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https://www.readbyqxmd.com/read/29029322/a-dynamic-mathematical-model-of-bile-acid-clearance-in-heparg-cells
#1
Daniel Kaschek, Ahmad Sharanek, André Guillouzo, Jens Timmer, Richard J Weaver
A dynamic model based on ordinary differential equations that describes uptake, basolateral and canalicular export of taurocholic acid in human HepaRG cells is presented. The highly reproducible inter-assay experimental data were used to reliably estimate model parameters. Primary human hepatocytes were similarly evaluated to establish a mathematical model, but with notably higher inter-assay differences in taurocholic acid clearance and bile canaliculi dynamics. By use of the HepaRG cell line, the simultaneous taurocholic acid clearance associated to basolateral uptake, canalicular and sinusoidal efflux, was predicted...
September 18, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29028769/activation-of-the-nuclear-receptor-fxr-improves-intestinal-cell-tolerance-to-ischemia-reperfusion-injury
#2
Xuan Wang, Shuo Li, Man Chen, Jing Liu, Ruirui Dong, Humin Wang, Shigong Zhu
The farnesoid X receptor (FXR) plays an important role in bile acid metabolism, intestinal homeostasis, and intestinal ischemia-reperfusion (I/R) injury. We aimed to clarify the potential effects of FXR on intestinal epithelial cell tolerance to intestinal I/R injury and reveal the underlying mechanisms. An intestinal I/R injury model was established by the occlusion of the superior mesenteric artery for ischemia for 1 h, followed by reperfusion for 4 h in C57BL/6 (wild-type; WT)and FXR mice. The small intestine injury was assessed by histological analysis...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/29028359/complex-interaction-between-circadian-rhythm-and-diet-on-bile-acid-homeostasis-in-male-rats
#3
Hannah M Eggink, Johanneke E Oosterman, Paul de Goede, Emmely M de Vries, Ewout Foppen, Martijn Koehorst, Albert K Groen, Anita Boelen, Johannes A Romijn, Susanne E la Fleur, Maarten R Soeters, Andries Kalsbeek
Desynchronization between the master clock in the brain, which is entrained by (day) light, and peripheral organ clocks, which are mainly entrained by food intake, may have negative effects on energy metabolism. Bile acid metabolism follows a clear day/night rhythm. We investigated whether in rats on a normal chow diet the daily rhythm of plasma bile acids and hepatic expression of bile acid metabolic genes is controlled by the light/dark cycle or the feeding/fasting rhythm. In addition, we investigated the effects of high caloric diets and time-restricted feeding on daily rhythms of plasma bile acids and hepatic genes involved in bile acid synthesis...
October 13, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29027248/ursodeoxycholic-acid-protects-cardiomyocytes-against-cobalt-chloride-induced-hypoxia-by-regulating-transcriptional-mediator-of-cells-stress-hypoxia-inducible-factor-1%C3%AE-and-p53-protein
#4
Anis Syamimi Mohamed, Noorul Izzati Hanafi, Siti Hamimah Sheikh Abdul Kadir, Julina Md Noor, Narimah Abdul Hamid Hasani, Sharaniza Ab Rahim, Rosfaiizah Siran
In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca(2+) ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca(2+) ]i , and S1P-Gαi -coupled-receptor...
October 12, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29024782/dysregulation-of-%C3%AE-4-3-oxosteroid-5%C3%AE-reductase-in-diabetic-patients-implications-and-mechanisms
#5
Leila Valanejad, Mwlod Ghareeb, Stephanie Shiffka, Christina Nadolny, Yuan Chen, Liangran Guo, Ruchi Verma, Sangmin You, Fatemeh Akhlaghi, Ruitang Deng
Aldo-keto reductase family 1 member D1 (AKR1D1) is a Δ(4)-3-oxosteroid 5β-reductase required for bile acid synthesis and steroid hormone metabolism. Both bile acids and steroid hormones, especially glucocorticoids, play important roles in regulating body metabolism and energy expenditure. Currently, our understanding on AKR1D1 regulation and its roles in metabolic diseases is limited. We found that AKR1D1 expression was markedly repressed in diabetic patients. Consistent with repressed AKR1D1 expression, hepatic bile acids were significantly reduced in diabetic patients...
