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Parker Rex A RA Cardiovascular Discovery Biology, Bristol-Myers Squibb Pharmaceutical Research and Development, Pennington, NJ 08534, USA. - - 2013
Proprotein convertase subtilisin-kexin-9 (PCSK9) inhibition markedly augments the LDL lowering action of statins. The combination is being evaluated for long-term effects on atherosclerotic disease outcomes. However, effects of combined treatment on hepatic cholesterol and bile acid metabolism have not yet been reported. To study this, PCSK9-Y119X mutant (knockout) and wild-type ...
de Aguiar Vallim Thomas Q TQ Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, - - 2013
Enzymatic oxidation of cholesterol generates numerous distinct bile acids that function both as detergents that facilitate digestion and absorption of dietary lipids, and as hormones that activate four distinct receptors. Activation of these receptors alters gene expression in multiple tissues, leading to changes not only in bile acid metabolism but ...
Zwicker Brittnee L - - 2013
Bile acids have emerged as important biological molecules that support the solubilization of various lipids and lipid-soluble compounds in the gut, and the regulation of gene expression and cellular function. Bile acids are synthesized from cholesterol in the liver and eventually released into the small intestine. The majority of bile ...
Kohli Rohit R Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. - - 2013
Bariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We ...
Marin Jose J G - - 2013
Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Since mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effect of ...
Andriantsoanirina Valérie - - 2013
Bifidobacteria are part of the human gastrointestinal microbiota and are used as probiotics in functional food products because of their health promoting properties. However, only few data are available on the phenotypic characteristics displayed by human bifidobacteria strain populations. In this study we compared the in vitro tolerance to acid, ...
Abe Takuya - - 2013
SLC10A4 belongs to the sodium bile acid cotransporter family, but has no transport activity for bile acids. We performed multiple amino acid alignments and examined the relationships between the SLC10 proteins. The extracellular N-terminus of SLC10A4 was predicted to be relatively longer at the amino acid level than those of ...
Iwamoto Junichi - - 2013
BACKGROUND:: Recent studies have suggested that the downregulation of pregnane X receptor (PXR) may contribute to the susceptibility and exacerbation of Crohn's disease (CD). Because bile acid malabsorption is one of the features of CD and bile acids are potential activators of PXR, we explored the relationship between bile acid ...
Chen Jianbo - - 2013
OBJECTIVE: To identify possible biomarkers for the clinical grading of intrahepatic cholestasis of pregnancy (ICP) through serum bile acid (SBA) profiling in women with ICP. METHODS: Serum samples were collected in the last trimester of pregnancy from 33 women with severe ICP, 28 women with mild ICP, and 35 women ...
Pradhan M M Department of Obstetrics and Gynecology, the first affiliated hospital of Chongqing medical university, Chongqing, - - 2013
Intrahepatic cholestasis of pregnancy (ICP) is the pregnancy induced liver disorder causing intense itching of palm, sole or even whole body especially in the evening at late second and third trimester. This disease is categorized into mild and severe ICP according to raised level of LFT including serum level of ...
Claro da Silva Tatiana T Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, - - 2013
The solute carrier (SLC) family 10 (SLC10) comprises influx transporters of bile acids, steroidal hormones, various drugs, and several other substrates. Because the seminal transporters of this family, namely, sodium/taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2), were primarily bile acid transporters, the term ...
Alemi Farzad F Department of Surgery, UCSF, San Francisco, California 94121, - - 2013
Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ...
Murai Tsuyoshi - - 2013
A method has been developed for the measurement of transport activities in membrane vesicles obtained from Sf9 cells for 3β-hydroxy-Δ5-bile acids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Calibration curves for the bile acids were linear over the range of 10 to 2000 pmol/mL, and the detection limit was less ...
Njauw Ching-Wei - - 2013
It has been known that the addition of bile salts into lecithin organosols induces the formation of reverse wormlike micelles and the worms are similar to long polymer chains which entangle each other to form viscoelastic solutions. In this study, we further investigated the effects of different bile salts and ...
Shan Jing - - 2013
BACKGROUND AND AIM: Immune-mediated mucosal inflammation characterized by the production of interleukin (IL)-8 is associated with the development of gastroesophageal reflux disease (GERD). The effects of bile acids, which are major components of reflux fluid, on the production of IL-8 and related mechanisms remain unclear. This study aimed to address ...
Gardès Christophe C Cardiovascular and Metabolic Diseases DTA, F. Hoffmann-La Roche AG, Basel, Switzerland. - - 2013
Modulating bile acid synthesis has long been considered a good strategy by which to improve cholesterol homeostasis in humans. The farnesoid X receptor (FXR), the key regulator of bile acid synthesis, was, therefore, identified as an interesting target for drug discovery. We compared the effect of four, structurally unrelated, synthetic ...
