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Liu Jie J University of Kansas Medical Center, Kansas City, KS 66160 USA Zunyi Medical College, Zunyi, China - - 2014
Bile acids (BAs) are known to regulate their own homeostasis, but the potency of Individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes ...
Ding Lili - - 2014
The Danning tablets (DNts) is commonly prescribed in China as a cholagogic formula. Our previous studies showed that DNts exerted the protective effect on alpha-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in a dose-dependent mannar. However, the detailed molecular mechanisms of DNts against ANIT-induced cholestasis are still not fully explored. Danning ...
Walker Alesia - - 2014
A metabolic disorder such as Type 2 Diabetes mellitus (T2DM) is a complex disease induced by genetic, environmental and nutritional factors. The db/db mouse model, bearing a non-functional leptin receptor is widely used to investigate the pathophysiology of T2DM. Fecal extracts of db/db and wild type littermates were studied to ...
Hendrick Siobhán M SM Royal College of Surgeons in - - 2014
Bile acids resulting from the aspiration of gastroesophageal refluxate are often present in the lower airways of people with cystic fibrosis and other respiratory distress diseases. Surprisingly, there is little or no information on the modulation of airway epithelial ion transport by bile acids. The secretory effect of a variety ...
Shang Quan Q Rutgers, New Jersey Medical - - 2014
Aims: It was proposed that CYP7A1 expression is suppressed through a gut-hepatic signaling pathway FGF15/19-FGFR4, which is initiated by activation of FXR in the intestine rather than in the liver. The present study tested whether portal bile acid flux alone without ileal FGF19 could down-regulate CYP7A1 expression in rabbits. Methods: ...
Gioiello Antimo A Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06122 Perugia (Italy). Electronic address: - - 2014
Deficiency of 3β-hydroxy-Δ(5)-C27-steroid oxidoreductase (HSD3B7), an enzyme catalyzing the second step in the pathway for bile acid synthesis, leads to a complete lack of the primary bile acids, cholic and chenodeoxycholic acids, and the accumulation of 3β,7α-dihydroxy- and 3β,7α,12α-trihydroxy-Δ(5)-cholenoic acids. Patients affected by this autosomal recessive genetic defect develop cholestatic ...
Luciano Randy L RL Section of Nephrology, Yale University School of Medicine, New Haven, - - 2014
Bile acid nephropathy, also known as cholemic nephrosis or nephropathy, is an entity that can be seen in patients with severe cholestatic liver disease. It typically is associated with acute kidney injury (AKI) with various forms of hepatic disease. Most often, patients with severe obstructive jaundice develop this lesion, which ...
McAdam E E Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, UK, SA2 - - 2014
Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease (GORD) is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic ...
Appleby Richard N RN Section of Hepatology and Gastroenterology, Imperial College London, Imperial College Healthcare, Hammersmith Hospital, London, - - 2014
Bile acids are increasingly implicated in the pathogenesis of functional GI disorders. New mechanisms have recently been described in the irritable bowel syndrome, chronic diarrhea and chronic idiopathic constipation. Identification of bile acid signaling through farnesoid X receptor (FXR), transmembrane G-coupled receptor 5 (TGR5) and fibroblast growth factor 19 (FGF19) ...
Kurien M M Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, - - 2014
Bile acid diarrhoea (BAD) is a recognised cause of chronic diarrhoea, however detection remains sub-optimal. Knowledge of factors predictive of BAD could help improve detection. This study evaluates factors predictive of BAD (7 day SeHCAT retention <10%) and determines long treatment outcomes in those instigated on medical therapy. 515 patients ...
Ajouz Hana - - 2014
Bile acids were first proposed as carcinogens in 1939. Since then, accumulated evidence has linked exposure of cells of the gastrointestinal tract to repeated high physiologic levels of bile acids as an important risk factor for gastrointestinal cancers. High exposure to bile acids may occur in a number of settings, ...
Gärtner Stefanie S a BAM Federal Institute for Materials Research and Testing , Berlin , - - 2014
ABSTRACT Bile acids are relevant markers for clinical research. This study reports the production of antibodies for isolithocholic acid, the isomer of the extensively studied lithocholic acid. The IgG titer and affinity maturation were monitored during the immunizations of three mice and two rabbits. In both animal models, polyclonal antibodies ...
