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https://www.readbyqxmd.com/read/28453831/sortilin-1-loss-of-function-protects-against-cholestatic-liver-injury-by-attenuating-hepatic-bile-acid-accumulation-in-bile-duct-ligated-mice
#1
Jibiao Li, Benjamin L Woolbright, Wen Zhao, Yifeng Wang, David Matye, Bruno Hagenbuch, Hartmut Jaeschke, Tiangang Li
Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid metabolism. This study further investigated the role of Sort1 in modulating bile acid detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 KO mice had attenuated liver injury 24 h after BDL, which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger bile acid pool size than sham-operated WT mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic bile acid accumulation and smaller bile acid pool size...
April 26, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28453659/udp-glucuronosyltransferase-ugt-2b-subfamily-interspecies-differences-in-carnivores
#2
Takamitsu Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, Mayumi Ishizuka
UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (e.g., estrogens, androgens, and bile acids) and exogenous compounds (opioids, NSAIDs, and environmental pollutants)...
April 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28448890/metabolic-profiles-of-neotuberostemonine-and-tuberostemonine-in-rats-by-high-performance-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry
#3
Yongbin Tong, Weitong Xu, Yan Wu, Liting Ou, Mian Zhang, Xianghong Xu, Chaofeng Zhang
Neotuberostemonine (NS) and tuberostemonine (TS), a pair of stereoisomers, are the active components contained in Stemona tuberosa, an antitussive herbal medicine in China. Two isomers have different pharmacological efficacies, which will be related with their in vivo disposition. However, the metabolic fates of NS and TS remain unknown. A method of high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with mass detect filter technique was established to investigate the metabolites in rat plasma, bile, urine, and feces after oral administration of the equal doses of NS and TS...
April 17, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28446193/liver-morphometrics-and-metabolic-blood-profile-across-divergent-phenotypes-for-feed-efficiency-in-the-bovine
#4
Yuri Regis Montanholi, Livia Sadocco Haas, Kendall Carl Swanson, Brenda Lee Coomber, Shigeto Yamashiro, Stephen Paul Miller
BACKGROUND: Feed costs are a major expense in the production of beef cattle. Individual variation in the efficiency of feed utilization may be evident through feed efficiency-related phenotypes such as those related to major energetic sinks. Our objectives were to assess the relationships between feed efficiency with liver morphometry and metabolic blood profile in feedlot beef cattle. METHODS: Two populations (A = 112 and B = 45) of steers were tested for feed efficiency...
April 26, 2017: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/28446062/metabolite-sensing-g-protein-coupled-receptors-facilitators-of-diet-related-immune-regulation
#5
Jian K Tan, Craig McKenzie, Eliana Mariño, Laurence Macia, Charles R Mackay
Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28445245/ectopic-expression-of-innate-immune-protein-lipocalin-2-in-lactococcus-lactis-protects-against-gut-and-environmental-stressors
#6
Piu Saha, Benoit Chassaing, Beng San Yeoh, Emilie Viennois, Xia Xiao, Mary J Kennett, Vishal Singh, Matam Vijay-Kumar
BACKGROUND: Lipocalin-2 (Lcn2) is a multifunctional innate immune protein that exhibits antimicrobial activity by the sequestration of bacterial siderophores, regulates iron homeostasis, and augments cellular tolerance to oxidative stress. Studies in the murine model of colitis have demonstrated that Lcn2 deficiency exacerbates colitogenesis; however, the therapeutic potential of Lcn2 supplementation has yet to be elucidated. In light of its potential mucoprotective functions, we, herein, investigated whether expression of Lcn2 in the probiotic bacterium can be exploited to alleviate experimental colitis...
