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Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
Ineke S Roeling, Wim A Ozinga, Jerry van Dijk, Maarten B Eppinga, Martin J Wassen
Previous studies of Eurasian grasslands have suggested that nutrient ratios, rather than absolute nutrient availabilities and associated productivity, may be driving plant species richness patterns. However, the underlying assumption that species occupy distinct niches along nutrient ratio gradients remains to be tested. We analysed plant community composition and nutrient status of 644 Eurasian wet grassland plots. The importance of nutrient ratios driving variation in species composition was analysed using ordination methods (DCA and CCA)...
February 15, 2018: Oecologia
Naomi Dirckx, Robert J Tower, Evi M Mercken, Roman Vangoitsenhoven, Caroline Moreau-Triby, Tom Breugelmans, Elena Nefyodova, Ruben Cardoen, Chantal Mathieu, Bart Van der Schueren, Cyrille B Confavreux, Thomas L Clemens, Christa Maes
The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel-Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin...
February 12, 2018: Journal of Clinical Investigation
Sören Ocvirk, Stephen Jd O'Keefe
Purpose of review: To review the evidence for the tumorigenic effects of food-stimulated bile acids on the colon and interaction with the gut microbiota. Recent Findings: High-fat diets promote the hepatic synthesis of bile acids and increase their delivery to the colonic lumen. Here, they stimulate the growth and activity of 7α-dehydroxylating bacteria, which convert primary into secondary bile acids that show tumorigenic activity, especially deoxycholic acid (DCA)...
December 2017: Current Nutrition Reports
Yasmin Jahan, Sm Atiqur Rahman, Abu Sayeed Chowdhury, Md Moshiur Rahman
Background: Pneumonia is a major cause of child mortality among children under 5 years, worldwide. Pneumonia infection may be caused by bacteria, viruses, or fungi in single or in both lungs. According to recent criteria developed by the World Health Organization(WHO) in September (2013), pneumonia can be classified into severe pneumonia, pneumonia and no pneumonia. Most of the deaths occur from severe pneumonia. Methods: Disease management of severe childhood pneumonia requires early identification,prompt referral and the availability of intensive quality care...
2018: Health Promotion Perspectives
Sana Belkahla, Abrar Ul Haq Khan, Delphine Gitenay, Catherine Alexia, Claire Gondeau, Dang-Nghiem Vo, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Guillaume Cartron, Javier Hernandez, Martine Daujat-Chavanieu, Nerea Allende-Vega, Martin Villalba Gonzalez
Changes in metabolism require the efflux and influx of a diverse variety of metabolites. The ABC superfamily of transporters regulates the exchange of hundreds of substrates through the impermeable cell membrane. We show here that a metabolic switch to oxidative phosphorylation (OXPHOS), either by treating cells with dichloroacetate (DCA) or by changing the available substrates, reduced expression of ABCB1, ABCC1, ABCC5 and ABCG2 in wild-type p53-expressing cells. This metabolic change reduced histone changes associated to active promoters...
January 2, 2018: Oncotarget
Shuichi P Obuchi, Shuichi Tsuchiya, Hisashi Kawai
BACKGROUND: Gait speed is useful in predicting adverse health outcomes among older adults. In previous studies, gait speed has typically been measured when subjects walk in laboratory settings, where they are able to intentionally change their gait speed. Thus, it is unclear whether the gait speed captured in a laboratory setting is representative of the subjects' actual walking pace in daily life. RESEARCH QUESTION: This study proposes using the more accurate "daily life gait speed" (DGS), measured as the subject's average gait speed over a week-long period using the global positioning system (GPS) in their smartphone...
January 30, 2018: Gait & Posture
Lewin Small, Amanda E Brandon, Lake-Ee Quek, James R Krycer, David E James, Nigel Turner, Gregory J Cooney
Pyruvate dehydrogenase (PDH) activity is a key component of the glucose/fatty acid cycle hypothesis for the regulation of glucose uptake and metabolism. We have investigated whether acute activation of PDH in muscle can alleviate the insulin resistance caused by feeding animals a high fat diet. The importance of PDH activity in muscle glucose disposal under insulin-stimulated conditions was determined by infusing the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) into high fat diet-fed (HFD) Wistar rats during a hyperinsulinemic-euglycemic clamp...