Hofmann Alan F AF University of California, San Diego, United States; - - 2014
During the last 80 years there have been extraordinary advances in our knowledge of the chemistry and biology of bile acids. We present here a brief history of the major achievements as we perceive them. Bernal, a physicist, determined the x-ray structure of cholesterol crystals and his data together with ...
König Alexander A Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany; German Center for Infection Research - - 2014
The human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has recently been identified as liver-specific receptor for infection of hepatitis B virus (HBV) which attaches via the myristoylated preS1 (myr-preS1) peptide domain of its large surface protein to NTCP. Since binding of the myr-preS1 peptide to NTCP is an ...
He Sihui S CREOL, The College of Optics and Photonics, University of Central Florida, Orlando, Florida 32816, - - 2014
The interaction between bile acids and surfactants at interfaces plays an important role in fat digestion. In this paper, we study the competitive adsorption of cholic acid (CA) at the sodium dodecyl sulfate (SDS)-laden liquid crystal (LC)/aqueous interface formed with cyanobiphenyl (nCB, n = 5-8) and the mixture of 5CB ...
Jones Mitchell Lawrence ML Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Physiology and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, H3A 2B4, - - 2014
The human gut microbiome produces potent ligands to bile acid receptors, and probiotics could act as therapeutics of bile acid dysmetabolism. A recent study in Cell Reports demonstrates that probiotic VSL#3 affects bile acid deconjugation and excretion, as well as the gut-liver FXR-FGF15 axis.
Kuipers Folkert F Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700RB Groningen, - - 2014
Over the past decade, it has become apparent that bile acids are involved in a host of activities beyond their classic functions in bile formation and fat absorption. The identification of the farnesoid X receptor (FXR) as a nuclear receptor directly activated by bile acids and the discovery that bile ...
Poša Mihalj M Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljka 3, 21000 Novi Sad, Serbia. Electronic address: - - 2014
Bile acid salts are biosurfactants which form mixed micelles with phospholipids in vertebrates. These mixed micelles are suitable for solubilisation of cholesterol. For therapeutic purposes some bile acid salts as sodium ursocholate are used. However, bile acid anions posses low capacity for solubilisation of cholesterol. Thus, synthesis of more hydrophobic ...
Vallapragada Venkata Vivekanand VV 1 Invagen Pharmaceutical Inc., 7 Oser Avenue, Hauppauge, NY 11788, - - 2014
A simple, precise and accurate gradient reverse-phase ultra-performance liquid chromatographic method was developed for the quantitative determination of bile acids [glycocholic acid (GCA), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA)) in in vitro bile acid-binding study of Welchol tablets. The method was developed using Phenomenex Kinetex C18 (50 × 2.10 ...
Qi Yunpeng Y Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai 200433, - - 2014
Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet ...
Roda Aldo A University of - - 2014
We report on the relationship between the structure-pharmacokinetics, metabolism, and therapeutic activity of semi-synthetic bile acid analogues including 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (a selective FXR receptor agonist), 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (a specific TGR5 receptor agonist), and 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-sulfate (a dual FXR/TGR5 agonist). We measured the main physicochemical properties of these molecules, including ionization constants, ...
Sonne David Peick DP D Sonne, Department of Medicine, Gentofte Hospital, Diabetes Research Division, Hellerup, - - 2014
Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol to bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In ...
Shivanna Vinay V Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, 1800 Denison Avenue, KS 66506, United - - 2014
Replication of porcine enteric calicivirus (PEC) in LLC-PK cells is dependent on the presence of bile acids in the medium. However, the mechanism of bile acid-dependent PEC replication is unknown. Understanding of bile acid-mediated PEC replication may provide insight into cultivating related human noroviruses, currently uncultivable, which are the major ...
Autio Kaija J - - 2014
Cholesterol is catabolized to bile acids by peroxisomal β-oxidation in which the side-chain of C27-bile acid intermediates is shortened by three carbon atoms to form mature C24-bile acids. Knock-out mouse models deficient in α-methylacyl coenzyme A racemase (Amacr) or multifunctional enzyme type 2 (Mfe-2), in which this β-oxidation pathway is ...
Woolbright Benjamin L BL Department of Pharmacology, Toxicology & Therapeutics, Kansas University Medical Center, - - 2014
Lithocholic acid (LCA) supplementation in the diet results in intrahepatic cholestasis and bile infarcts. Previously we showed that an innate immune response is critical for cholestatic liver injury in the bile duct ligated mice. Thus, the purpose of this study was to investigate the role of neutrophils in the mechanism ...
