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https://www.readbyqxmd.com/read/29446045/effects-of-extracellular-orotic-acid-on-acute-contraction-induced-adaptation-patterns-in-c2c12-cells
#1
Thomas Beiter, Jens Hudemann, Christof Burgstahler, Andreas M Nieß, Barbara Munz
Dietary administration of orotic acid (OA), an intermediate in the pyrimidine biosynthetic pathway, is considered to provide a wide range of beneficial effects, including cardioprotection and exercise adaptation. Its mechanisms of action, when applied extracellularly, however, are barely understood. In this study, we evaluated potential effects of OA on skeletal muscle using an in vitro contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By analyzing a subset of genes representing inflammatory, metabolic, and structural adaptation pathways, we could show that OA supplementation diminishes the EPS-provoked expression of inflammatory transcripts (interleukin 6, Il6; chemokine (C-X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of nuclear receptor subfamily 4 group A member 3 (Nr4A3), early growth response 1 (Egr1), activating transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA isoform (Myh2)...
February 14, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29433939/targeted-mrna-therapy-for-ornithine-transcarbamylase-deficiency
#2
Mary G Prieve, Pierrot Harvie, Sean D Monahan, Debashish Roy, Allen G Li, Teri L Blevins, Amber E Paschal, Matt Waldheim, Eric C Bell, Anna Galperin, Jean-Rene Ella-Menye, Michael E Houston
We describe a novel, two-nanoparticle mRNA delivery system and show that it is highly effective as a means of intracellular enzyme replacement therapy (i-ERT) using a murine model of ornithine transcarbamylase deficiency (OTCD). Our Hybrid mRNA Technology delivery system (HMT) comprises an inert lipid nanoparticle that protects the mRNA from nucleases in the blood as it distributes to the liver and a polymer micelle that targets hepatocytes and triggers endosomal release of mRNA. This results in high-level synthesis of the desired protein specifically in the liver...
January 4, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29345914/comparative-analysis-of-epa-dha-pl-forage-and-liposomes-in-orotic-acid-induced-non-alcoholic-fatty-liver-rats-and-their-related-mechanisms
#3
Mengru Chang, Tiantian Zhang, Xiuqing Han, Qingjuan Tang, Teruyoshi Yanagita, Jie Xu, Changhu Xue, YuMing Wang
Non-alcoholic fatty liver disease (NAFLD) has become one predictive factor of death from various illnesses. The present study was to comparatively investigate the effects of eicosapentaenoic acid-enriched and docosahexaenoic acid-enriched phospholipids forage (EPA-PL and DHA-PL) and liposomes (lipo-EPA and lipo-DHA) on NAFLD and demonstrate possible protective mechanisms involved. The additive doses of EPA-PL and DHA-PL in all treatment groups were 1 % of total diets, respectively. Results showed that Lipo-EPA could significantly improve hepatic function by down-regulating orotic acid-induced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels by 55...
January 18, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29331465/genome-wide-association-study-for-milk-infrared-wavenumbers
#4
Qiuyu Wang, Henk Bovenhuis
Individual wavenumbers of the infrared (IR) spectra of bovine milk have been shown to be moderately to highly heritable. The objective of this study was to identify genomic regions associated with individual milk IR wavenumbers. This is expected to provide information about the genetic background of milk composition and give insight in the relation between IR wavenumbers and milk components. For this purpose, a genome-wide association study was performed for a selected set of 50 individual IR wavenumbers measured on 1,748 Dutch Holstein cows...
January 10, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29315647/antiviral-activity-of-a771726-the-active-metabolite-of-leflunomide-against-jun%C3%A3-n-virus
#5
Claudia S Sepúlveda, Cybele C García, Elsa B Damonte
The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, against the infection with Junín virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non-cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose-dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain...
