Fucose-appended dendrimer/α-cyclodextrin conjugate as a novel NF-κB decoy carrier to Kupffer cells infulminant hepatitis mice induced by lipopolysaccharide

Fulminant hepatitis is a serious, life-threatening disorder and is associated with inflammatory cytokines produced by Kupffer cells. However, a number of clinical trials for the treatment of fulminant hepatitis did not show enough substantial benefits. Since NF-κB is a key mediator of inflammatory response in Kupffer cells, NF-κB decoy would be an attractive candi-datefor the treatment of fulminant hepatitis.

Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review

BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate(GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.AIM To survey the literature to capture the involvement of genes regulating core Nlinked fucosylation in hepatocellular carcinoma METHODS The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma(LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.RESULTS A total of 27 citations involving one or more of the core fucosylation-related genes(FPGT, FUK, FUT8, GMDS, SLC35 C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the371 patients with liver cancer in the LIHC dataset to identify the frequency of m RNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to moresamples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS(27 samples) and TSTA3(78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.CONCLUSION Amplification of genes involved in the de novo pathway for generation of GDPfucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.

Protective effect of Cardiospermum halicacabum leaf extract on glycoprotein components on STZ-induced hyperglycemic rats

Objective:To investigate the protective role of Cardiospermum halicacabum(C.halicacabum) leaf extract on glycoprotein metabolism in streptozotocin(STZ)-induced diabetic rats.Methods: Diabetes was induced in male albino Wistar rats by intraperitonial administration of STZ.The C.halicacabum leaf extract(CHE) was administered orally to normal and STZ-diabetic rats for 45 days.The effects of C.halicacabum leaf extract(CHE) on plasma and tissue glycoproteins (hexose,hexosamine,fucose and sialic acid) were determined.Results:The levels of plasma and tissues glycoproteins containing hexose,hexosamine and fucose were significantly increased in STZ-induced diabetic rats.In addition,the level of sialic acid significantly increased in plasma and liver while decreased in kidney of STZ-induced diabetic rats.After administration of CHE to diabetic rats,the metabolic alteration of glycoprotein reverted towards normal levels. Conclusions:The present study indicates that the CHE possesses a protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.

The re-emergence of the GP73 and fucosylated liver cancer biomarkers

The study shows that GP73 alone may not be sufficient to achieve the discrimination in every population. This is because many other clinical factors may influence the levels of the biomarker. This review attempts to identify some of these clinical variables,and helps provide a means of using these clinical values,in combination with GP73,to achieve the best use of the entire clinical biomarker family.

Glycosylation of recombinant human thyroid peroxidase ectodomain of insect cell origin has little effect on recognition by serum thyroid peroxidase antibody

Background Thyroid peroxidase （TPO） is an important autoantigen in Hashimoto＇s thyroiditis （HT）, and almost all epitopes are located in TPO ectodomain. The glycosylation of TPO might contribute to breaking self-tolerance, therefore, pudfied glycosylated recombinant TPO ectodomain is prerequisite of elucidating its role in the pathogenesis of HT. The aim of our study was to investigate whether the glycosylation has influence on the antigenic determinants of recombinant TPO. Methods Bac-to-Bac baculovirus expression system was used to generate recombinant human TPO ectodomain. The antigenicity was analyzed by antigen specific enzyme-linked immunosorbant assays （ELISAs）. The glycosylation of recombinant human TPO ectodomain of High Five insect cell origin was detected by lectin-ELISAs. Results TPO ectodomain was recovered from the culture media as a soluble protein, and it was fused with a hexahistidine tag which allowed purification by nickel-affinity chromatography. The recombinant TPO ectodomain could be recognized by all the 54 HT patients and three TPO monoclonal antibodies. Fucose, sialic acid and galactose were all detected on the recombinant TPO ectodomain. Sera TPOAb binding decreased slightly after non-specific deglycosylation of TPO by periodic acid. Conclusions High Five insect cells derived recombinant human TPO ectodomain had N-glycosylation sites, which might have little effect on recognition by serum TPOAb.

Glycosylation engineering of therapeutic IgG antibodies： challenges for the safety, functionality and efficacy

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex.type oligosaccharide attached to Asn297 of the Fc is essen- tial for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that gen- erate structural heterogeneity （glycoforms） exhibit unique biological activities. Hence, efficient and quan- titative glycan analysis techniques have been increas- ingly important for the development and quality control of therapeutic antibodies, and g｜ycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosy- lation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibili- ties for the design of novel antibody therapeutics. Fur- thermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosyn- thases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next- generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety,functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.

Glycoprotein fucosylation is increased in seminal plasma of subfertile men

Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitro by fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin （AAL）. Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, a1-acid glycoprotein, a1-antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade.