823 results match your criteria depletes intracellular

Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in KO Mice.

Nutrients 2021 May 15;13(5). Epub 2021 May 15.

Food Science & Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. Read More

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Red light stimulates vasodilation through extracellular vesicle trafficking.

J Photochem Photobiol B 2021 Jul 12;220:112212. Epub 2021 May 12.

Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, USA; Cardiovascular Center, Medical College of Wisconsin, USA; Clement J Zablocki VA Medical Center, USA. Electronic address:

Red light (670 nm) promotes ex vivo dilation of blood vessels in a nitric oxide (NO) dependent, but eNOS independent manner by secreting a quasi-stable and transferable vasoactive substance with the characteristics of S-nitrosothiols (RSNO) from the endothelium. In the present work we establish that 670 nm light mediated vasodilation occurs in vivo and is physiologically stable. Light exposure depletes intracellular S-nitroso protein while concomitantly increasing extracellular RNSO, suggesting vesicular pathways are involved. Read More

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Muscarinic Receptors and BK Channels Are Affected by Lipid Raft Disruption of Salivary Gland Cells.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Korea.

Activity-dependent fluid secretion is the most important physiological function of salivary glands and is regulated via muscarinic receptor signaling. Lipid rafts are important for G-protein coupled receptor (GPCR) signaling and ion channels in plasma membranes. However, it is not well understood whether lipid raft disruption affects all membrane events or only specific functions in muscarinic receptor-mediated water secretion in salivary gland cells. Read More

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From Plant to Patient: Thapsigargin, a Tool for Understanding Natural Product Chemistry, Total Syntheses, Biosynthesis, Taxonomy, ATPases, Cell Death, and Drug Development.

Prog Chem Org Nat Prod 2021 ;115:59-114

Department of Oncology, Prostate Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Maryland, The Johns Hopkins University School of Medicine, Baltimore, The Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD, 21231, USA.

Thapsigargin, the first representative of the hexaoxygenated guaianolides, was isolated 40 years ago in order to understand the skin-irritant principles of the resin of the umbelliferous plant Thapsia garganica. The pronounced cytotoxicity of thapsigargin is caused by highly selective inhibition of the intracellular sarco-endoplasmic Ca-ATPase (SERCA) situated on the membrane of the endo- or sarcoplasmic reticulum. Thapsigargin is selective to the SERCA pump and to a minor extent the secretory pathway Ca/Mn ATPase (SPCA) pump. Read More

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A smart MnO-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy simultaneous oxygenation and glutathione depletion.

Acta Pharm Sin B 2021 Mar 7;11(3):823-834. Epub 2020 Aug 7.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.

The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. Read More

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Autoantibodies Targeting Intracellular and Extracellular Proteins in Autoimmunity.

Front Immunol 2021 8;12:548469. Epub 2021 Mar 8.

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.

Detecting autoantibodies provides foundational information for the diagnosis of most autoimmune diseases. An important pathophysiological distinction is whether autoantibodies are directed against extracellular or intracellular proteins. Autoantibodies targeting extracellular domains of proteins, such as membrane receptors, channels or secreted molecules are often directly pathogenic, whereby autoantibody binding to the autoantigen disrupts the normal function of a critical protein or pathway, and/or triggers antibody-dependent cell surface complement killing. Read More

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Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Pathology and Laboratory Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033;

Phosphorus (P) is an essential component of core biological molecules. In bacteria, P is acquired mainly as inorganic orthophosphate (Pi) and assimilated into adenosine triphosphate (ATP) in the cytoplasm. Although P is essential, excess cytosolic Pi hinders growth. Read More

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Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells.

Cell Death Dis 2021 03 3;12(3):230. Epub 2021 Mar 3.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, Sichuan, PR China.

Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Read More

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Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth.

Cell Metab 2021 May 19;33(5):1013-1026.e6. Epub 2021 Feb 19.

Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. Electronic address:

Mitochondrial respiration is critical for cell proliferation. In addition to producing ATP, respiration generates biosynthetic precursors, such as aspartate, an essential substrate for nucleotide synthesis. Here, we show that in addition to depleting intracellular aspartate, electron transport chain (ETC) inhibition depletes aspartate-derived asparagine, increases ATF4 levels, and impairs mTOR complex I (mTORC1) activity. Read More

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Polyprodrug with glutathione depletion and cascade drug activation for multi-drug resistance reversal.

Biomaterials 2021 03 6;270:120649. Epub 2021 Jan 6.

Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, PR China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, PR China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, PR China. Electronic address:

High intracellular glutathione (GSH) levels play an important role in multidrug resistance (MDR) in cancer cells. It remains challenging to develop a drug delivery system that is simultaneously capable of GSH depletion and drug activation for multidrug resistance reversal. Herein, we designed a polyprodrug (denoted as PSSD) based on poly(disulfide) conjugated with doxorubicin (DOX) on the polymer side chains that exhibits GSH depletion and cascade DOX activation for drug resistance reversal. Read More

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HPLC-electrospray ionization-mass spectrometry optimization by high-performance design of experiments for astrocyte glutamine measurement.

J Mass Spectrom 2021 Feb;56(2):e4680

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana, 71201, USA.

The amino acid glutamine (Gln) is a likely source of energy in the brain during neuroglucopenia. Effects of glucose deficiency on astrocyte Gln homeostasis remain unclear, as analytical tools of requisite sensitivity for quantification of intracellular levels of this molecule are not currently available. Here, a primary hypothalamic astrocyte culture model was used in conjunction with design of experiments (DOE)-refined high-performance liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) methodology to investigate the hypothesis that glucoprivation alters astrocyte Gln content in a sex-specific manner. Read More

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February 2021

The metabolic-epigenetic nexus in type 2 diabetes mellitus.

Free Radic Biol Med 2021 Jan 8. Epub 2021 Jan 8.

Ulster University, Genomic Medicine Research Group, Biomedical Sciences Research Institute, Coleraine, Northern Ireland, UK.

The prevalence of type 2 diabetes mellitus (T2DM) continues to rise globally. Yet the aetiology and pathophysiology of this noncommunicable, polygenic disease, is poorly understood. Lifestyle factors, such as poor dietary intake, lack of exercise, and abnormal glycaemia, are purported to play a role in disease onset and progression, and these environmental factors may disrupt specific epigenetic mechanisms, leading to a reprogramming of gene transcription. Read More

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January 2021

Dual-targeted 5-aminolevulinic acid derivatives with glutathione depletion function for enhanced photodynamic therapy.

J Photochem Photobiol B 2021 Feb 20;215:112107. Epub 2020 Dec 20.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China; Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. Electronic address:

Photodynamic therapy (PDT) is a promising tumor therapy which utilizes reactive oxygen species (ROSs) to cause tumor cells death. 5-aminolevulinic acid (ALA) and two of its esters are FDA-approved photosensitizers. However, their clinical application suffers from their instability and lack of tumor selectivity. Read More

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February 2021

Endogenous Retroelement Activation by Epigenetic Therapy Reverses the Warburg Effect and Elicits Mitochondrial-Mediated Cancer Cell Death.

Cancer Discov 2021 May 18;11(5):1268-1285. Epub 2020 Dec 18.

Division of Hematology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, CIBERONC, Pamplona, Spain.

For millions of years, endogenous retroelements have remained transcriptionally silent within mammalian genomes by epigenetic mechanisms. Modern anticancer therapies targeting the epigenetic machinery awaken retroelement expression, inducing antiviral responses that eliminate tumors through mechanisms not completely understood. Here, we find that massive binding of epigenetically activated retroelements by RIG-I and MDA5 viral sensors promotes ATP hydrolysis and depletes intracellular energy, driving tumor killing independently of immune signaling. Read More

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De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function.

Sci Adv 2020 Dec 16;6(51). Epub 2020 Dec 16.

Center for Childhood Cancer and Blood Diseases, Hematology/Oncology and BMT, Abigail Wexner Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, OH 43205, USA.

Robust and effective T cell-mediated immune responses require proper allocation of metabolic resources through metabolic pathways to sustain the energetically costly immune response. As an essential class of polycationic metabolites ubiquitously present in all living organisms, the polyamine pool is tightly regulated by biosynthesis and salvage pathway. We demonstrated that arginine is a major carbon donor and glutamine is a minor carbon donor for polyamine biosynthesis in T cells. Read More

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December 2020

Specifically Eliminating Tumor-Associated Macrophages with an Extra- and Intracellular Stepwise-Responsive Nanocarrier for Inhibiting Metastasis.

ACS Appl Mater Interfaces 2020 Dec 16;12(52):57798-57809. Epub 2020 Dec 16.

