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Kamron N Khan, Keren Carss, F Lucy Raymond, Farrah Islam, Nihr BioResource-Rare Diseases Consortium, Anthony T Moore, Michel Michaelides, Gavin Arno
Vitamin A deficiency is the leading cause of preventable blindness in children worldwide and results in a well-recognized ocular phenotype. Herein we describe a patient presenting to the eye clinic with a retinal dystrophy and ocular colobomata. This combination of clinical signs and consanguineous pedigree structure suggested a genetic basis for the disease, a hypothesis that was tested using whole genome sequencing. Bi-allelic mutations in RBP4 were identified (c.248+1G>A), consistent with a diagnosis of inherited vitamin A deficiency...
November 28, 2016: Ophthalmic Genetics
William S Blaner, Yang Li, Pierre-Jacques Brun, Jason J Yuen, Seung-Ah Lee, Robin D Clugston
It is well established that chylomicron remnant (dietary) vitamin A is taken up from the circulation by hepatocytes, but more than 80 % of the vitamin A in the liver is stored in hepatic stellate cells (HSC). It presently is not known how vitamin A is transferred from hepatocytes to HSCs for storage. Since retinol-binding protein 4 (RBP4), a protein that is required for mobilizing stored vitamin A, is synthesized solely by hepatocytes and not HSCs, it similarly is not known how vitamin A is transferred from HSCs to hepatocytes...
2016: Sub-cellular Biochemistry
Joseph L Napoli
Multiple binding and transport proteins facilitate many aspects of retinoid biology through effects on retinoid transport, cellular uptake, metabolism, and nuclear delivery. These include the serum retinol binding protein sRBP (aka Rbp4), the plasma membrane sRBP receptor Stra6, and the intracellular retinoid binding-proteins such as cellular retinol-binding proteins (CRBP) and cellular retinoic acid binding-proteins (CRABP). sRBP transports the highly lipophilic retinol through an aqueous medium. The major intracellular retinol-binding protein, CRBP1, likely enhances efficient retinoid use by providing a sink to facilitate retinol uptake from sRBP through the plasma membrane or via Stra6, delivering retinol or retinal to select enzymes that generate retinyl esters or retinoic acid, and protecting retinol/retinal from excess catabolism or opportunistic metabolism...
2016: Sub-cellular Biochemistry
G P Laliotis, A Marantidis, M Avdi
: The aim of the present study was to determine any potential association of the BF, RBP4, and ESR2 genes with reproduction traits in an autochthonous Greek pig population. The PCR-RFLP methodology was implemented for genotyping purposes of the examined genes. No deviation from the Hardy-Weinberg equilibrium was observed for the examined loci, while the B allele noted to be the more frequent in all analyzed genes. In addition, sows with the AA genotype of BF gene found to produce significantly lower numbers of the total born piglets (TNB) and number of piglets born alive (TNA), while the respective BB genotype significantly exceeded in TNB and NBA traits compared to the other two genotypes (P < 0...
November 8, 2016: Animal Biotechnology
Nadine M P Daan, Maria P H Koster, Marlieke A de Wilde, Gerdien W Dalmeijer, Annemieke M V Evelein, Bart C J M Fauser, Wilco de Jager
OBJECTIVE: To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. DESIGN: Cross-sectional comparison of serum biomarkers. SETTING: University Medical Center Utrecht. PATIENTS: Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30)...
2016: PloS One
Spencer J Thompson, Ashot Sargsyan, Seung-Ah Lee, Jason J Yuen, Jinjin Cai, Rana Smalling, Norbert Ghyselinck, Manuel Mark, William S Blaner, Timothy E Graham
RBP4 is produced mainly by hepatocytes. In type 2 diabetes and obesity, circulating RBP4 is increased and may act systemically to cause insulin-resistance and glucose intolerance. Observations that adipocyte RBP4 mRNA increases in parallel with circulating RBP4 in these conditions, whereas liver RBP4 mRNA does not, led to a widely held hypothesis that elevated circulating RBP4 is a direct result of increased production by adipocytes. To test this, we generated mice with hepatocyte-specific deletion of RBP4 (liver RBP4 knockout or 'LRKO' mice)...
