Sialic Acid

Actinomyces naeslundii genospecies 1 and 2 express type-2 fimbriae (FimA subunit polymers) with variant Galbeta binding specificities and Actinomyces odontolyticus a sialic acid specificity to colonize different oral surfaces. However, the fimbrial nature of the sialic acid binding property and sequence information about FimA proteins from multiple strains are lacking. Here we have sequenced fimA genes from strains of A.naeslundii genospecies 1 (n = 4) and genospecies 2 (n = 4), both of which harboured variant Galbeta-dependent hemagglutination (HA) types, and from A.odontolyticus PK984 with a sialic acid-dependent HA pattern. Three unique subtypes of FimA proteins with 63.8-66.4% sequence identity were present in strains of A. naeslundii genospecies 1 and 2 and A. odontolyticus. The generally high FimA sequence identity (> 97.2%) within a genospecies revealed species specific sequences or segments that coincided with binding specificity. All three FimA protein variants contained...

Sialic acid-containing glycoconjugates are generally considered to be unique to the deuterostomes, a lineage of the animal kingdom which includes animals from the echinoderms up to the vertebrates. There are, however, two isolated reports of sialic acid occurring in the insect species Drosophila melanogaster and Galleria mellonella. Since insects are classified as protostomes, these findings call previous assumption on the phylogenetic distribution and thus on the evolution of sialic acids into question. Here, we report the occurrence of N-acetylneuraminic acid (Neu5Ac) in larvae of the cicada Philaenus spumarius. Cytochemical analysis of larval sections with lectins from Sambucus nigra and Limax flavus suggested the presence of sialic acids in the concrement vacuoles of the Malpighian tubules. The monoclonal antibody MAb 735, which is specific for polysialic acid, labelled the same structures. A chemical analysis performed by HPLC of fluorescent derivatives of sialic acids and by GLC-MS provided sound evidence for the presence of Neu5Ac in the Philaenus spumarius larvae. These data suggest that in this cicada Neu5Ac occurs in α2,8-linked polysialic acid structures and in α2,6-linkages. The results provide further evidence for the existence of sialic acids in insects and in linkages known to occur in glycoconjugates of deuterostomate origin.

A periodate-resorcinol microassay for the quantitation of total sialic acid (TSA) has been developed. A 96-well microtiter plate format was used as a single reagent mixing well. The principle of this newly-developed assay is the periodate-resorcinol procedure. Conditions for the quantitation of sialic acid in serum, such as the concentration of periodate, resorcinol, incubation time and human serum volume, were optimized. It was found that the optimal concentration of periodic acid and resorcinol reagent were 1.3 mM and 0.6%, respectively. An incubation time of 60 minutes for the reaction of periodic acid and resorcinol with samples was found to give the highest absorbance. These new procedures were used for the quantitation of sialic acid in human serum. It was found that only 5 µL samples were needed to give a varied coefficient of the intra- and inter-assay of 0.79% and 4.68%, respectively. Furthermore, this method demonstrated the recovery percentage of 94.25% by the addition of...

This study was undertaken to determine the occurrence of uronic acid in chicken eggshell membranes and to compare chemical compositions among the inner and outer eggshell membranes and the organic matter of eggshell. We report here for the first time the occurrence of uronic acid in chicken eggshell membranes. Uronic acid concentrations were similar (P > 0.05) between the inner shell membrane and outer shell membrane but approximately fivefold higher (P < 0.05) in the organic matter of eggshell. Sialic acid concentrations were (

CD33 also known as Siglec-3 is endogenously expressed in stem cells and is a marker for the myeloid lineage
of cells. Increased expression of CD33 thus allows it to bind to any Sialic Acids (SIAs). These acids are binding
sites for pathogens and toxins. By binding to these acids, CD33 can prevent invasion of hosts by these pathogens.
Down-regulation of CD33, increase the release of the pro-inflammatory cytokine TNF-α by monocytes that increases
reactive oxygen species that are involved in diseases like diabetes mellitus, Alzheimer’s, cardiovascular diseases
asthma, and in various cancers.
The up-regulation of CD33 using Metadichol® was studied using Wharton’s Jelly Mesenchymal Stem Cells
(MSCs) isolated from human umbilical cord and were grown in p-35 dishes until confluent and treatment was
carried out with different concentrations. One dish was untreated and considered as control. The treated and
untreated cells were analyzed using Flow Cytometry. The cells treated at 100 pg of Metadichol® has shown the
highest increase (>400 fold) in CD33++ expression (48.77%) compared to untreated control (0.11%).

The use of CNS cultures for detection and quantification of neuronotrophic activity in the CNS has been analyzed. In particular the development, i.e., neurotransmitter uptake characteristics, and survival of dopaminergic and GABAergic neurons in fetal mouse (E13)-dissociated mesencephalic cells cultured in serum-free, hormone-supplemented medium have been assessed as a function of culture time and cell density. At all times, more than 98% of the cells were classified as neurons on the basis of immunocytochemical criteria. Results indicate that the increase of cell density in vitro significantly enhances specific high-affinity dopamine uptake per dopaminergic cell and cell survival. This effect is not limited to the dopaminergic cells and suggests that the development of neurotransmitter-related traits and cell survival are influenced by cell density-derived trophic signals. The above-mentioned cultures and parameters have also been used to detect neuronotrophic activity in adult mam...

Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, the hemagglutinin-neuraminidase (HN), that is involved in attachment to sialic acid receptors, promotion of fusion, and removal of sialic acid from infected cells and progeny virions. Previously we showed that Newcastle disease virus (NDV) HN contained a pliable sialic acid recognition site that could take two states, a binding state and a catalytic state. Here we present evidence for a second sialic acid binding site at the dimer interface of HN and present a model for its involvement in cell fusion. Three different crystal forms of NDV HN now reveal identical tetrameric arrangements of HN monomers, perhaps indicative of the tetramer association found on the viral surface.

