7,575,017 results match your criteria Metabolism: clinical and experimental[Journal]

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One-carbon metabolism nutrient intake and the association between body mass index and urinary arsenic metabolites in adults in the Chihuahua cohort.

Environ Int 2018 Dec 12;123:292-300. Epub 2018 Dec 12.

Environmental Science and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Curriculum in Toxicology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

Background: Exposure to inorganic arsenic (iAs) via drinking water is a serious global health threat. Various factors influence susceptibility to iAs-associated health outcomes, including differences in iAs metabolism. Previous studies have shown that obesity is associated with iAs metabolism. Read More

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December 2018
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Antibacterial properties of nanofibers containing chrysanthemum essential oil and their application as beef packaging.

Int J Food Microbiol 2018 Dec 8;292:21-30. Epub 2018 Dec 8.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China. Electronic address:

This study was aimed to develop novel antibacterial packaging materials in order to reduce the microbial contamination of food surface. Chrysanthemum essential oil (CHEO) was successfully incorporated into chitosan nanofibers (CS/NF) through electrospinning which was demonstrated by SEM and AFM analysis. The antibacterial mechanism of CHEO against Listeria monocytogenes (L. Read More

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December 2018

Acid sphingomyelinase: No potential as a biomarker for multiple sclerosis.

Mult Scler Relat Disord 2018 Nov 30;28:44-49. Epub 2018 Nov 30.

Department of Molecular Cell biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC - location VUmc, Amsterdam, The Netherlands.

Background: Multiple sclerosis (MS) lacks reliable biomarkers that reflect disease activity. Recent evidence suggests that an altered sphingolipid metabolism is associated with MS pathogenesis.

Objective: To explore acid sphingomyelinase (ASM) activity and altered sphingolipid metabolism as potential biomarkers in serum of MS patients, to predict active and progressive disease, and response to disease modifying therapy (DMT). Read More

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November 2018
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Alternative Type II NAD(P)H Dehydrogenases in the Mitochondria of Protists and Fungi.

Protist 2018 Nov 10;170(1):21-37. Epub 2018 Nov 10.

Department of Bioenergetics, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland.

Plants, fungi, and some protists possess a more branched electron transport chain in their mitochondria compared to canonical one. In these organisms, the electron transport chain contains several rotenone-insensitive NAD(P)H dehydrogenases. Some are located on the outer surface, and others are located on the inner surface of the inner mitochondrial membrane. Read More

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November 2018

Gut microbiota: a potential manipulator for host adipose tissue and energy metabolism.

J Nutr Biochem 2018 Nov 10;64:206-217. Epub 2018 Nov 10.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

Normally, the gut microbiota has a mutually beneficial association with host health and maintains its commensal status in mammals. Conversely, it can also negatively influence host physiology under some certain circumstances, including obesity and other disease states. Although numerous gut microbial functions directly affect the gastrointestinal tract, in this paper, we focus on the influences of the gut microbiota on host adipose tissue and energy metabolism, particularly lipometabolism. Read More

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November 2018

Effects of cellular differentiation in human primary bronchial epithelial cells: Metabolism of 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone.

Toxicol In Vitro 2018 Dec 12. Epub 2018 Dec 12.

Division of Genetic and Molecular Toxicology, Division of Biochemical Toxicology, National Center for Toxicological Research, U.S Food and Drug Administration, Jefferson, AR 72079, United States. Electronic address:

Many of the toxicants in tobacco smoke undergo biotransformation in the lungs of smokers, both to reactive and to detoxified derivatives. Human air-liquid-interface (ALI) airway tissue models have emerged as an advanced in vitro model for evaluating the toxicity of inhaled substances; however, the metabolic potential of these cultures has not been evaluated extensively. In this study, we compared the metabolic activities of an ALI tissue model to the undifferentiated normal human primary bronchial epithelial (NHBE) cells from which it was derived. Read More

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December 2018
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Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision.

Life Sci 2018 Dec 12. Epub 2018 Dec 12.

Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. Electronic address:

Cyclophosphamide (CP) is an important anticancer drug which belongs to the class of alkylating agent. Cyclophosphamide is mostly used in bone marrow transplantation, rheumatoid arthritis, lupus erythematosus, multiple sclerosis, neuroblastoma and other types of cancer. Dose-related cardiotoxicity is a limiting factor for its use. Read More

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December 2018
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The testosterone metabolite 3α-androstanediol inhibits oxidative stress-induced ERK phosphorylation and neurotoxicity in SH-SY5Y cells through an MKP3/DUSP6-dependent mechanism.