April 25, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#7
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442498/identification-and-characterization-of-a-novel-ppar%C3%AE-regulated-and-7%C3%AE-hydroxyl-bile-acid-preferring-cytosolic-sulfotransferase-ml-stl-sult2a8
#8
Lu Feng, Yee-Lok Yuen, Jian Xu, Xing Liu, Martin Yan-Chun Chan, Kai Wang, Wing-Ping Fong, Wing-Tai Cheung, Susanna Sau-Tuen Lee
PPARα has been known to play a pivotal role in orchestrating lipid, glucose, and amino acid metabolism via transcriptional regulation of its target genes expression during energy deprivation. Recent evidence also suggesting PPARα is involved in bile acid metabolism, but how PPARα modulates the homeostasis of bile acids during fasting is still not clear. In a mechanistic study aiming to dissect the spectrum of PPARα target genes involved in metabolic response to fasting, we identified a novel mouse gene (herein named mL-STL) which shared extensive homology to Sult2a subfamily of a superfamily of cytosolic sulfotransferases, implying its potential function in sulfonation...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28442495/aspirin-prevents-nf-%C3%AE%C2%BAb-activation-and-cdx2-expression-stimulated-by-acid-and-bile-salts-in-oesophageal-squamous-cells-of-patients-with-barrett-s-oesophagus
#9
Xiaofang Huo, Xi Zhang, Chunhua Yu, Edaire Cheng, Qiuyang Zhang, Kerry B Dunbar, Thai H Pham, John P Lynch, David H Wang, Robert S Bresalier, Stuart J Spechler, Rhonda F Souza
OBJECTIVE: In previous studies using oesophageal squamous cells from patients with Barrett's oesophagus (normal oesophageal squamous (NES)-B cells) and from patients without Barrett's oesophagus (NES-G cells), we showed that acid and bile salts induced caudal-related homeobox transcription factor 2 (CDX2) expression only in NES-B cells. CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin...
April 25, 2017: Gut
https://www.readbyqxmd.com/read/28442273/the-role-of-bile-acids-in-nonalcoholic-fatty-liver-disease-and-nonalcoholic-steatohepatitis
#10
REVIEW
Monica D Chow, Yi-Horng Lee, Grace L Guo
Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is started by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear...
April 22, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28441661/defective-platelet-activation-and-bleeding-complications-upon-cholestasis-in-mice
#11
Nina Sarah Gowert, Meike Klier, Maria Reich, Friedrich Reusswig, Lili Donner, Verena Keitel, Dieter Häussinger, Margitta Elvers
BACKGROUND/AIMS: Platelets are essential mediators of hemostasis to avoid excessive blood loss. Cirrhosis and chronic liver diseases are characterized by alterations in hemostasis. Alterations in the secondary hemostasis have been well studied, while defects in primary hemostasis, especially the consequences of cholestatic liver disease on platelet function are not well defined. METHODS: After bile duct ligation (BDL) platelet activation and thrombus formation were analyzed in mice...
April 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28439767/a-bacillus-subtilis-strain-as-probiotic-in-poultry-selection-based-on-in-vitro-functional-properties-and-enzymatic-potentialities
#12
Houda Hmani, Lobna Daoud, Mouna Jlidi, Karim Jalleli, Manel Ben Ali, Adel Hadj Brahim, Mansour Bargui, Alaeddine Dammak, Mamdouh Ben Ali
We have proposed and validate an in vitro probiotic selection, based on enzymatic potentialities associated to well-established probiotic functional properties. A new Bacillus subtilis HB2 isolate, selected based on its high extracellular enzyme production, was chosen as a probiotic candidate for application as animal feed supplement. The HB2 strain showed an excellent acid and bile salts tolerance, a strong adhesion to chick enterocytes and produced antimicrobials against pathogens. An in vivo trial in poultry farming was conducted to evaluate the HB2 probiotic performance...
April 24, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28439489/detection-and-analysis-of-lactobacillus-paracasei-penicillin-binding-proteins-revealed-the-presence-of-cholate-sensitive-penicillin-binding-protein-3-and-an-elongated-cell-shape-in-a-cholate-sensitive-strain
#13
Masahiro Hattori, Glaezel Angelique Torres, Naoto Tanaka, Sanae Okada, Akihito Endo, Junichi Nakagawa
Penicillin-binding proteins (PBPs) are responsible for peptidoglycan synthesis. By using biotinylated ampicillin, we detected PBPs of Lactobacillus paracasei strains. Ten PBPs were identified, 7 of which had apparent molecular sizes similar to those of Escherichia coli. In the presence of cholate, strain NRIC 0625 showed an elongated shape, and its putative PBP3 showed cholate-sensitive penicillin-binding activity. Furthermore, this strain was highly sensitive to cefalexin, which is known to inhibit cell division by inactivating PBP3...
2017: Bioscience of Microbiota, Food and Health
https://www.readbyqxmd.com/read/28438205/expression-of-the-clonostachys-rosea-lactonohydrolase-gene-by-lactobacillus-reuteri-to-increase-its-zearalenone-removing-ability
#14
Wen-Chun Yang, Tsui-Chun Hsu, Kuan-Chen Cheng, Je-Ruei Liu
BACKGROUND: Mycotoxins are secondary metabolites produced by filamentous fungi that can contaminate agricultural crops in the field as well as during harvest, transportation, processing, or storage. Zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, produced by Fusarium species, has been shown to be associated with reproductive disorders in farm animals and to a lesser extent in hyperoestrogenic syndromes in humans. Thus, the decontamination of ZEN in foods and feeds is an important issue...
