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Poša Mihalj - - 2013
Bile salts (BSs), in addition to their physiological role in the digestion of lipids in vertebrates, are also of significant importance in biomedical investigations. For predicting biological-pharmacological activity and physico-chemical properties of BSs it is important to develop such molecular descriptors that adequately describe the structural characteristics of the steroid ...
di Gregorio M Chiara - - 2013
In this paper, the preparation and characterization of an anionic and a cationic surfactant obtained by chemical modifications of a natural bile acid (cholic acid) are reported. The bile acid was modified by introducing a diamine or a dicarboxylic aromatic residue on the lateral chain. The pure cationic surfactant self-assembles ...
Ipharraguerre Ignacio R - - 2013
Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve intestinal adaptation in weanling pigs. During the ...
Sabit Hairat - - 2013
Human apical sodium-dependent bile acid transporter (hASBT, SLC10A2) is responsible for intestinal reabsorption of bile acids and plays a key role in cholesterol homeostasis. We used a targeted and systematic approach to delineate the role of highly conserved transmembrane helix 2 on the expression and function of hASBT. Cysteine mutation ...
Murashita Koji - - 2013
Bile acid transporters belonging to the SLC10A protein family, Na+ taurocholate cotransporting polypeptide (NTCP or SLC10A1), apical sodium-dependent bile salt transporter (ASBT or SLC10A2), and organic solute transporter alpha (Ost-alpha) have been known to play critical roles in the enterohepatic circulation of bile acids in mammals. In this study, ntcp, ...
Martinefski Manuela R - - 2013
Intrahepatic cholestasis of pregnancy is a high-risk liver disease given the eventual deleterious consequences that may occur in the foetus. It is accepted that the abnormal accumulation of hydrophobic bile acids in maternal serum are responsible for the disease development. Hydrophobic bile acids induce oxidative stress and apoptosis leading to ...
O'Brien Kate M - - 2013
During obstructive cholestasis, increased concentrations of bile acids activate ERK1/2 in hepatocytes, which up-regulates early growth response factor 1, a key regulator of proinflammatory cytokines, such as macrophage inflammatory protein 2 (MIP-2), which, in turn, exacerbates cholestatic liver injury. Recent studies have indicated that IL-17A contributes to hepatic inflammation during ...
Shu-Yao Z - - 2013
The glucuronidation process has been regarded as the key elimination process for toxic bile acids. UDP-glucuronosyltransferase (UGT) 1A3 is one important metabolizing enzyme involved in this process. To evaluate the inhibition of UGT1A3 by scutellarein which is an important herbal ingredient using in vitro method, trying to indicate the possibility ...
Cai Kai K Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, 92093-0704, - - 2013
DGKs (diacylglycerol kinases) catalyse the conversion of diacylglycerol into PA (phosphatidic acid), a positive modulator of mTOR (mammalian target of rapamycin). We have found that chenodeoxycholic acid and the synthetic FXR (farnesoid X receptor) ligand GW4064 induce the mRNA and protein expression of DGKθ in the HepG2 cell line and ...
Yuan Quan - - 2013
Liver is the sole organ responsible for the final elimination of cholesterol from the body either as biliary cholesterol or bile acids. High-density lipoprotein (HDL)-derived cholesterol is the major source of biliary sterols and represents a mechanism for the removal of cholesterol from peripheral tissues including artery wall-associated macrophage foam ...
Berrabah Wahiba - - 2013
Bile acid metabolism is intimately linked to the control of energy homeostasis and glucose and lipid metabolism. The nuclear receptor FXR plays a major role in the enterohepatic cycling of bile acids, but the impact of nutrients on bile acid homeostasis is poorly characterized. Metabolically active hepatocytes cope with increases ...
Pattni S S - - 2013
Bile acid diarrhoea is a common, under-diagnosed cause of chronic watery diarrhoea, responding to specific treatment with bile acid sequestrants. We previously showed patients with bile acid diarrhoea have lower median levels compared with healthy controls, of the ileal hormone fibroblast growth factor 19 (FGF19), which regulates bile acid synthesis. ...
Maeda Y - - 2013
The aim of this study was to investigate the differences between rats and hamsters, Two of the most widely used experimental animals, with respect to the effects of microsomal membrane solubilization on the inhibition of liver 11β-hydroxysteroid dehydrogenase (11β-HSDI) enzyme by bile acids. Liver microsome fractions were prepared, and the ...