Neurosci Lett 2018 Dec 12. Epub 2018 Dec 12.

Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada. Electronic address:

Testosterone exerts neuroprotective effects on the brain, but the mechanisms by which these effects are exerted appear to be different in males and females. While in females they involve local conversion to estradiol, in males they may be androgen receptor-dependent, or mediated through metabolism to neurosteroids such as 5α-androstane-3α,17β-diol (3α-diol), which acts through different mechanisms than testosterone itself. Recently, we demonstrated that 3α-diol can protect neurons and neuronal-like cells against oxidative stress-induced neurotoxicity associated with prolonged phosphorylation of the extracellular signal-regulated kinase (ERK). Read More

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December 2018

Administration of eicosapentaenoic and docosahexaenoic acids may improve the remodeling and browning in subcutaneous white adipose tissue and thermogenic markers in brown adipose tissue in mice.

Mol Cell Endocrinol 2018 Dec 12. Epub 2018 Dec 12.

Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

The role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in browning and thermogenesis has not been fully elucidated. Thus, we meant to evaluate the effect of EPA and DHA, administered alone or combined, with the activation of browning markers in subcutaneous white adipose tissue (sWAT), and thermogenic markers in brown adipose tissue (BAT). C57BL/6 adult male mice received a control diet or a high-fructose diet (HFru) for eight weeks, but after the first three weeks, HFru was divided into new groups: HFru, HFru + EPA, HFru + DHA, and HFru-EPA + DHA. Read More

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December 2018

Molecular Mechanisms of Glutaredoxin Enzymes: Versatile Hubs for Thiol-Disulfide Exchange between Protein Thiols and Glutathione.

J Mol Biol 2018 Dec 12. Epub 2018 Dec 12.

School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.

The tripeptide glutathione (GSH) and its oxidized form glutathione disulfide (GSSG) constitute a key redox couple in cells. In particular, they partner protein thiols in reversible thiol-disulfide exchange reactions that act as switches in cell signaling and redox homeostasis. Disruption of these processes may impair cellular redox signal transduction and induce redox misbalances that are linked directly to aging processes and to a range of pathological conditions including cancer, cardiovascular diseases and neurological disorders. Read More

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December 2018

Association of allostatic load with health-related quality of life in patients with arterial hypertension: a cross-sectional analysis.

Swiss Med Wkly 2018 Dec 15;148:w14689. Epub 2018 Dec 15.

Department of Medical Psychology and Psychotherapy, Medical University of Graz, Austria / Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Austria.

Aims Of The Study: Allostatic load (AL), as a marker of cumulative stress, is associated with higher morbidity and mortality, and reduced health-related quality of life (HrQoL) in healthy adults. In patients with hypertension, AL and its association with HrQoL have not been investigated. Therefore, this study aimed to (1) explore AL in a cohort of hypertensive patients and to (2) determine its association with HrQoL, while controlling for other health-related variables. Read More

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December 2018

Adipose Tissue Dendritic Cells in Steady-State.

Immunology 2018 Dec 15. Epub 2018 Dec 15.

William Harvey Research Institute, Barts and the London, Queen Mary University of London, London, UK.

Healthy white adipose tissue (WAT) participates in regulating systemic metabolism, whilst dysfunctional WAT plays a prominent role in the development of obesity-associated comorbidities. Tissue resident immune cells are important for maintaining WAT homeostasis, including conventional dendritic cells (cDCs) which are critical in the initiation and regulation of adaptive immune responses. Due to phenotypic overlap with other myeloid cells, the distinct contribution of WAT cDCs has been poorly understood. Read More

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December 2018

A comparative effectiveness study of degludec and insulin glargine 300U/mL in insulin-naïve patients with type 2 diabetes.

Diabetes Obes Metab 2018 Dec 15. Epub 2018 Dec 15.

Clinical Research, Endocrine and Metabolic Consultants, Rockville, MD, USA.

Aims: To compare the real-world effectiveness of insulin degludec (degludec) and glargine 300 units/mL (glargine U300) in insulin-naïve adult patients with type 2 diabetes in routine US clinical practice.

