GPD1 Enhances the Anticancer Effects of Metformin by Synergistically Increasing Total Cellular Glycerol-3-Phosphate

Cancer Research, Год журнала: 2020, Номер 80(11), С. 2150 - 2162

Опубликована: Март 16, 2020

Abstract Metformin is an oral drug widely used for the treatment of type 2 diabetes mellitus. Numerous studies have demonstrated value metformin in cancer treatment. However, to elicit effects on often requires a high dosage, and any underlying mechanism how improve its inhibitory remains unknown. Here, we found that low mRNA expression glycerol-3-phosphate dehydrogenase 1 (GPD1) may predict poor response 15 cell lines. In vitro vivo, alone significantly suppressed proliferation, phenotype enhanced by GPD1 overexpression. Total cellular concentration was increased combination overexpression treatment, which growth via inhibition mitochondrial function. Eventually, reactive oxygen species structural damage observed GPD1-overexpressing lines treated with metformin, contribute death. summary, this study demonstrates enhances anticancer activity patients tumor cells respond better therapy. Significance: effect through synergistic function, thereby providing new insight into metformin-mediated

Язык: Английский

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Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication

Virologica Sinica, Год журнала: 2021, Номер 36(6), С. 1532 - 1542

Опубликована: Сен. 14, 2021

Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus (H1N1), a single-stranded, negative-sense RNA with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues human epithelial (A549) cells. detail, expression of hexokinase 2 (HK2), first enzyme glycolysis, was upregulated H1N1-infected A549 cells, pyruvate kinase M2 (PKM2) dehydrogenase 3 (PDK3) tissues. Pharmacologically inhibiting glycolytic pathway or targeting hypoxia-inducible factor 1 (HIF-1), central transcriptional critical significantly reduced H1N1 replication, revealing requirement during infection. addition, pharmacologically enhancing further promoted Furthermore, change replication upon inhibition enhancement independent interferon signaling. Taken together, these findings suggest induces thus facilitates efficient viral This study raises possibility metabolic inhibitors, such as those target could be used treat infection future.

Язык: Английский

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Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

Metabolites, Год журнала: 2020, Номер 10(12), С. 492 - 492

Опубликована: Ноя. 30, 2020

Approaches to the identification of metabolites have progressed from early biochemical pathway evaluation modern high-dimensional metabolomics, a powerful tool identify and characterize biomarkers health disease. In addition its relevance classic metabolic diseases, metabolomics has been key emergence immunometabolism, an important area study, as leukocytes generate are impacted by innate adaptive immunity. Herein, we discuss metabolomic signatures pathways perturbed activation human immune system during infection vaccination. For example, induces changes in lipid (e.g., free fatty acids, sphingolipids, lysophosphatidylcholines) amino acid tryptophan, serine, threonine), while vaccination can trigger carbohydrate bile pathways. Amino acid, carbohydrate, lipid, nucleotide metabolism is relevant immunity both infections vaccinations. Metabolomics holds substantial promise provide fresh insight into molecular mechanisms underlying host response. Its integration with other systems biology platforms will enhance studies

Язык: Английский

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Reprogramming of glucose metabolism in virus infected cells

Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 478(11), С. 2409 - 2418

Опубликована: Янв. 28, 2023

Язык: Английский

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Single Cell Metabolomics: A Future Tool to Unmask Cellular Heterogeneity and Virus-Host Interaction in Context of Emerging Viral Diseases

Frontiers in Microbiology, Год журнала: 2020, Номер 11

Опубликована: Июнь 3, 2020

Viral emergence is an unpredictable but obvious event, particularly in the era of climate change and globalization. Efficient management viral outbreaks depends on pre-existing knowledge alertness. The potential hotspots often remain neglected information related to them insufficient, for emerging viruses. replication transmission rely upon usurping host metabolic machineries. So altered pathways can be exploited containment these Metabolomics provides insight tracing out such checkpoints. Consequently introspection alteration at virus-host interface has evolved as prime area current virology research. Chromatographic separation followed by mass spectrometry been used predominant analytical platform bulk analyses nuclear magnetic resonance (NMR) fluorescence based techniques. Although valuable regarding modulation extracted ambiguity superseded real events due population effect over infected cells. Exploration cellular heterogeneity differentiation cells from nearby healthy ones become essential. Single cell metabolomics (SCM) emerges necessity explore minute details. Mass imaging (MSI) coupled with several soft ionization techniques electrospray (ESI), laser ablation (LAESI), matrix assisted desorption/ionization (MALDI), matrix-free desorption (LDI) have best suited platforms SCM analyses. already resolve biological conundrums. Thus knocking door interface.

