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Core fucosylation is catalyzed by α‐1,6‐fucosyltransferase (FUT8), which fucosylates the innermost GlcNAc of N‐glycans. Given the association of FUT8 with various diseases, including cancer, selective FUT8 inhibitors applicable to in vivo or cell‐based systems are highly sought‐after. Herein, we report the discovery of a compound that selectively inhibits FUT8 in cell‐based assays. High‐throughput screening revealed a FUT8‐inhibiting pharmacophore, and further structural optimization yielded an inhibitor with a KD value of 49 nM. Notably, this binding occurs only in the presence of GDP (a product of the enzymatic reaction catalyzed by FUT8). Mechanistic studies suggested that this inhibitor generates a highly reactive naphthoquinone methide derivative at the binding site in FUT8, which subsequently reacts with FUT8. Furthermore, prodrug derivatization of this inhibitor improved its stability, enabling suppression of core fucose expression and subsequent EGFR and T‐cell signaling in cell‐based assays, paving the way for the development of drugs targeting core fucosylation. [ABSTRACT FROM AUTHOR]

This article describes the carbohydrate composition of early and mature placentas from bitches, detected by lectin histochemistry. Formalin‐fixed placental samples from 11 mixed‐breed bitches have been assigned to the 'early' or the 'mature' placenta group, processed by the routine histological technique and labelled with a panel of 14 biotinylated lectins. The glycan distribution was almost completely preserved over pregnancy. Cytotrophoblast cells expressed high‐mannose N‐linked residues and N‐acetyl‐D‐glucosamine, whereas mannose N‐linked residues, N‐acetyl‐D‐glucosamine and β‐ and α‐D‐galactose/N‐acetyl‐D‐galactosamine have been found in the syncytiotrophoblast. The maternal and foetal endothelial binding pattern was enriched in β‐D‐galactose, α‐D‐mannose in non‐bisected bi/tri‐antennary N‐linked complex and Galα1,3Gal‐Galα1,4Gal. Both deep and superficial glands showed a great variety of glycoconjugates, such as D‐mannose, D‐glucose, N‐acetyl‐D‐glucosamine, N‐acetyl‐D‐galactosamine, galactose, N‐acetylneuraminic acid and fucose. Most results in this study were consistent with those previously reported in canine and feline mature placentas; here, early placentas have been analysed and the lectin binding pattern of mature placentas has been further described. These studies on canine placentas contribute to detecting and understanding glycome changes in pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Fucose, fucose-containing oligosaccharides, and fucose-containing polysaccharides have been widely applied in the fields of food and medicine, including applications in Helicobacter pylori eradication and renal function protection. Fucose-containing carbohydrates (FCCs) derived from marine organisms such as seaweed, invertebrates, microalgae, fungi, and bacteria have garnered growing attention due to their diverse bioactivities and potential therapeutic applications. Marine-derived FCCs characterized by high fucose residue content and extensive sulfate substitution, including fucoidan, fucosylated chondroitin sulfate, and fucose-rich microbial exopolysaccharides, have demonstrated significant potential in promoting gastrointestinal health. This review describes the unique structural features of FCCs and summarizes their health benefits, including regulation of gut microbiota, modulation of microbial metabolism, anti-adhesion activities against H. pylori and gut pathogens, protection against inflammatory injuries, and anti-tumor activities. Additionally, this review discusses the structural characteristics that influence the functional properties and the limitations related to the activity research and preparation processes of FCCs, providing a balanced perspective on the application potential and challenges of FCCs with specific structures for the regulation of gastrointestinal health and diseases. [ABSTRACT FROM AUTHOR]

Control over glycosylation is an important quality parameter in recombinant protein production. Here, we demonstrate the generation of a marker-free genome edited Nicotiana benthamiana N-glycosylation mutant (NbXF-KO) carrying inactivated β1,2-xylosyltransferase and α1,3-fucosyltransferase genes. The knockout of seven genes and their stable inheritance was confirmed by DNA sequencing. Mass spectrometric analyses showed the synthesis of N-glycans devoid of plant-specific β1,2-xylose and core α 1,3-fucose on endogenous proteins and a series of recombinantly expressed glycoproteins with different complexities. Further transient glycan engineering towards more diverse human-type N-glycans resulted in the production of recombinant proteins decorated with β1,4-galactosylated and α2,6-sialylated structures, respectively. Notably, a monoclonal antibody expressed in the NbXF-KO displayed glycosylation-dependent activities. Collectively, the engineered plants grow normally and are well suited for upscaling, thereby meeting industrial and regulatory requirements for the production of high-quality therapeutic proteins.

Wildtype Escherichia coli cells cannot grow on L-1,2-propanediol, as the fucAO operon within the fucose (fuc) regulon is thought to be silent in the absence of L-fucose. Little information is available concerning the transcriptional regulation of this operon. Here, we first confirm that fucAO operon expression is highly inducible by fucose and is primarily attributable to the upstream operon promoter, while the fucO promoter within the 3'-end of fucA is weak and uninducible. Using 5'RACE, we identify the actual transcriptional start site (TSS) of the main fucAO operon promoter, refuting the originally proposed TSS. Several lines of evidence are provided showing that the fucAO locus is within a transcriptionally repressed region on the chromosome. Operon activation is dependent on FucR and Crp but not SrsR. Two Crp-cAMP binding sites previously found in the regulatory region are validated, where the upstream site plays a more critical role than the downstream site in operon activation. Furthermore, two FucR binding sites are identified, where the downstream site near the first Crp site is more important than the upstream site. Operon transcription relies on Crp-cAMP to a greater degree than on FucR. Our data strongly suggest that FucR mainly functions to facilitate the binding of Crp to its upstream site, which in turn activates the fucAO promoter by efficiently recruiting RNA polymerase.

GDP-fucose is synthesised via two pathways: de novo and salvage. The first uses GDP-mannose as a substrate, and the second uses free fucose. To date, these pathways have been considered to work separately and not to have an influence on each other. We report the mutual response of the de novo and salvage pathways to the lack of enzymes from a particular route of GDP-fucose synthesis. We detected different efficiencies of GDP-fucose and fucosylated structure synthesis after a single inactivation of enzymes of the de novo pathway. Our study demonstrated the unequal influence of the salvage enzymes on the production of GDP-fucose by enzymes of the de novo biosynthesis pathway. Simultaneously, we detected an elevated level of one of the enzymes of the de novo pathway in the cell line lacking the enzyme of the salvage biosynthesis pathway. Additionally, we identified dissimilarities in fucose uptake between cells lacking TSTA3 and GMDS proteins. [ABSTRACT FROM AUTHOR]

