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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 following either a regular chow (RC) or high-fat diet (HFD)...
August 9, 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.
July 11, 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
Chao-Hung Chen, Liang-Yin Ke, Hua-Chen Chan, An-Sheng Lee, Kun-Der Lin, Chih-Sheng Chu, Mei-Yueh Lee, Pi-Jung Hsiao, Chin Hsu, Chu-Huang Chen, Shyi-Jang Shin
Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells...
August 2016: Journal of Lipid Research
Masanobu Abe, Satoshi Yamashita, Yoshiyuki Mori, Takahiro Abe, Hideto Saijo, Kazuto Hoshi, Toshikazu Ushijima, Tsuyoshi Takato
BACKGROUND: Early detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients. Oral leukoplakias (OLs), known as the most common premalignant lesions in the oral cavity, often precede OSCCs. Especially, OLs with dysplasia are known to have a high risk of malignant transformation. Here, we searched for the promoter methylation characteristic of high-risk OLs. METHODS: To identify methylation-silenced genes, a combined analysis of methylated DNA immunoprecipitation (MeDIP) - CpG island (CGI) microarray analysis and expression microarray analysis after treatment with a demethylating agent was performed in two OSCC cell lines (Ca9-22 and HSC-2)...
2016: BMC Cancer
Seung-Ah Lee, Jason J Yuen, Hongfeng Jiang, Barbara B Kahn, William S Blaner
: There is considerable evidence that both retinoids and retinol-binding protein 4 (RBP4) contribute to the development of liver disease. To understand the basis for this, we generated and studied transgenic mice that express human RBP4 (hRBP4) specifically in adipocytes (adi-hRBP4 mice). When fed a chow diet, these mice show an elevation in adipose total RBP4 (mRBP4 + hRBP4) protein levels. However, no significant differences in plasma RBP4 or retinol levels, or differences in hepatic or adipose retinoid (retinol, retinyl ester, and all-trans-retinoic acid) levels were observed...
May 26, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Mary Kelly, M Airanthi K Widjaja-Adhi, Grzegorz Palczewski, Johannes von Lintig
Vitamin A bound to retinol binding protein 4 (RBP4) constitutes the major transport mode for retinoids in fasting circulation. Emerging evidence suggests that membrane protein, STRA6 (stimulated by retinoic acid 6), is the RBP4 receptor and vitamin A channel; however, the role of STRA6 in vitamin A homeostasis remains to be defined in vivo We subjected Stra6-knockout mice to diets sufficient and insufficient for vitamin A and used heterozygous siblings as controls. We determined vitamin A levels of the eyes, brain, and testis, which highly express Stra6, as well as of tissues with low expression, such as lung and fat...
August 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sarah C Cottin, Lorraine Gambling, Helen E Hayes, Valerie J Stevens, Harry J McArdle
Iron deficiency impairs vitamin A (VA) metabolism in the rat but the mechanisms involved are unknown and the effect during development has not been investigated. We investigated the effect of pregnancy and maternal iron deficiency on VA metabolism in the mother and fetus. 54 rats were fed either a control or iron deficient diet for 2weeks prior to mating and throughout pregnancy. Another 15 female rats followed the same diet and were used as non-pregnant controls. Maternal liver, placenta and fetal liver were collected at d21 for total VA, retinol and retinyl ester (RE) measurement and VA metabolic gene expression analysis...
June 2016: Journal of Nutritional Biochemistry
Kaja Plucińska, Ruta Dekeryte, David Koss, Kirsty Shearer, Nimesh Mody, Phillip D Whitfield, Mary K Doherty, Marco Mingarelli, Andy Welch, Gernot Riedel, Mirela Delibegovic, Bettina Platt
AIMS: β-Secretase 1 (BACE1) is a key enzyme in Alzheimer's disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4)...
July 2016: Diabetologia
Ayo Priscille Doumatey, Jie Zhou, Ming Zhou, DaRue Prieto, Charles N Rotimi, Adebowale Adeyemo
OBJECTIVE: The metabolically healthy obesity (MHO) phenotype is an important obesity subtype in which obesity is not accompanied by any metabolic comorbidity. However, the underlying molecular mechanisms remain elusive. In this study, a shotgun proteomics approach to identify circulating biomolecules and pathways associated with MHO was used. METHODS: The subjects were 20 African-American women: 10 MHO cases and 10 metabolically abnormal individuals with obesity (MAO) controls...
June 2016: Obesity
Wei Gao, Hao Wang, Lin Zhang, Yang Cao, Ji-Zhang Bao, Zheng-Xia Liu, Lian-Sheng Wang, Qin Yang, Xiang Lu
Insulin resistance plays a major role in the development and progression of cardiac hypertrophy and heart failure. Heart failure in turn promotes insulin resistance and increases the risk for diabetes. The vicious cycle determines significant mortality in patients with heart failure and diabetes. However, the underlying mechanisms for the vicious cycle are not fully elucidated. Here we show that circulating levels and adipose expression of retinol-binding protein 4 (RBP4), an adipokine that contributes to systemic insulin resistance, were elevated in cardiac hypertrophy induced by transverse aortic constriction and angiotensin-II (Ang-II) infusion...
June 2016: Endocrinology
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