February 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Dandan Zheng, Vivek Verma, Shuo Wang, Xiaoying Liang, Sumin Zhou
PURPOSE: Conventional dose algorithms (Type A and Type B) for lung SBRT can display considerable target dose errors compared to Type-C algorithms. Intensity-modulated techniques (IMRT/VMAT) are increasingly being utilized for lung SBRT. Therefore, our study aimed to assess whether intensity modulation increased target dose calculation errors by conventional algorithms over conformal techniques. METHODS: Twenty lung SBRT patients were parallely planned with both IMRT and dynamic conformal arc (DCA) techniques using a Type-A algorithm, and another 20 patients were parallely planned with IMRT, VMAT, and DCA using a Type-B algorithm...
February 1, 2018: Journal of Applied Clinical Medical Physics
Kristen M Vogelhuber, Ryan S Booth, Christopher J Annesley
There is a need to replace current hydrazine fuels with safer propellants, and dicyanamide- (DCA--) based systems have emerged as promising alternatives because they autoignite when mixed with some oxidizers. Previous studies of the hypergolic reaction mechanism have focused on the reaction between DCA- and the oxidizer HNO3; here we compare the calculated pathway of DCA- + HNO3 with the reaction coordinate of the ion pair sodium dicyanamide with nitric acid, Na[DCA] + HNO3. Enthalpies and free energies are calculated in the gas phase and in solution using a quantum mechanical continuum solvation model, SMD-GIL...
January 31, 2018: Journal of Physical Chemistry. A
Michal K Handzlik, Dumitru Constantin-Teodosiu, Paul L Greenhaff, Mark A Cole
The pattern of metabolic reprogramming in chronic hypoxia shares similarities with that following myocardial infarction or hypertrophy, however the response of the chronically hypoxic heart to subsequent acute injury, and the role of metabolism is not well understood. Here, we determined the myocardial tolerance of the chronically hypoxic heart to subsequent acute injury, and hypothesised that activation of a key regulator of myocardial metabolism, the pyruvate dehydrogenase complex (PDC), could improve hypoxic tolerance...
January 31, 2018: Journal of Physiology
Fan Zhang, Yingting Duan, Lili Xi, Mengmeng Wei, Axi Shi, Yan Zhou, Yuhui Wei, Xinan Wu
Bile acids (BAs), the most important endogenous and signaling molecules regulate the target transporters and enzymes at transcriptional level, participate in a wide variety of processes throughout the entire gastrointestinal tract to orchestrate homeostasis in vivo. BAs and their metabolism and transportation appear to follow the clear circadian rhythms, and they are recently proposed also as the potential chronobiological signals that can affect the molecular clock mechanism. Cholecystectomy are believed to affect the circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes systems and their regulatory signaling pathways, for the reason that the circadian cycle of gallbladder filling and emptying play a pivotal role in controlling the flow of bile into the intestine and the enterohepatic circulation of BAs...
January 30, 2018: Chronobiology International
Xiaoying Liu, Grace L Guo, Bo Kong, David B Hilburn, Susan C Hubchak, Seong Park, Brian LeCuyer, Antony Hsieh, Li Wang, Deyu Fang, Richard M Green
Bile acids are endogenous ligands of the nuclear receptor farnesoid X receptor (FXR), and pharmacologic FXR modulators are under development for the treatment of several liver disorders. The inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the unfolded protein response (UPR) is a protective cellular signaling pathway activated in response to endoplasmic reticulum stress. We investigated the role of FXR signaling in the activation of the hepatic XBP1 pathway. Mice were treated with deoxycholic acid (DCA), cholestyramine, GW4064 or underwent bile duct ligation (BDL) and the hepatic UPR activation was measured...
January 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Sumit Kumar Ray, Rayhan Gafur Biswas, Arun Suneja, Milon Mohan Sadhu, Vinod K Singh
An efficient diastereo- and enantioselective route to access a wide range of highly substituted pyrrolidine and pyrrolizidine derivatives has been described via (1,3)- and double (1,3)-dipolar cycloaddition (DCA) reactions catalyzed by (R)-DM-SEGPHOS-Ag(I) complex. The reactions proceed smoothly at ambient temperature affording a variety of pyrrolidines and pyrrolizidines in high yields (up to 93%) with up to 99:1 dr and excellent enantioselectivities (up to 98% ee) without any additives. The newly synthesized pyrrolidine and pyrrolizidine derivatives contain four and seven contiguous stereogenic centers respectively...