October 19, 2016: Diabetes
Zoe Daniel, Angelina Swali, Richard Emes, Simon C Langley-Evans
BACKGROUND: Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. METHODS: Pregnant rats were fed control or a low protein diet from conception to day 13 gestation...
2016: Genes & Nutrition
W-J Guan, G-J Yang
OBJECTIVE: We investigated the significance of a change in retinol binding protein (RBP4) levels in the plasma of patients with coronary heart disease complicated with hyperlipidemia. PATIENTS AND METHODS: 66 cases of coronary heart disease (CHD) patients in Cardiovascular Department of our Hospital from December 2014 to December 2015 were selected. Based on the diagnostic criteria of hyperinsulinemia, patients were divided into a CHD Group with 35 cases and a CHD-Hyperinsulinemia Group (CHD-H group) with 31 cases...
October 2016: European Review for Medical and Pharmacological Sciences
José María Sayagués, Luís Antonio Corchete, María Laura Gutiérrez, Maria Eugenia Sarasquete, María Del Mar Abad, Oscar Bengoechea, Encarna Fermiñán, María Fernanda Anduaga, Sofia Del Carmen, Manuel Iglesias, Carmen Esteban, María Angoso, Jose Antonio Alcazar, Jacinto García, Alberto Orfao, Luís Muñoz-Bellvis
Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases...
September 20, 2016: Oncotarget
R A Marschner, G Pinto, J Borges, M M Markoski, B D Schaan, A M Lehnen
Elevated serum retinol binding protein 4 (RBP4) levels were previously described in insulin-resistance states. Exercise training can improve insulin sensitivity and RBP4, but the time-response effect of exercise detraining on RBP4 has not been studied. Thus, we examined the effects of exercise training and short-term detraining on insulin resistance, serum RBP4 levels, and GLUT4 expression in spontaneously hypertensive rats (SHR). Thirty-two male SHR, 4 months old, were submitted to 10-week treadmill training, 5 times/week or kept sedentary, followed by a 2- and 4-day detraining period...
September 2, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Raheleh Torabi, Kowsar Bagherzadeh, Hedayatollah Ghourchian, Massoud Amanlou
Type two diabetes is one of the primary health issues threatening public well-being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer ssDNA aptamer instead of conventional antibodies. However, there is no structural information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to RBP4 still remains unexplored. The objective of the present study is to achieve a better understanding of specific binding interactions of the target protein (RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide detailed information on fluctuations, conformational changes, critical bases and effective forces to develop regulated aptamers to be employed in designing new aptamers for many useful recognition applications...
September 14, 2016: Organic & Biomolecular Chemistry
Ahmad Al-Attar, Steven R Presnell, Charlotte A Peterson, D Travis Thomas, Charles T Lutz
We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56(dim) NK cell responses to a variety of stimuli and with CD56(bright)/CD56(dim) NK cell ratio. We also present the correlation of retinol binding protein (RBP)-4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56(dim) NK cell responses...
September 2016: Data in Brief
Yan Liu, Di Mu, Hongen Chen, Di Li, Jiayi Song, Yuan Zhong, Min Xia
CONTEXT AND OBJECTIVE: Elevated serum retinol-binding protein 4 (RBP4) has been implicated in insulin resistant and nonalcoholic fatty liver disease (NAFLD) subjects; however, the molecular mechanism of RBP4 in NAFLD remains obscure. DESIGN AND PARTICIPANTS: Hepatic RBP4 mRNA level and its association with lipid accumulation were examined in NAFLD patients and mouse model. Furthermore, human RBP4 overexpressing (RBP4-Tg) mice were metabolically phenotyped after either a regular chow or high-fat diet...
November 2016: Journal of Clinical Endocrinology and Metabolism
K Polak, A Czyzyk, T Simoncini, B Meczekalski
Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. The diagnostic criteria include two out of three features: hyperandrogenism, polycystic ovaries on ultrasound and menstrual irregularities (Rotterdam Criteria 2003). PCOS patients are more vulnerable to develop diabetes, cardiovascular diseases and metabolic syndrome. Insulin resistance (IR) is prevalent in women with PCOS independently of obesity and is critically involved in reproductive and metabolic complications of the syndrome...