Institution of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Metastasis is the primary cause of death for most cancer patients, in which tumor-associated macrophages (TAMs) are involved through several mechanisms. While hitherto there is still a lack of study on exclusive elimination of TAMs to inhibit metastasis due to the difficulties in specific targeting of TAMs, we construct an extra- and intracellular stepwise-responsive delivery system -(aminomethyl)benzoic acid (PAMB)/doxorubicin (DOX) to achieve specific TAM depletion for the first time, thereby preventing tumor metastasis. Once accumulated into the tumor, PAMB/DOX would stepwise responsively (hypoxia and reactive oxygen species (ROS) responsively) disintegrate to expose the TAM-targeting ligand and release DOX sequentially, which depletes TAMs effectively . Read More

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December 2020

Roflumilast, a cAMP-Specific Phosphodiesterase-4 Inhibitor, Reduces Oxidative Stress and Improves Synapse Functions in Human Cortical Neurons Exposed to the Excitotoxin Quinolinic Acid.

ACS Chem Neurosci 2020 12 1;11(24):4405-4415. Epub 2020 Dec 1.

Neuroinflammation Group, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.

The overexpression of phosphodiesterase 4 (PDE4) enzymes is reported in several neurodegenerative diseases. PDE4 depletes cyclic 3'-5' adenosine monophosphate (cAMP) and, in turn, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), the key players in cognitive function. The present study was undertaken to investigate the mechanism behind the protective effects of roflumilast (ROF), a cAMP-specific PDE4 inhibitor, against quinolinic acid (QUIN)-induced neurotoxicity using human primary cortical neurons. Read More

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December 2020

NMDAR in cultured astrocytes: Flux-independent pH sensor and flux-dependent regulator of mitochondria and plasma membrane-mitochondria bridging.

FASEB J 2020 12 1;34(12):16622-16644. Epub 2020 Nov 1.

Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Department of Cognitive Neuroscience, Universidad Nacional Autónoma de México, México City, México.

Glutamate N-methyl-D-aspartate (NMDA) receptor (NMDAR) is critical for neurotransmission as a Ca channel. Nonetheless, flux-independent signaling has also been demonstrated. Astrocytes express NMDAR distinct from its neuronal counterpart, but cultured astrocytes have no electrophysiological response to NMDA. Read More

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December 2020

Triclosan depletes the membrane potential in Pseudomonas aeruginosa biofilms inhibiting aminoglycoside induced adaptive resistance.

PLoS Pathog 2020 10 30;16(10):e1008529. Epub 2020 Oct 30.

Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America.

Biofilm-based infections are difficult to treat due to their inherent resistance to antibiotic treatment. Discovering new approaches to enhance antibiotic efficacy in biofilms would be highly significant in treating many chronic infections. Exposure to aminoglycosides induces adaptive resistance in Pseudomonas aeruginosa biofilms. Read More

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October 2020

Two Encephalopathy Variants in the Calmodulin-Binding Helix A Exhibit Dominant-Negative Effects and Altered PIP Interaction.

Front Physiol 2020 11;11:1144. Epub 2020 Sep 11.

Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.

Heterozygous missense variants in , which encodes the potassium channel subunit Kv7.2, are among the most common genetic causes of severe neonatal-onset epileptic encephalopathy. Because about 20% of known severe Kv7. Read More

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September 2020

Mechanism of Zinc Excitotoxicity: A Focus on AMPK.

Front Neurosci 2020 15;14:577958. Epub 2020 Sep 15.

Neural Injury Research Laboratory, Department of Neurology, University of Ulsan College of Medicine, Seoul, South Korea.

Over the last 20 years, it has been shown that complex signaling cascades are involved in zinc excitotoxicity. Free zinc rapidly induces PKC activation, which causes reactive oxygen species (ROS) production at least in part through NADPH oxidase. It also promotes neuronal nitric oxide synthase, thereby increasing nitric oxide (NO) production. Read More

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September 2020

Piperine Regulates Nrf-2/Keap-1 Signalling and Exhibits Anticancer Effect in Experimental Colon Carcinogenesis in Wistar Rats.

Biology (Basel) 2020 Sep 21;9(9). Epub 2020 Sep 21.

Division of Veterinary Biochemistry, Faculty of Veterinary Science and Animal Husbandry, SKUAST-Kashmir, Alustang, Shuhama 190006, J&K, India.

Colon cancer is the most common cancer in men and women globally, killing millions of people annually. Though there widespread development has been made in the management of colorectal cancer, still there is an urgent need to find novel targets for its effective treatment. Piperine is an alkaloid found in black pepper having anticancer, anti-inflammatory activities, safe and nutritive for human consumption. Read More

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September 2020

Illuminating Platinum Transportation while Maximizing Therapeutic Efficacy by Gold Nanoclusters Simultaneous Near-Infrared-I/II Imaging and Glutathione Scavenging.

