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https://www.readbyqxmd.com/read/30306382/bile-acids-and-their-effects-on-diabetes
#1
REVIEW
Cynthia Rajani, Wei Jia
Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia...
October 10, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/30298207/choline-and-choline-related-nutrients-in-regular-and-preterm-infant-growth
#2
REVIEW
Wolfgang Bernhard, Christian F Poets, Axel R Franz
BACKGROUND: Choline is an essential nutrient, with increased requirements during development. It forms the headgroup of phosphatidylcholine and sphingomyelin in all membranes and many secretions. Phosphatidylcholine is linked to cell signaling as a phosphocholine donor to synthesize sphingomyelin from ceramide, a trigger of apoptosis, and is the major carrier of arachidonic and docosahexaenoic acid in plasma. Acetylcholine is important for neurodevelopment and the placental storage form for fetal choline supply...
October 8, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/30288474/placebo-controlled-randomized-trial-of-an-intestinal-bile-salt-transport-inhibitor-for-pruritus-in-alagille-syndrome
#3
Benjamin L Shneider, Cathie Spino, Binita M Kamath, John C Magee, Lee M Bass, Kenneth D Setchell, Alexander Miethke, Jean P Molleston, Cara L Mack, Robert H Squires, Karen F Murray, Kathleen M Loomes, Philip Rosenthal, Saul J Karpen, Daniel H Leung, Stephen L Guthery, Danny Thomas, Averell H Sherker, Ronald J Sokol
Medically refractory, severe, cholestasis-induced pruritus in Alagille syndrome may be improved by surgical interruption of the enterohepatic circulation. This multicenter trial (NCT02057692) tested the hypothesis that the intestinal bile acid transport inhibitor maralixibat would similarly reduce pruritus in Alagille syndrome. Thirty-seven children with Alagille syndrome were randomly assigned to double-blinded administration of placebo, 70, 140, or 280 µg/kg/day of maralixibat for 13 weeks. Pruritus was assessed by caregiver (itch-reported outcome instrument [ItchRO]) and clinician report (range, 0-4 [severe])...
October 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30279125/ivacaftor-restores-fgf19-regulated-bile-acid-homeostasis-in-cystic-fibrosis-patients-with-an-s1251n-or-a-g551d-gating-mutation
#4
Ivo P van de Peppel, Marcela Doktorova, Gitte Berkers, Hugo R de Jonge, Roderick H J Houwen, Henkjan J Verkade, Johan W Jonker, Frank A J A Bodewes
OBJECTIVE: Disruption of the enterohepatic circulation of bile acids (BAs) is part of the gastrointestinal phenotype of cystic fibrosis (CF). Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, improves pulmonary function in CF patients with class III gating mutations. We studied the effect of ivacaftor on the enterohepatic circulation by assessing markers of BA homeostasis and their changes in CF patients. METHODS: In CF patients with an S1251N mutation (N = 16; age 9-35 years S125N study/NTR4873) or a G551D mutation (N = 101; age 10-24 years; GOAL study/ NCT01521338) we analyzed plasma fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) levels, surrogate markers for intestinal BA absorption and hepatic synthesis, respectively, before and after treatment with ivacaftor...
September 29, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/30275402/inflammation-and-the-gut-liver-axis-in-the-pathophysiology-of-cholangiopathies
#5
REVIEW
Debora Maria Giordano, Claudio Pinto, Luca Maroni, Antonio Benedetti, Marco Marzioni
Cholangiocytes, the epithelial cells lining the bile ducts, represent the unique target of a group of progressive diseases known as cholangiopathies whose pathogenesis remain largely unknown. In normal conditions, cholangiocytes are quiescent and participate to the final bile volume and composition. Following exogenous or endogenous stimuli, cholangiocytes undergo extensive modifications of their phenotype. Reactive cholangiocytes actively proliferate and release a set of proinflammatory molecules, which act in autocrine/paracrine manner mediating the cross-talk with other liver cell types and innate and adaptive immune cells...
October 1, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30259754/fxr-modulators-for-enterohepatic-and-metabolic-diseases
#6
Hong Wang, Qingxian He, Guangji Wang, Xiaowei Xu, Haiping Hao
Farnesoid X receptor (FXR), a nuclear receptor mainly expressed in enterohepatic tissues, is a master regulator for bile acid, lipid and glucose homeostasis. Additionally, it acts as a direct cell protector with unclear mechanism but may be implicated in combating against inflammation, fibrosis and cancers. FXR has thus been accepted as a promising target particularly for the enterohepatic diseases, and a plenty of FXR modulators have been patented and developed. Areas covered: This review provides an update on the development of FXR modulators for enterohepatic diseases and offers an in-depth perspective on new strategies for the development of novel FXR modulators...