January 5, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29279777/ornithine-transcarbamylase-deficiency-if-at-first-you-do-not-diagnose-try-and-try-again
#6
Christan D Santos, Robert A Ratzlaff, Jennifer C Meder, Paldeep S Atwal, Nicole E Joyce
Ornithine transcarbamylase (OTC) deficiency is well known for its diagnosis in the neonatal period. Presentation often occurs after protein feeding and manifests as poor oral intake, vomiting, lethargy progressing to seizure, respiratory difficulty, and eventually coma. Presentation at adulthood is rare (and likely underdiagnosed); however, OTC deficiency can be life-threatening and requires prompt investigation and treatment. Reports and guidelines are scarce due to its rarity. Here, we present a 59-year-old woman with a past history of irritable bowel syndrome who underwent a reparative operation for rectal prolapse and enterocele...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/29274060/biosynthesis-of-mono-acylated-mannosylerythritol-lipid-in-an-acyltransferase-gene-disrupted-mutant-of-pseudozyma-tsukubaensis
#7
Azusa Saika, Yu Utashima, Hideaki Koike, Shuhei Yamamoto, Takahide Kishimoto, Tokuma Fukuoka, Tomotake Morita
The basidiomycetous yeast genus Pseudozyma produce large amounts of mannosylerythritol lipids (MELs), which are biosurfactants. A few Pseudozyma strains produce mono-acylated MEL as a minor compound using excess glucose as the sole carbon source. Mono-acylated MEL shows higher hydrophilicity than di-acylated MEL and has great potential for aqueous applications. Recently, the gene cluster involved in the MEL biosynthesis pathway was identified in yeast. Here, we generated an acyltransferase (PtMAC2) deletion strain of P...
December 23, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29215882/theoretical-models-for-quantitative-description-of-the-acid-base-equilibria-of-the-5-6-substituted-uracils
#8
Margarita G Ilyina, Edward M Khamitov, Sergey Petrovich Ivanov, Akhat G Mustafin, Sergey L Khursan
The acidities of 18 5,6-substituted uracils have been numerically estimated as pKa values in terms of three theoretical models. The first scheme includes the calculation of the gas-phase acidity of uracil with the G3MP2B3 method and taking into account the solvent effect using the polarizable continuum approximation PCM(SMD)-TPSS/aug-cc-pVTZ. The second model is one-step and implies calculating of the free Gibbs energies of the hydrate complex of uracil (and its anion) with 5 water molecules by the TPSS/aug-cc-pVTZ method...
December 7, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29197344/lactation-related-metabolic-mechanism-investigated-based-on-mammary-gland-metabolomics-and-4-biofluids-metabolomics-relationships-in-dairy-cows
#9
Hui-Zeng Sun, Kai Shi, Xue-Hui Wu, Ming-Yuan Xue, Zi-Hai Wei, Jian-Xin Liu, Hong-Yun Liu
BACKGROUND: Lactation is extremely important for dairy cows; however, the understanding of the underlying metabolic mechanisms is very limited. This study was conducted to investigate the inherent metabolic patterns during lactation using the overall biofluid metabolomics and the metabolic differences from non-lactation periods, as determined using partial tissue-metabolomics. We analyzed the metabolomic profiles of four biofluids (rumen fluid, serum, milk and urine) and their relationships in six mid-lactation Holstein cows and compared their mammary gland (MG) metabolomic profiles with those of six non-lactating cows by using gas chromatography-time of flight/mass spectrometry...
December 2, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29178779/synthesis-of-bis-phosphate-iminoaltritol-enantiomers-and-structural-characterization-with-adenine-phosphoribosyltransferase
#10
Lawrence D Harris, Rajesh K Harijan, Rodrigo G Ducati, Gary B Evans, Brett M Hirsch, Vern L Schramm
Phosphoribosyl transferases (PRTs) are essential in nucleotide synthesis and salvage, amino acid and vitamin synthesis. Transition state analysis of several PRTs has demonstrated ribocation-like transition states with a partial positive charge residing on the pentose ring. Core chemistry for synthesis of transition state analogues related to the 5-phospho--D-ribosyl 1-pyrophosphate (PRPP) reactant of these enzymes could be developed by stereospecific placement of bis-phosphate groups on an iminoaltritol ring...