ACS Nano 2020 10 18;14(10):13536-13547. Epub 2020 Sep 18.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, No. 1023, South Shatai Road, Guangzhou 510515, China.

Killing tumor cells with a visualized system is a promising strategy in tumor therapy to achieve minimal side effects and high efficiency. Herein, a theranostic nanomedicine (AuNCs-Pt) is developed based on nanocarrier gold nanoclusters (AuNCs) with bifunctions of both NIR-I/NIR-II imaging and glutathione-scavenging abilities. AuNCs-Pt possesses NIR-II imaging capability on a fatal high-grade serous ovarian cancer (HGSOC) model in the deep abdomen, thus facilitating it to be a promising tool for monitoring platinum transportation. Read More

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October 2020

GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer.

Sci Adv 2020 Sep 2;6(36). Epub 2020 Sep 2.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China.

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. Read More

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September 2020

The tryptophan biosynthetic pathway is essential for Mycobacterium tuberculosis to cause disease.

J Shaun Lott

Biochem Soc Trans 2020 10;48(5):2029-2037

Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, The University of Auckland, Auckland, New Zealand.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is the most significant cause of death from a single infectious agent worldwide. Antibiotic-resistant strains of M. tuberculosis represent a threat to effective treatment, and the long duration, toxicity and complexity of current chemotherapy for antibiotic-resistant disease presents a need for new therapeutic approaches with novel modes of action. Read More

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October 2020

Tumor Microenvironment Stimuli-Responsive Fluorescence Imaging and Synergistic Cancer Therapy by Carbon-Dot-Cu Nanoassemblies.

Angew Chem Int Ed Engl 2020 11 11;59(47):21041-21048. Epub 2020 Sep 11.

Cixi Institute of Biomedical Engineering, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, 1219 ZhongGuan West Road, Ningbo, 315201, China.

A method is developed to fabricate tumor microenvironment (TME) stimuli-responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs-Ce6) and Cu . The as-obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs-Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Read More

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November 2020

Marathon running transiently depletes the myocardial lipid pool.

Physiol Rep 2020 09;8(17):e14543

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Lipids, stored as intracellular triacylglycerol droplets within the myocardium, serve as an important source of energy, particularly in times of prolonged increased energy expenditure. In only a few studies, the acute effects of exercise on such ectopic myocardial lipid storage were investigated. We studied the dynamic behavior of the myocardial lipid pool in response to completing the 2017 Amsterdam Marathon using proton magnetic resonance (MR) spectroscopy ( H-MRS). Read More

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September 2020

Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation.

Nat Microbiol 2020 11 17;5(11):1418-1427. Epub 2020 Aug 17.

Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

Sensing of microbes activates the innate immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondrial activity by delivering toxins via outer membrane vesicles (OMVs). How macrophages respond to pathogenic microbes that target mitochondria remains unclear. Read More

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November 2020

xCT inhibitor sulfasalazine depletes paclitaxel-resistant tumor cells through ferroptosis in uterine serous carcinoma.

Oncol Lett 2020 Sep 6;20(3):2689-2700. Epub 2020 Jul 6.

Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.

Glutathione (GSH) is a primary antioxidant that protects cells against reactive oxygen species (ROS), and high levels of GSH promote cancer cell survival and resistance to chemotherapy. The glutamine transporter xCT is essential for the intracellular synthesis of GSH, whereby xCT determines the intracellular redox balance. However, whether xCT inhibition can overcome GSH-mediated resistance to chemotherapeutic agents in uterine serous carcinoma (USC) remains unclear. Read More

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September 2020

Angiopoietin-like protein 3, an emerging cardiometabolic therapy target with systemic and cell-autonomous functions.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 12 8;1865(12):158791. Epub 2020 Aug 8.

Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Anatomy, Faculty of Medicine, University of Helsinki, Finland. Electronic address:

Angiopoietin like protein 3 (ANGPTL3) is best known for its function as an inhibitor of lipoprotein and endothelial lipases. Due to the capacity of genetic or pharmacologic ANGPTL3 suppression to markedly reduce circulating lipoproteins, and the documented cardioprotection upon such suppression, ANGPTL3 has become an emerging therapy target for which both antibody and antisense oligonucleotide (ASO) therapeutics are being clinically tested. While the antibody is relatively selective for circulating ANGPTL3, the ASO also depletes the intra-hepatocellular protein, and there is emerging evidence for cell-autonomous functions of ANGPTL3 in the liver. Read More

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December 2020