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urea cycle

Wei Liu, Guanghui Han, Yalin Yin, Shuai Jiang, Guojun Yu, Qing Yang, Wenhui Yu, Xiangdong Ye, Yanting Su, Yajun Yang, Gerald W Hart, Hui Sun
O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm. O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development, and nascent polypeptide chains stabilization. However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research. Herein, we report that a lectin, AANL (Agrocybe aegerita GlcNAc specific lectin), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification...
March 19, 2018: Glycobiology
Fabricio Castro Machado, Caio Haddad Franco, Jose Vitorino Dos Santos Neto, Karina Luiza Dias-Teixeira, Carolina Borsoi Moraes, Ulisses Gazos Lopes, Bertal Huseyin Aktas, Sergio Schenkman
Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T...
March 20, 2018: Scientific Reports
Zhi-Shu Tang, Yan-Ru Liu, Yang Lv, Jin-Ao Duan, Shi-Zhong Chen, Jing Sun, Zhong-Xing Song, Xiao-Min Wu, Li Liu
BACKGROUND: Common farming environmental elements, such as longitude, latitude, and altitude, and physiological conditions, such as age and body weight, are thought to influence medicinal animal homeostasis and material quality by altering endocrine functions for primary and secondary metabolite formation. However, the currently available methods for evaluating complex components of traditional Chinese animal medicines have insufficient sensitivity and specificity. PURPOSE: Characterizing the primary/secondary metabolomes of medicinal animals is essential for understanding their material basis, controlling product quality, and reflecting on distribution interactions...
March 6, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Maxime Mallet, Nicolas Weiss, Dominique Thabut, Marika Rudler
Hyperammonemia plays a key role in the pathophysiology of hepatic encephalopathy (HE) and most HE treatments are ammonia-lowering drugs. However, the usefulness of measuring ammonemia in routine practice remains controversial and not recommended systematically even when neurological symptoms are present. First, ammonemia measurement should be carefully performed in order to avoid a falsely elevated result. When performed, a normal ammonemia in a cirrhotic patient with neurological symptoms should lead to reconsider the diagnosis of HE...
March 15, 2018: Clinics and Research in Hepatology and Gastroenterology
Oscar H L Bing
Ammonia plays a central role in the life and death of all living organisms and has been studied for over one hundred years. Ammonia is necessary for growth and development but it is toxic in excess and, as a result, differing methods of ammonia neutralization have evolved. Following physiological and pathological stress to the heart, tissue ammonia levels rise. Local ammonia neutralization may be inadequate and excess ammonia may exert its toxic effects. Phenylbutyrate (PBA), which is FDA approved for the treatment of elevated blood ammonia in urea cycle disorders, provides an accessory pathway for ammonia clearance...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Louise Crowe, Vicki Anderson, Winita Hardikar, Avihu Boneh
Ornithine Trans-Carbamylase (OTC) deficiency is the most common disorder of the urea cycle. Cognitive impairments in skills such as attention and executive function have been reported in individuals with OTC deficiency who are managed with medication. In some cases, children undergo liver transplantation (LTx) to correct the metabolic defect. The metabolic and medical outcomes of LTx are generally good. However, little is known about the impacts on cognition. In this study, four children (three female) completed detailed neuropsychological batteries prior to (n = 6) and following LTx (n = 8 assessments)...
March 10, 2018: JIMD Reports
Karen Louise Thomsen, Francesco De Chiara, Krista Rombouts, Hendrik Vilstrup, Fausto Andreola, Rajeshwar P Mookerjee, Rajiv Jalan
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from steatosis, through non-alcoholic steatohepatitis (NASH) to cirrhosis. The development of fibrosis is the most important factor contributing to NASH-associated morbidity and mortality. Hepatic stellate cells (HSCs) are responsible for extracellular matrix deposition in conditions of frank hepatocellular injury and are key cells involved in the development of fibrosis. In experimental models and patients with NASH, urea cycle enzyme gene and protein expression is reduced resulting in functional reduction in the in vivo capacity for ureagenesis and subsequent hyperammonemia at a pre-cirrhotic stage...
