapies in mitigating complications associated with obesity and enhancing metabolic health.

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

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