RBP Levels Research Articles

The inverse association between fasting blood glucose and the occurrence of gallbladder cancer in type 2 diabetes mellitus patients: a case-control study.

This study aimed to explore the correlation between diabetes mellitus (DM) and gallbladder cancer (GBC) in an epidemiological setting. The study summarized the clinical and laboratory data of 2210 GBC Chinese patients in the authors' hospital. A total of 17 influencing factors for GBC, including gender, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FINS), the homeostasis model assessment of insulin resistance (HOMA-IR), retinol-binding protein 4 (RBP4), and lipid indexes were analyzed using unconditional logistic regression analysis. Based on the results of univariate logistic regression, the risk of GBC was significantly and positively correlated with serum triglyceride, low-density lipoprotein, FINS, HOMA-IR, being female, BMI, DM, non-alcoholic fatty liver disease, and gallbladder stone disease (GSD), and significantly negatively correlated with high-density lipoprotein and FBG concentrations in serum, as well as hypertension. According to multivariate analysis, FINS was significantly positively associated with GBC risk, while DM showed an insignificant negative association; FBG was also not important. The most significant independent factor of GBC risk in patients with DM was HOMA-IR. Fasting blood glucose levels showed a significant negative relationship with GBC in patients with DM. In addition, this study indicated a significantly negative association between serum RBP levels and GBC. The findings of the current study revealed that the efficient treatment of insulin resistance is an important approach for decreasing GBC risk, as opposed to lowering blood sugar only, particularly in patients with DM. Interestingly, FBG may have had an inverse association with the development of GBC in patients with type 2 DM. Of note, the study found that a dramatic initial drop in RBP may help predict the occurrence of GBC.

Ajugol attenuates renal injury in multiple myeloma by blocking LILRB4 signaling pathway to reduce PFKFB3 expression

Motherwort exhibits a curative effect on kidney damage and its component, ajugol, also might improve kidney damage. Therefore, this study assesses the mechanism whereby ajugol alleviates renal injury in multiple myeloma. After establishment of animal model of multiple myeloma (n = 30), mice received treatment with low-dose and high-dose ajugol (n = 10, each group). And 10 healthy mice were taken as control group and 10 modeled mice were untreated (model group). Following treatment, the serum and spinal cord samples of the mice were collected, in which the levels of Cys-C, RBP, Cr, UN, CD4+, CD8+, and CD25+ were examined and the expression of LILRB4 and PFKFB3 proteins in myeloma tissue were detected. Compared with model group, the levels of serum Cys-c, RBP, Cr and UN in low-dose and high-dose groups decreased, but were still higher than those in control group (P <0.05). Of ajugol groups, the levels in high-dose group were lower (P <0.05). Importantly, the treatment of ajugol greatly alleviated lesions of myeloma tissue and reduced infiltration of inflammatory cells via lowering the levels of serum CD4+, CD8+, and CD25+. Besides, ajugol dose-dependently decreased LILRB4 and PFKFB3 expression in myeloma tissue samples. Ajugol, a bioactive component of motherwort, blocked the LILRB4 signaling and reduced PFKFB3 expression to inhibit the activity of immune cells and thereby alleviating renal injury in multiple myeloma. This is related to significant inhibition of multiple myeloma cell glycolysis and reduction of intracellular energy metabolism, indicating the anti-cancer potential of ajugol.

Clinical study on prescription used for invigorating spleen, reinforcing kidney and warming yang combined with calcium dobesilate in treatment of senile diabetic nephropathy

ABSTRACT Objective. To analyze the clinical effect of prescription used for invigorating spleen, reinforcing kidney and warming yang combined with calcium dobesilate to treat senile diabetic nephropathy (DN). Methods. The clinical data of 110 elderly patients with DN in our hospital from November 2020 to November 2021 were selected for retrospective analysis, and they were divided into the observation group (OG, n = 55) and the control group (CG, n = 55) according to the principle of random grouping. The CG received conventional therapy and calcium dobesilate, and the OG received conventional therapy, calcium dobesilate and prescription used for invigorating spleen, reinforcing kidney and warming yang to evaluate the clinical value of different treatment programs by comparing their clinical indicators after treatment. Results. The total effective rate of clinical treatment in the OG was clearly higher than the CG (P < 0.05). The blood glucose indexes, and the levels of ALB and RBP in the OG were visibly lower than the CG after treatment (P < 0.001). After treatment, the average levels of BUN and Cr in the OG were visibly lower than the CG (P < 0.001), while the average eGFR level was significantly higher than the CG (P < 0.001). Conclusion. The prescription used for invigorating spleen, reinforcing kidney and warming yang combined with calcium dobesilate is a reliable method to improve the hemorheology indexes and renal function of DN patients, which benefits patients, and further studies are helpful to establish a better solution for such patients.