Язык: Английский

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Antiviral effects of bovine lactoferrin on human norovirus

Biochemistry and Cell Biology, Год журнала: 2020, Номер 99(1), С. 166 - 172

Опубликована: Апрель 29, 2020

Human noroviruses cause significant morbidity and mortality worldwide, but lack approved antivirals or vaccines to treat prevent infections. The recent development of two cell culture systems in human transformed B cells (BJABs) non-transformed intestinal enteroid cultures overcomes a main limitation identifying molecules with anti-norovirus activities. Lactoferrin is an iron-binding glycoprotein found the milk most mammals, broad spectrum antimicrobial activities, including against related murine norovirus culture. In Japanese clinical trial, ingestion lactoferrin reduced incidence infectious gastroenteritis participants. Because were common Japan during trial period, we sought determine whether could inhibit infection norovirus. Our study, using model, demonstrates that reduces infection. mechanism antiviral action likely indirect may involve induction innate interferon responses. Therefore, future studies are warranted test efficacy patients.

Язык: Английский

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Alteration in Cellular Signaling and Metabolic Reprogramming during Viral Infection

mBio, Год журнала: 2021, Номер 12(5)

Опубликована: Сен. 14, 2021

Cellular activities are finely regulated by numerous signaling pathways to support specific functions of complex life processes. Viruses obligate intracellular parasites. Each step viral replication is ultimately governed the interaction a virus with its host cells. Because demands replication, nutritional needs virus-infected cells differ from those uninfected To improve their chances survival and viruses have evolved commandeer cellular processes, including cell metabolism, augmenting these processes needs. This article summarizes recent findings regarding virus-induced alterations major metabolic focusing on how modulate various cascades induce changes. We begin general introduction describing role played in metabolism. then discuss different target reprogram metabolism favor highlight gaps understanding metabolism-related virus-host interactions studying changes will enhance our fundamental involved regulation. Finally, we potential harness combat diseases, as well other disorders cancers.

Язык: Английский

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Human Norovirus Efficiently Replicates in Differentiated 3D-Human Intestinal Enteroids

Journal of Virology, Год журнала: 2022, Номер 96(22)

Опубликована: Ноя. 7, 2022

Human norovirus (HNoV) accounts for one-fifth of all acute viral gastroenteritis worldwide and an economic burden ~$60 billion globally. The lack treatment options against HNoV is in part due to the cultivation systems. Recently, a model infection biopsy-derived human intestinal enteroids (HIE) has been described: 3D-HIE are first dispersed 2D-monolayers differentiated prior infection, resulting labor-intensive, time-consuming procedure. Here, we present alternative protocol 3D-HIE. We found that as efficiently 2D-monolayers. In addition, immunofluorescence-based quantification UEA-1, lectin stains villus brush border, revealed ~80% spontaneously undergo polarity inversion, allowing without need microinjection. Infection with GII.4-positive stool samples attained fold-increase over inoculum ~2 Log10 at 2 days postinfection or up 3.5 when ruxolitinib, JAK1/2-inhibitor, was added. Treatment GII.4-infected polymerase inhibitor 2'-C-Methylcytidine (2CMC) other antivirals showed reduction suggesting excellent platform test anti-infectives. transcriptional host response then investigated by RNA sequencing infected versus uninfected presence ruxolitinib focus on virus-associated signatures while limiting interferon-stimulated gene signatures. analysis upregulated hormone neurotransmitter signal transduction pathways downregulated glycolysis hypoxia-response upon infection. Overall, have proven be highly robust study screen antivirals, investigate IMPORTANCE clinical socio-economic impact calls immediate action development Physiologically relevant vitro models hence needed biology, tropism, mechanisms viral-associated disease, also identify antiviral agents. Biopsy-derived biomimetic epithelium were recently described supports However, established labor-intensive. Therefore, sought develop simplified 3D undergoes differentiation spontaneous inversion. Advantages this shorter experimental time, better yield, spatial integrity epithelium. This potentially suitable pathogens infect cells from apical surface but unraveling interactions between indigenous bacteria microbiome.

Язык: Английский

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The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses

Molecules, Год журнала: 2022, Номер 27(18), С. 5928 - 5928

Опубликована: Сен. 12, 2022

Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to infection. Among changes, most prominent is upregulated glycolysis process as main pathway glucose utilization. Glycolysis activation a common mechanism adaptation viral infections, including noroviruses, rhinoviruses, influenza virus, Zika cytomegalovirus, coronaviruses others. Such provide potential targets for therapeutic approaches could reduce impact inhibitors, especially 2-deoxy-D-glucose (2-DG), have been intensively studied antiviral agents. However, 2-DG’s poor pharmacokinetic properties limit its wide clinical application. Herein, we discuss 2-DG novel analogs potent promising drugs with special emphasis on targeted intracellular processes.

Язык: Английский

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Redox Regulation and Metabolic Dependency of Zika Virus Replication: Inhibition by Nrf2-Antioxidant Response and NAD(H) Antimetabolites

Journal of Virology, Год журнала: 2023, Номер 97(2)

Опубликована: Янв. 23, 2023

Zika virus (ZIKV) is a major public health concern of international proportions. While the incidence ZIKV infections has declined substantially in recent years, potential for reemergence or reintroduction remains high.

Язык: Английский

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