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DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3β/mTOR Signaling.

Front Aging Neurosci 2021 21;13:513605. Epub 2021 Apr 21.

Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China.

Accumulating evidences supported that knock-down of DHCR24 is linked to the pathological risk factors of AD, suggesting a potential role of DHCR24 in AD pathogenesis. However, the molecular mechanism link between DHCR24 and tauopathy remains unknown. Here, in order to elucidate the relationship between DHCR24 and tauopathy, we will focus on the effect of DHCR24 on the tau hyperphosphorylation at some toxic sites. Read More

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Lysosomal alkalization to potentiate eradication of intraosteoblastic Staphylococcus aureus in the bone and joint infection setting.

Clin Microbiol Infect 2021 May 4. Epub 2021 May 4.

CIRI - Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre de Référence pour la prise en charge des Infections ostéo-articulaires complexes (CRIOAc Lyon; www.crioac-lyon.fr), Hospices Civils de Lyon, Lyon, France; Service des maladies infectieuses et tropicales, Hospices Civils de Lyon, Lyon, France. Electronic address:

Objectives: Beyond intracellular penetration, acidic lysosomal pH might affect the intracellular activity of some antimicrobials. This study evaluated the ability of lysosomotropic alkalizing agents to potentiate antimicrobial eradication of intraosteoblastic S. aureus reservoir in the bone and joint infection (BJI) setting. Read More

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Knockdown of Gastrin Promotes Apoptosis of Gastric Cancer Cells by Decreasing ROS Generation.

Biomed Res Int 2021 14;2021:5590037. Epub 2021 Apr 14.

Immunology Department, School of Medicine, Qinghai University, Qinghai 810000, China.

Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Read More

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Insights into Multifunctional Nanoparticle-Based Drug Delivery Systems for Glioblastoma Treatment.

Molecules 2021 Apr 14;26(8). Epub 2021 Apr 14.

Interdisciplinary Nanotechnology Centre, Aligarh Muslim University, Aligarh 202002, U.P., India.

Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development of resistance of tumor cells to radiation in the areas of hypoxia decreases the efficiency of such treatments. Read More

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Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies.

Biomedicines 2021 Apr 2;9(4). Epub 2021 Apr 2.

Research Area Neurodegenerative Diseases, Center for Biosciences, Faculty of Medicine/Dental Medicine, Danube Private University, 3500 Krems an der Donau, Austria.

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. Read More

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Ubiquitous membrane-bound DNase activity in podosomes and invadopodia.

J Cell Biol 2021 Jul;220(7)

Department of Physics and Astronomy, Iowa State University, Ames, IA.

Podosomes and invadopodia, collectively termed invadosomes, are adhesive and degradative membrane structures formed in many types of cells and are well known for recruiting various proteases. However, another major class of degradative enzymes, deoxyribonuclease (DNase), remains unconfirmed and not studied in invadosomes. Here, using surface-immobilized nuclease sensor (SNS), we demonstrated that invadosomes recruit DNase to their core regions, which degrade extracellular double-stranded DNA. Read More

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Enhanced Glutamate Synthesis and Export by the Thermotolerant Emerging Industrial Workhorse in Response to High Osmolarity.

Front Microbiol 2021 8;12:640980. Epub 2021 Apr 8.

Laboratory for Microbiology, Department of Biology, Philipps-University Marburg, Marburg, Germany.

The thermotolerant methylotroph MGA3 was originally isolated from freshwater marsh soil. Due to its ability to use methanol as sole carbon and energy source, is increasingly explored as a cell factory for the production of amino acids, fine chemicals, and proteins of biotechnological interest. During high cell density fermentation in industrial settings with the membrane-permeable methanol as the feed, the excretion of low molecular weight products synthesized from it will increase the osmotic pressure of the medium. Read More

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Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration.

Sci Rep 2021 Apr 22;11(1):8781. Epub 2021 Apr 22.

College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Suite 401 Veterinary medicine Bldg., Yuseong, Daejeon, 34134, Korea.

Obesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Read More

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Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells.

Cell Microbiol 2021 Apr 16:e13343. Epub 2021 Apr 16.

Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Bacterial pathogens have evolved multiple strategies to disassemble epithelial cell apical junctional complexes (AJCs) and infect epithelial cells. Leptospirosis is a widespread zoonotic infection, mainly caused by Leptospira interrogans, and its dissemination across host cell barriers is essential for its pathogenesis. However, the mechanism of bacterial dissemination across epithelial cell barriers remains poorly characterised. Read More

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Non-invasive adapted N-95 mask sampling captures variation in viral particles expelled by COVID-19 patients: Implications in understanding SARS-CoV2 transmission.

PLoS One 2021 12;16(4):e0249525. Epub 2021 Apr 12.