November 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29158663/a-comparative-pharmacokinetic-and-tolerability-analysis-of-the-novel-orotic-acid-salt-form-of-tenofovir-disoproxil-and-the-fumaric-acid-salt-form-in-healthy-subjects
#11
Yu Kyong Kim, Mun Ju Choi, Tae Young Oh, Kyung-Sang Yu, SeungHwan Lee
A novel orotic acid salt form of tenofovir disoproxil (DA-2802) was developed and is expected to replace the fumaric acid salt form. The pharmacokinetic (PK) characteristics and tolerability profiles of DA-2802 were compared to those of tenofovir disoproxil fumarate (TDF, Viread(®)) in healthy subjects. A randomized, open-label, single-dose study was conducted in 36 healthy subjects using a two-treatment, two-period, and two-sequence crossover design. Subjects received a single oral dose of 319 mg DA-2802 or 300 mg TDF, during each period, with a 7-day washout...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28939132/peak-hyperammonemia-and-atypical-acute-liver-failure-the-eruption-of-an-urea-cycle-disorder-during-hyperemesis-gravidarum
#12
REVIEW
Nicolas Weiss, Fanny Mochel, Marika Rudler, Sophie Demeret, Pascal Lebray, Filomena Conti, Damien Galanaud, Chris Ottolenghi, Jean-Paul Bonnefont, Marc Dommergues, Jacques Bernuau, Dominique Thabut
Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected...
September 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28887792/liver-failure-as-the-presentation-of-ornithine-transcarbamylase-deficiency-in-a-13-month-old-female
#13
Farrah Rajabi, Lance H Rodan, Maureen M Jonas, Janet S Soul, Nicole J Ullrich, Ann Wessel, Susan E Waisbren, Wen-Hann Tan, Gerard T Berry
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with variable expressivity in heterozygous females. While liver function testing is often abnormal in patients with OTCD, liver failure is uncommon on presentation. A 13-month-old female with no significant past medical history presented with irritability, right arm weakness, and decreased appetite. Initial workup revealed hepatic dysfunction with an INR of 3.4, ammonia level of 75 μmol/L, and abnormal brain MRI with gyral edema with restricted diffusion, and patchy signal abnormality in basal ganglia...
September 9, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28830776/the-crystallization-behavior-of-poly-lactic-acid-with-different-types-of-nucleating-agents
#14
Yongqi Feng, Piming Ma, Pengwu Xu, Ruyin Wang, Weifu Dong, Mingqing Chen, Kees Joziasse
The effects of six nucleating agents (NAs), i.e., orotic acid (OA), potassium salt of 3,5-bis(methoxycarbonyl)benzenesulfonate (LAK-301), substituted-aryl phosphate salts (TMP-5), talc (TALC), N'(1),N'(6)-dibenzoyladipohydrazide (TMC-306) and N(1),N(1')-(ethane-1,2-diyl)bis(N(2)-phenyloxalamide) (OXA), on the crystallization behavior of poly(lactic acid) (PLA) were compared by DSC. Under the same dosing of 0.5wt%, the nucleation effect of the NAs for PLA declines in the order of TMC-306≈OXA > TALC > TMP-5≈LAK-301≈OA...
August 19, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28708927/orotidine-containing-rna-implications-for-the-hierarchical-selection-systems-chemistry-emergence-of-rna
#15
Eun-Kyong Kim, Vincent Martin, Ramanarayanan Krishnamurthy
The prebiotic synthesis of canonical nucleobases from HCN is a cornerstone for the RNA world hypothesis. However, their role in the primordial pathways to RNA is still debated. The very same process starting from HCN also gives rise to orotic acid, which (via orotidine) plays a crucial role in extant biology in the de novo synthesis of uridine and cytidine, the informational base-pairs in RNA. However, orotidine itself is absent in RNA. Given the prebiotic and biological relevance of orotic acid vis-à-vis uracil, we investigated orotidine-containing RNA oligonucleotides and show that they have severely compromised base-pairing properties...