Materials And Methods: CONFIRM is a non-interventional comparative effectiveness study following US patients across the continuum of care, through electronic medical records from multiple health systems and integrated delivery networks. Propensity-score matching controlled for confounding. Read More

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December 2018

Nasal insulin administration does not affect hepatic glucose production at systemic fasting insulin levels.

Diabetes Obes Metab 2018 Dec 15. Epub 2018 Dec 15.

Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.

Aim: Pharmacologic administration of insulin as nasal spray in humans has demonstrated a modulation of endogenous glucose production via the brain when systemic insulin levels are high. Results are conflicting under fasting insulin concentrations. To evaluate effects of brain insulin on endogenous glucose production in fasting humans with focus on hepatic glucose release, we performed a randomized, placebo controlled, blinded, cross-over experiment. Read More

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December 2018
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SIRT4 Depletion Promotes HCC Tumorigenesis through Regulating AMPKα/mTOR Axis.

Hepatology 2018 Dec 15. Epub 2018 Dec 15.

Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

Sirtuin 4 (SIRT4) has been reported to play a vital role in the maintenance of glutamine catabolism and ATP homeostasis, but its character in hepatocellular carcinomas (HCCs) remains obscure. In this study, we observed low expression of SIRT4 in both HCC cell lines and HCCs from patients. Decreased disease-free survival time is associated with low tumor levels of SIRT4 in patients. Read More

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December 2018

Variability in sleep disturbance, physical activity and quality of life according to level of depressive symptoms in women with Type 2 diabetes.

Diabet Med 2018 Dec 15. Epub 2018 Dec 15.

Department of Social Sciences and Health Policy, Wake Forest School of Medicine.

Aims: To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; physical activity; physical health-related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables.

Methods: Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health-related quality of life and global quality of life. Read More

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December 2018
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Patterns of altered regional brain glucose metabolism in borderline personality disorder and bipolar II disorder.

Acta Psychiatr Scand 2018 Dec 15. Epub 2018 Dec 15.

Institute of Clinical Medicine, University of Oslo, Norway.

Objective: The relationship between borderline personality disorder (BPD) and bipolar II disorder (BIP-II) is disputed but understudied. Here, we investigated brain glucose metabolism in these patient groups and healthy control subjects (HCs).

Methods: Sixty-five subjects, 22 BPD (19 females); 22 BIP-II (17 females); 21 HC (14 females) were examined using 2-deoxy-2[18F]-fluoro-d-glucose Positron-Emission Tomography (PET) scanning. Read More

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December 2018

A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer.

Cancer Med 2018 Dec 14. Epub 2018 Dec 14.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

Background: Prognosis among patients with differentiated thyroid cancer is widely variable. Better understanding of biologic subtypes is necessary to stratify patients and improve outcomes.

Methods: In patients diagnosed with classic histology papillary thyroid cancer treated from 1973 to 2009, BRAF V600E mutation status was determined on surgical tumor specimens by restriction fragment length polymorphism analysis. Read More

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December 2018

Expression of genes related to liver fatty acid metabolism in fat-tailed and thin-tailed lambs during negative and positive energy balances.

J Anim Physiol Anim Nutr (Berl) 2018 Dec 14. Epub 2018 Dec 14.

Departmen of Animal Science, University of Tehran, Karaj, Iran.

Fat-tailed sheep breeds can tolerate periods of negative energy balance without suffering from elevated concentration of plasma non-esterified fatty acid (NEFA). This ability was attributed to unique metabolism of fat-tailed adipose depot, whereas role of liver as an influential organ in fatty acid metabolism was not evaluated yet. Hence, current study was conducted to evaluate the effects of negative and positive energy balances on liver expression of genes related to fatty acid metabolism in fat-tailed and thin-tailed lambs. Read More

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December 2018

From avatars to body swapping: The use of virtual reality for assessing and treating body-size distortion in individuals with anorexia.

J Clin Psychol 2018 Dec 15. Epub 2018 Dec 15.

Department of Psychology, Università Cattolica del Sacro Cuore, Milan, Italy.

In the last 30 years, virtual reality (VR) has offered innovative solutions for assessing and treating body representation disturbances in anorexia nervosa (AN). The most recent and innovative trend is the exploitation of the so-called VR-based body swapping illusion. The aim of this case study was to report the use of this VR protocol within a multidisciplinary treatment of AN. Read More

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December 2018

A three dimensional microfluidized liver system to assess hepatic drug metabolism and hepatotoxicity.