Attakpa Eugène S - - 2013
Abstract Background: Bile acids are synthesized in the liver from cholesterol. Method: This study investigated the impact and expression of different carriers of bile acid in the liver and kidneys. Eight-week-old male mice were used, which were fed for 15 days and divided into two groups: 15 mice fed with ...
Murai Tsuyoshi - - 2013
A method for the determination of conjugated and unconjugated 3β-hydroxy-Δ(5)-bile acids and related bile acids in human urine and serum has been developed using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Calibration curves for the bile acids were linear over the range of 10-2000pmol/mL, and the detection limit was less than ...
Wu Lili - - 2013
Abstract Aims and objectives. The aim is to determine the efficacy of internal and external biliary drainage (ED) with special reference to the effect of bile acid on intestinal epithelium during experimental biliary obstruction. Methods. A total of 59 male Sprague Dawley rats were randomly assigned to four groups: (I) ...
Setchell Kenneth D R KD Department of Pathology and Laboratory Medicine, Children's Hospital Medical Center, Cincinnati, OH 45229, USA. - - 2013
The final step in bile acid synthesis involves conjugation with glycine and taurine, which promotes a high intraluminal micellar concentration to facilitate lipid absorption. We investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some ...
Nagasaka Hironori - - 2013
BACKGROUND: Intrahepatic congenital portosysstemic venous shunt (CPSVS) presents hyperammonemia, cholestasis, hypergalactosemia and imbalanced vasomediators. Especially, fluctuating plasma ammonia often causing neurological signs and symptoms is a serious problem in the daily life. 4-phenylacetate (4-PA) has effects to eliminate blood ammonia, bile acids and bilirubin. 4-PA might be expected to improve ...
Sayin Sama I SI Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, 413 45 Gothenburg, - - 2013
Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition ...
Saeki Tohru - - 2013
ABSTRACT: BACKGROUND: SLC10A2-mediated reabsorption of bile acids at the distal end of the ileum is the first step in enterohepatic circulation. Because bile acids act not only as detergents but also as signaling molecules in lipid metabolism and energy production, SLC10A2 is important as the key transporter for understanding the ...
Dai Jiaqi - - 2013
We observed that free bile acids (CA, DCA, and CDCA) inhibited the growth of cholangiocarcinoma cells by promoting cell apoptosis, while the conjugated bile acids (GCA, GDCA, and GCDCA) stimulated cell growth. Consistently, we found that GDCA stimulated tumor growth and CDCA decreased tumor growth in xenografted mice. Further, the ...
Matsuhisa Takeshi - - 2013
BACKGROUND: The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured. PATIENTS AND METHODS: This study was carried out with the participation of 14 facilities in ...
Yamazaki Makoto - - 2013
Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats ...
Vivian Diana D Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, - - 2013
To synthesize a trifluorinated bile acid that can be used for (19)F magnetic resonance imaging (MRI) of bile acid enterohepatic circulation, characterize its in vitro transporter affinity, stability, and (19)F-MRI signal, and assess its ability to concentrate in the gallbladder of C57BL/6 mice. Target compound CA-lys-TFA was synthesized and tested ...
Lu Jinrong - - 2013
Two fan-shaped bile acid trimers have been synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) 'click chemistry', and their extraction experiments of cresol red sodium (CR) and pyrene were investigated in the polar and non-polar solvents, respectively. The transmission electron microscopy (TEM) results showed that the homogenous hollow capsules formed with the ...
Wang Xijun - - 2013
BACKGROUND: Metabolomics has been proposed to be a hallmark of cancer, yet a systematic characterization of a metabolite and metabolic pathways in human hepatocarcinoma (HCC) remains challenge. METHODS: Using ultra-performance liquid-chromatography/quadrupole-time-of-flight coupled with high-definition mass spectrometry (UPLC-Q-TOF-HDMS) in conjunction with multivariate data analysis methods, we identified and measured the metabolite ...
Abu-Hayyeh Shadi - - 2013
Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, ...
Brborić J - - 2013
The partition coefficients (log P) of theoretically possible alkyliodinated iminodiacetic acid (IDA) derivatives and commercial IDA derivatives were calculated using two computer programs: ChemSketch Log P and ChemOffice Ultra. Newly synthesized ligands (DIETHYLIODIDA and DIISOPROPYLIODIDA) with the highest calculated log P were labeled with technetium-99m. The biodistribution and the influence ...
Niu Yuge - - 2013
The effects of sulfation, hydroxypropylation and succinylation on gelling, water uptake, swelling, and bile acid-binding capacities of psyllium were examined and compared on a same molar substitution degree. Sulfated, hydroxypropyl and succinyl psyllium were prepared with a substitution level of 1.02, 0.88 and 0.79, respectively, and their structures were characterized ...
