A high fat diet fosters elevated bisretinoids.

High dietary fat intake is associated with metabolic dysregulation, but little is known regarding the effects of a high fat diet (HFD) on photoreceptor cell functioning. We explored the intersection of an HFD and the visual cycle adducts that form in photoreceptor cells by nonenzymatic reactions. In black C57BL/6J mice and albino C57BL/6Jc2j mice raised on an HFD until age 3, 6, or 12 months, chromatographically quantified bisretinoids were increased relative to mice on a standard diet. In vivo measurement of fundus autofluorescence, the source of which is bisretinoid, also revealed a significant increase in the HFD mice. Additionally, mice provided with a diet high in fat presented with elevated retinol-binding protein 4, the protein responsible for transporting retinol in plasma. Vitamin A was elevated in plasma although not in ocular tissue. Bisretinoids form in photoreceptor cell outer segments by random reactions of retinaldehyde with phosphatidylethanolamine. We found that the latter phospholipid was significantly increased in mice fed an HFD versus mice on a control diet. In leptin-deficient ob/ob mice, a genetic model of obesity, plasma levels of retinol-binding protein 4 were higher but bisretinoids in retina were not elevated. Photoreceptor cell viability measured as outer nuclear layer thickness was reduced in the ob/ob mice relative to WT. The accelerated formation of bisretinoid we observed in diet-induced obese mice is related to the high fat intake and to increased delivery of vitamin A to the visual cycle.

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.

Vitamin A biomarkers were associated with α(1)-acid glycoprotein and C-reactive protein over the course of a human norovirus challenge infection.

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.

Predictive value of serum retinol binding protein in severity and complications of acute pancreatitis: a retrospective cohort study.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Serum RBP had predictive value for AP severity, local and systemic complications.

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

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.

Prediction of Pesticide Interactions with Proteins Involved in Human Reproduction by Using a Virtual Screening Approach: A Case Study of Famoxadone Binding CRBP-III and Izumo.

In recent years, the awareness that pesticides can have other effects apart from generic toxicity is growing. In particular, several pieces of evidence highlight their influence on human fertility. In this study, we investigated, by a virtual screening approach, the binding between pesticides and proteins present in human gametes or associated with reproduction, in order to identify new interactions that could affect human fertility. To this aim, we prepared ligand (pesticides) and receptor (proteins) 3D structure datasets from online structural databases (such as PubChem and RCSB), and performed a virtual screening analysis using Autodock Vina. In the comparison of the predicted interactions, we found that famoxadone was predicted to bind Cellular Retinol Binding Protein-III in the retinol-binding site with a better minimum energy value of -10.4 Kcal/mol and an RMSD of 3.77 with respect to retinol (-7.1 Kcal/mol). In addition to a similar network of interactions, famoxadone binding is more stabilized by additional hydrophobic patches including L20, V29, A33, F57, L117, and L118 amino acid residues and hydrogen bonds with Y19 and K40. These results support a possible competitive effect of famoxadone on retinol binding with impacts on the ability of developing the cardiac tissue, in accordance with the literature data on zebrafish embryos. Moreover, famoxadone binds, with a minimum energy value between -8.3 and -8.0 Kcal/mol, to the IZUMO Sperm-Egg Fusion Protein, interacting with a network of polar and hydrophobic amino acid residues in the cavity between the 4HB and Ig-like domains. This binding is more stabilized by a predicted hydrogen bond with the N185 residue of the protein. A hindrance in this position can probably affect the conformational change for JUNO binding, avoiding the gamete membrane fusion to form the zygote. This work opens new interesting perspectives of study on the effects of pesticides on fertility, extending the knowledge to other typologies of interaction which can affect different steps of the reproductive process.

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.

Products of the visual cycle are detected in mice lacking retinol binding protein 4, the only known vitamin A carrier in plasma.

