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Food & Function Jun 2022Evodiamine (EVO) is an alkaloid extracted from and has various pharmacological activities, including hypolipidemic, anti-inflammatory, anti-infective, and antitumor...
Evodiamine (EVO) is an alkaloid extracted from and has various pharmacological activities, including hypolipidemic, anti-inflammatory, anti-infective, and antitumor effects. However, the therapeutic effects of EVO on type 2 diabetes mellitus (T2DM) and the possible mechanisms remain unknown. In this study, we used a T2DM rat model using a high-fat diet (HFD) combined with streptozotocin (STZ) injections followed by treatment with EVO. First, we evaluated the therapeutic effects of EVO on T2DM rats, following which we evaluated the anti-inflammatory and anti-oxidative effects of EVO on T2DM rats. Finally, we analyzed the metabolic regulatory mechanism of EVO in T2DM rats using an untargeted metabolomics approach. The results showed that EVO treatment alleviated the hyperglycemia, hyperlipidemia, insulin resistance (IR), and pathological changes of the liver, pancreas and kidneys in T2DM rats. Moreover, EVO treatment ameliorated the oxidative stress and decreased the serum levels of pro-inflammatory cytokines in T2DM model rats. Serum untargeted metabolomics analysis indicated that the EVO treatment affected the levels of 26 metabolites, such as methionine, citric acid, cholesterol, taurocholic acid, pilocarpine, adrenic acid, and other metabolites. These metabolites were mainly related to the amino sugar and nucleotide sugar metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, and tryptophan metabolism pathways. In conclusion, EVO can reduce blood glucose and improve oxidative stress and inflammatory response in T2DM rats. These functions are related to the regulation of amino sugar and nucleotide sugar metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, and tryptophan metabolism pathways.
Topics: Amino Sugars; Animals; Arginine; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glutathione; Metabolomics; Nucleotides; Proline; Quinazolines; Rats; Streptozocin; Tryptophan
PubMed: 35635367
DOI: 10.1039/d1fo04396j -
Food & Function Sep 2023Ulcerative colitis (UC) is a chronic gastrointestinal disease whose incidence is increasing rapidly worldwide. Anti-inflammatory medications, including 5-aminosalicylic...
Ulcerative colitis (UC) is a chronic gastrointestinal disease whose incidence is increasing rapidly worldwide. Anti-inflammatory medications, including 5-aminosalicylic acid (5-ASA), corticosteroids, and immunosuppressants, are used for its treatment; however, new alternatives would be required due to the serious side effects of some of these medications. -Acetylglucosamine (NAG) is an amino sugar composed of mucin that is secreted by intestinal epithelial cells. It is also used to promote the growth of intestinal bacteria. The current study aimed to determine the efficacy of NAG against dextran sulfate sodium (DSS)-induced chronic colitis and elucidate its mechanism of action. Mice were randomly divided into control, DSS, 0.1% sulfasalazine, 0.1% NAG, 0.3% NAG, and 0.3% NAG-dimer (NAG-D) groups, and results showed that colitis-induced body weight loss, disease activity, colonic tissue damage, colon length shortening, and the loss of mucin-secreting area were significantly improved in the NAG-D group. The intestinal permeability indicator, serum CD 14 level, and expression of the tight junction protein, occludin, were both improved in the 0.3% NAG group. Inflammatory biomarkers, including GATA3, IFN-γ, p-IκBα, COX2, TGF-β1, and Smad7, were significantly lower in the 0.3% NAG and NAG-D groups than in the DSS group. The intestinal microbial composition was most significantly altered in the 0.3% NAG group, showing decreased ratios of pathogenic bacteria, such as , especially . The results overall suggested that NAG or NAG-D supplementation can alleviate inflammation by strengthening the intestinal barrier function and maintaining gut microbiota homeostasis in a DSS-induced colitis mouse model.
Topics: Animals; Mice; Acetylglucosamine; Colitis; Inflammation; Colitis, Ulcerative
PubMed: 37655824
DOI: 10.1039/d3fo00282a -
Carbohydrate Research Nov 2021N-sugar substituted chiral aziridines were synthesized via Gabriel-Cromwell reaction. Novel pure diastereomers of aziridine derivatives (4 diastereomers) were readily...