Ye Weijian - - 2013
The efficient synthesis of some bile acid-derived cationic amphiphiles with a flexible long hydrocarbon tail was investigated. Firstly, the modification on the side-chain carboxyl of bile acids was carried out efficiently by one-pot amidation of bile acids and a long-chain aliphatic amine in the presence of HOBt and DCC to ...
Penno Carlos A CA Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, - - 2013
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediates glucocorticoid activation and is currently considered as therapeutic target to treat metabolic diseases; however, biomarkers to assess its activity in vivo are still lacking. Recent in vitro experiments suggested that human 11β-HSD1 metabolizes the secondary bile acid 7-oxolithocholic acid (7-oxoLCA) to chenodeoxycholic acid (CDCA) ...
Groen Albert K - - 2013
Extensive transcriptional networks maintain sterol homeostasis across species, underscoring the importance of sterol balance for healthy life. Magner et al. (2013) now show that, in C. elegans, the nuclear receptor NHR-8 is key in regulation of cholesterol balance and production of dafachronic acid, a bile acid-like steroid that controls longevity.
Magner Daniel B DB Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse, Cologne, - - 2013
Hormone-gated nuclear receptors (NRs) are conserved transcriptional regulators of metabolism, reproduction, and homeostasis. Here we show that C. elegans NHR-8 NR, a homolog of vertebrate liver X and vitamin D receptors, regulates nematode cholesterol balance, fatty acid desaturation, apolipoprotein production, and bile acid metabolism. Loss of nhr-8 results in a ...
Sreekanth Vedagopuram - - 2013
We have synthesized two series of bile acid tamoxifen conjugates using three bile acids Lithocholic Acid (LCA), Deoxycholic Acid (DCA) and Cholic Acid (CA). These bile acid-tamoxifen conjugates possess 1, 2, 3 tamoxifen molecules attached to hydroxyl groups of bile acids having free acid and amine functionalities at the tail ...
Vaquero Javier - - 2013
The farnesoid X receptor (FXR) is a key sensor in bile acid homeostasis. Although four human FXR isoforms have been identified, the physiological role of this diversity is poorly understood. Here we investigated their subcellular localization, agonist sensitivity and response of target genes. Measurement of mRNA revealed that liver predominantly ...
Mayorquín-Torres Martha C - - 2013
Palladium-catalyzed cross coupling of phenyboronic acid with acetylated bile acids in which the carboxyl functions have been activated by formation of a mixed anhydride with pivalic anhydride afforded moderate to good yield of 24-phenyl-24-oxo-steroids. Unambiguous assignments of the NMR signals were made with the aid of combined 1D and 2D ...
Chen Jiezhong - - 2013
SUMMARYCholestasis syndromes characterised by impairment of bile formation and secretion arecaused by many diseases. Estrogen-induced cholestasis among the cholestasis syndromes is a very common form. Based on the molecular studies of bile formation and transportation, a significant advancement has been achieved in understanding the mechanism of the disease. Estrogen can ...
Nakaki Junko - - 2013
Phosphate binders are used for the treatment of hyperphosphatemia in hemodialysis patients with chronic kidney disease. Sevelamer, a phosphate-binding polymer, has been reported to bind bile acids or fatty acids and thereby decrease its phosphate-binding capacity. The novel phosphate binder TRK-390 is a poly (allylamine) polymer that has been shown ...
Somalinga Vijayakumar V Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, - - 2013
RjpA in Rhodococcus jostii is the ortholog of a channel-forming porin, MspA. Deletion of rjpA delayed growth of R. jostii on cholate but not on cholesterol. Eventual growth on cholate involved increased expression of other porins, namely, RjpB, RjpC, and RjpD. Porins appear essential for the uptake of bile acids ...
Rainer Peter P PP Division of Cardiology, Medical University of Graz, , Graz, - - 2013
High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in ...
Travaglini Leana - - 2013
Biocompatible molecules that undergo self-assembly are of high importance in biological and medical applications of nanoscience. Peptides and bile acids are among the most investigated due to their ability to self-organize into many different, often stimuli-sensitive, supramolecular structures. With the aim of preparing molecules mixing the aggregation properties of bile ...