January 24, 2018: Journal of Organic Chemistry
Isabel Abánades Lázaro, Salame Haddad, José Rodrigo-Muñoz, Claudia Orellana-Tavra, Victoria Del Pozo, David Fairen-Jimenez, Ross S Forgan
The high drug loading and excellent biocompatibilities of metal-organic frameworks (MOFs) have led to their application as drug delivery systems (DDSs). Nanoparticle surface chemistry dominates both biostability and dispersion of DDSs while governing their interactions with biological systems, cellular and/or tissue targeting, and cellular internalisation, leading to a requirement for versatile and reproducible surface functionalisation protocols. Herein, we explore not only the effect of introducing different surface functionality to the biocompatible Zr-MOF UiO-66, but also the efficacy of three surface modification protocols: (i) direct attachment of biomolecules (folic acid, biotin) introduced as modulators of UiO-66 synthetic, (ii) our previously reported ''click-modulation" approach to covalently attach polymers (poly(ethylene glycol), poly-L-lactide, poly-N-isopropylacrylamide) to the surface of UiO-66 through click chemistry, and (iii) surface ligand exchange, to postsynthetically coordinate folic acid, biotin and heparin to UiO-66...
January 22, 2018: ACS Applied Materials & Interfaces
Takuya Kuno, Mio Hirayama-Kurogi, Shingo Ito, Sumio Ohtsuki
Antibiotic-caused changes in intestinal flora (dysbiosis) can have various effects on the host. Secondary bile acids produced by intestinal bacteria are ligands for specific nuclear receptors, which regulate glucose, lipid, and drug metabolism in the liver. The present study aimed to clarify the effect of changes in secondary bile acids caused by antibiotic-induced dysbiosis on the host physiology, especially glucose, lipid, and drug metabolism. After oral administration of non-absorbable antibiotics for 5 days, decreased amounts of secondary bile acid-producing bacteria in faeces and a reduction in secondary bile acid [lithocholic acid (LCA) and deoxycholic acid (DCA)] levels in the liver were observed...
January 19, 2018: Scientific Reports
Matteo Figliuzzi, Pierre Barrat-Charlaix, Martin Weigt
Global coevolutionary models of homologous protein families, as constructed by direct coupling analysis (DCA), have recently gained popularity in particular due to their capacity to accurately predict residueresidue contacts from sequence information alone, and thereby to facilitate tertiary and quaternary protein structure prediction. More recently, they have also been used to predict fitness effects of aminoacid substitutions in proteins, and to predict evolutionary conserved protein-protein interactions...
January 17, 2018: Molecular Biology and Evolution
Magdalena S Mroz, Natalia K Lajczak, Bridie J Goggins, Simon Keely, Stephen Joseph Keely
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although, bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable, supports was assessed over 48 hrs {plus minus} bile acids...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Parthasarathi Dastidar, Rajdip Roy, Tapas Kumar Adalder
A well-studied supramolecular synthon namely secondary ammonium monocarboxylate (SAM) was exploited to generate a new series of organic salts derived from variously substituted phenylacetic acid (PA) and dicyclohexyl amine (DCA) as potential low molecular weight gelators (LMWGs). As much as 25% of the SAM salts under study were gelators. The gels were characterized by rheology and the morphology of the gel networks was studied by high resolution electron microscopy. Single crystal and powder X-ray diffraction data were employed to study structure-property (gelation) correlation...
January 18, 2018: Chemistry, An Asian Journal
Tassia C Egea, Roberto da Silva, Maurício Boscolo, Janaina Rigonato, Diego A Monteiro, Danilo Grünig, Humberto da Silva, Frans van der Wielen, Rick Helmus, John R Parsons, Eleni Gomes
The isolation of microorganisms from soil impacted by xenobiotic chemicals and exposing them in the laboratory to the contaminant can provide important information about their response to the contaminants. The purpose of this study was to isolate bacteria from soil with historical application of herbicides and to evaluate their potential to degrade diuron. The isolation media contained either glucose or diuron as carbon source. A total of 400 bacteria were isolated, with 68% being Gram-positive and 32% Gram-negative...
December 2017: Heliyon
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