September 27, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/30244079/bile-acid-homeostasis-paradigm-and-its-connotation-with-cholestatic-liver-diseases
#7
REVIEW
Tingting Yang, Ghulam Jilany Khan, Ziteng Wu, Xue Wang, Luyong Zhang, Zhenzhou Jiang
Bile acid (BA) has an important role in signal transduction, and has clinical applicability as an early biomarker for the diagnosis and prevention of cholestatic liver disease, which has a close relationship with BA homeostasis. Understanding the regulatory factors, function, and regulation of BA homeostasis under physiological conditions and in cholestatic liver diseases could provide novel therapeutic approaches for treating cholestatic liver injury. Here, we review potential biomarkers of BA, and new therapeutic approaches and the latest therapeutic drugs for cholestasis...
September 20, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30227749/gut-microbiota-modulates-drug-pharmacokinetics
#8
Juanhong Zhang, Junmin Zhang, Rong Wang
Gut microbiota, one of the determinants of pharmacokinetics, has long been underestimated. It is now generally accepted that the gut microbiota plays an important role in drug metabolism during enterohepatic circulation either before drug absorption or through various microbial enzymatic reactions in the gut. In addition, some drugs are metabolized by the intestinal microbiota to specific metabolites that cannot be formed in the liver. More importantly, metabolizing drugs through the gut microbiota prior to absorption can alter the systemic bioavailability of certain drugs...
September 19, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/30209794/pharmacokinetics-and-bioavailability-enhancement-of-baicalin-a-review
#9
REVIEW
Ting Huang, Yanan Liu, Chengliang Zhang
Baicalin is one of the major bioactive components of Scutellaria radix, a Chinese herb that has been used since ancient times. Baicalin has various pharmacological activities, including antitumor, antimicrobial, and antioxidant, and has wide clinical applications. Baicalin displays a distinct pharmacokinetic profile including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated transport, and complicated metabolism. The in vivo disposition of baicalin is affected by combinations of other herbs and baicalin can interact with other co-administered drugs due to competition between metabolic enzymes and protein binding...
September 12, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30186169/ileal-bile-acid-transporter-inhibition-for-the-treatment-of-chronic-constipation-cholestatic-pruritus-and-nash
#10
REVIEW
Samer Al-Dury, Hanns-Ulrich Marschall
Bile acids are synthesized from cholesterol in the liver, excreted with bile into the duodenum, almost completely taken up again in the distal ileum and finally returned to the liver with portal blood in a process termed enterohepatic circulation. Bile acid synthesis, excretion, and reuptake are tightly regulated. The apical sodium-dependent bile acid transporter [ASBT; also known as ileal bile acid transporter (IBAT) and SLC10A2] is pivotal for the almost complete reabsorption of conjugated bile acids in the ileum...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30149692/highly-selective-nir-probe-for-intestinal-%C3%AE-glucuronidase-and-high-throughput-screening-inhibitors-to-therapy-intestinal-damage
#11
Lei Feng, Yongliang Yang, Xiaokui Huo, Xiangge Tian, Yujie Feng, Hanwen Yuan, Lijian Zhao, Chao Wang, Peng Chu, Feida Long, Wei Wang, Xiaochi Ma
β-Glucuronidase (GLU) as a vital factor in enterohepatic circulation and drug-inducing enteropathy has been given more and more attention in recent years. In this study, an off-on near-infrared (NIR) fluorescent probe (DDAO-glu) for selectively and sensitively sensing GLU was developed on the basis of its substrate preference. DDAO-glu can rapidly and selectively respond to bacterial GLU under physiological conditions for detecting the real-time intestinal GLU bioactivity of complex biological systems such as human feces in clinic...
September 28, 2018: ACS Sensors
https://www.readbyqxmd.com/read/30138902/multi-compartmental-toxicokinetic-modeling-of-fipronil-in-tilapia-accumulation-biotransformation-and-elimination
#12
Huizhen Li, Jing You, Wen-Xiong Wang
Bioaccumulation and biotransformation are critical processes modifying toxicity of easily metabolizable chemicals to aquatic organisms. In this study, tissue-specific accumulation, biotransformation and elimination of a current-use pesticide fipronil in tilapia (Oreochromis niloticus) were quantified by combining in vivo measurements and a newly developed multi-compartmental toxicokinetic model. Waterborne fipronil was taken up via gills and metabolized rapidly and solely to fipronil sulfone. Significant decrease of fipronil residues in liver and intestine during exposure period strongly suggested the induction of metabolism in these two organs...
October 15, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/30135133/targeting-fxr-and-fgf19-to-treat-metabolic-diseases-lessons-learned-from-bariatric-surgery
#13
REVIEW
Nadejda Bozadjieva, Kristy M Heppner, Randy J Seeley
Bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective interventions available for sustained weight loss and improved glucose metabolism. Bariatric surgery alters the enterohepatic bile acid circulation, resulting in increased plasma bile levels as well as altered bile acid composition. While it remains unclear why both VSG and RYGB can alter bile acids, it is possible that these changes are important mediators of the effects of surgery...