Efficient delivery of vitamin A to the retinal pigment epithelium is vital to the production of the light-sensitive visual chromophore 11-cis-retinal. Nevertheless, retinol binding protein 4 (RBP4) is the only known carrier of vitamin A in plasma. Here, we present new findings that further characterize the visual cycle in the presence of Rbp4 deficiency. In the face of impaired delivery of retinol in Rbp4-/- mice, we determined that 11-cis-retinaldehyde reached levels that were ∼60% of WT at 4 months of age and all-trans-retinyl ester was 18% of normal yet photoreceptor cell loss was apparent by 8 months of age. The lack of Rbp4 appeared to have a greater impact on scotopic rod-mediated responses than on cone function at early ages. Also, despite severely impaired delivery of retinol, bisretinoid lipofuscin that forms as a byproduct of the visual cycle was measurable by HPLC and by quantitative fundus autofluorescence. In mice carrying an Rpe65 amino acid variant that slows visual cycle kinetics, Rbp4 deficiency had a less pronounced effect on 11-cis-retinal levels. Finally, we found that ocular retinoids were not altered in mice expressing elevated adipose-derived total Rbp4 protein (hRBP4+/+AdiCre+/-). In conclusion, our findings are consistent with a model in which vitamin A can be delivered to the retina by Rbp4-independent pathways.

Urinary angiotensinogen is associated with albuminuria in adults with sickle cell anaemia.

We explored the association of novel urinary biomarkers with albumin-creatinine ratio (ACR) in adults with sickle cell anaemia. Of 37 participants, 13 (35.2%) had persistent albuminuria (PA). Urinary levels of clusterin (p = 0.002), retinol-binding protein 4 (p = 0.008), alpha-1 microglobulin (p = 0.002) and angiotensinogen (p = 0.006) were significantly higher in participants with PA than in those without PA. Although univariate analysis showed significant associations between both alpha-1 microglobulin (p = 0.035) and angiotensinogen (p = 0.0021) with ACR, only angiotensinogen was associated with ACR in multivariable analysis (p = 0.04). Our results suggest that urinary angiotensinogen may identify sickle cell anaemia patients at risk for kidney disease.

Ovariectomy Increases Circulating Retinol-Binding Protein Concentrations Independently of Sex-Dependent Differences in Retinol Concentrations in Rats.

BACKGROUND: There is a sex-dependent difference in blood retinol and RBP concentrations, and plasma RBP is associated with insulin resistance. OBJECTIVES: We aimed to clarify sex-dependent variations in body concentrations of retinol and RBPs and their association with sex hormones in rats. METHODS: Plasma and liver retinol concentrations and hepatic mRNA and plasma concentrations of RBP4 were analyzed in 3- and 8-wk-old male and female Wistar rats before and after sexual maturity (experiment 1) and in orchiectomized male Wistar rats (experiment 2) and ovariectomized female Wistar rats (experiment 3). Furthermore, the mRNA and protein concentrations of RBP4 in adipose tissue were measured in ovariectomized female rats (experiment 3). RESULTS: There were no sex-dependent differences in liver retinyl palmitate and retinol concentrations; however, the plasma retinol concentration was significantly higher in male rats than that in female rats after sexual maturity. Furthermore, the plasma retinol concentrations did not differ between the ovariectomized or orchiectomized rats and the control rats. Plasma Rbp4 mRNA concentrations were higher in male rats than those in female rats but not in castrated and control rats, a change consistent with plasma retinol concentration. Plasma RBP4 concentrations were also higher in male rats than those in female rats; however, unlike liver Rbp4 gene expression, plasma RBP4 concentrations were 7-fold higher in the ovariectomized rats than those in the control rats. Moreover, the Rbp4 mRNA concentrations in inguinal white adipose tissue was significantly higher in the ovariectomized rats than those in the control rats and correlated with plasma RBP4 concentrations. CONCLUSIONS: Hepatic Rbp4 mRNA is higher in male rats through a sex hormone-independent mechanism, which may contribute to sex differences in blood retinol concentrations. Furthermore, ovariectomy leads to an increase in adipose tissue Rbp4 mRNA and blood RBP4 concentrations, which may contribute to insulin resistance in ovariectomized rats and postmenopausal women.