Biotechnol Bioeng 2018 Dec 14. Epub 2018 Dec 14.

Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Naples, Italy.

In this work we propose the design and fabrication of a liver system on chip. We first chose the most suitable 3D liver-like model between cell spheroids and microtissue-precursors, both based on the use of hepatocellular carcinoma cells (HepG2) to provide proof-of-concept data. Spheroids displayed high cell density but low expression of the typical hepatic biomarkers, while microtissue-precursors showed stable viability and function over the entire culture time. Read More

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December 2018

Differential proteomic analysis reveals the mechanism of Musa paradisiaca responding to salt stress.

Mol Biol Rep 2018 Dec 14. Epub 2018 Dec 14.

School of Foreign Languages, Hainan University, Haikou, 570228, China.

Salinity is one of the most important abiotic stresses, which affects the yield and quality of banana (Musa paradisiaca). To understand the salinity tolerance mechanisms of banana, the iTRAQ technique is employed to reveal the proteomic response of Brazil banana under different durations of 60 mmol/L NaCl stress. We have identified 77 DEPs and classified them into nine functional categories, compared with control (0 mmol/L NaCl treatment). Read More

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December 2018
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In vitro characterization of hepatic toxicity of Alternaria toxins.

Mycotoxin Res 2018 Dec 14. Epub 2018 Dec 14.

Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.

Alternaria mycotoxins are secondary fungal metabolites which can contaminate food and feed. They are produced by Alternaria species with alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA), and tentoxin (TEN) as the main representatives for Alternaria mycotoxins in food. Once passing the intestinal barrier, Alternaria toxins can reach the liver to exert yet uncharacterized molecular effects. Read More

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December 2018
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Recent Advances on Relationship Between Inorganic Phosphate and Pathologic Calcification: Is Calcification After Breast Augmentation with Fat Grafting Correlated with Locally Increased Concentration of Inorganic Phosphate?

Aesthetic Plast Surg 2018 Dec 14. Epub 2018 Dec 14.

Department of Aesthetic and Reconstructive Breast Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, China.

Background: Pathologic calcification has frequently occurred after breast augmentation with fat grafting as well as other conditions such as breast cancer, trauma, myocardial infarction, arteriosclerosis and even after reduction mammoplasty. Inorganic phosphate, correlated with fat metabolism, is an important factor that induces pathologic calcification such as vascular calcification.

Methods: A literature search was conducted using PubMed with the keywords: calcification, inorganic phosphate, fat. Read More

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December 2018

How many cadherins do human endothelial cells express?

Cell Mol Life Sci 2018 Dec 14. Epub 2018 Dec 14.

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, Cantoblanco, 28049, Madrid, Spain.

The vasculature is the paradigm of a compartment generated by parallel cellular barriers that aims to transport oxygen, nutrients and immune cells in complex organisms. Vascular barrier dysfunction leads to fatal acute and chronic inflammatory diseases. The endothelial barrier lines the inner side of vessels and is the main regulator of vascular permeability. Read More

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December 2018

Relieving ER stress to target NASH-driven hepatocellular carcinoma.

Nat Rev Endocrinol 2018 Dec 14. Epub 2018 Dec 14.

Division of Diabetes & Metabolism, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

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December 2018

Identification of the salusin-β receptor using proteoliposomes embedded with endogenous membrane proteins.

Sci Rep 2018 Dec 14;8(1):17865. Epub 2018 Dec 14.

Protosera Inc., 4-3-22 Nishinakajima, Yodogawa-ku, Osaka, 532-0011, Japan.

Although orphan G protein-coupled receptors (GPCRs) have been used as targets to discover unidentified natural ligands, increasing numbers of non-GPCRs have been found to mediate important biological functions. Bioinformatics of genome and cDNA resources predict putative bioactive peptides, demanding an alternative approach to efficiently unravel cell surface targets. In silico analysis of a full-length cDNA library previously allowed us to identify salusin-β, a parasympathomimetic/pro-atherosclerotic peptide with unique physicochemical properties. Read More

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December 2018

Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9.

Nat Commun 2018 Dec 14;9(1):5319. Epub 2018 Dec 14.

Murdoch Children's Research Institute, Melbourne, 3052, VIC, Australia.

Disorders of sex development (DSDs) are conditions affecting development of the gonads or genitalia. Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs remains unknown. SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying this have not been identified in humans. Read More

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December 2018

MoVE identifies metabolic valves to switch between phenotypic states.