September 2018: Diabetes
https://www.readbyqxmd.com/read/30129377/elobixibat-the-first-in-class-ileal-bile-acid-transporter-inhibitor-for-the-treatment-of-chronic-idiopathic-constipation
#14
REVIEW
Philip B Miner
Elobixibat is the first in class ileal bile acid transporter (IBAT) inhibitor. IBAT inhibitors block ileal absorption of bile acids by: (1) interrupting the enterohepatic circulation of bile resulting in a fall in serum cholesterol and (2) increasing the delivery of bile acids into the colon. Increasing colonic bile acids causes mucosal fluid secretion and enhances colonic motor activity. Changes in colonic physiology may be useful in treating constipation. Areas covered: In this review, the author reviews the prevalence and medical cost of Chronic Idiopathic Constipation (CIC) and the heterogeneity of the CIC patient population as a complicating factor in drug development and clinical care...
August 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/30105488/influence-of-orally-administered-borneol-on-the-expression-of-hepatic-transporters-in-rats
#15
Lin Chen, Lu Liao, Ting Zhai, Xiangtao Huang, Yong Chen
BACKGROUND AND OBJECTIVE: Borneol, a traditional Chinese medicine (TCM), is often orally co-administered with other TCM and chemical drugs, but the drug-drug interactions between borneol and the other compounds remains unclear. This work investigates the effect of orally administered borneol on the transcription and expression of hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) in rats, aiming to obtain essential information to guide its clinical applications...
August 13, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30105244/peroxisome-proliferator-activated-receptor-%C3%AE-prevents-cholesterol-gallstone-formation-in-c57bl-mice-by-regulating-bile-acid-synthesis-and-enterohepatic-circulation
#16
Gang Wang, Tao Han, ShiJia Wang, Min Chen, Yueming Sun, Zan Fu
To investigate the role of the peroxisome proliferator-activated receptor- γ (PPAR γ ) in the progression of cholesterol gallstone disease (CGD), C57bl/6J mice were randomized to the following groups (n=7/group): L (lithogenic diet, LGD), LM (LGD+pioglitazone), CM (chow diet+pioglitazone), and NC (normal control, chow diet). Gallbladder stones were observed by microscopy. Histological gallbladder changes were assessed. Bile acids (BA) and cholesterol were measured in the serum, bile, and feces. Proteins and mRNA expression of genes involved in BA metabolism and enterohepatic circulation were assessed by western blotting and real-time RT-PCR...
2018: BioMed Research International
https://www.readbyqxmd.com/read/30095299/high-fat-diet-overfeeding-promotes-non-detrimental-liver-steatosis-in-female-mice
#17
Lino Arisqueta, Hiart Navarro-Imaz, Ibone Labiano, Yuri Rueda, Olatz Fresnedo
High fat diet (HFD) feeding or leptin deficient mice are extensively used as models resembling features of human non-alcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild type (Wt) and ob/ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia...
August 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30067158/guts-and-gall-bile-acids-in-regulation-of-intestinal-epithelial-function-in-health-and-disease
#18
Peter Hegyi, Joszef Maléth, Julian R Walters, Alan F Hofmann, Stephen J Keely
Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer...
October 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/30061734/18%C3%AE-glycyrrhetinic-acid-protects-against-alpha-naphthylisothiocyanate-induced-cholestasis-through-activation-of-the-sirt1-fxr-signaling-pathway
#19
Shou-Yan Wu, Shi-Chao Cui, Le Wang, Yi-Ting Zhang, Xiao-Xia Yan, Heng-Lei Lu, Guo-Zhen Xing, Jin Ren, Li-Kun Gong
Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect...
July 30, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/30053282/infant-formula-feeding-increases-hepatic-cholesterol-7%C3%AE-hydroxylase-cyp7a1-expression-and-fecal-bile-acid-loss-in-neonatal-piglets
#20
Kelly E Mercer, Sudeepa Bhattacharyya, Maria Elena Diaz-Rubio, Brian D Piccolo, Lindsay M Pack, Neha Sharma, Mousumi Chaudhury, Mario A Cleves, Sree V Chintapalli, Kartik Shankar, Martin J J Ronis, Laxmi Yeruva
Background: During the postnatal feeding period, formula-fed infants have higher cholesterol synthesis rates and lower circulating cholesterol concentrations than their breastfed counterparts. Although this disparity has been attributed to the uniformly low dietary cholesterol content of typical infant formulas, little is known of the underlying mechanisms associated with this altered cholesterol metabolism phenotype. Objective: We aimed to determine the molecular etiology of diet-associated changes in early-life cholesterol metabolism with the use of a postnatal piglet feeding model...
May 1, 2018: Journal of Nutrition
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