Intravenous dexamethasone administration during anesthesia induction can improve postoperative nutritional tolerance of patients following elective gastrointestinal surgery: A post-hoc analysis.

To investigate the effect of intravenous dexamethasone administration on postoperative enteral nutrition tolerance in patients following gastrointestinal surgery. Based on the previous results of a randomized controlled study to explore whether intravenous administration of dexamethasone recovered gastrointestinal function after gastrointestinal surgery, we used the existing research data from 1 to 5 days post operation in patients with enteral nutrition tolerance and nutrition-related analyses of the changes in serum indices, and further analyzed the factors affecting resistance to enteral nutrition. The average daily enteral caloric intake was significantly higher in patients receiving intravenous administration of dexamethasone during anesthesia induction than in controls (8.80 ± 0.92 kcal/kg/d vs. 8.23 ± 1.13 kcal/kg/d, P = 0.002). Additionally, intravenous administration of 8 mg dexamethasone during anesthesia induction can reduce the changes in postoperative day (POD) 3, POD5, and preoperative values of serological indices, including ΔPA, ΔALB, and ΔRBP (P < 0.05). In the subgroup analysis, dexamethasone significantly increased the average daily enteral nutrition caloric intake in patients undergoing enterotomy (8.98 ± 0.87 vs. 8.37 ± 1.17 kcal/kg/d, P = 0.010) or in female patients (8.94 ± 0.98 vs. 8.10 ± 1.24 kcal/kg/d, P = 0.019). The changes of serological indexes (ΔPA, ΔALB, and ΔRBP) in the dexamethasone group were also significantly different on POD3 and POD5 (P < 0.05). In addition, multivariate analysis showed that dexamethasone use, surgical site, and age might influence enteral nutrition caloric tolerance. Postoperative enteral nutrition tolerance was significantly improved in patients receiving intravenous administration of dexamethasone during anesthesia induction, especially in patients following enterotomy surgery, with significant improvements in average daily enteral caloric intake, PA levels, ALB levels, and RBP levels. http://www.chictr.org.cn, identifier: ChiCTR1900024000.

396 ARE BLOOD LEVELS OF RETINOL BINDING PROTEIN USEFUL IN DIAGNOSING ATTR-CA? A NEGATIVE STUDY, SO FAR

Abstract Introduction Retinol binding protein (RBP) is a protein synthesized in the liver which forms, along with transthyretin (TTR) the retinol-transport-complex. This complex ligates retinol and thyroxine and transports them in the human plasma. TTR is a protein longer and heavier than RBP. It ligates RBP preventing its renal filtration. Our hypothesis is that the relationship between RBP and TTR is dual: TTR avoids renal filtration of RBP, but also RBP itself, functioning as an endogenous ligand, has an action on TTR by stabilizing and avoiding TTR misfolding. Misfolded TTR proteins form amyloid fibrils rich in beta-cross-sheets that can infiltrate healthy tissues altering their physiology. The infiltration of these fibrils in the cardiac tissue leads to the well-known condition of TTR cardiac amyloidosis (ATTR CA). Our hypothesis is that the lack of TTR stabilization that can happen with low blood levels of RBP is a risk factor for developing ATTR CA. The main goal of our study is to understand if high or normal values of RBP can help exclude any pathological condition linked to the accumulation of misfolded TTR proteins. Methods All patients referred to our Cardiomyopathy Clinic with a clinical and echographic suspicion of CA were consecutively enrolled. All patients underwent a complete diagnostic workup in order to confirm or exclude CA, comprehending lab tests (including RBP4), SPECT, cardiac MR, genetic testing and cardiac biopsy as recommended by current recommendations. At the end of the diagnostic process, patients with ATTR-wt CA were enrolled as cases, and patients with no CA were considered as controls. Patients with ATTR-mutated CA or AL CA were excluded from the present analysis. Results Fifty-nine consecutive patients (42 males, age 77+/-13 years) were enrolled. Of those, 27 had a definitive diagnosis of ATTR-wt CA, while 32 had another diagnosis. Mean levels of RBP4 were not different between patients with and without CA (5.4+/-1.9 vs. 5.0+/-1.8 mg/dl; p=ns) as were Troponin I, BNP and NT-proBNP levels (all p=ns). Among patients with a definitive diagnosis of ATTR-wt CA and a positive SPECT, RBP4 levels were similar between Perugini 2 and 3 scores (5.4+/-2.1 vs. 5.6+/-2.0 mg/dl; p=ns). Discussion From our findings, it seems that there is no significant correlation between low levels of RBP and the presence of ATTR CA as we found no difference in the distribution of RBP levels between cases and controls. It also did not seem to be a useful marker to stratify the levels of myocardial infiltration as long as there is no difference in RBP between Perugini score 2 and 3.