April 24, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28437712/raspberry-pomace-alters-cecal-microbial-activity-and-reduces-secondary-bile-acids-in-rats-fed-a-high-fat-diet
#15
Bartosz Fotschki, Jerzy Juśkiewicz, Adam Jurgoński, Neil Rigby, Michał Sójka, Krzysztof Kołodziejczyk, Alan Mackie, Zenon Zduńczyk
The profile of bile acids (BA) largely depends on the enzymatic activity of the microbiota, but this can be modulated by the dietary addition of biologically active compounds, e.g., polyphenols and polyunsaturated fatty acids. The aim of this study was to examine the effect of dietary raspberry pomace as a rich source of biologically active compounds on microbial activity and the BA profile in the caecum of rats fed a high-fat diet. Wistar rats were fed the standard diet AIN-93, a high-fat diet or a modified high-fat diet enriched with 7% different types of processed raspberry pomaces produced by standard grinding and fine grinding, with or without seeds...
April 7, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#16
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28437442/relationship-between-early-onset-severe-intrahepatic-cholestasis-of-pregnancy-and-higher-risk-of-meconium-stained-fluid
#17
Maria C Estiú, Maria A Frailuna, Carla Otero, Marcela Dericco, Catherine Williamson, Jose J G Marin, Rocio I R Macias
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disease. The risk of adverse fetal outcome has been associated with the severity of maternal hypercholanemia after diagnosis. OBJECTIVE: To investigate whether there is a relationship between the severity and timing of onset of hypercholanemia and the risk of meconium-stained amniotic fluid (MSAF) and adverse neonatal events. STUDY DESIGN: The study included 382 pregnancies complicated by ICP managed at a referral hospital in Buenos Aires (Argentina) between June 2009 and December 2013...
2017: PloS One
https://www.readbyqxmd.com/read/28436439/discovery-of-tauroursodeoxycholic-acid-biotransformation-enzymes-from-the-gut-microbiome-of-black-bears-using-metagenomics
#18
Can Song, Bochu Wang, Jun Tan, Liancai Zhu, Deshuai Lou
Tauroursodeoxycholic acid (TUDCA) has been used to treat many diseases effectively. 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH) are two key enzymes that drive the efficient biosynthesis of TUDCA from taurochenodeoxycholic acid (TCDCA) in vitro. In this study, a metagenomic approach was used to isolate 7α- and 7β-HSDHs from fecal samples of black bears. Five new 7α-HSDHs and one new 7β-HSDH enzyme were discovered and identified from the gut microbiota of black bears, and four of them presented good enzymatic properties...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435224/investigation-of-triamterene-as-an-inhibitor-of-the-tgr5-receptor-identification-in-cells-and-animals
#19
Yingxiao Li, Kai Chun Cheng, Chiang-Shan Niu, Shih-Hsiang Lo, Juei-Tang Cheng, Ho-Shan Niu
BACKGROUND: G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) has been shown to participate in glucose homeostasis. In animal models, a TGR5 agonist increases incretin secretion to reduce hyperglycemia. Many agonists have been developed for clinical use. However, the effects of TGR5 blockade have not been studied extensively, with the exception of studies using TGR5 knockout mice. Therefore, we investigated the potential effect of triamterene on TGR5. METHODS: We transfected the TGR5 gene into cultured Chinese hamster ovary cells (CHO-K1 cells) to express TGR5...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28434196/role-of-gut-microbiota-bile-acids-and-their-crosstalk-in-the-effects-of-bariatric-surgery-on-obesity-and-type-2-diabetes
#20
Haijun Liu, Cheng Hu, Xueli Zhang, Weiping Jia
Type 2 diabetes mellitus is becoming increasingly prevalent worldwide and has become one of the greatest threats to global health. Bariatric surgery was initially designed to achieve weight loss and subsequently was noted to induce improvements or remission of type 2 diabetes. Currently, these bariatric operations such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective procedures for the treatment of obesity and type 2 diabetes mellitus worldwide. However, the specific mechanism mediating the beneficial effects of metabolic surgery has remained largely unknown...
April 23, 2017: Journal of Diabetes Investigation
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