The Foundation for Medical Research, Mumbai, Maharashtra, India.

Infectious respiratory particles expelled by SARS-CoV-2 positive patients are attributed to be the key driver of COVID-19 transmission. Understanding how and by whom the virus is transmitted can help implement better disease control strategies. Here we have described the use of a noninvasive mask sampling method to detect and quantify SARS-CoV-2 RNA in respiratory particles expelled by COVID-19 patients and discussed its relationship to transmission risk. Read More

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The susceptibility of the rat pulmonary and caval vein myocardium to the catecholamine-induced ectopy changes oppositely in postnatal development.

J Physiol 2021 Apr 6. Epub 2021 Apr 6.

Institute of Neuroscience, Kazan State Medial University, Butlerova st. 49, Kazan, 420012, Russia.

Key Points: The developmental changes of the caval (SVC) and pulmonary vein (PV) myocardium electrophysiology are traced throughout postnatal ontogenesis. The myocardium in SVC as well as in PV demonstrate age-dependent differences in the ability to maintain resting membrane potential, to manifest automaticity in a form of ectopic action potentials in basal condition and in responses to the adrenergic stimulation. Electrophysiological characteristics of two distinct types of thoracic vein myocardium change in an opposite manner during early postnatal ontogenesis with increased proarrhythmicity of pulmonary and decreased automaticity in caval veins. Read More

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The structure of CLEC-2: mechanisms of dimerization and higher-order clustering.

Platelets 2021 Apr 5:1-11. Epub 2021 Apr 5.

Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham.

The platelet C-type lectin-like receptor CLEC-2 drives inflammation-driven venous thrombosis in mouse models of thrombo-inflammatory disease with a minimal effect on hemostasis identifying it as a target for a new class of antiplatelet agent. Here, we discuss how the protein structure and dynamic arrangement of CLEC-2 on the platelet membrane helps the receptor, which has a single YxxL motif (known as a hemITAM), to trigger intracellular signaling. CLEC-2 exists as a monomer and homo-dimer within resting platelets and forms higher-order oligomers following ligand activation, a process that is mediated by the multivalent nature of its ligands and the binding of the tandem SH2 domains of Syk to the phosphorylated hemITAM and concomitantly to PIP or PIP to localize it to the membrane. Read More

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Regulation of the Mitochondrion-Fatty Acid Axis for the Metabolic Reprogramming of Chlamydia trachomatis during Treatment with β-Lactam Antimicrobials.

mBio 2021 03 30;12(2). Epub 2021 Mar 30.

Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.

Infection with the obligate intracellular bacterium is the most common bacterial sexually transmitted disease worldwide. Since no vaccine is available to date, antimicrobial therapy is the only alternative in infection. However, changes in chlamydial replicative activity and the occurrence of chlamydial persistence caused by diverse stimuli have been proven to impair treatment effectiveness. Read More

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The photosensitiser azure A disrupts mitochondrial bioenergetics through intrinsic and photodynamic effects.

Toxicology 2021 05 26;455:152766. Epub 2021 Mar 26.

Department of Biochemistry, Laboratory of Biological Oxidations and Laboratory of Experimental Steatosis, State University of Maringá, Maringá, 87020-900, Paraná, Brazil; Department of Biochemistry, Laboratory of Plant Biochemistry, State University of Maringá, Maringá, 87020-900, Paraná, Brazil. Electronic address:

Azure A (AA) is a cationic molecule of the class of phenothiazines that has been applied in vitro as a photosensitising agent in photodynamic antimicrobial chemotherapy. It is a di-demethylated analogue of methylene blue (MB), which has been demonstrated to be intrinsically and photodynamically highly active on mitochondrial bioenergetics. However, as far as we know, there are no studies about the photodynamic effects of AA on mammalian mitochondria. Read More

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Electroporation with nanosecond pulses and bleomycin or cisplatin results in efficient cell kill and low metal release from electrodes.

Bioelectrochemistry 2021 Mar 9;140:107798. Epub 2021 Mar 9.

University of Ljubljana, Faculty of Electrical Engineering, Tržaška cesta 25, 1000 Ljubljana, Slovenia. Electronic address:

Nanosecond electric pulses have several potential advantages in electroporation-based procedures over the conventional micro- and millisecond pulses including low level of heating, reduced electrochemical reactions and reduced muscle contractions making them alluring for use in biomedicine and food industry. The aim of this study was to evaluate if nanosecond pulses can enhance the cytotoxicity of chemotherapeutics bleomycin and cisplatin in vitro and to quantify metal release from electrodes in comparison to 100 μs pulses commonly used in electrochemotherapy. The effects of nanosecond pulse parameters (voltage, pulse duration, number of pulses) on cell membrane permeabilization, resealing and on cell survival after electroporation only and after electrochemotherapy with bleomycin and cisplatin were evaluated on Chinese hamster ovary cells. Read More

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Exposure to 1-Butanol Exemplifies the Response of the Thermoacidophilic Archaeon Sulfolobus acidocaldarius to Solvent Stress.

