Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(7), P. 499 - 515

Published: Feb. 21, 2022

Language: Английский

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The glycosylation in SARS-CoV-2 and its receptor ACE2

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 15, 2021

Coronavirus disease 2019 (COVID-19), a highly infectious caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 235 million individuals and led to 4.8 deaths worldwide as of October 5 2021. Cryo-electron microscopy topology show that the SARS-CoV-2 genome encodes lots glycosylated proteins, such spike (S), envelope (E), membrane (M), ORF3a which are responsible for host recognition, penetration, binding, recycling pathogenesis. Here we reviewed detections, substrates, biological functions glycosylation in proteins well human receptor ACE2, also summarized approved undergoing therapeutics associated with glycosylation. This review may not only broad understanding viral glycobiology, but provide key clues development new preventive therapeutic methodologies against its variants.

Language: Английский

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Glycoproteomics

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: June 23, 2022

Language: Английский

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D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(8)

Published: Feb. 18, 2022

Significance PD-L1 is well known as an immune checkpoint molecule, which suppresses surveillance through binding to its receptor PD-1. Intracellular can also protect messenger RNAs of several DNA damage repair–related genes from degradation and enhance tumor resistance DNA-damaging therapy. Triple-negative breast cancer (TNBC) has the worst prognosis highest risk distant relapse in shows immunotherapy radiotherapy. In this study, we found that D-mannose promote significantly radiotherapy TNBC. Since TNBC treatment still a clinical challenge, our findings provide strategies therapeutic efficacy may have application.

Language: Английский

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Mucus sialylation determines intestinal host-commensal homeostasis

Cell, Journal Year: 2022, Volume and Issue: 185(7), P. 1172 - 1188.e28

Published: March 1, 2022

Language: Английский

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Carbohydrate-based drugs launched during 2000−2021

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(10), P. 3783 - 3821

Published: May 23, 2022

Carbohydrates are fundamental molecules involved in nearly all aspects of lives, such as being formating the genetic and energy materials, supporting structure organisms, constituting invasion host defense systems, forming antibiotics secondary metabolites. The naturally occurring carbohydrates their derivatives have been extensively studied therapeutic agents for treatment various diseases. During 2000 to 2021, totally 54 carbohydrate-based drugs which contain carbohydrate moities major structural units approved or diagnostic agents. Here we provide a comprehensive review on chemical structures, activities, clinical trial results these drugs, categorized by indications into antiviral antibacterial/antiparasitic anticancer antidiabetics cardiovascular nervous system other

Language: Английский

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The Multifaceted Biology of PCSK9

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(3), P. 558 - 582

Published: Oct. 9, 2021

This article reviews the discovery of PCSK9, its structure-function characteristics, and presently known proposed novel biological functions. The major critical function PCSK9 deduced from human mouse studies, as well cellular structural analyses, is role in increasing levels circulating LDL-cholesterol (LDLc), via ability to enhance sorting escort cell surface LDL receptor (LDLR) lysosomes. implicates binding catalytic domain EGF-A LDLR. also requires presence C-terminal Cys/His-rich (CHRD), secreted cytosolic cyclase associated protein 1 (CAP-1), possibly another membrane-bound "protein X". Curiously, PCSK9-deficient mice, an alternative downregulation LDLR by taking place liver female mice a 17β-estradiol-dependent manner still unknown mechanism. Recent studies have extended our understanding functions namely implication septic shock, vascular inflammation, viral infections (Dengue; SARS-CoV-2) or immune checkpoint modulation cancer regulation T-cell MHC-I, which govern anti-tumoral activity CD8 + T cells. Because inhibition may be advantageous these processes, availability injectable safe inhibitors (PCSK9i) that reduces 50-60% LDLc above effect statins highly valuable. Indeed, mAb siRNA could added current immunotherapies cancer/metastasis.

Language: Английский

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Precise, fast and comprehensive analysis of intact glycopeptides and modified glycans with pGlyco3

Nature Methods, Journal Year: 2021, Volume and Issue: 18(12), P. 1515 - 1523

Published: Nov. 25, 2021

Abstract Great advances have been made in mass spectrometric data interpretation for intact glycopeptide analysis. However, accurate identification of glycopeptides and modified saccharide units at the site-specific level with fast speed remains challenging. Here, we present a glycan-first search engine, pGlyco3, to comprehensively analyze N- O-glycopeptides, including units. A glycan ion-indexing algorithm developed makes pGlyco3 5–40 times faster than other glycoproteomic engines without decreasing accuracy or sensitivity. By combining electron-based dissociation spectra, integrates dynamic programming-based termed pGlycoSite localization. Our evaluation shows that localization probabilities estimated by are suitable localize glycans. With confidently identified N-glycopeptides O-mannose were extensively ammonia adducts yeast samples. The freely available is an flexible tool can be used identify

Language: Английский

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Probing the binding specificities of human Siglecs by cell-based glycan arrays

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(17)

Published: April 23, 2021

Significance Siglecs are immunomodulatory receptors that recognize sialic acid–carrying glycans with important functions in immunity. However, many of their natural ligands poorly defined. We generated a cell-based glycan array comprised library isogenic human cells displaying the greater complexity acids on diverse structures and glycoconjugates context cell surface. applied this to reveal fine binding specificities for sialoglycans, informed underlying required glycosyltransferase genes, provided evidence selective by presentation distinct protein sequences. Insight into will advance understanding biological benefit therapeutic targeting autoimmunity, inflammation, cancer, Alzheimer’s disease.

Language: Английский

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Analytical and Biochemical Perspectives of Protein O-GlcNAcylation

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(3), P. 1513 - 1581

Published: Jan. 8, 2021

Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a unique monosaccharide discovered in the early 1980s. With technological advances past several decades, great progress has been made to reveal biochemistry of O-GlcNAcylation, substrates and functional importance protein O-GlcNAcylation. As nutrient sensor, O-GlcNAcylation plays important roles almost all biochemical processes examined. Although proteins extensively reviewed previously, chemical aspects have not fully addressed. In this review, by critically evaluating key publications 35 years, we aim provide comprehensive understanding post-translational (PTM) from analytical perspectives. Specifically, will cover (1) multiple characterization O-GlcNAc cycling components (i.e., substrate donor UDP-GlcNAc, two enzymes transferase O-GlcNAcase, proteins), (2) with variety tools, (3) exploration its modulating chemicals as potential biomarkers therapeutic drugs for diseases. Last but least, discuss challenges possible solutions basic translational research future.

Language: Английский

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