In LPS‐stimulated mouse inflammation model, Laoshan black tea polysaccharides (BTPSs) showed significant anti‐inflammatory activity. Three water‐soluble acidic polysaccharides (BTPS 3‐1, BTPS 3‐2, and BTPS 3‐3) were purified. They contained glucose (Glc), galactose (Gal), fucose (Fuc), rhamnose (Rha), glucuronic acid (GlcA), and mannose (Man) at molar ratios of 9.0 : 4.9 : 4.9 : 1.7 : 1.5 : 1.0, 9.5 : 5.3 : 4.9 : 1.7 : 1.6 : 1.0, and 5.3 : 3.5 : 2.0 : 2.1 : 0.9 : 1.0 with average molecular weights of 28.38, 14.39, and 11.00 kDa, respectively. Three polysaccharides reduced the levels of NO, TNF‐α, and IL‐6 in LPS‐induced RAW 264.7 cells, and BTPS 3‐2 had the strongest anti‐inflammatory effects. Based on analyses of the monosaccharide composition, methylation, and NMR, the main chain of BTPS 3‐2 was composed of ⟶4) ‐β‐D‐Glcp‐ (1⟶, ⟶2) ‐α‐L‐Fucp‐ (1⟶, and ⟶6) ‐β‐D‐Galp‐ (1⟶, and Rhap, GlcpA, and Manp units were attached as side chains to the backbone. BTPS 3‐2 also downregulated the expression levels of p‐NF‐κB p65, p‐IκBα, TLR4, MyD88, COX‐2, TNF‐α, and IL‐6. BTPS 3‐2 ameliorated LPS‐induced inflammation by regulating the TLR4/MyD88/NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dictyophora rubrovalvata is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from D. rubrovalvata. Their structures were characterized by chemical composition, monosaccharide composition analysis, methylation analysis and nuclear magnetic resonance spectroscopy. The results showed that DRP-I and DRP-II were neutral heteropolysaccharides with molecular weights of 5.79 × 103 and 1.25 × 104 Da, respectively, which were composed of mannose, galactose, glucose, xylose and fucose. The main chains were → 6)-α-D-Galp-(1 → 6)-α-D-Galp-(2,1 → 6)-α-D-Manp-(2,1 → 6)-α-D-Galp-(1, and branch chains were β-D-Xylp-(1 → 3)-α-L-Fucp-(1 → 4)-α-D-Manp-(1 → and α-D-Galp-(1 → 3)-α-D-Galp-(1 →. The in vitro immunoactivity assays on dendritic cells showed that DRP-I and DRP-II could up-regulate the expression of IL-10 and IL-6 and inhibit the expression of TNF-α in a concentration-dependent manner. This research indicated that DRP-I and DRP-II possessed immunoactivity by balancing the excessive inflammation, and molecular weight is an important factor affecting immunoactivity. [ABSTRACT FROM AUTHOR]

Copyright of Acta Edulis Fungi is the property of Acta Edulis Fungi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Precancerous and cancerous lesions and conditions with high incidence rates is occurring in many countries including in India, Pakistan, Bangladesh, Sri Lanka and Taiwan. So many causative factors like Smoking, alcoholism, and betel nut chewing are considered to be the main risk factors for oral precancerous and cancerous lesions. Further, deaths from oral cancer have increased year by year. Although several oral cancer-associated biomarkers have been reported, very few useful biomarkers have been applied for early diagnosis. Therefore, the investigation of oral cancer-specific biomarkers is urgently needed. In this, to determine the role of serum fucose, HsCRP and lipid profile as a reliable biomarker for early detection of malignant transformation of potentially malignant lesions, conditions and prediction of biologic behavior of the malignant lesions. 200 samples collected and divided into four groups, OSMF, Oral Leukolplakia, Oral Cancer and healthy controls, each group has 50 samples for the analysis of reliable tests for biomarkers (Serum Fucose, Hs CRP and Lipid Profile). After completion of study we were found, these biomarkers reliable for early detection for precancerous and cancerous lesions and conditions. [ABSTRACT FROM AUTHOR]

Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria. Authors profile the antimicrobial activity of an Escherichia coli bacteriophage (in vivo and in vitro), isolated from chicken faeces. [ABSTRACT FROM AUTHOR]

Mucins are a family of high-molecular-weight O-linked glycoproteins which are the primary structural components of mucus and maintain homeostasis in the oral cavity. The present study was conducted as the first step towards establishing a correlation of aberrant mucin glycosylation with tobacco-associated clinical conditions. Tobacco habituates for the study were identified on the basis of type, duration, amount, and frequency of using tobacco products. The secretory mucin and its saccharides were determined from the saliva collected from smokers, smokeless tobacco habituates, and healthy, nonsmoking individuals. On the one hand, the salivary mucin content was markedly reduced in smokeless tobacco habituates with respect to smokers. On the other hand, the amount of sialic acid and fucose moieties of salivary mucin was increased in both smokers and smokeless tobacco habituates compared to the healthy cohort. Furthermore, the duration of tobacco exposure have been identified as the main factor influencing the extent of damage to the oral mucosa in terms of mucin secretion. The reduced secretory mucin content with aberrant glycosylation in the oral cavity may have a significant role in the further development or progression of oral diseases. [ABSTRACT FROM AUTHOR]

Biosynthesis of macromolecules requires precursors such as sugars or amino acids, originating from exogenous/dietary sources, reutilization/salvage of degraded molecules, or de novo synthesis. Since these sources are assumed to contribute to one homogenous pool, their individual contributions are often overlooked. Protein glycosylation uses monosaccharides from all the above sources to produce nucleotide sugars required to assemble hundreds of distinct glycans. Here, we demonstrate that cells identify the origin/heritage of the monosaccharide, fucose, for glycosylation. We measured the contribution of GDP-fucose from each of these sources for glycan synthesis and found that different fucosyltransferases, individual glycoproteins, and linkage-specific fucose residues identify and select different GDP-fucose pools dependent on their heritage. This supports the hypothesis that GDP-fucose exists in multiple, distinct pools, not as a single homogenous pool. The selection is tightly regulated since the overall pool size remains constant. We present novel perspectives on monosaccharide metabolism, which may have a general applicability.