Nat Commun 2018 Dec 14;9(1):5332. Epub 2018 Dec 14.

Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.

Metabolism is highly regulated, allowing for robust and complex behavior. This behavior can often be achieved by controlling a small number of important metabolic reactions, or metabolic valves. Here, we present a method to identify the location of such valves: the metabolic valve enumerator (MoVE). Read More

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December 2018

miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA-mediated gene repression.

Nat Commun 2018 Dec 14;9(1):5321. Epub 2018 Dec 14.

Department of Pediatrics, Stanford University, Stanford, 94305, CA, USA.

miR-122 is a highly expressed liver microRNA that is activated perinatally and aids in regulating cholesterol metabolism and promoting terminal differentiation of hepatocytes. Disrupting expression of miR-122 can re-activate embryo-expressed adult-silenced genes, ultimately leading to the development of hepatocellular carcinoma (HCC). Here we interrogate the liver transcriptome at various time points after genomic excision of miR-122 to determine the cellular consequences leading to oncogenesis. Read More

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December 2018

Pan-cancer analysis of transcriptional metabolic dysregulation using The Cancer Genome Atlas.

Nat Commun 2018 Dec 14;9(1):5330. Epub 2018 Dec 14.

Department of Cancer Genetics and Genomics, Roswell Park Cancer Institute, Buffalo, 14263, NY, USA.

Understanding metabolic dysregulation in different disease settings is vital for the safe and effective incorporation of metabolism-targeted therapeutics in the clinic. Here, using transcriptomic data for 10,704 tumor and normal samples from The Cancer Genome Atlas, across 26 disease sites, we present a novel bioinformatics pipeline that distinguishes tumor from normal tissues, based on differential gene expression for 114 metabolic pathways. We confirm pathway dysregulation in separate patient populations, demonstrating the robustness of our approach. Read More

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December 2018

Injury factors alter miRNAs profiles of exosomes derived from islets and circulation.

Aging (Albany NY) 2018 Dec 14. Epub 2018 Dec 14.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Islets damage is a major abnormality underling diabetes. Recent studies suggested the value of exosomes in diagnosis. This study aimed to investigate the impact of injury factors on the miRNA profiles of islet exosomes and determine whether circulating exosomal miRNAs is suitable as biomarkers of islets damage. Read More

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December 2018

Hypoglycemic side effects of sulfonylureas and repaglinide in ageing patients - knowledge and self-management.

J Physiol Pharmacol 2018 Aug 9;69(4). Epub 2018 Dec 9.

Thuringia Clinic Saalfeld "Georgius Agricola", Department of Internal Medicine II, Division of Gastroenterology, Teaching Hospital of the University of Jena, Saalfeld/Saale, Germany.

Insulinotropic oral antidiabetics (OAD) such as sulfonylureas and (SU) glinides are among the frequently prescribed OAD. Side effects are the potential to induce hypoglycemias and weight gain. The aim was to assess the self-managing skills in case of a hypoglycemic event in an elderly type 2 diabetic patient population. Read More

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Empagliflozin, an SGLT2 inhibitor, reduced the mortality rate after acute myocardial infarction with modification of cardiac metabolomes and anti-oxidants in diabetic rats.

J Pharmacol Exp Ther 2018 Dec 14. Epub 2018 Dec 14.

Sapporo Medical University

Background: Mechanism by which sodium glucose cotransporter 2 (SGLT2) inhibitors reduce cardiac events in diabetic patients remains unclear. Here we examined effects of an SGLT2 inhibitor on the acute survival rate after myocardial infarction (MI) in an animal model of type 2 diabetes mellitus (DM) and possible involvement of modification of cardiac metabolomes and anti-oxidative proteins.

Methods And Results: MI was induced in DM rats (OLETF) and control rats (LETO). Read More

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December 2018

Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function.

J Lipid Res 2018 Dec 14. Epub 2018 Dec 14.

Nanjing Agricultural University, China

In obesity and diabetes, intramuscular fat (IMF) content correlates markedly with insulin sensitivity, which makes IMF manipulation an area of therapeutic interest. Melatonin, an important circadian rhythm-regulating hormone, reportedly regulates fat deposition, but its effects on different types of adipose vary. Little is known about the role of melatonin in IMF deposition. Read More

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December 2018

Erythrocyte PUFAs, circulating acylcarnitines, and metabolic syndrome risk: a prospective study in Chinese.