Sajisha V S - - 2013
Supramolecular chemistry is an emerging tool for devising materials that can perform specified functions. The self-assembly of facially amphiphilic bile acid molecules has been extensively utilized for the development of functional soft materials. Supramolecular hydrogels derived from the bile acid backbone act as useful templates for the intercalation of multiple ...
Liu Hong-Tao - - 2013
The apical sodium-dependent bile salt transporter (ASBT) plays a pivotal role in maintaining bile acid homeostasis. Inhibition of ASBT would reduce bile acid pool size and lower cholesterol levels. In this report, a series of novel arylsulfonylaminobenzanilides were designed and synthesized as potential inhibitors of ASBT. Most of them demonstrated ...
Posa Mihalj - - 2013
In this paper, bile acids' retention parameter, R(M), obtained in normal phase thin-layer chromatography is determined as a function of the temperature (293-323 K). Analyzed bile acids belong to congeneric group with two oxygen atoms (OH or oxo groups) on the steroid core and congeneric group with three oxygen atoms. ...
Xu Qing - - 2013
The objective of the present study was to investigate the cholesterol-reducing effect of medium-chain fatty acids (MCFAs) completed by elevated excretion of fecal neutral steroids and/or bile acids. Blood and liver lipid profiles, fecal neutral steroids, bile acids, and mRNA and protein expression of the genes relevant to cholesterol homeostasis ...
Chanda Dipanjan - - 2013
Bile acids concentration in liver is tightly regulated to prevent cell damage. Previous studies have demonstrated that deregulation of bile acid homeostasis can lead to cholestatic liver disease. Recently, we have shown that ER-bound transcription factor Crebh is a downstream effector of hepatic Cb1r signaling pathway. In this study, we ...
Sabbatini Paola - - 2013
Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and metabolic diseases have extended the scope of this ...
Koga Kenjiro - - 2013
The purpose of this study was to evaluate absorption and elimination from the gastrointestinal tract of glycyrrhizic acid diethyl ester (GZ-DE) which was prepared as a prodrug of glycyrrhizic acid (a poorly absorbed compound) in rats. After the GZ-DE solution was administered via the intravenous, intraduodenal, intraileal, and stomach routes, ...
Ellis Ewa C S - - 2013
Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. FRG ...
Perreault Martin - - 2013
Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in ...
Hagey Lee R LR Department of Medicine, University of California at San Diego, USA. - - 2013
Many current experiments investigating the effects of diet, dietary supplements, and pre- and probiotics on the intestinal environments do not take into consideration the potential for using bile salts as markers of environmental change. Intestinal bacteria in vertebrates can metabolize bile acids into a number of different structures, with deamidation, ...
Zhu Qiong N QN Department of Pharmacology and Key Lab of Basic Pharmacology of Guizhou, Zunyi Medical College , Zunyi , - - 2013
Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats. Materials and ...
Ruiz Lorena L Laboratory of Probiotics and Prebiotics, Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias - Consejo Superior de Investigaciones Científicas Asturias, - - 2013
Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been ...
Barrasa Juan I - - 2012
Bile acids are natural detergents mainly involved in facilitating the absorption of dietary fat in the intestine. In addition to this absorptive function, bile acids are also essential in the maintenance of the intestinal epithelium homeostasis. To accomplish this regulatory function, bile acids may induce programmed cell death fostering the ...
Cummings Bethany P - - 2012
Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of ...
Potthoff Matthew J MJ Departments of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, - - 2013
Bile acid sequestrants are nonabsorbable resins designed to treat hypercholesterolemia by preventing ileal uptake of bile acids, thus increasing catabolism of cholesterol into bile acids. However, sequestrants also improve hyperglycemia and hyperinsulinemia through less characterized metabolic and molecular mechanisms. Here, we demonstrate that the bile acid sequestrant, colesevelam, significantly reduced ...
Bera Tanmay - - 2012
The concentration level of bile acids is a clinical biomarker for the diagnosis of intestinal diseases because individuals suffering from intestinal diseases have a sharply increased concentration of bile acids at micromolar levels. Here, we report the detection of lithocholic acid (LCA) in aqueous solution by using surfactant-stabilized 4-n-pentyl-4'-cyanobiphenyl (5CB) ...
Hu Guohua - - 2012
The objective of this study was to investigate the possibility of using hemicellulose from rice bran to scavenge cholesterol and bile acid in vitro study. This paper demonstrates that rice bran hemicellulose A (RBHA), rice bran hemicellulose B (RBHB) and rice bran hemicellulose C (RBHC) have the potential for binding ...
Gomez-Mendoza Miguel - - 2012
Bile acids (BAs) are a family of natural steroids biosynthesized from cholesterol in the liver that tend to form aggregates in solution. A fluorescent derivative of cholic acid, namely 3-Dns-ChA, was employed as a reporter to establish the speciation diagrams of the most abundant BAs that can be found mainly ...
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