Objective: As the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates. Materials and methods: The study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC). Results: Among the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96. Conclusion: A predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes. [ABSTRACT FROM AUTHOR]

Biopreservation refers to the use of natural or controlled microbial single strains or consortia, and/or their metabolites such as short‐chain carboxylic acids (SCCA), to improve the shelf‐life of foods. This study aimed at establishing a novel Lactobacillaceae‐driven bioprocess that led to the production of the SCCA propionate through the cross‐feeding on 1,2‐propanediol (1,2‐PD) derived from the deoxyhexoses rhamnose or fucose. When grown as single cultures in Hungate tubes, strains of Lacticaseibacillus rhamnosus preferred fucose over rhamnose and produced 1,2‐PD in addition to lactate, acetate, and formate, while Limosilactobacillus reuteri metabolized 1,2‐PD into propionate, propanol and propanal. Loigolactobacillus coryniformis used fucose to produce 1,2‐PD and only formed propionate when supplied with 1,2‐PD. Fermentates collected from batch fermentations in bioreactor using two‐strain consortia (L. rhamnosus and L. reuteri) or fed‐batch fermentations of single strain cultures of L. coryniformis with rhamnose contained mixtures of SCCA consisting of mainly lactate and acetate and also propionate. Synthetic mixtures that contained SCCA at concentrations present in the fermentates were more antimicrobial against Salmonella enterica if propionate was present. Together, this study (i) demonstrates the potential of single strains and two‐strain consortia to produce propionate in the presence of deoxyhexoses extending the fermentation metabolite profile of Lactobacillaceae, and (ii) emphasizes the potential of applying propionate‐containing fermentates as biopreservatives. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC) subsets play a crucial role in shaping anti‐tumour immunity. Cancer escapes from the control immune system by hijacking DC functions. Yet, bases for such subversion are only partially understood. Tumour cells display aberrant glycan motifs on surface glycoproteins and glycolipids. Such carbohydrate patterns can be sensed by DCs through C‐type lectin receptors (CLRs) that are critical to shape and orientate immune responses. We recently demonstrated that melanoma tumour cells harboured an aberrant 'glyco‐code,' and that circulating and tumour‐infiltrating DCs from melanoma patients displayed major perturbations in their CLR profiles. To decipher whether melanoma, through aberrant glycan patterns, may exploit CLR pathways to mislead DCs and evade immune control, we explored the impact of glycan motifs aberrantly found in melanoma (neoglycoproteins [NeoGP] functionalised with Gal, Man, GalNAc, s‐Tn, fucose [Fuc] and GlcNAc residues) on features of human DC subsets (cDC2s, cDC1s and pDCs). We examined the ability of glycans to bind to purified DCs, and assessed their impact on DC basal properties and functional features using flow cytometry, confocal microscopy and multiplex secreted protein analysis. DC subsets differentially bound and internalised NeoGP depending on the nature of the glycan. Strikingly, Fuc directly remodelled the expression of activation markers and immune checkpoints, as well as the cytokine/chemokine secretion profile of DC subsets. NeoGP interfered with Toll like receptor (TLR)‐signalling and pre‐conditioned DCs to exhibit an altered response to subsequent TLR stimulation, dampening antitumor mediators while triggering pro‐tumoral factors. We further demonstrated that DC subsets can bind NeoGP through CLRs, and identified GalNAc/MGL and s‐Tn/ C‐type lectin‐like receptor 2 (CLEC2) as potential candidates. Moreover, DC dysfunction induced by tumour‐associated carbohydrate molecules may be reversed by interfering with the glycan/CLR axis. These findings revealed the glycan/CLR axis as a promising checkpoint to exploit in order to reshape potent antitumor immunity while impeding immunosuppressive pathways triggered by aberrant tumour glycosylation patterns. This may rescue DCs from tumour hijacking and improve clinical success in cancer patients. [ABSTRACT FROM AUTHOR]

Long since, carbohydrates were thought to be used just as an energy source and structural material. However, in recent years, with the emergence of the field of glycobiology and advances in glycomics, much has been learned about the biological role of oligosaccharides, a carbohydrate polymer containing a small number of monosaccharides, in cell–cell interaction, signal transduction, immune response, pathogen adhesion processes, early embryogenesis, and apoptosis. The function of oligosaccharides in these processes is diversified by fucosylation, also known as modification of oligosaccharides. Fucosylation has allowed the identification of more than 100 different oligosaccharide structures that provide functional diversity. ABO blood group and Lewis antigens are among the best known fucosyl-linked oligosaccharides. In addition, the antigens in the ABO system are composed of various sugar molecules, including fucosylated oligosaccharides, and Lewis antigens are structurally similar to ABO antigens but differ in the linkage of sugars. Variation in blood group antigen expression affects the host’s susceptibility to many infections. However, altered expression of ABO and Lewis antigens is related with prognosis in carcinoma types. In addition, many pathogens recognize and bind to human tissues using a protein receptor with high affinity for the fucose molecule in glycoconjugates, such as lectin. Fucosylated oligosaccharides also play vital roles during fertilization and early embryogenesis. Learning and memory-related processes such as neurite growth, neurite migration, and synapse formation seen during the development of the brain, which is among the first organs to develop in embryogenesis, are regulated by fucosylated oligosaccharides. In conclusion, this review mentions the vital roles of fucosylated oligosaccharides in biology, drawing attention to their importance in the development of chemical tools to be used in function analysis and the investigation of various therapeutic targets.

Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important human fungal pathogen. However, the molecular motifs in mucins that inhibit filamentation remain unclear despite their potential for therapeutic interventions. Here, we determined that mucins display an abundance of virulence-attenuating molecules in the form of mucin O-glycans. We isolated and cataloged >100 mucin O-glycans from three major mucosal surfaces and established that they suppress filamentation and related phenotypes relevant to infection, including surface adhesion, biofilm formation and cross-kingdom competition between C. albicans and the bacterium Pseudomonas aeruginosa. Using synthetic O-glycans, we identified three structures (core 1, core 1 + fucose and core 2 + galactose) that are sufficient to inhibit filamentation with potency comparable to the complex O-glycan pool. Overall, this work identifies mucin O-glycans as host molecules with untapped therapeutic potential to manage fungal pathogens.

Summary: Land plants evolved multiple adaptations to restrict transpiration. However, the underlying molecular mechanisms are not sufficiently understood.We used an ozone‐sensitivity forward genetics approach to identify Arabidopsis thaliana mutants impaired in gas exchange regulation.High water loss from detached leaves and impaired decrease of leaf conductance in response to multiple stomata‐closing stimuli were identified in a mutant of MURUS1 (MUR1), an enzyme required for GDP‐l‐fucose biosynthesis. High water loss observed in mur1 was independent from stomatal movements and instead could be linked to metabolic defects. Plants defective in import of GDP‐l‐Fuc into the Golgi apparatus phenocopied the high water loss of mur1 mutants, linking this phenotype to Golgi‐localized fucosylation events. However, impaired fucosylation of xyloglucan, N‐linked glycans, and arabinogalactan proteins did not explain the aberrant water loss of mur1 mutants.Partial reversion of mur1 water loss phenotype by borate supplementation and high water loss observed in boron uptake mutants link mur1 gas exchange phenotypes to pleiotropic consequences of l‐fucose and boron deficiency, which in turn affect mechanical and morphological properties of stomatal complexes and whole‐plant physiology. Our work emphasizes the impact of fucose metabolism and boron uptake on plant–water relations. [ABSTRACT FROM AUTHOR]