Erlinger Serge S University of Paris 7, 75013 Paris, France. Electronic address: - - 2014
The elegant paper by Fickert et al. on bile duct ligated mice provides convincing evidence for the hypothesis that bile acids retained in the serum during cholestasis and excreted through the kidneys are toxic to collecting duct cells. The authors propose that bile acids initiate a chain of reactions leading ...
Ryan Karen K KK Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, Ohio 45237, - - 2014
Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal ...
Walters Julian R F JR Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, - - 2014
Chronic diarrhoea induced by bile acids is common and the underlying mechanisms are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast growth factor 19 (FGF19). Increasing evidence, including that from several large case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis, indicates that bile acid ...
De Bruyn Tom T Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O&N2, Leuven, 3000, - - 2014
This study aimed to characterize the in vitro hepatic transport mechanisms in primary rat and human hepatocytes of the fluorescent bile acid derivative N-(24-[7-(4-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole)]amino-3α,7α,12α-trihydroxy-27-nor-5β-cholestan-26-oyl)-2'-aminoethanesulfonate (tauro-nor-THCA-24-DBD), previously synthesized to study the activity of the bile salt export pump (BSEP). The fluorescent bile acid derivative exhibited saturable uptake kinetics in suspended rat ...
Xiong Aizhen - - 2014
Pyrrolizidine alkaloids (PAs) are among the most hepatotoxic natural products that produce irreversible injury to humans via consumption of herbal medicine, tea preparation, and honey. Toxicity and death caused by PA exposure have been reported worldwide. Metabolomics and genomics provide scientific and systematic views of living organism, and have become ...
Kakiyama Genta G Virginia Commonwealth University / McGuire VA Medical Center, United - - 2014
We have developed a simple and accurate HPLC method for measurement of fecal bile acids using phenacyl derivatives of unconjugated bile acids, and applied it to the measurement of fecal bile acids in cirrhotic patients. The HPLC method has the following steps: 1) lyophilization of stool sample; 2) reconstitution in ...
Ridlon Jason M JM aDepartment of Microbiology and Immunology, Virginia Commonwealth University bMcGuire VA Medical Center cDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, - - 2014
We examine the latest research on the emerging bile acid-gut microbiome axis and its role in health and disease. Our focus revolves around two key microbial pathways for degrading bile salts, and the impact of bile acid composition in the gut on the gut microbiome and host physiology. Bile acid ...
Quinn Matthew M Department of Internal Medicine, Texas A&M Health Science Center College of Medicine, Temple, TX, - - 2014
The blood brain barrier tightly regulates the passage of molecules into the brain and becomes leaky following obstructive cholestasis. The aim of this study was to determine if increased serum bile acids observed during cholestasis permeabilize the blood brain barrier. Rats underwent bile duct ligation or deoxycholic or chenodeoxycholic acid ...
Boesjes Marije - - 2014
In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bile acids influence metabolism via ...
Choi Sy-Bing SB School of Industrial Technology, Universiti Sains Malaysia , Penang , Malaysia - - 2014
Abstract Probiotic microorganisms have been documented over the past two decades to play a role in cholesterol-lowering properties via various clinical trials. Several mechanisms have also been proposed and the ability of these microorganisms to deconjugate bile via production of bile salt hydrolase (BSH) has been widely associated with their ...
Wang Lirui L Department of Medicine, University of California San Diego, La Jolla, - - 2014
Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated ...
Sato Shinichiro S Faculty of Textile Science and Technology, Shinshu University, Tokida 3-15-1, Ueda, Nagano 386-8567 - - 2014
The differences in the interaction of monoglycerides with bile acids or cholesterol have been investigated from a physico-chemical point of view. A Langmuir trough and fluorescence microscope was used to study mixed monolayers of dl-α-palmitin (a monoglyceride) and cholesterol or deoxycholic acid (a bile acid) at the air/aqueous interface. The ...
Wunsch Ewa E Liver Research Laboratories, Pomeranian Medical University, Szczecin, - - 2014
Ursodeoxycholic acid (UDCA) is no longer recommended for the management of adult patients with primary sclerosing cholangitis (PSC). We undertook prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range 10-15mg/kg/day) were included. Paired blood samples for liver ...