J Lipid Res 2018 Dec 14. Epub 2018 Dec 14.

Chinese Academy of Sciences, China;

Effects of PUFAs on metabolic syndrome (MetS) remain to be characterized, particularly in Asians. We aimed to investigate the prospective associations of PUFAs with MetS and the role of acylcarnitines in these associations in Chinese. Among 1,245 Chinese aged 50-70 who completed a 6-yr follow-up, baseline erythrocyte FAs and plasma acylcarnitines were profiled using gas chromatography coupled with positive chemical ionization and liquid chromatography-tandem mass spectrometry, respectively. Read More

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December 2018

Sphingoid bases of dietary ceramide 2-aminoethylphosphonate, a marine sphingolipid, absorb into lymph in rats.

J Lipid Res 2018 Dec 14. Epub 2018 Dec 14.

Kyoto University, Japan;

Various functions of dietary sphingolipids have been reported; however, little is known about marine sphingolipids. Ceramide 2-aminoethylphosphonate (CAEP), an abundant sphingolipid in marine molluscs, frequently has a unique triene-type of sphingoid base (2-amino-9-methyl-4,8,10-octadecatriene-1,3-diol, or d19:3). We previously reported that dietary CAEP prepared from the skin of squid was digested in the intestinal mucosa of mice via ceramides to yield free sphingoid bases. Read More

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December 2018
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RagC phosphorylation autoregulates mTOR complex 1.

EMBO J 2018 Dec 14. Epub 2018 Dec 14.

School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia

The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) controls cell growth, proliferation, and metabolism in response to diverse stimuli. Two major parallel pathways are implicated in mTORC1 regulation including a growth factor-responsive pathway mediated via TSC2/Rheb and an amino acid-responsive pathway mediated via the Rag GTPases. Here, we identify and characterize three highly conserved growth factor-responsive phosphorylation sites on RagC, a component of the Rag heterodimer, implicating cross talk between amino acid and growth factor-mediated regulation of mTORC1. Read More

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December 2018

Genome-scale fluxome of Synechococcus elongatus UTEX 2973 using transient 13C-labeling data.

Plant Physiol 2018 Dec 14. Epub 2018 Dec 14.

The Pennsylvania State University CITY: University Park STATE: Pennsylvania POSTAL_CODE: n/a United States Of America [US]

Synechococcus elongatus UTEX 2973 (Synechococcus 2973) has the shortest reported doubling time (2.1 h) among cyanobacteria, making it a promising platform for the solar-based production of biochemicals. In this meta-analysis, its intracellular flux distribution was re-computed using genome-scale Isotopic Non-Stationary-13C-Metabolic Flux Analysis (INST-MFA) given the labeling dynamics of 13 metabolites reported in an earlier study. Read More

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December 2018

Loss of adult 5-HT1A autoreceptors results in a paradoxical anxiogenic response to antidepressant treatment.

J Neurosci 2018 Dec 14. Epub 2018 Dec 14.

Ottawa Hospital Research Institute (Neuroscience), Ottawa, Canada

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are first-line antidepressants, but require several weeks to elicit their actions. Chronic SSRI treatment induces desensitization of 5-HT1A autoreceptors to enhance 5-HT neurotransmission. Mice (both sexes) with gene deletion of 5-HT1A autoreceptors in adult 5-HT neurons (1AcKO) were tested for response to SSRIs. Read More

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December 2018

Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

Ann Rheum Dis 2018 Dec 14. Epub 2018 Dec 14.

Immunology Development, AbbVie, North Chicago, Illinois, USA.

Objective: To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA).

Methods: Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. Read More

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December 2018

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

Ann Rheum Dis 2018 Dec 14. Epub 2018 Dec 14.

Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain

Objective: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. Read More

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December 2018

Aging of Antiviral CD8 Memory T Cells Fosters Increased Survival, Metabolic Adaptations, and Lymphoid Tissue Homing.

J Immunol 2018 Dec 14. Epub 2018 Dec 14.

Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045;

Aging of established antiviral T cell memory can foster a series of progressive adaptations that paradoxically improve rather than compromise protective CD8 T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8 memory T cell (T) homeostasis. Over time, CD8 T generated in the wake of an acute infection with the natural murine pathogen lymphocytic choriomeningitis virus become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8 T quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8 T from blood and nonlymphoid tissues to lymphatic organs results in CD8 T accumulations in bone marrow, splenic white pulp, and, particularly, lymph nodes. Read More

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December 2018

Pancreas Volume Declines During the First Year After Diagnosis of Type 1 Diabetes and Exhibits Altered Diffusion at Disease Onset.