A possible mechanism of the antitumor activity of gold nanoparticles (GNPs) with a surface modified by carbohydrate residues tropic for tumor cell membrane lectins was studied using human colon adenocarcinoma (Caco-2) cells. Caco-2 cells were incubated for 2 and 8 h with GNP solutions. GNPs reduced the level of SH groups during a 2-hour incubation with the cells by an average of 20 times (p < 0.05); during an 8-hour incubation, by an average of 10 times (p < 0.05). The transmembrane potential of mitochondria was observed to decrease on average up to 58% (p < 0.05) after incubation for 8 h with GNP with a surface modified by fucose and lactose. GNPs modified with fucose residues increased the malondialdehyde (MDA) level by 1.5 times (p < 0.05) and the amount of proapoptotic transcription factor p53, by >2.5 times (p < 0.05) after incubation for 8 h. Thus, GNPs with surfaces modified by fucose, lactose, and galactose residues had a cytotoxic effect on Caco-2 cells, activating lipid peroxidation (Au-Fuc) and possibly initiating one of the apoptosis pathways through stimulation of the transcription factor p53 and decreasing the transmembrane potential of mitochondria. [ABSTRACT FROM AUTHOR]

Slc35c1 encodes an antiporter that transports GDP-fucose into the Golgi and returns GMP to the cytoplasm. The closely related gene Slc35c2 encodes a putative GDP-fucose transporter and promotes Notch fucosylation and Notch signaling in cultured cells. Here, we show that HEK293T cells lacking SLC35C1 transferred reduced amounts of O-fucose to secreted epidermal growth factor-like repeats from NOTCH1 or secreted thrombospondin type I repeats from thrombospondin 1. However, cells lacking SLC35C2 did not exhibit reduced fucosylation of these epidermal growth factor-like repeats or thrombospondin type I repeats. To investigate SLC35C2 functions in vivo, WW6 embryonic stem cells were targeted for Slc35c2. Slc35c2[-/-] mice were viable and fertile and exhibited no evidence of defective Notch signaling during skeletal or T cell development. By contrast, mice with inactivated Slc35c1 exhibited perinatal lethality and marked skeletal defects in late embryogenesis, typical of defective Notch signaling. Compound Slc35c1[-/-]Slc35c2[-/-] mutants were indistinguishable in skeletal phenotype from Slc35c1[-/-] embryos and neonates. Double mutants did not exhibit the exacerbated skeletal defects predicted if SLC35C2 was functionally important for Notch signaling in vivo. In addition, NOTCH1 immunoprecipitated from Slc35c1[-/-]Slc35c2[-/-] neonatal lung carried fucose detected by binding of Aleuria aurantia lectin. Given that the absence of both SLC35C1, a known GDP-fucose transporter, and SLC35C2, a putative GDPfucose transporter, did not lead to afucosylated NOTCH1 nor to the severe Notch signaling defects and embryonic lethality expected if all GDP-fucose transport were abrogated, at least one more mechanism of GDP-fucose transport into the secretory pathway must exist in mammals. [ABSTRACT FROM AUTHOR]

Glycan structure is often modulated in disease or predisease states, suggesting that such changes might serve as biomarkers. Here, we generated a monoclonal antibody (mAb) against the core fucose of the N-glycan in human IgG. Notably, this mAb can be used in Western blotting and ELISA. ELISA using this mAb revealed a low level of the core fucose of the N-glycan in IgG, suggesting that the level of acore fucosylated (noncore fucosylated) IgG was increased in the sera of the patients with lung cancer, chronic obstructive pulmonary disease, and interstitial pneumonia compared to healthy subjects. In a coculture analysis using human lung adenocarcinoma A549 cells and antibody-secreting B cells, the downregulation of the FUT8 (α1,6 fucosyltransferase) gene and a low level of core fucose of the N-glycan in IgG in antibody-secreting B cells were observed after coculture. A dramatic alteration in gene expression profiles for cytokines, chemokines, and their receptors were also observed after coculturing, and we found that the identified C-C motif chemokine 2 was partially involved in the downregulation of the FUT8 gene and the low level of core fucose of the N-glycan in IgG in antibody-secreting B cells. We also developed a latex turbidimetric immunoassay using this mAb. These results suggest that communication with C-C motif chemokine 2 between lung cells and antibody-secreting B cells downregulate the level of core fucose of the N-glycan in IgG, i.e., the increased level of acore fucosylated (noncore fucosylated) IgG, which would be a novel biomarker for the diagnosis of patients with pulmonary diseases. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the structure and functions of capsular exopolysaccharide (CPS) from Bifidobacterium breve NCIM 5671. Methods and results: A CPS produced by the probiotic bacteria B. breve NCIM 5671 was isolated and subjected to characterization through GC analysis, which indicated the presence of rhamnose, fucose, galactose, and glucose in a molar ratio of 3:1:5:3. The average molecular weight of the CPS was determined to be ∼8.5 × 105 Da. Further, NMR analysis revealed the probable CPS structure to be composed of major branched tetra- and penta-saccharide units alternately repeating and having both α- and β-configuration sugar residues. CPS displayed an encouraging prebiotic score for some of the studied probiotic bacteria. Compared to standard inulin, CPS showed better resistance to digestibility against human GI tract in vitro. DPPH, total antioxidant, and ferric reducing assays carried out for CPS displayed decent antioxidant activity too. Conclusion: This study indicates that the CPS from B. breve NCIM 5671 has the potential to be utilized as a prebiotic food supplement. It is a high-molecular-weight (∼8.5 × 105 Da) capsular heteropolysaccharide containing rhamnose, fucose, galactose, and glucose. [ABSTRACT FROM AUTHOR]

The development and function of the brain requires N-linked glycosylation of proteins, which is a ubiquitous modification in the secretory pathway. N-glycans have a distinct composition and undergo tight regulation in the brain, but the spatial distribution of these structures remains relatively unexplored. Here, we systematically employed carbohydrate binding lectins with differing specificities to various classes of N-glycans and appropriate controls to identify glycan expression in multiple regions of the mouse brain. Lectins binding high-mannose-type N-glycans, the most abundant class of brain N-glycans, showed diffuse staining with some punctate structures observed on high magnification. Lectins binding specific motifs of complex N-glycans, including fucose and bisecting GlcNAc, showed more partitioned labeling, including to the synapse-rich molecular layer of the cerebellum. Understanding the spatial distribution of N-glycans across the brain will aid future studies of these critical protein modifications in development and disease of the brain. [ABSTRACT FROM AUTHOR]

Objective:Sialic acid, hexoses, hexosamines and fucose are components of glycoprotein, glycolipid and/or ganglioside. These glycoconjugates are essential components of cellular membrane and receptors, which are required for normal cellular activities. The levels of these aforementioned glycans are likely to be obstructed under biological conditions (such as oxidative stress) that leads to cellular and tissue damage. Despite the efficacy of valproate as a broad-spectrum antiepileptic drug, it administration is linked to oxidative stress and multiple organ damage. Moringa oleifera leaves have been proven to be bioactive food with diverse biochemical benefits, that include antioxidant, wound healing and tissue protective effects.Methods:In this study, female Sprague-Dawley rats were grouped into four. Group 1: control group given physiological saline; Group 2: animals given only 70% ethanol Moringa leaves extract (0.3 g/kg b.w./day); Group 3: animals that received only sodium valproate (0.5 g/kg b.w./day); Group 4: animals given similar dose of sodium valproate + Moringa extract. The treatments were administered orally for 15 days, and the animals were then fasted overnight and sacrificed. Stomach tissues collected were homogenized in ice-cold normal saline, using a glass homogenizer to make up 10% w/v tissue homogenate.Results:Analysis revealed that valproate administration resulted in elevated levels of sialic acid, hexoses, hexosamine, and fucose in the stomach tissue homogenates. Conversely, the administration of Moringa extract mitigated the adverse effect of valproate on glycan levels.Conclusion:Thus, Moringa leave extract can be a good candidate for attenuating valproate-induced toxicity on stomach tissue.

ABSTRACTIntestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host–microbe interactions in the intestine. However, the association between fucose, gut bacteria, and ISCs stemness remains unclear. To investigate the effects of fucose on ISCs-mediated intestinal epithelial cells (IECs) development, we administered fucose to 4-week-old mice for 4 weeks. ISCs stemness, IECs proliferation, and differentiation were examined. Variations in gut microbes and metabolism were detected using 16S rDNA sequencing and metabolomic analysis. Fucose was added to the bacterial culture medium to further study its effects on metabolism. Crypts were isolated from the mouse ileum for organoids culture in vitro to evaluate the effects of metabolites and the underlying mechanism. The results showed that fucose accelerated ISCs proliferation and secretory lineage differentiation in mice, whereas antibiotics eliminated these effects. The composition and functions of gut bacteria were altered by fucose treatment, while significant increases in Akkermansia and propanoate metabolism were noted. Propionic acid and propionate have been shown to promote organoid development. Fucose fermentation increases the production of propionic acid in Akkermansia muciniphila and enhances its ability to increase the stemness of ISCs. Moreover, ileal contents from fucose-treated mice promoted organoid development in a Gpr41/Gpr43-dependent manner. Fucose administration activates the Wnt signaling pathway in ISCs, and Wnt inhibitors suppress the effects of fucose. We conclude that fucose accelerates ISC-mediated intestinal epithelial development by promoting Akkermansia-related propanoate metabolism. These findings provide new insights into the promotion of gut homeostasis and the application potential of fucose as a prebiotic.

Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production. These inhibitors are commonly used to alter the cell surface glycosylation. However, structural analysis of the released glycans has been limited. In this research, the cell membranes were enriched and the glycans were released to obtain the N-glycans of the glycocalyx. Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane. Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans. Kifunensine was the most effective, converting nearly 95% of glycans to high mannose types. The compound 6-alkynyl fucose inhibited some fucosylation but also incorporated into the glycan structure. Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2. Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.

Algae are a rich but unexplored source of fibers with the potential to contribute to the next generation of prebiotics. The sulfated brown algae polysaccharide, fucoidan, is mainly composed of the deoxy-hexose L-fucose, which can be metabolized to 1,2-propanediol (1,2-PD) or lactate by gut microbes as precursors of propionate and butyrate. It was the aim of this study to investigate the impact of fucoidan on the fermentation capacity of the fecal microbiota and to compare to fucose. In batch fermentations of fecal microbiota collected from 17 donor samples, fucose promoted the production of propionate while no consistent effect was observed for commercial fucoidan and Fucus vesiculosus extract prepared in this study containing laminarin and fucoidan. H2S production was detected under all tested conditions, and levels were significantly lower in the presence of fucose in a dose-dependent manner. The addition of high fucose levels led to higher relative abundance of microbial 1,2-PD and lactate cross-feeders. Our results highlight that fucose and not fucoidan addition impacted fermentation capacity and increased the proportions of propionate and butyrate, which allows for precise modulation of intestinal microbiota activity. [ABSTRACT FROM AUTHOR]

It has been optimized thermal acid hydrolytic pretreatment and enzymatic saccharification (Es) in flask culture of Undaria pinnatifida seaweed, which is a prebiotic. The optimal hydrolytic conditions were a slurry content of 8% (w/v), 180 mM H2SO4, and 121°C for 30 min. Es using Celluclast 1.5 L at 8 U/mL produced 2.7 g/L glucose with an efficiency of 96.2%. The concentration of fucose (a prebiotic) was 0.48 g/L after pretreatment and saccharification. The fucose concentration decreased slightly during fermentation. Monosodium glutamate (MSG) (3%, w/v) and pyridoxal 5′-phosphate (PLP) (30 μM) were added to enhance gamma-aminobutyric acid (GABA) production. To further improve the consumption of mixed monosaccharides, adaptation of Lactobacillus brevis KCL010 to high concentrations of mannitol improved the synbiotic fermentation efficiency of U. pinnatifida hydrolysates. [ABSTRACT FROM AUTHOR]

Fucose is a deoxyhexose sugar present and studied in mammals. The process of fucosylation has been the primary focus in studies relating to fucose in animals due to the presence of fucose in Lewis antigens. Very few studies have reported its presence in Fungi, mostly in Mucoromycotina. The constitution of 25% and 12% of this sugar in the carbohydrates of cell wall in the respective Umbelopsis and Mucorales strains boosts the need to bridge the gap of knowledge on fucose metabolism across the fungal tree of life. In the absence of a network map involving fucose proteins, we carried out an in-silico approach to construct the fucose metabolic map in Fungi. We analyzed the taxonomic distribution of 85 protein families in Fungi including diverse early diverging fungal lineages. The expression of fucose-related protein-coding genes proteins was validated with the help of transcriptomic data originating from representatives of early diverging fungi. We found proteins involved in several metabolic activities apart from fucosylation such as synthesis, transport and binding. Most of the identified protein families are shared with Metazoa suggesting an ancestral origin in Opisthokonta. However, the overall complexity of fucose metabolism is greater in Metazoa than in Fungi. Massive gene loss has shaped the evolutionary history of these metabolic pathways, leading to a repeated reduction of these pathways in most yeast-forming lineages. Our results point to a distinctive mode of utilization of fucose among fungi belonging to Dikarya and the early diverging lineages. We speculate that, while Dikarya used fucose as a source of nutrients for metabolism, the early diverging group of fungi depended on fucose as a building block and signaling compound. [ABSTRACT FROM AUTHOR]