Dietary Vitamin A Affects the Function of Incretin-Producing Enteroendocrine Cells in Male Mice Fed a High-Fat Diet.

BACKGROUND: Retinol-binding protein 2 (RBP2) is an intracellular carrier for vitamin A in the absorptive enterocytes. Mice lacking RBP2 (Rbp2-/-) display an unexpected phenotype of obesity, glucose intolerance, and elevated glucose-dependent insulinotropic polypeptide (GIP) levels. GIP and glucagon-like peptide 1 (GLP-1) are incretin hormones secreted by enteroendocrine cells (EECs). We recently demonstrated the presence of RBP2 and other retinoid-related proteins in EECs. OBJECTIVES: Given RBP2's role in intracellular retinoid trafficking, we aimed to evaluate whether dietary vitamin A affects incretin-secreting cell function and gene expression. METHODS: Male Rbp2-/- mice and sex- and age-matched controls (n = 6-9) were fed a high-fat diet (HFD) for 18 wk containing normal (VAN, 4000 IU/kg of diet) or low (VAL, 25% of normal) vitamin A concentrations. Body weight was recorded biweekly. Plasma GIP and GLP-1 levels were obtained fasting and 30 min after an oral fat gavage at week 16. Glucose tolerance tests were also performed. Mice were killed at week 18, and blood and tissue samples were obtained. RESULTS: Rbp2-/- mice displayed greater weight gain on the VAN compared with the VAL diet from week 7 of the intervention (P ≤ 0.01). Stimulated GIP levels were elevated in Rbp2-/- mice compared with their controls fed the VAN diet (P = 0.02), whereas their GIP response was lower when fed the VAL diet (P = 0.03). Although no differences in GLP-1 levels were observed in the VAN diet group, a lower GLP-1 response was seen in Rbp2-/- mice fed the VAL diet (P = 0.02). Changes in incretin gene expression and that of other genes associated with EEC lineage and function were consistent with these observations. Circulating and hepatic retinoid levels revealed no systemic vitamin A deficiency across dietary groups. CONCLUSIONS: Our data support a role for RBP2 and dietary vitamin A in incretin secretion and gene expression in mice fed a HFD.

Role of cellular retinol-binding protein, type 1 and retinoid homeostasis in the adult mouse heart: A multi-omic approach.

The main active metabolite of Vitamin A, all-trans retinoic acid (RA), is required for proper cellular function and tissue organization. Heart development has a well-defined requirement for RA, but there is limited research on the role of RA in the adult heart. Homeostasis of RA includes regulation of membrane receptors, chaperones, enzymes, and nuclear receptors. Cellular retinol-binding protein, type 1 (CRBP1), encoded by retinol-binding protein, type 1 (Rbp1), regulates RA homeostasis by delivering vitamin A to enzymes for RA synthesis and protecting it from non-specific oxidation. In this work, a multi-omics approach was used to characterize the effect of CRBP1 loss using the Rbp1-/- mouse. Retinoid homeostasis was disrupted in Rbp1-/- mouse heart tissue, as seen by a 33% and 24% decrease in RA levels in the left and right ventricles, respectively, compared to wild-type mice (WT). To further inform on the effect of disrupted RA homeostasis, we conducted high-throughput targeted metabolomics. A total of 222 metabolite and metabolite combinations were analyzed, with 33 having differential abundance between Rbp1-/- and WT hearts. Additionally, we performed global proteome profiling to further characterize the impact of CRBP1 loss in adult mouse hearts. More than 2606 unique proteins were identified, with 340 proteins having differential expression between Rbp1-/- and WT hearts. Pathway analysis performed on metabolomic and proteomic data revealed pathways related to cellular metabolism and cardiac metabolism were the most disrupted in Rbp1-/- mice. Together, these studies characterize the effect of CRBP1 loss and reduced RA in the adult heart.

Variable dysregulation of circulating lipocalin-2 in different obese phenotypes: Association with vasodilator dysfunction.