Cai Shi-Ying SY Yale - - 2014
Chronic cholestasis results in liver injury and eventually liver failure. Although ursodeoxycholic acid (UDCA) showed limited benefits in primary biliary cirrhosis, there is an urgent need to develop alternative therapy for chronic cholestatic disorders. Previous studies from our laboratory demonstrated that all-trans retinoic acid (atRA) is a potent suppressor of ...
Theriot Casey M CM 1] Division of Infectious Diseases, Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan 48109, USA [2] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan 48109, - - 2014
Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, ...
Barrientos Alvaro A Departmento de Biología Molecular. Universidad de León. Facultad de Veterinaria, 24007 León, - - 2014
Pseudomonas putida DOC21, a soil-dwelling proteobacterium, catabolises a variety of steroids and bile acids. Transposon mutagenesis and bioinformatics analyses identified four clusters of steroid degradation (std) genes encoding a single catabolic pathway. The latter includes three predicted acyl-CoA synthetases encoded by stdA1, stdA2 and stdA3, respectively. The ΔstdA1 and ΔstdA2 ...
Jasiewicz Beata B Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland. Electronic address: - - 2014
A series of novel salts made of nicotine alkaloids and bile acids were synthesized and their haemolytic activity was examined in vitro using human erythrocytes. All compounds were characterized by spectroscopic methods. The novel salts show membrane-perturbing properties inducing the erythrocyte shape alterations and haemolysis in dose-dependent manner. Nicotine decreases ...
Hrycay Eugene E Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, V6T1Z3, - - 2014
The bile salt export pump (BSEP/Bsep; gene symbol ABCB11/Abcb11) translocates bile salts across the hepatocyte canalicular membrane into bile in humans and mice. In humans, mutations in the ABCB11 gene cause a severe childhood liver disease known as progressive familial intrahepatic cholestasis type 2. Targeted inactivation of mouse Bsep produces ...
Lepist Eve-Irene EI Gilead Sciences, Inc., Foster City, California, United States of - - 2014
Inhibition of the transporter-mediated hepatobiliary elimination of bile salts is a putative mechanism for liver toxicity observed with some endothelin receptor antagonists (ERAs). Sandwich-cultured human hepatocytes were used to study the hepatobiliary distribution and accumulation of exogenous taurocholate, ERAs and endogenous bile acids. The molecular mechanisms for findings in hepatocytes ...
Telbisz Agnes A Institute of Molecular Pharmacology, Hungarian Academy of - - 2014
ABCG2 is a plasma membrane glycoprotein that actively extrudes xenobiotics and endobiotics from the cells and causes multidrug resistance in cancer. In the liver, ABCG2 is expressed in the canalicular membrane of hepatocytes and excretes its substrates into the bile. ABCG2 is known to require high membrane cholesterol content for ...
Geenes Victoria V Institute of Reproductive and Developmental Biology, Imperial College London, London, United - - 2014
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the ...
Pospieszny Tomasz T Laboratory of Microbiocide Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, Poznań 60-780, Poland. - - 2014
A novel method for the synthesis of bile acid derivatives has been developed using "click chemistry". Intermolecular 1,3-dipolar cycloaddition of the propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene gave a new quasi-podands with 1,2,3-triazole rings. The structures of the products were confirmed by spectral (1H-NMR, 13C-NMR, and ...
Li Xingnuo X College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. - - 2014
In an effort to decrease the toxicity of camptothecin (CPT) and improve selectivity for hepatoma and colon cancer cells, bile acid groups were introduced into the CPT 20 or 10 positions, resulting in the preparation of sixteen novel CPT-bile acid analogues. The compounds in which a bile acid group was ...
Brycki Bogumil B Laboratory of Microbiocide Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, Poznań 60-780, Poland. - - 2014
New quaternary 3-phthalimidopropylammonium conjugates of steroids were obtained by reaction of sterols (ergosterol, cholesterol, cholestanol) and bile acids (lithocholic, deoxycholic, cholic) with bromoacetic acid bromide to give sterol 3β-bromoacetates and bile acid 3α-bromoacetates, respectively. These intermediates were subjected to nuclephilic substitution with N,N-dimethyl-3-phthalimidopropylamine to give the final quaternary ammonium salts. ...
Trauner Michael M Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, - - 2014
Chronic inflammatory bile duct diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) result in progressive fibrosis of the biliary tract and ultimately cirrhosis of the liver. Since the etiology and pathogenesis of these fibrosing cholangiopathies are still poorly understood, therapeutic options are rather limited at present. ...
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