Fucosylation, or the attachment of a fucose moiety to a glycan or protein by the action of fucosyltransferases, happens extensively in all living organisms. It plays a vital role in multiple biological processes from development to immunity, and is thought to be highly associated with the occurrence of many human diseases. While the general principles of fucosylation are similar in all organisms, most insects synthesize less processed fucosylated glycans compared to humans. Recent studies in insects show that disruption of fucosylation causes developmental defects leading to lethality, suggesting an essential role in insects. However, because of the limited information available, the molecular mechanisms behind these phenotypes remain unresolved. This review provides an overview on insect fucosylation, including the principle and function of fucosylation, the phylogenesis of the fucosyltransferases, and the diversity and abundance of fucosylated glycans. To provide a better understanding of the different roles of fucosylation in insects, knowledge on fucosylation in mammals or other invertebrates is discussed. As the dynamic requirement for fucosylation in insects needs more research to elucidate the underlying mechanisms, we hope this overview of fucosylation could provide new insights into its role in insects for future studies. [ABSTRACT FROM AUTHOR]

Recently, L -fucose has received considerable attention as a potential cosmetic agent and substrate for human oligosaccharide synthesis. To date, only two methods have been reported for L -fucose biosynthesis: microbial biosynthesis based on the GDP- L -fucose pathway and enzymatic conversion using the L -fucose metabolic pathway enzymes. The lack of efficient biosynthetic methods has increased the price of L -fucose and other valuable chemicals synthesized from L -fucose. In this study, we introduced the L -fucose metabolic pathway from Escherichia coli into Saccharomyces cerevisiae and reverse-synthesized 7.75 mg/L L -fucose and 1.55 mg/L L -fuculose with lactaldehyde and glucose as substrates. L -fuculose was synthesized as a by-product of L -fucose biosynthesis. Conversion of lactaldehyde to 1,2 propanediol by an unknown oxidoreductase from S. cerevisiae is the bottleneck for fucose synthesis. To the best of our knowledge, this study is the first to reverse synthesize L -fucose and L -fuculose using whole cells via L -fucose metabolism. [Display omitted] • Overexpression of fucA , fucI and HXT4 enables yeast to synthesize L -fucose. • L -fuculose was synthesized as a by-product during the synthesis of L -fucose. • Conversion of lactaldehyde to 1,2 propanediol is bottleneck for L -fucose synthesis. [ABSTRACT FROM AUTHOR]

Mucin glycoproteins are essential components of the mucosal barrier, which protects the host from pathogens. Throughout evolution, bacteria have developed strategies to modulate and penetrate this barrier, and cause virulence by interacting with mucin O‐glycans at the epithelial cell‐surface. O‐fucosylated glycan epitopes on mucins are key ligands of many bacterial lectins. Here, a chemoenzymatic synthesis strategy is described to prepare a library of fucosylated mucin core glycopeptides to enable studies of mucin‐interacting and fucose‐binding bacterial lectins. Glycan cores with biologically important Lewis and H‐antigens were prepared decorating the peptide backbone at different sites and densities. The fucosylated mucin glycopeptides were applied in microarray binding studies to explore the importance of glycan core and peptide backbone presentation of these antigens in binding interactions with the P. aeruginosa lectin LecB and the C. difficile toxin A. [ABSTRACT FROM AUTHOR]

Misgurnus anguillicaudatus, also known as oriental weather loach, is widely consumed and favored in East Asia due to its superior nutritional values and excellent flavor. In this study, a crude Misgurnus anguillicaudatus carbohydrates (MAC) was isolated from Misgurnus anguillicaudatus. Subsequently, two parts, which were named MAO and MAP, respectively, were separated from MAC, and their primary structures and immunomodulatory activity were investigated. The results showed that MAO had a molecular weight of 2854 Da, and principally consisted of arabinose (77.11%) and rhamnose (21.97%), together with minor levels of fucose (0.92%); MAP, with a molecular weight of 3873 Da, was mainly composed of fucose (87.55%) and a small amount of rhamnose (8.86%) and galactose (3.59%). The in vitro assay showed that MAC could significantly enhance the proliferation of macrophages without cytotoxicity and increase the production of immune substances (TNF-α, IL-6). Together with Western blot results, we speculated that MAC could stimulate RAW264.7 murine macrophage cells to secrete TNF-α and IL-6 through up-regulating TLR4-MAPK-p38 signaling pathways. The results indicated that MAC could be a potential immune agent and might provide meaningful information for further chain conformation and immune mechanism research. [ABSTRACT FROM AUTHOR]

A comprehensive understanding of the phenotype of persistent HIV-infected cells, transcriptionally active and/or transcriptionally inactive, is imperative for developing a cure. The relevance of cell-surface glycosylation to HIV persistence has never been explored. We characterize the relationship between cell-surface glycomic signatures and persistent HIV transcription in vivo. We find that the cell surface of CD4+ T cells actively transcribing HIV, despite suppressive therapy, harbors high levels of fucosylated carbohydrate ligands, including the cell extravasation mediator Sialyl-LewisX (SLeX), compared with HIV-infected transcriptionally inactive cells. These high levels of SLeX are induced by HIV transcription in vitro and are maintained after therapy in vivo. Cells with high-SLeX are enriched with markers associated with HIV susceptibility, signaling pathways that drive HIV transcription, and pathways involved in leukocyte extravasation. We describe a glycomic feature of HIV-infected transcriptionally active cells that not only differentiates them from their transcriptionally inactive counterparts but also may affect their trafficking abilities.

The majority of nonbacterial gastroenteritis in humans and livestock is caused by noroviruses. Like most RNA viruses, frequent mutations result in various norovirus variants. The strain-dependent binding profiles of noroviruses to fucose are supposed to facilitate norovirus infection. It remains unclear, however, what the molecular mechanism behind strain-dependent functioning is. In this study, by applying atomic force microscopy (AFM) nanoindentation technology, we studied norovirus-like particles (noroVLPs) of three distinct human norovirus variants. We found differences in viral mechanical properties even between the norovirus variants from the same genogroup. The noroVLPs were then subjected to fucose treatment. Surprisingly, after fucose treatment, the previously found considerable differences in viral mechanical properties among these variants were diminished. We attribute a dynamic switch of the norovirus P domain upon fucose binding to the reduced differences in viral mechanical properties across the tested norovirus variants. These findings shed light on the mechanisms used by norovirus capsids to adapt to environmental changes and, possibly, increase cell infection. Hereby, a new step towards connecting viral mechanical properties to viral prevalence is taken. [ABSTRACT FROM AUTHOR]

We first investigated the interactions between several algae‐derived lectins and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). We created lectin columns using high‐mannose (HM)–type glycan‐specific lectins OAA and KAA‐1 or core fucose–specific lectin hypninA‐2 and conducted binding experiments with SARS‐CoV‐2. The results showed that these lectins were capable of binding to the virus. Furthermore, when examining the neutralization ability of nine different lectins, it was found that KAA‐1, ESA‐2, and hypninA‐2 were effective in neutralizing SARS‐CoV‐2. In competitive inhibition experiments with glycoproteins, neutralization was confirmed to occur through HM‐type or core fucose–type glycans. However, neutralization was not observed with other lectins, such as OAA. This trend of KAA‐1 and ESA‐2 having the neutralizing ability and OAA not having it was also similar to influenza viruses. Electron microscopy observations revealed that KAA‐1 and hypninA‐2 strongly aggregated SARS‐CoV‐2 particles, while OAA showed a low degree of aggregation. It is believed that the neutralization of SARS‐CoV‐2 involves multiple factors, such as glycan attachment sites on the S protein, the size of lectins, and their propensity to aggregate, which cause inhibition of receptor binding or aggregation of virus particles. This study demonstrated that several algae‐derived lectins could neutralize SARS‐CoV‐2 and that lectin columns can effectively recover and concentrate the virus. [ABSTRACT FROM AUTHOR]