BACKGROUND: Obesity is linked with heightened cardiovascular risk, especially when accompanied by metabolic abnormalities. Lipocalin (LCN) 2 and retinol-binding protein (RBP) 4, two members of the lipocalin family, may be upregulated in insulin resistance and atherosclerosis. We analyzed whether changes in circulating LCN2 and RBP4 in obese individuals relate with impaired vasodilator reactivity, an early stage in atherosclerosis. METHODS: Obese individuals (n = 165), without (n = 48) or with (n = 117) metabolic abnormalities, and lean subjects (n = 42) participated in this study. LCN2 and RBP4 were measured by Luminex assay. Endothelium-dependent and -independent vasodilation to acetylcholine and sodium nitroprusside, respectively, was assessed by strain-gauge plethysmography. RESULTS: Circulating LCN2 was higher in obese than in lean subjects (p < 0.001), whereas RBP4 was not different between the two groups (p = 0.12). The vasodilator responses to both acetylcholine and nitroprusside were impaired in obese individuals (p < 0.001 vs lean subjects), with no difference between those with metabolically healthy or unhealthy obesity (p > 0.05). In the whole population, vasodilator responses to acetylcholine (R = 0.23, p = 0.01) and nitroprusside (R = 0.38, p < 0.001) had an inverse, linear relationship with circulating LCN2; no correlation, by contrast, was observed between circulating RBP4 and vasodilator reactivity (both p > 0.05). In a subgroup of obese patients with diabetes (n = 20), treatment with metformin (n = 10) or pioglitazone (n = 10) did not modify circulating LCN2 and RBP4 or vascular reactivity (all p > 0.05). CONCLUSIONS: Circulating LCN2, but not RBP4, is higher in obese than in lean individuals. Interestingly, changes in LCN2 inversely relate to those in vasodilator function, thereby making this protein a potential biomarker for risk stratification in obesity.

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

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.

Urinary orosomucoid and retinol binding protein levels as early diagnostic markers for diabetic kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, which has been a major cause of end-stage renal failure. Diagnosing diabetic kidney disease is important to prevent long-term kidney damage and determine the prognosis of patients with diabetes. In this study, we investigated the clinical significance of combined detection of urine orosomucoid and retinol-binding protein for early diagnosis of diabetic kidney disease. METHODS: We recruited 72 newly diagnosed patients with type 2 diabetes and 34 healthy persons from August 2016 to July 2018 at the First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital). Using the Mogensen grading criteria, participants were classified as having diabetes or diabetic kidney disease, and healthy persons constituted the control group. Urine orosomucoid and retinol-binding protein levels were measured and correlated with other variables. RESULTS: With the aggravation of renal damage, the level of urinary mucoid protein gradually increased. Urinary retinol-binding protein and microalbumin levels were significantly higher in the diabetes group than in control and nephropathy groups. Orosomucoid and retinol-binding protein might be independent risk factors for diabetes and diabetic kidney disease. Urinary orosomucoid significantly correlated with retinol-binding protein and microalbumin levels in the diabetic kidney disease group. CONCLUSION: Elevated urine orosomucoid and retinol-binding protein levels can be detected in the early stages of type 2 diabetic kidney disease. Both of these markers are important for diabetic kidney disease detection and early treatment.

Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study.

BACKGROUND: Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level. METHODS: The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models. RESULTS: The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01-2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17-3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 µg/mL compared with the day workers. CONCLUSIONS: Shift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.

Longitudinal Change of Plasma Retinol-Binding Protein 4 and its Relation to Neurological-Function Recovery, Relapse, and Death in Acute Ischemic Stroke Patients.