A Prognostic Model for In-Hospital Mortality in Critically Ill Patients with Pneumonia.

To determine the utility of a novel serum biomarker for the outcome prediction of critically ill patients with pneumonia. A retrospective analysis of critically ill patients was performed at an emergency department. The expression and prediction value of parameters were assessed. Binary logistic regression analysis was utilized to determine the indicators associated with in-hospital mortality of pneumonia patients. The Last Absolute Shrinkage and Selection Operator was used to further determine the independent predictors, which were validated by multiple logistic regression. The receiver operator characteristic curve was performed to assess their prediction values. A prognostic nomogram model was finally established for the outcome prediction for critically ill patients with pneumonia. Retinol-binding protein (RBP) was significantly reduced in non-survived and pneumonia patients. CURB-65 score, levels of RBP, and blood urea nitrogen (BUN) were associated with in-hospital mortality of critically ill patients with pneumonia. Their combination was determined to be an ideal prognostic predictor (area under the curve of 0.762) and further developed into a nomogram prediction model (c-index 0.764). RBP is a novel in-hospital mortality predictor, which well supplements the CURB-65 score for critical pneumonia patients.

Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis.

RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.

Effects of Iron and Vitamin A Levels on Pregnant Women and Birth Outcomes: Complex Relationships Untangled Using a Birth Cohort Study in Uganda

IntroductionWomen and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants’ growth.MethodsWe determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers (ferritin, soluble transferrin receptor [sTFR], body iron stores [BIS], hemoglobin and retinol binding protein [RBP]) and birth outcomes (body weight, Z-scores, head circumference, small-for-gestational-age and preterm birth) in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes.ResultsAfter adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births (AOR: 0.67; 95% CI 0.48–0.94). For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (β = 0.12, p < 0.030).DiscussionThese findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes.Clinicaltrials.gov as NCT04233944.

Analysis of early renal damage markers under different renal ultrasonic manifestations in gout patients

Objective: To observe the relationship between early renal damage markers and renal ultrasonic manifestations in gout patients, and whether early renal damage is reversible after uric acid-reducing treatment. Methods: The gout patients from the Department of Rheumatology of Beijing Haidian Hospital and Peking University People's Hospital between July 2016 and December 2017 were recruited in this study. According to the results of renal ultrasonography, the patients were divided into the following three groups. Group A was normal. Group B was punctate crystallization. Group C was renal calculi. Each group included 30 patients. The patients in group B and group C who could insist on regular uric acid-reducing treatment for one year were selected. The levels of urinary RBP, β(2)-MG and NAG were measured in different groups and one year before and after uric acid-reducing treatment. Results: The urinary concentration of β(2)-MG in group A, group B and group C were (128.59±107.32), (316.08±207.41) and (311.25±162.85)mg/L, respectively. There were significant differences among the three groups (P<0.001). The urinary concentration of NAG were (13.41±5.12)U/L,(17.88±6.19)U/L and (18.48±9.84)U/L, respectively. There were differences among the three groups (P<0.01).There was no significant difference in urinary RBP concentration among the three groups (P=0.188). After one year of uric acid-reducing treatment, the levels of urinary RBP, β(2)-MG and NAG were lower than that before treatment. There were significant differences before and after treatment in each group (P<0.05). Compared with group C, the levels of urinary β(2)-MG and NAG were decreased in group B after uric acid-reducing treatment (all P<0.05). Conclusions: Renal ultrasonography is helpful for the diagnosis of early renal damage in gout patients. Early renal damage markers in gout patients decreased after uric acid-reducing treatment, suggesting that early renal damage can be reversible if early diagnosis and timely treatment can be made in gout patients.

Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination.

Maximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to explain study discrepancies and to provide guidance for the future use of vitamin supplements at the time of vaccination. We conducted a randomized, blinded, placebo-controlled study of influenza virus vaccination and vitamin supplementation among 2 to 8 (inclusive) year old children over three seasons, including 2015–2016 (n = 9), 2016–2017 (n = 44), and 2017–2018 (n = 26). Baseline measurements of vitamins A and D were obtained from all participants. Measurements were of serum retinol, retinol-binding protein (RBP, a surrogate for retinol), and 25-hydroxyvitamin D (25(OH)D). Participants were stratified into two groups based on high and low incoming levels of RBP. Children received two doses of the seasonal influenza virus vaccine on days 0 and 28, either with an oral vitamin supplement (termed A&D; 20,000 IU retinyl palmitate and 2000 IU cholecalciferol) or a matched placebo. Hemagglutination inhibition (HAI) antibody responses were evaluated toward all four components of the influenza virus vaccines on days 0, 28, and 56. Our primary data were from season 2016–2017, as enrollment was highest in this season and all children exhibited homogeneous and negative HAI responses toward the Phuket vaccine at study entry. Responses among children who entered the study with insufficient or deficient levels of RBP and 25(OH)D benefited from the A&D supplement (p < 0.001 for the day 28 Phuket response), whereas responses among children with replete levels of RBP and 25(OH)D at baseline were unaffected or weakened (p = 0.02 for the day 28 Phuket response). High baseline RBP levels associated with high HAI titers, particularly for children in the placebo group (baseline RBP correlated positively with Phuket HAI titers on day 28, r = 0.6, p = 0.003). In contrast, high baseline 25(OH)D levels associated with weak HAI titers, particularly for children in the A&D group (baseline 25(OH)D correlated negatively with Phuket HAI titers on day 28, r = −0.5, p = 0.02). Overall, our study demonstrates that vitamin A&D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at baseline. Results provide guidance for the appropriate use of vitamins A and D in future clinical vaccine studies.

Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model

BackgroundContrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms. MethodsWe established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and β-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed. ResultsThe levels of Bun, Scr, serum and urinary RBP and β-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro. ConclusionsRA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.

The Effectivity of Extracts Soybean on Increasing Concentration of RBP (Retinol binding protein) in White Rat (Rattus norvegicus) Kwashiorkor Model

Kwashiorkor is a disease caused by a deficiency of protein in terms of both quality and quantity. Kwashiorkor cause dysfunction in various organ systems. The purpose of this study was to determine the role of soy in increasing serum RBP levels in rat models of kwashiorkor. The liver is a vital organ for protein synthesis, one RBP. The liver is particularly vulnerable to the effects of kwashiorkor. The method used is the mice given low-protein diet for 30 days and then given extract of soybean meal for 30 days subsequent serum RBP levels were evaluated using ELISA method. The results showed that the soy extract can increase the levels of RBP in mice models of kwashiorkor. Keywords: RBP, soybean extracts and kwashiorkor

Effect of dietary protein against excess vitamin A induced hepatotoxicity in rats

Vitamin A deficiency is a serious nutritional deficiency disease. In most cases vitamin A deficiency is associated with protein malnutrition. Excess vitamin A cannot be transported for want of transport protein. We aimed to investigate the quantity of protein required in diet to protect excess vitamin A fed hepatotoxicity in rats. Normal and excess amount of vitamin A (4000 IU/kg and 40000 IU/kg)) with three different levels of dietary protein (6%, 18% and 30%) were administered orally for 30 consecutive days in rats. In low protein diet vitamin A level significantly increased in liver and decreased in plasma and, lipids level were found to be high in liver. Administration of excessive doses of vitamin A resulted in significant decrease in the levels of serum and liver RBP. Excess vitamin A in low protein state significantly induced oxidative stress in the liver, leading to increased serum levels of liver enzyme markers aminotransferases, total and direct bilirubin. Lipid remains in liver for want of transport protein and aggravates the formation of fatty liver. Both lipids and lipoprotein levels are also measured to assess the liver function in hypervitaminosis; a state where abnormally high storage levels of vitamins can lead to toxic symptoms.

Retinol binding protein and vitamin D associations with serum antibody isotypes, serum influenza virus-specific neutralizing activities and airway cytokine profiles.