April 2018: Medical Hypotheses
Nina Hediger, Markus A Landolt, Carmen Diez-Fernandez, Martina Huemer, Johannes Häberle
Neonatal onset hyperammonemia in patients with urea cycle disorders (UCDs) is still associated with high morbidity and mortality. Current protocols consistently recommend emergency medical and dietary management. In case of increasing or persistent hyperammonemia, with continuous or progressive neurological signs, dialysis is performed, mostly as ultima ratio. It is presently unknown whether the currently defined ammonia threshold (e.g., at 500 μmol/L) to start dialysis is useful to improve clinical outcome...
March 8, 2018: Journal of Inherited Metabolic Disease
C Chen, M Pérez de Nanclares, J F Kurtz, M P Trudeau, L Wang, D Yao, M Saqui-Salces, P E Urriola, L Torunn Mydland, G C Shurson, M Overland
Rapeseed (RS) is an abundant and inexpensive source of energy and AA in diets for monogastrics and a sustainable alternative to soybean meal. It also contains diverse bioactive phytochemicals that could have antinutritional effects at high dose. When the RS-derived feed ingredients (RSF) are used in swine diets, the uptake of these nutrients and phytochemicals is expected to affect the metabolic system. In this study, two groups of young pigs (17.8 ± 2.7 kg initial BW) were equally fed a soybean meal-based control diet and a RSF-based diet, respectively, for 3 wk...
March 6, 2018: Journal of Animal Science
Mathieu Odijk, Albert van den Berg
In this review, we summarize recent advances in nanoscale electrochemistry, including the use of nanoparticles, carbon nanomaterials, and nanowires. Exciting developments are reported for nanoscale redox cycling devices, which can chemically amplify signal readout. We also discuss promising high-frequency techniques such as nanocapacitive CMOS sensor arrays or heterodyning. In addition, we review electrochemical microreactors for use in (drug) synthesis, biocatalysis, water treatment, or to electrochemically degrade urea for use in a portable artificial kidney...
March 8, 2018: Annual Review of Analytical Chemistry
Marshall L Summar, Nicholas Ah Mew
The urea cycle disorders are a group of inherited biochemical diseases caused by a complete or partial deficiency of any one of the enzymes or transport proteins required to convert toxic ammonia into urea and to produce arginine and citrulline. The clinical manifestations of these disorders are mostly the result of acute or chronic hyperammonemia, which affects the central nervous system. Affected individuals can also develop hepatic dysfunction. These disorders can present at any age from the immediate newborn to later in life...
April 2018: Pediatric Clinics of North America
Yuan Yan Sin, Laurel L Ballantyne, Christopher R Richmond, Colin D Funk
Progress in gene editing research has been accelerated by utilizing engineered nucleases in combination with induced pluripotent stem cell (iPSC) technology. Here, we report transcription activator-like effector nuclease (TALEN)-mediated reincorporation of Arg1 exons 7 and 8 in iPSCs derived from arginase-1-deficient mice possessing Arg1Δ alleles lacking these terminal exons. The edited cells could be induced to differentiate into hepatocyte-like cells (iHLCs) in vitro and were subsequently used for transplantation into our previously described (Sin et al...
March 2, 2018: Molecular Therapy. Nucleic Acids
Nasser A M Barakat, Ahmed G El-Deen, Zafar Khan Ghouri, Saeed Al-Meer
NiFe nanoparticles-decorated & N-doped graphene is introduced as an effective and stable non-precious electrocatalyst for ORR in the acid medium. Compared to conventional Pt/C electrodes under the same conditions, the proposed nanocatalyst shows closer onset potential and current density. Typically, the observed onset potentials and current densities for the synthesized and Pt/C electrodes are 825 and 910 mV (vs. NHE) and -3.65 and -4.31 (at 5 mV.s-1 ), respectively. However, the most important advantage of the introduced metallic alloy-decorated graphene is its distinct stability in acid medium; the retention in the electrocatalytic performance after 1,000 successive cycles is approximately 98%...