L-Fucose is one of the key metabolites in human–gut microbiome interactions. It is continuously synthesized by humans in the form of fucosylated glycans and fucosyl-oligosaccharides and delivered into the gut throughout their lifetime. Gut microorganisms metabolize L-fucose and produce short-chain fatty acids, which are absorbed by epithelial cells and used as energy sources or signaling molecules. Recent studies have revealed that the carbon flux in L-fucose metabolism by gut microorganisms is distinct from that in other sugar metabolisms because of cofactor imbalance and low efficiencies in energy synthesis of L-fucose metabolism. The large amounts of short-chain fatty acids produced during microbial L-fucose metabolism are used by epithelial cells to recover most of the energy used up during L-fucose synthesis. In this review, we present a detailed overview of microbial L-fucose metabolism and a potential solution for disease treatment and prevention using genetically engineered probiotics that modulate fucose metabolism. Our review contributes to the understanding of human–gut microbiome interactions through L-fucose metabolism. Key points: • Fucose-metabolizing microorganisms produce large amounts of short-chain fatty acids • Fucose metabolism differs from other sugar metabolisms by cofactor imbalance • Modulating fucose metabolism is the key to control host–gut microbiome interactions [ABSTRACT FROM AUTHOR]

Fucose is a signaling carbohydrate that is attached at the end of glycan processing. It is involved in a range of processes, such as the selectin‐dependent leukocyte adhesion or pathogen‐receptor interactions. Mass‐spectrometric techniques, which are commonly used to determine the structure of glycans, frequently show fucose‐containing chimeric fragments that obfuscate the analysis. The rearrangement leading to these fragments—often referred to as fucose migration—has been known for more than 25 years, but the chemical identity of the rearrangement product remains unclear. In this work, we combine ion‐mobility spectrometry, radical‐directed dissociation mass spectrometry, cryogenic IR spectroscopy of ions, and density‐functional theory calculations to deduce the product of the rearrangement in the model trisaccharides Lewis x and blood group H2. The structural search yields the fucose moiety attached to the galactose with an α(1→6) glycosidic bond as the most likely product. [ABSTRACT FROM AUTHOR]

Fucose ist ein signalgebendes Kohlenhydrat, das am Ende der Glykosylierung angehängt wird. Es ist an einer Reihe von Prozessen beteiligt, z. B. an der Selectin‐abhängigen Leukozytenadhäsion oder an Pathogen‐Rezeptor‐Interaktionen. Massenspektrometrische Verfahren, die üblicherweise zur Bestimmung der Struktur von Glykanen eingesetzt werden, zeigen häufig Fucose‐haltige, chimäre Fragmente, die die Analyse verzerren. Die Umlagerung, die zu diesen Fragmenten führt – oft als Fucose‐Migration bezeichnet – ist seit mehr als 25 Jahren bekannt, aber die chemische Identität des Umlagerungsproduktes bleibt unklar. In dieser Arbeit kombinieren wir Ionenmobilitätsspektrometrie, Massenspektrometrie mit radikalinduzierter Dissoziation, kryogene IR‐Spektroskopie und Computersimulationen mittels Dichtefunktionaltheorie, um das Produkt der Umlagerung der prototypischen Trisaccharide Lewis x und Blutgruppe H2 zu bestimmen. Die Struktursuche ergibt, dass die Fucose, die mit einer α(1→6)‐glykosidischen Bindung an die Galaktose gebunden ist, das wahrscheinlichste Produkt ist. [ABSTRACT FROM AUTHOR]

Aims: The anticancer function of superoxide dismutases (SODs) is still controversial. SOD3 is an extracellular superoxide dismutase and contains a single N-glycan chain. The role played by the N-glycosylation of SOD3, as it relates to lung cancer, is poorly understood. For this, we performed the structural and functional analyses of the N-glycan of SOD3 in lung cancer. Results: We report herein that the fucose structure of the N-glycan in SOD3 was increased in the sera of patients with lung cancer. In cell lines of non-small lung cancer cell (NSCLC), we also found a high level of the core fucose structure in the N-glycan of SOD3, as determined by lectin blotting and mass spectrometry analysis. To address the roles of the core fucose structure of SOD3, we generated FUT8 (α1,6-fucosyltransferase) gene knockout A549 cells. Using these cells, we found that the core fucose structure of SOD3 was required for its secretion and enzymatic activity, which contributes to the suppression of cell growth of NSCLC cells. Innovation: The core fucosylation is required for the secretion and enzymatic activity of SOD3, which contributes to anti-tumor functions such as the suppression of cell growth of NSCLC. Conclusion: The N-glycans, especially those with core fucose structures, regulate the anti-tumor functions of SOD3 against NSCLC. Antioxid. Redox Signal. 38, 1201–1211. [ABSTRACT FROM AUTHOR]

Background: Recently, it has been found that nitrogen (N) deposition strongly affects the coverage of biocrusts. However, we know little about the response of exopolysaccharides (EPSs), the key cementing material in the formation and stability of biocrusts, to N deposition. Method: Three N-sources including nitrate, ammonia and urea were added to biocrusts at three rates (2 mg/g, 4 mg/g, 8 mg/g) to evaluate the effect of N additions on the growth of biocrusts and the abundance of EPS. Results: Our results showed 2 mg/g of nitrate–N had no obvious effect on the cyanobacterial biomass, while 4 and 8 mg/g of nitrate–N inhibited the growth of Microcoleus vaginatus, the dominant cyanobacterium in biocrusts, but promoted other cyanobacteria growth. Ammonia-N and urea-N strongly decreased the cyanobacterial biomass, indicated by chlorophyll-a and 16 s rRNA gene copy-numbers. On the whole, N additions had a positive impact on the α-biodiversity of biocrusts. However, Ammonia-N and urea-N shifted the bacterial communities from more Cyanobacteria to more Proteobacteria and Actinobacteria. Notably, lesser-N (2 mg/g) promoted the excretion of EPSs, while greater-N (8 mg/g) had the opposite effect, and the total proportion of rhamnose and fucose in EPSs decreased in all treatment groups. Conclusion: N additions (except 2 mg/g of nitrate–N) reduced cyanobacterial biomass and affected the bacterial communities in biocrusts, which would obstruct the development and succession of biocrusts. Meanwhile, the simultaneous reductions of the EPSs contents and proportion of rhamnose and fucose in EPSs may further reduce stability and persistence of cyanobacterial biocrusts, after N additions. [ABSTRACT FROM AUTHOR]