Diabetes Care 2018 Dec 14. Epub 2018 Dec 14.

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN

Objective: This study investigated the temporal dynamics of pancreas volume and microstructure in children and adolescents with recent-onset type 1 diabetes (T1D) and individuals without diabetes, including a subset expressing autoantibodies associated with the early stages of T1D.

Research Design And Methods: MRI was performed in individuals with recent-onset stage 3 T1D ( = 51; median age 13 years) within 100 days after diagnosis (mean 67 days), 6 months, and 1 year postdiagnosis. Longitudinal MRI measurements were also made in similarly aged control participants ( = 57) and in autoantibody-positive individuals without diabetes ( = 20). Read More

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December 2018

Circulating Exosomal miR-20b-5p is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle.

Diabetes 2018 Dec 14. Epub 2018 Dec 14.

Department of Physiology and Pharmacology Karolinska Institutet, SE-171 77 Stockholm, Sweden,

MicroRNAs (miRNAs) are noncoding RNAs representing an important class of gene expression modulators. Extracellular circulating miRNAs are both candidate biomarkers for disease pathogenesis and mediators of cell-to-cell communication. We examined the miRNA expression profile of total serum and serum derived exosome-enriched extracellular vesicles in people with normal glucose tolerance or type 2 diabetes. Read More

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December 2018

Genetic Nicotinamide N-Methyltransferase () Deficiency in Male Mice Improves Insulin Sensitivity in Diet-Induced Obesity but Does Not Affect Glucose Tolerance.

Diabetes 2018 Dec 14. Epub 2018 Dec 14.

Sanofi Research and Development, Industriepark Hoechst, H823, D-64926 Frankfurt am Main, Germany.

Antisense oligonucleotide knockdown (ASO-KD) of nicotinamide N-methyltransferase (NNMT) in high-fat diet (HFD)-fed mice has been reported to reduce weight gain, plasma insulin and improve glucose tolerance. Using NNMT-ASO-KD or NNMT knockout mice (NNMT), we tested the hypothesis that deletion protects against diet-induced obesity and its metabolic consequences in males and females on obesity-inducing diets. We also examined samples from a human weight reduction (WR) study for adipose (a) expression and plasma 1-methylnicotinamide (MNAM) levels. Read More

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December 2018

A genome-Wide Association Study Confirming a Strong Effect of HLA and Identifying Variants in on Chromosome 12q13.13 Associated with Susceptibility to Fulminant Type 1 Diabetes.

Diabetes 2018 Dec 14. Epub 2018 Dec 14.

Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka, Japan

The first genome-wide association study of fulminant type 1 diabetes mellitus was performed in Japanese individuals. As previously reported using a candidate gene approach, a strong association was observed with multiple SNPs in the HLA region, and the strongest association was observed with rs9268853 in the class II DR region (P=1.56 x 10, odds ratio [OR] 3. Read More

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December 2018
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A Call for Improved Reporting of Human Islet Characteristics in Research Articles.

Diabetes 2018 Dec 14. Epub 2018 Dec 14.

Institute of Cellular Medicine, Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne, U.K.

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December 2018

Meeting the Challenge of Predicting Hepatic Clearance of Compounds Slowly Metabolized by Cytochrome P450 Using a Novel Hepatocyte Model, HepatoPac.

Drug Metab Dispos 2019 Jan 14;47(1):58-66. Epub 2018 Dec 14.

Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (T.S.C., H.Y., D.T.); Hepregen Corporation, Medford, Massachusetts (A.M.); and Mechanical and Biomedical Engineering, Colorado State University, Fort Collins, Colorado (S.R.K.).

Generating accurate in vitro intrinsic clearance data is an important aspect of predicting in vivo human clearance. Primary hepatocytes in suspension are routinely used to predict in vivo clearance; however, incubation times have typically been limited to 4-6 hours, which is not long enough to accurately evaluate the metabolic stability of slowly metabolized compounds. HepatoPac is a micropatterened hepatocyte-fibroblast coculture system that can be used for continuous incubations of up to 7 days. Read More

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January 2019
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