Miyata Masaaki - - 2013
The ileal apical sodium-dependent bile acid transporter (ASBT or SLC10A2) has a crucial role in intestinal bile acid absorption. We previously reported that enterobacteria-mediated bile acid conversion was involved in the alteration of ileal ASBT expression levels. In the present study, to investigate the hypothesis that ileal ASBT protein levels ...
Ridlon Jason M - - 2013
A picture is now starting to emerge regarding the liver-bile acid-microbiome axis. Increasing levels of the primary bile acid cholic acid (CA) causes a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of the harmful secondary bile acid deoxycholic acid (DCA). During progression of cirrhosis, the ...
Fernández-Rojo Manuel A - - 2013
Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1-/- mice exhibited impaired hepatic peroxisome proliferator-activated ...
Lefèvre Cathérine M T - - 2013
The human bile acid-sensitive ion channel (hBASIC) is a cation channel of the degenerin/epithelial Na(+) channel gene family that is expressed in the intestinal tract and can be activated by bile acids. Here, we show that in addition to its sensitivity for bile acids, hBASIC shares further key features with ...
Zhang Xiaoqing - - 2013
A capillary electrically driven assay with electrochemiluminescent (ECL) detection for total bile acids in human serum was developed and fully validated. Quantification was performed by multiple reactions. First, the bile acids react with nicotinamide adenine dinucleotide (NAD(+)) under catalysis of 3α-hydroxysteroid dehydrogenase (3α-HSD), which is converted to 3-ketosteroid and concomitantly ...
Myronovych Andriy - - 2013
Objective: Our objective was to investigate the role of bile acids in hepatic steatosis reduction after vertical sleeve gastrectomy (VSG). Design and Methods: High fat diet (HFD) induced obese C57Bl/6 mice were randomized to: VSG, Sham operation (Sham), Sham operation with pair feeding to VSG (Sham-PF), or non-surgical controls (Naïve). ...
Patiño Cano Laura P - - 2013
From the organic extracts of the sponge Siphonochalina fortis, collected at Bahía Bustamante, Chubut, Argentina, three major compounds were isolated and identified as deoxycholic acid 3, 12-diacetate (1), cholic acid 3, 7, 12-triacetate (2) and cholic acid, 3, 7, 12-triacetate. (3). This is the first report of acetylated bile acids ...
Tee Wf - - 2013
This study investigated the survival of encapsulated potential probiotic Lactobacillus plantarum which isolated from fermented cocoa beans. κ-carrageenan was used to encapsulate the probiotic. Encapsulation techniques such as emulsification, freeze-drying or extrusion were adopted to encapsulate the probiotic. Freeze-drying and extrusion methods showed higher (p < 0.05) efficiency (89.48 ± 3.21 and 92.26 ± 1.45%, respectively) ...
Langhi Cédric C Department of Biochemistry and Molecular Biology, School of Pharmacy and Institute of Biomedicine of University of Barcelona, Barcelona, - - 2013
Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol and vitamin A (retinol) metabolism in the liver. Because previous studies have shown that human ADH1 enzymes may participate in bile acid metabolism, we investigated whether the bile acid-activated nuclear receptor farnesoid X receptor (FXR) regulates ADH1 genes. In ...
Trottier Jocelyn - - 2013
Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes detoxifies cholestatic bile acids (BAs). We aimed at i) characterizing the circulating BA-glucuronide (-G) pool composition in humans, ii) evaluating how sex and UGT polymorphisms influence this composition, and iii) analyzing the effects of lipid-lowering drug fenofibrate on the circulating BA-G profile in 300 ...
Perreault Martin - - 2013
Bile acids (BA) are essential modulators of lipid, glucose and cholesterol homeostasis, but exert cytotoxic effects in the cholestatic liver. Glucuronidation, catalyzed by the UDP-glucuronosyltransferase (UGT) enzymes is a pharmacologically-relevant BA detoxification process. The present study aimed at characterizing the BA-conjugating activity of the little-studied human UGTs of subfamily 2A, ...
Peters A Michael - - 2013
Measurement of the whole body retention of orally administered (75)SeHCAT is used to investigate patients with unexplained diarrhoea. Retention values of <15 % at 7 days post-administration are taken to indicate bile acid malabsorption (BAM). Whilst idiopathic BAM is frequently diagnosed with (75)SeHCAT, functional and morphological studies of the terminal ileum rarely ...
Dawson Paul A PA Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. - - 2013
Hypercholesterolemia is a major cause of cardiovascular disease and can be treated by targeting bile acid and cholesterol metabolism. Vergnes et al. (2013) now identify Diet1 as a novel regulator of fibroblast growth factor 15/19 production and bile acid biosynthesis.
Hanly Ruth - - 2013
The intestinal absorption of vitamin D is linked to bile acid absorption. This link may be abnormal in patients with osteoporosis. The aim of this study was to investigate a possible relation between osteoporosis and bile acid turnover, measured as whole-body Se-75-HCAT retention (WBR), in postmenopausal women. Whole-body counts were ...
Taguchi Kaori - - 2013
A number of analysis methods for bile acids using LC-MS and GC-MS have been reported. However, there is no reported method for the simultaneous analysis of bile acids using supercritical fluid chromatography (SFC). In this study, we have successfully developed a rapid method using SFC coupled to electrospray ionization tandem ...
Lan Tian T Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, - - 2013
Interruption of the enterohepatic circulation of bile acids induces hepatic bile acid synthesis, increases hepatic cholesterol demand, and increases clearance of apoB-containing lipoproteins in plasma. Based on these effects, bile acid sequestrants have been used for many years to treat hypercholesterolemia and the associated atherosclerosis. The objective of this study ...
Xie Guoxiang G Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, - - 2013
Our understanding of the bile acid metabolism is limited by the fact that previous analyses have primarily focused on a selected few circulating bile acids; the bile acid profiles of the liver and gastrointestinal tract pools are rarely investigated. Here, we determined how chronic ethanol consumption altered the bile acids ...
Ogawa Shoujiro - - 2013
This paper describes a method for the chemical synthesis of 7α,12α-dihydroxy-4-cholesten-3-one (1a) and its biological precursor, 7α-hydroxy-4-cholesten-3-one (1b), both of which are key intermediates in the major pathway of bile acid biosynthesis from cholesterol. The principal reactions involved were (1) building of the cholesterol (iso-octane) side chain by 3-carbon elongation ...
Soroka Carol J - - 2013
The bile salt export pump (BSEP, ABCB11) is the primary transporter of bile acids from the hepatocyte to the biliary system. This rate-limiting step in bile formation is essential to the formation of bile salt dependent bile flow, the enterohepatic circulation of bile acids, and the digestion of dietary fats. ...
Blazquez Marina M Unidad de Hepatología Experimental, CIBERehd, Instituto de Investigación Sanitaria La Fe, Valencia 46009, - - 2013
The development of hepatoma-based in vitro models to study hepatocyte physiology is an invaluable tool for both industry and academia. Here, we develop an in vitro model based on the HepG2 cell line that produces chenodeoxycholic acid, the main bile acid in humans, in amounts comparable to human hepatocytes. A ...
Turumin J L - - 2013
The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid) in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid), thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation ...
Dosa Peter I - - 2013
Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti-apoptotic activity in both in vitro and in vivo models. However, its utility is hampered by limited aqueous solubility. As such, water-soluble prodrugs of UDCA could have an advantage over the parent bile acid in indications where intravenous administration might be preferable, such ...
Francis Michael B - - 2013
Clostridium difficile spores must germinate in vivo to become actively growing bacteria in order to produce the toxins that are necessary for disease. C. difficile spores germinate in vitro in response to certain bile acids and glycine. In other sporulating bacteria, proteins embedded within the inner membrane of the spore ...
Voelker Troy - - 2013
Background: Quantification of bile acids using LC-MS has previously been very challenging on triple quadrupole MS systems due to the absence of a primary fragment ion for unconjugated bile acids. Results: A LC-high-resolution/accurate mass MS method for the analysis of six bile acids (cholic acid, chenodeoxycholic acid, taurocholic acid, deoxycholic ...
Burrin D D USDA Children's Nutrition Research Center, Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Houston, TX 77030, USA. - - 2013
Bile acids have historically been considered to mainly function in cholesterol homeostasis and facilitate fat digestion in the gastrointestinal tract. Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G protein-coupled bile acid receptor 1 (GPBAR1/G-protein-coupled bile acid receptor ...
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