Vitamin A supports the induction of immunoglobulin (Ig)A responses at mucosal surfaces in mice, but much less is known about the influence of vitamins on antibody isotype expression in humans. To address this knowledge gap, we examined 46 residual blood samples from adults and children, some of whom were experiencing influenza virus infections of the respiratory tract. Assays were performed for retinol binding protein (RBP, a surrogate for vitamin A), vitamin D (a related vitamin) and antibody isotypes. Results showed that all but two tested samples exhibited RBP and/or vitamin D insufficiencies or deficiencies. Vitamin D correlated with blood IgM and IgG3, while RBP correlated with IgG4 and IgA. RBP also correlated positively with age and with influenza virus-specific antibody neutralization titres. Individuals with low blood RBP levels exhibited the highest frequencies of over-expressed cytokines and growth factors in nasal wash samples, an indication of inflamed mucosal tissues. While cause-effect relationships were not discerned, results support a hypothesis that vitamins directly influence B cell isotype expression in humans, and by so doing may help protect mucosal surfaces from respiratory viral disease.

Retinol-binding protein-4 and hs-CRP levels in patients with migraine.

Retinol-binding protein-4 (RBP4) and high-sensitivity C-reactive protein (hs-CRP) levels are associated with inflammation in patients with migraine. The release of proinflammatory cytokines during migraine results in recurrent sterile neurogenic inflammation. This study aimed to determine the correlation between RBP4 and hs-CRP levels, and migraine, which is considered an inflammatory disease. The study included 48 migraine patients and 40 age- and gender-matched controls. Migraine was diagnosed according to International Classification of Headache Disorders-II. The serum RBP4 level was measured using a commercial ELISA kit and hs-CRP was measured using an enzyme immunoassay test kit. The serum RBP4 level was significantly lower in the migraine patients than in the controls (P < 0.001), whereas the hs-CRP level was significantly higher in the migraine patients (P < 0.001). RBP4 and hs-CRP levels did not differ between the migraine patients with and without aura (P > 0.05). Migraine headache severity, frequency and duration were not correlated with serum RBP or hs-CRP levels (P > 0.05). The observed high hs-CRP level and low RBP4 level in migraine patients suggest that vitamin A might play a major role in the pathogenesis of migraine. It is known that inflammation is a key factor in many diseases. Additional research might result in a better understanding of the anti-inflammatory effects of vitamin A.

HIV and schistosomiasis in rural Zimbabwe: the association of Retinol-binding protein with disease progression, inflammation and mortality

Vitamin A has widespread effects on immune function and is therefore interesting in HIV-infection. Retinol-binding protein (RBP or RBP4) is a negative acute-phase protein and a marker of vitamin A status. Our aim was to investigate the association of RBP with HIV progression, infection with schistosomiasis, inflammatory cytokines, and mortality. The study included 192 HIV-infected and 177 HIV-uninfected individuals from Mupfure in rural Zimbabwe. Of these, 208 were infected with Schistosoma haematobium, 27 with S. mansoni and 48 with both. Plasma RBP, HIV-RNA, CD4 cell count, haemoglobin, cytokines, clinical staging (CDC category), self-reported level of function (Karnoffsky Performance Score, KPS) and schistosomiasis status were assessed at baseline. Participants were followed up for survival 3-4 years post-enrolment. RBP levels were lower in HIV-infected individuals(p<0.0001). Among HIV-infected individuals, multivariable analysis showed RBP to be positively correlated with CD4 cell count(p=0.050), KPS(p=0.003), and haemoglobin(p<0.0001) and negatively correlated with HIV-RNA(p<0.0001), CDC category(p<0.0001), tumor necrosis factor-receptor II(p<0.0001) and interleukin(IL)-6(p=0.004), as well as with IL-8(p=0.005) and IL-10(p=0.003) for HIV-infected men. Furthermore, among HIV-infected individuals RBP correlated negatively with schistosomiasis(p=0.038) and intensity of infection: circulating anodic antigen(p=0.014), circulating cathodic antigen(p<0.0001) and faecal egg output(p=0.004). In HIV-infected individuals, RBP was negatively associated with levels of inflammatory markers, markers of HIV progression, infection with schistosomiasis and markers of schistosomal intensity.

Dissecting the expression landscape of RNA-binding proteins in human cancers.

BackgroundRNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level.ResultsWe explore the expression of more than 800 RBPs in sixteen healthy human tissues and their patterns of dysregulation in cancer genomes from The Cancer Genome Atlas project. We show that genes encoding RBPs are consistently and significantly highly expressed compared with other classes of genes, including those encoding regulatory components such as transcription factors, miRNAs and long non-coding RNAs. We also demonstrate that a set of RBPs, numbering approximately 30, are strongly upregulated (SUR) across at least two-thirds of the nine cancers profiled in this study. Analysis of the protein–protein interaction network properties for the SUR and non-SUR groups of RBPs suggests that path length distributions between SUR RBPs is significantly lower than those observed for non-SUR RBPs. We further find that the mean path lengths between SUR RBPs increases in proportion to their contribution to prognostic impact. We also note that RBPs exhibiting higher variability in the extent of dysregulation across breast cancer patients have a higher number of protein–protein interactions. We propose that fluctuating RBP levels might result in an increase in non-specific protein interactions, potentially leading to changes in the functional consequences of RBP binding. Finally, we show that the expression variation of a gene within a patient group is inversely correlated with prognostic impact.ConclusionsOverall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.

Fenretinide Treatment Prevents Diet-Induced Obesity in Association With Major Alterations in Retinoid Homeostatic Gene Expression in Adipose, Liver, and Hypothalamus

The synthetic retinoid, Fenretinide (FEN), inhibits obesity and insulin resistance in mice and is in early clinical trials for treatment of insulin resistance in obese humans. We aimed to determine whether alterations in retinoic acid (RA)-responsive genes contribute to the beneficial effects of FEN. We examined the effect of FEN on 3T3-L1 adipocyte differentiation and alterations in gene expression in C57Bl/6 and retinaldehyde dehydrogenase (RALDH) 1 knockout (KO) mice fed a high-fat (HF) diet. FEN completely inhibited adipocyte differentiation by blocking CCAAT/enhancer-binding protein (C/EBP) α/peroxisome proliferator–activated receptor (PPAR) γ−mediated induction of downstream genes and upregulating RA-responsive genes like cellular retinol-binding protein-1. In mice fed an HF diet, RA-responsive genes were markedly increased in adipose, liver, and hypothalamus, with short-term and long-term FEN treatment. In adipose, FEN inhibited the downregulation of PPARγ and improved insulin sensitivity and the levels of adiponectin, resistin, and serum RBP (RBP4). FEN inhibited hyperleptinemia in vivo and leptin expression in adipocytes. Surprisingly, hypothalamic neuropeptide Y expression was completely suppressed, suggesting a central effect of FEN to normalize hyperglycemia. Moreover, FEN induced RA-responsive genes in RALDH1 KO mice, demonstrating that FEN can augment RA signaling when RA synthesis is impaired. We show that FEN-mediated beneficial effects are through alterations in retinoid homeostasis genes, and these are strong candidates as therapeutic targets for the treatment of obesity and insulin resistance.

Vitamin A and systemic inflammation as protective factors in multiple sclerosis

Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS). Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation. Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders. Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95). Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology.

Hypertriglyceridemic waist, cytokines and hyperglycaemia in Chinese

Abdominal obesity and hypertriglyceridemia confer high risk for cardiometabolic disease. Few studies have investigated the associations of hypertriglyceridemic waist with cytokines and hyperglycaemia in Chinese. Anthropometric indexes, fasting plasma concentrations of glucose, glycohemoglobin, insulin, lipid profile, inflammatory factors and adipokines were measured among 3289 Chinese men and women 50-70 years of age. An increment of every 2 cm of waist circumference was associated with increased levels of high-sensitive C-reactive protein (hsCRP), interleukin 6 and RBP 4 by 0·033 mg/L, 0·018 ng/L and 0·556 mg/L and reduced levels of adiponectin by 0·269 mg/L (all P<0·05), respectively, with controlling for potential confounders. For triglycerides, each an increment of 20 mg/dL was associated with increased levels of hsCRP, RBP4, and decreased levels of adiponectin by 0·021 mg/L, 0·655 mg/L, and 0·371 mg/L (all P<0·05), respectively. Individuals with hypertriglyceridemic waist had increased risks of having hyperglycaemia (OR: 1·48; 95% CI: 1·09, 2·00) and diabetes mellitus (OR: 2·12; 95% CI: 1·47, 3·04) compared with those with neither of the phenotypes. Hypertriglyceridemic waist is associated with a worse profile of inflammatory factors and adipokines as well as with an increased risk of having hyperglycaemia among Chinese.