Appl Environ Microbiol 2021 May 11;87(11). Epub 2021 May 11.

Molecular Enzyme Technology and Biochemistry (MEB), Environmental Microbiology and Biotechnology (EMB), Centre for Water and Environmental Research (CWE), University of Duisburg-Essen, Essen, Germany

is a thermoacidophilic crenarchaeon with optimal growth at 80°C and pH 2 to 3. Due to its unique physiological properties, allowing life at environmental extremes, and the recent availability of genetic tools, this extremophile has received increasing interest for biotechnological applications. In order to elucidate the potential of tolerating process-related stress conditions, we investigated the response of toward the industrially relevant organic solvent 1-butanol. Read More

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De novo formation of early endosomes during Rab5-to-Rab7a transition.

J Cell Sci 2021 Apr 27;134(8). Epub 2021 Apr 27.

Department of Biosciences, University of Oslo, 0371 Oslo, Norway.

Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch, where Rab5 is gradually exchanged by Rab7a on the same endosome. Here, we provide new insight into the mechanism of endosomal maturation, for which we have discovered a stepwise Rab5 detachment, sequentially regulated by Rab7a. Read More

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Short-term administration of stimulates insulin signaling, suppresses fatty acids metabolism, and increases glucose uptake and utilization in the hearts of healthy rats.

Saudi J Biol Sci 2021 Mar 6;28(3):1966-1977. Epub 2021 Jan 6.

Depatrtment of Radiology Science, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.

This study evaluated the effect of aqueous extract on cardiac substrate utilization and insulin signaling in adult male healthy Wistar rats. Rats (n = 18/group) were either administered normal saline (vehicle) or treated with aqueous extract (200 mg/kg) for 7 days, daily. Fasting plasma glucose and insulin levels were not significantly changed in -treated rats but were significantly reduced after both the intraperitoneal glucose or insulin tolerance tests. Read More

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Brain ACE2 activation following brain aminopeptidase A blockade by firibastat in salt-dependent hypertension.

Clin Sci (Lond) 2021 Mar;135(6):775-791

Laboratory of Central Neuropeptides in the Regulation of Body Fluid Homeostasis and Cardiovascular Functions, INSERM U1050, Paris F-75231 France.

In the brain, aminopeptidase A (APA), a membrane-bound zinc metalloprotease, generates angiotensin III from angiotensin II. Brain angiotensin III exerts a tonic stimulatory effect on the control of blood pressure (BP) in hypertensive rats and increases vasopressin release. Blocking brain angiotensin III formation by the APA inhibitor prodrug RB150/firibastat normalizes arterial BP in hypertensive deoxycorticosterone acetate (DOCA)-salt rats without inducing angiotensin II accumulation. Read More

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Chitosan and Chitin Deacetylase Activity Are Necessary for Development and Virulence of Ustilago maydis.

mBio 2021 03 2;12(2). Epub 2021 Mar 2.

Max Planck Institute for Terrestrial Microbiology, Department of Organismic Interactions, Marburg, Germany

The biotrophic fungus harbors a chitin deacetylase (CDA) family of six active genes as well as one pseudogene which are differentially expressed during colonization. This includes one secreted soluble CDA (Cda4) and five putatively glycosylphosphatidylinositol (GPI)-anchored CDAs, of which Cda7 belongs to a new class of fungal CDAs. Here, we provide a comprehensive functional study of the entire family. Read More

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Environment-Sensitive Polymeric Micelles Encapsulating SN-38 Potently Suppress Growth of Neuroblastoma Cells Exhibiting Intrinsic and Acquired Drug Resistance.

ACS Pharmacol Transl Sci 2021 Feb 4;4(1):240-247. Epub 2020 Dec 4.

Department of Pediatrics, The Children's Hospital of Philadelphia, Abramson Research Building, Suite 702, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-4318, United States.

Conventional treatment approaches fail to provide durable control over aggressive malignancies due to intrinsic or acquired drug resistance characteristic of high-risk disease. SN-38, a potent camptothecin analog specifically targeting DNA topoisomerase I cleavage complexes, has shown promise in preclinical studies against aggressive solid tumors. However, its clinical utility is limited by inadequate solubility in pharmaceutically acceptable vehicles and by poor chemical and metabolic stability. Read More

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February 2021

. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype.

Nutrients 2021 Jan 29;13(2). Epub 2021 Jan 29.

Department of Biochemistry, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany.

. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. Read More

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January 2021

Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems.

Transl Res 2021 Feb 7. Epub 2021 Feb 7.

Department of Obstetrics and Gynecology, State University of New York, Downstate Medical University, College of Medicine, Brooklyn, New York.

Nociception and opioid antinociception in females are pliable processes, varying qualitatively and quantitatively over the reproductive cycle. Spinal estrogenic signaling via membrane estrogen receptors (mERs), in combination with multiple other signaling molecules [spinal dynorphin, kappa-opioid receptors (KOR), glutamate and metabotropic glutamate receptor 1 (mGluR)], appears to function as a master coordinator, parsing functionality between pronociception and antinociception. This provides a window into pharmacologically accessing intrinsic opioid analgesic/anti-allodynic systems. Read More

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February 2021

Common differentially expressed genes and pathways correlating both coronary artery disease and atrial fibrillation.

EXCLI J 2021 18;20:126-141. Epub 2021 Jan 18.

Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.

Coronary artery disease (CAD) and atrial fibrillation (AF) share common risk factors, such as hypertension and diabetes. The patients with CAD often suffer concomitantly AF, but how two diseases interact with each other at cellular and molecular levels remain largely unknown. The present study aims to dissect the common differentially expressed genes (DEGs) that are concurrently associated with CAD and AF. Read More

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January 2021

Intermittent fasting promotes anxiolytic-like effects unrelated to synaptic mitochondrial function and BDNF support.

Behav Brain Res 2021 Apr 4;404:113163. Epub 2021 Feb 4.

Laboratório de Neurotrauma e Biomarcadores - Departamento de Bioquímica, Programa de Pós-Graduação em Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.

Anxiety disorders are linked to mitochondrial dysfunction and decreased neurotrophic support. Since anxiolytic drugs target mitochondria, non-pharmacological approaches to improve mitochondrial metabolism such as intermittent fasting (IF) may cause parallel behavioral benefits against anxiety disorders. Here, we investigated whether a chronic IF regimen could induce anxiolytic-like effects concomitantly to modulation in mitochondrial bioenergetics and trophic signaling in mice brain. Read More

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Antioxidant-Based Therapies in Male Infertility: Do We Have Sufficient Evidence Supporting Their Effectiveness?

Antioxidants (Basel) 2021 Feb 2;10(2). Epub 2021 Feb 2.

Alma Res Fertility Center, Laboratory of Obstetrics and Ginecology, Via Parenzo 12, 00199 Rome, Italy.

Under physiological conditions, reactive oxygen species (ROS) play pivotal roles in various processes of human spermatozoa. Indeed, semen requires the intervention of ROS to accomplish different stages of its maturation. However, ROS overproduction is a well-documented phenomenon occurring in the semen of infertile males, potentially causing permanent oxidative damages to a vast number of biological molecules (proteins, nucleic acids, polyunsaturated fatty acids of biological membrane lipids), negatively affecting the functionality and vitality of spermatozoa. Read More

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February 2021

Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K Current.

Int J Mol Sci 2021 Jan 28;22(3). Epub 2021 Jan 28.

Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City 70101, Taiwan.

Kynurenic acid (KYNA, 4-oxoquinoline-2-carboxylic acid), an intermediate of the tryptophan metabolism, has been recognized to exert different neuroactive actions; however, the need of how it or its aminoalkylated amide derivative -(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) exerts any effects on ion currents in excitable cells remains largely unmet. In this study, the investigations of how KYNA and other structurally similar KYNA derivatives have any adjustments on different ionic currents in pituitary GH cells and hippocampal mHippoE-14 neurons were performed by patch-clamp technique. KYNA or KYNA-A4 increased the amplitude of M-type K current () and concomitantly enhanced the activation time course of the current. Read More

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January 2021

The longevity gene mIndy (I'm Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms.

JCI Insight 2021 01 25;6(2). Epub 2021 Jan 25.

Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital and Medical Faculty Carl Gustav Carus and.

Reduced expression of the plasma membrane citrate transporter INDY (acronym I'm Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates sympathoadrenal support of BP. Read More

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January 2021

Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice.

Mol Metab 2021 03 20;45:101166. Epub 2021 Jan 20.

Montreal Diabetes Research Center, CRCHUM, Montréal, QC, Canada; Department of Medicine, Université de Montréal, Montréal, QC, Canada. Electronic address:

Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (α, β, and δ cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. Read More

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Host cell glutamine metabolism as a potential antiviral target.

Clin Sci (Lond) 2021 01;135(2):305-325

Interdisciplinary Program of Health Sciences, Cruzeiro do Sul University, GalvãoBueno, 868, Liberdade, 01506-000, SãoPaulo, São Paulo, Brazil.

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. Read More

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January 2021