Introduction: Infection with strongly b-hemolytic strains of Brachyspira hyodysenteriae leads to swine dysentery (SD), a production-limiting disease that causes mucohemorrhagic diarrhea and typhlocolitis in pigs. This pathogen has strong chemotactic activity toward mucin, and infected pigs often have a disorganized mucus layer and marked de novo expression of MUC5AC, which is not constitutively expressed in the colon. It has been shown that fucose is chemoattractant for B. hyodysenteriae, and a highly fermentable fiber diet can mitigate and delay the onset of SD. Methods: We used lectins targeting sialic acids in a-2,6 or a-2,3 linkages, Nacetylglucosamine (GlcNAc), a-linked L-fucose, and an immunohistochemical stain targeting N-glycolylneuraminic acid (NeuGc) to investigate the local expression of these mucin glycans in colonic tissues of pigs with acute SD. We used a commercial enzyme-linked immunosorbent assay (ELISA) to quantify fecal MUC5AC in infected pigs and assess its potential as a diagnostic monitoring tool and RNA in situ hybridization to detect IL-17A in the colonic mucosa. Results: Colonicmucin glycosylation during SD has an overall increase in fucose, a spatially different distribution of GlcNAc with more expression within the crypt lumens of the upper colonic mucosa, and decreased expression or a decreased trend of sialic acids in a-2,6 or a-2,3 linkages, and NeuGc compared to the controls. The degree of increased fucosylation was less in the colonic mucosa of pigs with SD and fed the highly fermentable fiber diet. There was a significant increase in MUC5AC in fecal and colonic samples of pigs with SD at the endpoint compared to the controls, but the predictive value for disease progression was limited. Discussion: Fucosylation and the impact of dietary fiber may play important roles in the pathogenesis of SD. The lack of predictive value for fecal MUC5AC quantification by ELISA is possibly due to the presence of other non-colonic sources of MUC5AC in the feces. The moderate correlation between IL-17A, Frontiers in neutrophils and MUC5AC confirms its immunoregulatory and mucin stimulatory role. Our study characterizes local alteration of mucin glycosylation in the colonic mucosa of pigs with SD after B. hyodysenteriae infection and may provide insight into host-pathogen interaction. [ABSTRACT FROM AUTHOR]

Objective: Sialic acid, hexoses, hexosamines and fucose are components of glycoprotein, glycolipid and/or ganglioside. These glycoconjugates are essential components of cellular membrane and receptors, which are required for normal cellular activities. The levels of these aforementioned glycans are likely to be obstructed under biological conditions (such as oxidative stress) that leads to cellular and tissue damage. Despite the efficacy of valproate as a broad-spectrum antiepileptic drug, it administration is linked to oxidative stress and multiple organ damage. Moringa oleifera leaves have been proven to be bioactive food with diverse biochemical benefits, that include antioxidant, wound healing and tissue protective effects. Methods: In this study, female Sprague-Dawley rats were grouped into four. Group 1: control group given physiological saline; Group 2: animals given only 70% ethanol Moringa leaves extract (0.3 g/kg b.w./day); Group 3: animals that received only sodium valproate (0.5 g/kg b. w./day); Group 4: animals given similar dose of sodium valproate + Moringa extract. The treatments were administered orally for 15 days, and the animals were then fasted overnight and sacrificed. Stomach tissues collected were homogenized in ice-cold normal saline, using a glass homogenizer to make up 10% w/v tissue homogenate. Results: Analysis revealed that valproate administration resulted in elevated levels of sialic acid, hexoses, hexosamine, and fucose in the stomach tissue homogenates. Conversely, the administration of Moringa extract mitigated the adverse effect of valproate on glycan levels. Conclusion: Thus, Moringa leave extract can be a good candidate for attenuating valproate-induced toxicity on stomach tissue. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies reported that fucose plays a protective role in inhibiting pathogens. Fusobacterium nucleatum (Fn) was recently found to promote the progression of colitis. However, the effects of fucose on Fn are poorly understood. This study aimed to explore whether fucose could ameliorate the proinflammatory property of Fn in colitis and the underlying mechanisms. Methods: To validate our hypothesis, mice were administrated with Fn and fucose-treated Fn (Fnf) before dextran sulfate sodium (DSS) treatment to establish Fn related colitis model. The metabolism variation of Fn was detected by metabolomic analysis. To verify the effects of bacterial metabolites on intestinal epithelial cells (IECs), Caco-2 cells were treated with bacterial supernatant. Results: More severe inflammation, intestinal barrier damage, autophagy block, and apoptosis in the colon were noted in DSS mice that were administrated with Fn or Fnf. However, the severity degree in Fnf+DSS group was less compared to Fn+DSS group. Metabolic pathways of Fn were altered after fucose treatment and proinflammatory metabolites were decreased. The supernatant of Fnf induced a lower level of inflammation than Fn in Caco-2 cells. One of the decreased metabolites, homocysteine thiolactone (HT), was proven to induce inflammatory effects in Caco-2 cells. Discussion: In conclusion, fucose ameliorates the proinflammatory property of Fn via altering its metabolism and these findings provide evidence for the application of fucose as functional food or prebiotic in the treatment of Fn related colitis. [ABSTRACT FROM AUTHOR]

This study evaluates the chemical structure of a heteropolysaccharide (SP-1a) from the fruiting bodies of Stropharia rugosoannulata and the antioxidant activity and enzyme inhibitory activity of its derivatives. The results showed that SP-1a (2.29 ×104 Da) contained fucose, glucose and galactose, and possessed the backbone of [→3)-α- D -Glc p -(1→] and [→3,6)-α- D -Glc p -(1→] with side chains [→6)-α- D -Gal p -(1→] and T-α- D -Gal p. Furthermore, carboxymethylated and phosphorylated modification of SP-1a (named as CSP-1a and PSP-1a) had good thermal stability and strong rehydration. Moreover, CSP-1a displayed stable DPPH scavenging ability (46.77%) and reducing power ability (0.434), as well as α-glucosidase inhibitory activity (60.98%) and α-amylase inhibitory activity (67.20%). Besides, PSP-1a presented significant hydroxyl radical scavenging ability (94.18%). The findings suggested that appropriate chemical modifications can improve the physicochemical properties and biological activities of polysaccharides from Stropharia rugosoannulata , providing hints and theoretical supports for further development of corresponding drug or food ingredients. [Display omitted] • The structure of polysaccharide (SP-1a) from S. rugosoannulata was established. • SP-1a was carboxymethylated and phosphorylated successfully. • Carboxymethylated SP-1a showed stronger antioxidant and enzyme inhibitory activities. • Phosphorylated SP-1a presented significant hydroxyl radical scavenging ability. [ABSTRACT FROM AUTHOR]