October 9, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29024779/kinetic-characterization-of-bile-salt-transport-by-human-ntcp-slc10a1
#6
Márton Jani, Erzsébet Beéry, Teresa Heslop, Beáta Tóth, Bhavana Jagota, Emese Kis, B Kevin Park, Peter Krajcsi, Richard J Weaver
The transport of bile acids facilitated by NTCP is an important factor in establishing bile flow. In this study, we examine the kinetics associated with human NTCP-dependent transport of two quantitatively important bile acids comprising the human bile acid pool, chenodeoxycholic acid and glycine-chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of potential toxicological significance. The study employed human NTCP overexpressing Chinese Hamster Ovary cells and results compared with taurocholate, a prototypical bile salt commonly used in transporter studies...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29024427/combined-liver-kidney-perfusion-enhances-protective-effects-of-normothermic-perfusion-on-livers-grafts-from-donation-after-cardiac-death
#7
Xiaoshun He, Fei Ji, Zhiheng Zhang, Yunhua Tang, Lu Yang, Shanzhou Huang, Wenwen Li, Qiao Su, Wei Xiong, Zebin Zhu, Linhe Wang, Lei Lv, Jiyou Yao, Linan Zhang, Longjuan Zhang, Zhiyong Guo
It has been showed that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after cardiac death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage group (Group A), liver alone NMP group (Group B), or combined liver-kidney NMP group (Group C)...
October 10, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/29024022/novel-%C3%AE-catenin-fxr-interaction-regulates-hepatic-bile-acid-metabolism-during-cholestasis
#8
EDITORIAL
Laurent Ehrlich, Shannon S Glaser
No abstract text is available yet for this article.
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023813/dual-catenin-loss-in-murine-liver-causes-tight-junctional-deregulation-and-progressive-intrahepatic-cholestasis
#9
Tirthadipa Pradhan-Sundd, Lili Zhou, Ravi Vats, An Jiang, Laura Molina, Sucha Singh, Minakshi Poddar, Jacquelyn M Russell, Donna B Stolz, Michael Oertel, Udayan Apte, Simon Watkins, Sarangarajan Ranganathan, Kari N Nejak-Bowen, Prithu Sundd, Satdarshan Pal Monga
β-Catenin, the downstream effector of the Wnt signaling, plays important roles in hepatic development, regeneration and tumorigenesis. However, its role at hepatocyte adherens junctions (AJ) is relatively poorly understood, chiefly due to spontaneous compensation by γ-catenin. Here, we simultaneously ablate β- and γ-catenin expression in mouse liver by interbreeding β-catenin-γ-catenin double-floxed mice and albumin-cre transgenic mice. Double knockout mice (DKO) show failure to thrive, impaired hepatocyte differentiation, cholemia, ductular reaction, progressive cholestasis, inflammation, fibrosis and tumorigenesis, which was associated with deregulation of tight junctions (TJ) and bile acid transporters, leading to early morbidity and mortality, a phenotype reminiscent of Progressive Familial Intrahepatic Cholestasis (PFIC)...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023408/rational-design-of-nucleoside-bile-acid-conjugates-incorporating-a-triazole-moiety-for-anticancer-evaluation-and-sar-exploration
#10
Maria Luisa Navacchia, Elena Marchesi, Lara Mari, Nicola Chinaglia, Eleonora Gallerani, Riccardo Gavioli, Massimo Luigi Capobianco, Daniela Perrone
Herein we report a study on the synthesis and biological evaluation of a library of nucleoside-bile acid conjugates prepared by combining 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxyuridine as well as adenosine and guanosine derivatives with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid derivatives by means of the click reaction. The new nucleoside-bile acid conjugates incorporating a triazole moiety were tested in vitro against leukemic K562 and HCT116 colon carcinoma, as well as on normal fibroblast cells...