February 28, 2018: Scientific Reports
Ruvanthi N Kularatne, Katherine E Washington, Chandima Bulumulla, Erika L Calubaquib, Michael C Biewer, David Oupicky, Mihaela C Stefan
The short chain fatty acid, 4-phenylbutyric acid (PBA), is used for the treatment of urea cycle disorders and sickle cell disease as an endoplasmic reticulum stress inhibitor. PBA is also known as a histone deacetylase inhibitor (HDACi). We report here the effect of combination therapy on HeLa cancer cells using PBA as the HDACi together with the anticancer drug, doxorubicin (DOX). We synthesized γ-4-phenylbutyrate-ε-caprolactone monomer which was polymerized to form poly(γ-4-phenylbutyrate-ε-caprolactone) (PPBCL) homopolymer using NdCl3 ·3TEP/TIBA (TEP = triethyl phosphate, TIBA = triisobutylaluminum) catalytic system...
February 27, 2018: Biomacromolecules
Wei Wang, Bo Xu, Qixiang Li, Dechun Jiang, Suying Yan
The RAF/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK (RAF/MEK/ERK) signaling cascade serves a prominent role in hepatocellular carcinoma (HCC) proliferation. Sorafenib (BAY 43‑9006) is a potent multikinase inhibitor of RAF kinases and a few receptor tyrosine kinases. Additionally, sorafenib causes apoptosis in a number of human tumor cell lines such as leukemia cell lines. Sorafenib is the first targeted drug to prolong the overall survival of patients with advanced HCC...
February 16, 2018: Molecular Medicine Reports
Jing Wu, Shang Liu, Zhi-Wei Yuan, Jian-He Liu, Jiong-Ming Li, Tao Chen, Ke-Wei Fang
BACKGROUND/AIMS: We examined the effects of microRNA-27a (miR-27a) on detrusor fibrosis in streptozotocin (STZ)-induced diabetic rats. METHODS: Eighty healthy Sprague-Dawley (SD) rats were randomly allocated into control, diabetic, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siRNA-PRKAA2 (siPRKAA2) and inhibitors + siPRKAA2 groups (the latter 7 groups were established as STZ-induced diabetic rat models and treated in different manners)...
February 15, 2018: Cellular Physiology and Biochemistry
Mehdi Ghasemi, Yunis Mayasi, Anas Hannoun, Seyed Majid Eslami, Raphael Carandang
Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology...
February 17, 2018: Neuroscience
Carolina Gonzalez-Riano, Miriam Sanz-Rodríguez, Juan Escudero-Ramirez, Mª Paz Lorenzo, Coral Barbas, Beatriz Cubelos, Antonia Garcia
The optic nerve is made of highly specialized neurons and the energetic supply to their axons is crucial due to their great demand. The energy comes basically through the oxidative phosphorylation in the mitochondria, supported by glial cells metabolism. Mitochondrial dysfunction is a shared feature encountered within the optic neuropathies, including Leber's Hereditary Optic Neuropathy, Leigh's Syndrome, or Kjer's syndrome. In an effort to investigate the metabolic alterations produced within the optic nerve in a mutant mouse model of Neurological Visual Disease (NVD), a rapid, robust, and efficient one-single phase extraction methodology has been developed and validated for the GC-MS platform...
May 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
Dong-Feng Li, Wei-Qing Huang, Lan-Rong Zou, Anlian Pan, Gui-Fang Huang
Elimination of pollutants from water is one of the greatest challenges in resolving global environmental issues. Herein, we report a high-surface-area mesoporous g-C3N4 nanosheet with remarkable high adsorption capacity and photocatalytic performance, which is prepared through directly polycondensation of urea followed by a consecutive one-step thermal exfoliation strategy. This one-pot method to prepare mesoporous g-C3N4 nanosheet is facile and rapid in comparison with others. The superior adsorption capacity of the fabricated mesoporous g-C3N4 nanostructures is demonstrated by a model organic pollutant-methylene blue (MB), which is up to 72...
August 1, 2018: Journal of Nanoscience and Nanotechnology
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