July 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28652707/development-of-new-promising-antimetabolite-dfp-11207-with-self-controlled-toxicity-in-rodents
#16
Masakazu Fukushima, Kenzo Iizuka, Cheng Jin, Chun Zhang, Mei Hong, Kiyoshi Eshima
To reduce 5-fluorouracil (5-FU)-induced serious toxicities without loss of antitumor activity, we have developed DFP-11207, a novel fluoropyrimidine, which consists of 1-ethoxymethyl-5-fluorouracil (EM-FU; a precursor form of 5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-FU degradation), and citrazinic acid (CTA; an inhibitor of 5-FU phosphorylation). In vitro studies of DFP-11207 indicated that it strongly inhibited the degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD) in homogenates of the rat liver, and also inhibited the phosphorylation of 5-FU by orotate phosphoribosyltransferase (OPRT) in tumor tissues in a similar magnitude of potency by CDHP and CTA, respectively...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28592010/-clinical-diagnosis-and-treatment-of-three-cases-with-hyperornithinemia-hyperammonemia-homocitrullinuria-syndrome
#17
H Z Guan, Y Ding, D X Li, H Dong, J Q Song, Y Jin, Z J Zhu, L Y Sun, Y L Yang
Objective: To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. Method: From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. Result: The three patients' age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months...
June 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28467471/multilocus-sequence-typing-biochemical-and-antibiotic-resistance-characterizations-reveal-diversity-of-north-american-strains-of-the-honey-bee-pathogen-paenibacillus-larvae
#18
Sasiprapa Krongdang, Jay D Evans, Jeffery S Pettis, Panuwan Chantawannakul
Paenibacillus larvae is a Gram positive bacterium and the causative agent of the most widespread fatal brood disease of honey bees, American foulbrood (AFB). A total of thirty-three independent Paenibacillus larvae isolates from various geographical origins in North America and five reference strains were investigated for genetic diversity using multilocus sequence typing (MLST). This technique is regarded to be a powerful tool for epidemiological studies of pathogenic bacteria and is widely used in genotyping assays...
2017: PloS One
https://www.readbyqxmd.com/read/28374713/-the-influence-of-potassium-orotate-on-neocollagenogenesis-in-implantation-of-polypropylene-endoprosthesis-and-polypropylene-combined-with-polylactic-acid-endoprosthesis
#19
S V Ivanov, V A Lazarenko, I S Ivanov, I P Parfenov, A V Tsukanov, D V Tarabrin, E G Ob''edkov
AIM: To study neocollagenogenesis after implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis on background of «potassium orotate» administration. MATERIAL AND METHODS: We used two different types of endoprosthesis in the experiment. The first type was made of just polypropylene, the second type was made of polypropylene combined with polylactic acid. Histological examination was performed using polarizing microscopy...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28291252/influence-of-ad-libitum-feeding-of-piglets-with-bacillus-subtilis-fermented-liquid-feed-on-gut-flora-luminal-contents-and-health
#20
Yuyong He, Chunxia Mao, Hong Wen, Zhiyu Chen, Tao Lai, Lingyu Li, Wei Lu, Huadong Wu
Some scholars caution that long-term ad libitum feeding with probiotic fermented food poses potential health risks to baby animals. We conducted a feeding experiment to investigate the influence of ad libitum feeding of pre-and post-weaned piglets with a Bacillus subtilis fermented diet on the gut microbiome, gut metabolomic profiles, bile acid metabolism, proinflammatory cytokines and faecal consistency. Compared with piglets fed a Bacillus subtilis-supplemented pellet diet, piglets fed the Bacillus subtilis fermented liquid diet had lower intestinal bacterial diversity (P > 0...
March 14, 2017: Scientific Reports
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