N-sugar substituted chiral aziridines were synthesized via Gabriel-Cromwell reaction. Novel pure diastereomers of aziridine derivatives (4 diastereomers) were readily obtained in high yields and their structures were confirmed by means of H NMR, C NMR, FT-IR, Mass and optical rotations. This is, to the best of our knowledge, the unique example of N-sugar aziridine synthesis. Diastereomeric effects for prostate (PC3) and cervix (HeLa) cancers were screened and it has been observed that the epimers bearing the same sugars showed different results against PC3 and HeLa cancer cells. The novel sugar aziridines were investigated as promising prodrug candidates for prostate cancer (PC3) therapy. Moreover, the drug likeness calculations (Lipinski's rule, physicochemical properties, lipophilicity, solubility, pharmacokinetics and bioavailability radar) have indicated that the sugar aziridines can be good candidates as oral drugs.
Topics: Aziridines
PubMed: 34488002
DOI: 10.1016/j.carres.2021.108430 -
Cells Jan 2021Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various... (Review)
Review
Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function.
Topics: Humans; Killer Cells, Natural; Lymphocyte Activation; Receptors, Cell Surface; Sialic Acids; Viral Proteins
PubMed: 33572710
DOI: 10.3390/cells10020263 -
Journal of Virology Mar 2022Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of...
Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, -acetylneuraminic acid (NeuAc) and -glycolylneuraminic acid (NeuGc). NeuGc is produced in most mammals, including horses and pigs, but is absent in humans, ferrets, and birds. The only known naturally occurring IAV that exclusively bind NeuGc are extinct highly pathogenic equine H7N7 viruses. We determined the crystal structure of a representative equine H7 hemagglutinin (HA) in complex with NeuGc and observed high similarity in the receptor-binding domain with an avian H7 HA. To determine the molecular basis for NeuAc and NeuGc specificity, we performed systematic mutational analyses, based on the structural insights, on two distant avian H7 HAs and an H15 HA. We found that the A135E mutation is key for binding α2,3-linked NeuGc but does not abolish NeuAc binding. The additional mutations S128T, I130V, T189A, and K193R converted the specificity from NeuAc to NeuGc. We investigated the residues at positions 128, 130, 135, 189, and 193 in a phylogenetic analysis of avian and equine H7 HAs. This analysis revealed a clear distinction between equine and avian residues. The highest variability was observed at key position 135, of which only the equine glutamic acid led to NeuGc binding. These results demonstrate that genetically distinct H7 and H15 HAs can be switched from NeuAc to NeuGc binding and vice versa after the introduction of several mutations, providing insights into the adaptation of H7 viruses to NeuGc receptors. Influenza A viruses cause millions of cases of severe illness and deaths annually. To initiate infection and replicate, the virus first needs to bind to a structure on the cell surface, like a key fitting in a lock. For influenza A viruses, these "keys" (receptors) on the cell surface are chains of sugar molecules (glycans). The terminal sugar on these glycans is often either -acetylneuraminic acid (NeuAc) or -glycolylneuraminic acid (NeuGc). Most influenza A viruses bind NeuAc, but a small minority bind NeuGc. NeuGc is present in species like horses, pigs, and mice but not in humans, ferrets, and birds. Here, we investigated the molecular determinants of NeuGc specificity and the origin of viruses that bind NeuGc.
Topics: Animals; Hemagglutinin Glycoproteins, Influenza Virus; Horses; Humans; Influenza A Virus, H7N7 Subtype; N-Acetylneuraminic Acid; Neuraminic Acids; Phylogeny; Polysaccharides; Protein Binding
PubMed: 35044215
DOI: 10.1128/jvi.02120-21 -
Cancer Letters Nov 2022Immunoglobulin G (IgG) is the predominant component in humoral immunity and the major effector of neutralizing heterogeneous antigens. Glycosylation, as excessive... (Review)
Review
Immunoglobulin G (IgG) is the predominant component in humoral immunity and the major effector of neutralizing heterogeneous antigens. Glycosylation, as excessive posttranscriptional modification, can modulate IgG immune function. Glycosylated IgG has been reported to correlate with tumor progression, presenting several characteristic modifications, including the core fucose, galactose, sialic acid, and the bisect N-acetylglucosamine (GlcNAc). Meanwhile, IgG glycosylation regulates tumor immunity involved in tumor progression and is thus a potential target. Herein, we summarized the research progression to provide novel insight into the application of IgG glycosylation in tumor diagnosis and treatment.