July 29, 2016: Journal of Endocrinological Investigation
Wan Zhou, Shandong Ye, Jing Li
This study aims to investigate the expression of retinol binding protein 4 (RBP4) and the activity of nuclear factor-kappa B (NF-κB) in diabetic rats with atherosclerosis, and to evaluate the intervention effect of pioglitazone. A total of 75 Wistar rats were randomly divided into four groups: Normal control (NC), diabetic rats (DM1), diabetic rats with atherosclerosis (DM2) and diabetic rats treated with pioglitazone (DM + Pio). The activity of NF-κB, the levels of serum and adipose tissue RBP4, fasting plasma glucose (FPG), fasting insulin (FINS), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG) and arteria caudilis systolic blood pressure (SBP) were measured...
August 2016: Experimental and Therapeutic Medicine
Yu Fu, Lana Gaelings, Petri Jalovaara, Laura Kakkola, Mervi T Kinnunen, Hannimari Kallio-Kokko, Miia Valkonen, Anu Kantele, Denis E Kainov
Influenza A viruses (IAV) mutate rapidly and cause seasonal epidemics and occasional pandemics, which result in substantial number of patient visits to the doctors and even hospitalizations. We aimed here to identify inflammatory proteins, which levels correlated to clinical severity of the disease. For this we analysed 102 cytokines and growth factors in human nasopharyngeal aspirate (NPA) samples of 27 hospitalized and 27 outpatients diagnosed with influenza A(H1N1)pdm09 virus infection. We found that the relative levels of monocyte differentiation antigen CD14, lipocalin-2 (LCN2), C-C-motif chemokine 20 (CCL20), CD147, urokinase plasminogen activator surface receptor (uPAR), pro-epidermal growth factor (EGF), trefoil factor 3 (TFF3), and macrophage migration inhibitory factor (MIF) were significantly lower (p<0...
October 2016: Cytokine
Stefano Romeo, Luca Valenti
No abstract text is available yet for this article.
November 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fengyang Huang, Blanca Estela Del-Río-Navarro, Saúl Torres-Alcántara, José Alfredo Pérez-Ontiveros, Eliseo Ruiz-Bedolla, Omar Josué Saucedo-Ramírez, Santiago Villafaña, Fausto Sánchez-Muñoz, Guadalupe Bravo, Enrique Hong
OBJECTIVE: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. METHODS: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified...
June 23, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Qi Lu, Chongdong Liu, Ye Liu, Nawei Zhang, Haiteng Deng, Zhenyu Zhang
AIM: Pre-eclampsia (PE) is a disorder of pregnancy associated with maternal and fetal mortality and morbidity. The aim of the present study was to use proteomics to identify biomarkers of, and elucidate the pathogenesis of, PE. METHODS: Serum samples were analyzed using peptide ligand library beads (PLLB) on liquid chromatography-mass spectrometry/mass spectrometry. Retinol-binding protein 4 (RBP4) was used as the target protein for further validation on enzyme-linked immunosorbent assay, immunohistochemistry and real-time polymerase chain reaction...
September 2016: Journal of Obstetrics and Gynaecology Research
J Jing, N Isoherranen, C Robinson-Cohen, I Petrie, B R Kestenbaum, C K Yeung
Vitamin A, via retinoic acid (RA), is a critical micronutrient. Normally, plasma concentrations are tightly regulated. Concentrations of vitamin A metabolites (13cis-RA, atRA) and relationships between RBP4 and retinoids have never been fully evaluated in adult patients with CKD. We measured retinoid and RBP4 concentrations in plasma and urine from 55 adult patients with CKD and 21 matched healthy subjects. RBP4 and retinol levels were increased approximately twofold in patients with CKD, with a negative correlation between plasma retinol and eGFR (p = 0...
August 2016: Clinical and Translational Science
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