Retinol-binding protein 4 (RBP4) promotes dyslipidemia, insulin resistance, inflammation, and atherosclerosis, etc. which may participate in the progression of acute ischemia stroke (AIS). This study aimed to evaluate the longitudinal change of RBP4 after disease onset and its correlation with prognosis in AIS patients. Plasma RBP4 was measured by enzyme-linked immunosorbent assays in 402 AIS patients at admission, one day (D1), 3 days (D3), 7 days (D7), and 30 days (D30) after admission; and in 100 healthy controls after enrollment. The neurological-function recovery was evaluated by the modified Rankin Scale (mRS) at 3 months (M3); disease relapse and death were also recorded during a median 20-month follow-up in AIS patients. Our study revealed that RBP4 was elevated in AIS patients compared with healthy controls. RBP4 was related to a history of diabetes mellitus, a history of cardiovascular disease, and elevated National Institutes of Health Stroke Scale score in AIS patients. Longitudinally, RBP4 was increased from admission to D1/D3, then reduced gradually to D30 in AIS patients. Notably, RBP4 at admission and D1 was elevated in AIS patients with mRS > 2 compared to those with mRS ≤ 2. Meanwhile, RBP4 at admission, D1, D3, D7, and D30 were all higher in AIS patients occurred relapse than those without; RBP4 at D3, D7, and D30 were also higher in AIS patients who died later than those who survived. In conclusion, plasma RBP4 originally elevates and continuously decreases during disease, which forecasts neurological-function recovery status, relapse, and death risk of AIS.

Low dietary protein increases vitamin A absorption and deposition into milk in periparturient rats.

Our objective was to study the effect of differing dietary crude protein and vitamin A on retinoid metabolism in a periparturient rat model. Sixty female rats, approximately 21 d before parturition, were fed rations containing either low protein (13%; LP) or high protein (22%; HP) crude protein and either low vitamin A (3 IU/g; LA) or high vitamin A (5 IU/g; HA), yielding treatments HPHA, HPLA, LPHA, and LPLA. Samples were collected at d -14, d +3, and +10 relative to parturition and analyzed for all-trans retinoid acid (RA), 13-Cis RA, and retinol. At d -14, serum all-trans RA concentrations decreased compared to baseline. At both d +3 and d +10, serum retinol increased and liver 13-Cis RA decreased. In the small intestine, 13-cis RA was higher in HPHA than HPLA pre-partum (0.93±0.12 vs. 0.40±0.12 ng/ml, P=0.04). Post-partum, 13-cis RA was lower in high vitamin HPHA and LPHA groups (0.35±0.06 and 0.38±0.06 ng/ml) than in low vitamin A HPLA and LPLA treatments (0.50±0.06 and 1.32±0.06 ng/ml, P<0.01). In rats fed LA diets, TNF-alpha expression tended to be lower in HPLA than LPLA groups on day +3 (0.69±0.34 vs 1.00±0.52, P=0.08), but not day +10 (0.56±0.25 vs. 1.00±0.49 fold change, P>0.10). Retinoids accumulated during pregnancy and were mobilized during lactation. The sequestration of retinoids was increased when dietary protein content was low. Further studies are needed to investigate how retinoid metabolism could be manipulated to improve vitamin A delivery to milk.

Towards a New Biomarker for Diabetic Retinopathy: Exploring RBP3 Structure and Retinoids Binding for Functional Imaging of Eyes In Vivo.

Diabetic retinopathy (DR) is a severe disease with a growing number of afflicted patients, which places a heavy burden on society, both socially and financially. While there are treatments available, they are not always effective and are usually administered when the disease is already at a developed stage with visible clinical manifestation. However, homeostasis at a molecular level is disrupted before visible signs of the disease are evident. Thus, there has been a constant search for effective biomarkers that could signal the onset of DR. There is evidence that early detection and prompt disease control are effective in preventing or slowing DR progression. Here, we review some of the molecular changes that occur before clinical manifestations are observable. As a possible new biomarker, we focus on retinol binding protein 3 (RBP3). We argue that it displays unique features that make it a very good biomarker for non-invasive, early-stage DR detection. Linking chemistry to biological function and focusing on new developments in eye imaging and two-photon technology, we describe a new potential diagnostic tool that would allow rapid and effective quantification of RBP3 in the retina. Moreover, this tool would also be useful in the future to monitor therapeutic effectiveness if levels of RBP3 are elevated by DR treatments.