Topics: Acetylglucosamine; Fucose; Galactose; Glycosylation; Humans; Immunoglobulin G; N-Acetylneuraminic Acid; Neoplasms
PubMed: 36096412
DOI: 10.1016/j.canlet.2022.215902 -
Chemico-biological Interactions Apr 2022O-linked N-acetylglucosamine transferase (OGT), a key protein in O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification, catalyzes O-GlcNAcylation by... (Review)
Review
O-linked N-acetylglucosamine transferase (OGT), a key protein in O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification, catalyzes O-GlcNAcylation by linking GlcNAc from glycosyl donors to protein Ser/Thr residues to regulate multiple biological processes. OGT has become a popular research topic in the field of glycobiology as a potential target. This report consists of three parts, namely: the basic information of OGT, the relationship between OGT and diseases, and the research progress of OGT inhibitors. This report aims to improve the understanding of OGT-related fields from the perspective of its structure. OGT inhibitors could aid the effective and efficient investigation of the O-GlcNAcylation mechanism, and provide new ideas and methods for the treatment of related diseases.
Topics: Acetylglucosamine; Protein Processing, Post-Translational
PubMed: 35288161
DOI: 10.1016/j.cbi.2022.109886 -
Yakugaku Zasshi : Journal of the... 2023Boronic acids are able to reversibly interact with the diol groups, a commonly found motif in biomolecules including sugars, ribose and catechols. For their...
Boronic acids are able to reversibly interact with the diol groups, a commonly found motif in biomolecules including sugars, ribose and catechols. For their carbohydrate-binding properties, they can be regarded as a synthetic mimic of lectins and often termed as "borono-lectins." Importantly, the borono-lectins platform can be chemically tailored to manifest a broad profile of binding strength and specificity. Besides the structural versatility, some derivatives can undergo a sharp inversion in the state of hydration in synchronization with the molecular recognitions. This feature, when combined with amphiphilic polymeric backbones, translates into many creative principles for fine-tuning or switching the hydration and more complex molecular assemblies in a way interactive with biology. Here we provide a brief overview of our recent efforts on the related applications with special focuses on smart insulin delivery systems and sialic acid detections relevant to cancer diagnosis and treatment among others.
Topics: Lectins; N-Acetylneuraminic Acid; Bioengineering
PubMed: 37121759
DOI: 10.1248/yakushi.22-00205-3 -
Chemical Record (New York, N.Y.) Oct 2021Carbohydrate-protein interactions are involved in a myriad of biological processes. Thus, glycomimetics have arisen as one of the most promising synthetic targets to... (Review)
Review
Carbohydrate-protein interactions are involved in a myriad of biological processes. Thus, glycomimetics have arisen as one of the most promising synthetic targets to that end. Within the broad variety of glycomimetics, thiodisaccharides have proven to be excellent tools to study these processes, and even more, some of them unveiled interesting biological activities. This review brings together research made on the introduction of N-acetylhexosamine residues into thiodisaccharides to date, passing through classic substitution (as S 2, thioglycosylation and ring-opening reactions) and addition (as thiol-ene coupling and Michael-type additions) reactions. Recent and interesting developments regarding addition reactions to vinyl azides, cross-coupling reactions and novel chemoenzymatic methods are also discussed.
Topics: Hexosamines
PubMed: 34170606
DOI: 10.1002/tcr.202100146 -
Journal of Immunology (Baltimore, Md. :... Nov 2023Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus...
Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic β cell-derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell-derived GlcNAc-specific IgM engages apoptosis-associated β cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.
Topics: Mice; Animals; Diabetes Mellitus, Type 1; Mice, Inbred NOD; Glucosamine; Acetylglucosamine; Pancreas
PubMed: 37747293
DOI: 10.4049/jimmunol.2300264