October 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29023123/a-comparison-study-on-polysaccharide-fractions-from-laminaria-japonica-structural-characterization-and-bile-acid-binding-capacity
#11
Jie Gao, Lianzhu Lin, Bao-Guo Sun, Mouming Zhao
Our previous study has suggested that the crude polysaccharide obtained from Laminaria japonica by acid assisted extraction (LP-A) have significant bile acid-binding capacity, which probably ascribed to its specific structure characterization. The relationship between structure characterization and bile acid-binding capacity of the purified LP-A fractions are still unknown. This paper conducted a comparison study on the structure characterization and bile acid-binding capacity of three LP-A fractions (LP-A4, LP-A6 and LP-A8)...
October 12, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29022907/p38%C3%AE-mapk-antagonizing-jnk-to-control-the-hepatic-fat-accumulation-in-pediatric-patients-onset-intestinal-failure
#12
Yongtao Xiao, Jun Wang, Weihui Yan, Kejun Zhou, Yi Cao, Wei Cai
The p38α mitogen-activated protein kinase (MAPK) has been related to gluconeogenesis and lipid metabolism. However, the roles and related mechanisms of p38α MAPK in intestinal failure (IF)-associated liver steatosis remained poor understood. Here, our experimental evidence suggested that p38α MAPK significantly suppressed the fat accumulation in livers of IF patients mainly through two mechanisms. On the one hand, p38α MAPK increased hepatic bile acid (BA) synthesis by upregulating the expression of the rate-limiting enzyme cholesterol 7-α-hydroxylase (CYP7A1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which in turn activated the transcription of the CYP7A1...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29020816/predictors-of-adverse-perinatal-outcomes-in-intrahepatic-cholestasis-of-pregnancy-with-dichorionic-diamniotic-twin-pregnancies
#13
Youwen Mei, Lan Gao, Yonghong Lin, Dan Luo, Xine Zhou, Li He
OBJECTIVE: The aim of our study was to investigate the predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with dichorionic diamniotic (DCDA) twin pregnancies. METHODS: This study was a retrospective study of women diagnosed with ICP and DCDA twin pregnancies in Chengdu's women and children's central hospital. These patients were subdivided into mild and severe ICP groups according to total bile acid (TBA) level. The clinical characteristics and perinatal outcomes were collected and compared between the two groups...
October 11, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29019072/mass-spectrometry-based-metabolomics-to-identify-taurine-modified-metabolites-in-heart
#14
Takashi Ito, Koei Okazaki, Daisuke Nakajima, Daisuke Shibata, Shigeru Murakami, Stephen Schaffer
Taurine is an abundant beta-amino acid found in high concentration in mammalian tissues. Taurine possesses many beneficial functions in mammalian cells. There are also a variety of taurine-conjugated products formed between taurine and bile acids, fatty acids, chloramine, mitochondrial tRNA, etc., and some of these have been identified as functional compounds. In the present study, we identified taurine-conjugated metabolites using LC-MS-based metabolome analysis of heart extracts prepared from hearts of wild-type and taurine transporter-knockout (TauTKO) mice, the latter being severely taurine deficient...
October 10, 2017: Amino Acids
https://www.readbyqxmd.com/read/29018422/novel-aggregation-promoting-factor-agge-contributes-to-the-probiotic-properties-of-enterococcus-faecium-bggo9-28
#15
Katarina Veljović, Nikola Popović, Marija Miljković, Maja Tolinački, Amarela Terzić-Vidojević, Milan Kojić
The understanding of mechanisms of interactions between various bacterial cell surface proteins and host receptors has become imperative for the study of the health promoting features of probiotic enterococci. This study, for the first time, describes a novel enterococcal aggregation protein, AggE, from Enterococcus faecium BGGO9-28, selected from a laboratory collection of enterococcal isolates with auto-aggregation phenotypes. Among them, En. faecium BGGO9-28 showed the strongest auto-aggregation, adhesion to components of ECM and biofilm formation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29018272/bile-acid-microbiota-crosstalk-in-gastrointestinal-inflammation-and-carcinogenesis
#16
REVIEW
Wei Jia, Guoxiang Xie, Weiping Jia
Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states...
October 11, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28994348/from-pathogenesis-to-novel-therapies-in-the-treatment-of-primary-biliary-cholangitis
#17
Vincenzo Ronca, Marco Carbone, Francesca Bernuzzi, Federica Malinverno, Hani S Mousa, M Eric Gershwin, Pietro Invernizzi
Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by chronic inflammation of the intrahepatic bile ducts, causing progressive ductopenia, cholestasis and fibrosis, and leading to liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapy for the treatment of PBC patients. This is effective in majority of patients; however, up to 20 percent of patients have an incomplete response to UDCA therapy and have a reduced prognosis as compared to healthy individuals. Obeticholic acid (OCA) has been recently registered as second-line therapy for patients with incomplete response to UDCA, with plans to demonstrate the long-term clinical efficacy...
October 10, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28993998/lithocholic-bile-acid-inhibits-lipogenesis-and-induces-apoptosis-in-breast-cancer-cells
#18
Trang H Luu, Jean-Marie Bard, Delphine Carbonnelle, Chloé Chaillou, Jean-Michel Huvelin, Christine Bobin-Dubigeon, Hassan Nazih
BACKGROUND: It has amply been documented that mammary tumor cells may exhibit an increased lipogenesis. Biliary acids are currently recognized as signaling molecules in the intestine, in addition to their classical roles in the digestion and absorption of lipids. The aim of our study was to evaluate the impact of lithocholic acid (LCA) on the lipogenesis of breast cancer cells. The putative cytotoxic effects of LCA on these cells were also examined. METHODS: The effects of LCA on breast cancer-derived MCF-7 and MDA-MB-231 cells were studied using MTT viability assays, Annexin-FITC and Akt phosphorylation assays to evaluate anti-proliferative and pro-apoptotic properties, qRT-PCR and Western blotting assays to assess the expression of the bile acid receptor TGR5 and the estrogen receptor ERα, and genes and proteins involved in apoptosis (Bax, Bcl-2, p53) and lipogenesis (SREBP-1c, FASN, ACACA)...
October 9, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28993159/prevention-of-cholesterol-gallstone-disease-by-schaftoside-in-lithogenic-diet-induced-c57bl-6-mouse-model
#19
Meijing Liu, Changhui Liu, Hao Chen, Xiaotao Huang, Xiaohui Zeng, Juncheng Zhou, Suiqing Mi
Schaftoside (SS) is a bioactive compound present in the Herba Desmodii Styracifolii (DS), a herb that has been used to treat cholelithiasis and urolithiasis in Chinese medicine. Whether SS inhibits cholesterol (Ch) gallstone formation has not been investigated. This study examined the effects of oral intake of SS on Ch gallstone formation in C57BL/6 mice fed a lithogenic diet. The rate of gallstone formation was recorded. Levels of Ch, triglycerides (TG) and bile salts (BS) were measured in the bile and serum...
October 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28992322/human-cytosolic-sulphotransferase-sult1c3-genomic-analysis-and-functional-characterization-of-splice-variant-sult1c3a-and-sult1c3d
#20
Katsuhisa Kurogi, Takehiko Shimohira, Haruna Kouriki-Nagatomo, Guisheng Zhang, Ethan R Miller, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The cytosolic sulphotransferase SULT1C3 remained the most poorly understood human SULT. The SULT1C3 gene has been shown to contain alternative exons 7 and 8, raising the question concerning their evolutionary origin and implying the generation of multiple SULT1C3 variants. Two SULT1C3 splice variants, SULT1C3a and SULT1C3d, were investigated to verify the impact of alternative C-terminal sequences on their sulphating activity. Sequence homology and gene location analyses were performed to verify the orthology of the SULT1C3 gene...
June 29, 2017: Journal of Biochemistry
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