Drying is one of the essential processing steps for dried edible bird’s nest; however, sialic acid and
antioxidant can be highly thermosensitive and unstable. Therefore, aim of this study was to
determine the degradation kinetics of sialic acid and antioxidants during low-temperature drying at
25–40°C as compared to conventional hot air-drying at 70°C. These compounds’ degradation
exhibited first-order kinetics. Sialic acid and antioxidant retentions were 83.9 and 96.6%,
respectively, at 25°C, and 78.7 and 91.5% at 40°C, respectively, by low-temperature drying; while,
42.5 and 38.7%, respectively, at 70°C by conventional hot air-drying. Finally, empirical models were
significantly fitted to predict sialic acid and antioxidant retention as edible bird’s nest reached a
certain level of drying, which may be useful from the processing standpoint and validate the usage
of low-temperature drying as a process tool for retention of sialic acid and antioxidant in edible
bird’s nest.

Electronegative LDL (LDL(-)) constitutes a plasma subfraction of LDL with proinflammatory properties. Its proportion is increased in familial hypercholesterolemia (FH); however, the characteristics of LDL(-) isolated from FH subjects have not been previously studied. In this work, the composition, oxidative status, and inflammatory capacity on endothelial cells of LDL(-) from FH and normolipemic (NL) subjects were evaluated. LDL(-) from FH was relatively enriched in esterified and free cholesterol and triglyceride, and had lower apoB and phospholipid content compared with the non-electronegative fraction (LDL(+)). LDL(-) also contained increased amounts of apoE, apoC-III, sialic acid, and non-esterified fatty acids (NEFAs). The same was observed in NL subjects, except that esterified cholesterol and phospholipid were similar in LDL(-) and LDL(+). No difference was observed between the two fractions concerning malondialdehyde, fatty acid hydroxides, and antioxidants, thereby indicating the absence of increased oxidation of LDL(-) compared with LDL(+). When LDL(-) (100 mg/l) from NL and FH subjects was incubated for 24 h with human umbilical vein endothelial cells (HUVECs), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) increased twofold in the culture medium compared with LDL(+). Vascular cell adhesion molecule 1 (VCAM-1) expression was not increased by LDL(-). Our data indicate that LDL(-) from FH or NL subjects shows no evidence of increased oxidative modification compared to LDL(+); however, LDL(-) induces twofold the release of chemokines by endothelial cells. This effect, which may contribute to leukocyte recruitment and promote atherogenesis, may be greater in FH subjects in which LDL(-) can be up to eightfold higher than in NL subjects.

Humans face a constant threat from pathogens like influenza varieties H1N1, H5N1, and others and there is a need to prevent these from epidemics. The pathogens depend on successful colonization of the host in order to reproduce and multiply. Sialidases are known as neuraminidases are a group of enzymes, the most abundant of these being the exo-sialidases that can catalyze the cleavage of sialic acids from carbohydrates, glycoproteins or glycolipids. Sialidases have been thoroughly studied since their discovery 75 years ago and their occurrence in bacteria and viruses is widespread. They are found in diverse virus families and bacteria and other microbes. Moreover, sialic acids serve as a receptor for various pathogens. This allows bacteria like H1N1 or other influenza viruses, to enter the host cell. There is a need to block sialidases as they release sialic acid that serves as nutrition for the microbes and as well allows them to bind and invade the host cell where they can proliferate. This makes sialidases an interesting target to control pathogenic activity. Metadichol ® is nanoemulsion of long-chain lipid alcohols derived from food ingredients. In rats, it has an LD50 of 5000 mg/kilo and its ingredients are present in many foods we consume on a daily basis. It has antiviral and antibacterial and anti-parasitic properties. We studied inhibition of Sialidases by inducing it with Lipopolysaccharide (LPS) using THP1 cells. Metadichol showed inhibition at 1 picogram per ml to 1 nanogram per/ml. Compared to Prednisone. It is 100 times more active. Previous studies on Metadichol ® showed that it is toxic to cancer cells at higher concentrations. Since it is safer, it has the potential of being directly tested on humans without side effects and could have a potential role in mitigating the pathogens that a burden on the Public health system.

Sialic acid, oral glucose and plasma lipids were determined in 70 control subjects age range 20-60 and 150 individuals of age range 20-60 who were offspring of one type 2 diabetic parent. The number of first degree relatives who had impaired glucose tolerance were 50. The total sialic acid concentration was significantly higher (p&lt;0.05) in the first degree relatives when compared to the control subjects. However the total sialic acid concentration was significantly higher in the offspring with normal glucose tolerance than those with impaired glucose tolerance. There was no significant difference in the lipids between the control subjects and the offspring with normal glucose tolerance. But the total cholesterol and triglycerides were significantly higher in the offspring with impaired glucose tolerance when compared to the control subjects and the offspring with normal glucose tolerance. Our study shows that the desialylation of the vascular endothelium is an early event that pr...

Sialidases are glycohydrolytic enzymes present from virus to mammals that remove sialic acid from oligosaccharide chains. Four different sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and are involved in several cellular processes and pathological conditions. Molecular defects in NEU1 are responsible for sialidosis, an inherited disease characterized by lysosomal storage disorder and neurodegeneration. The studies on the biology of sialic acids and sialyltransferases, the anabolic counterparts of sialidases, have revealed a complex picture with more than 50 sialic acid variants selectively present in the different branches of the tree of life. The gain/loss of specific sialoconjugates have been proposed as key events in the evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen interactions. To date, less attention has been paid to the evolution of sialidases. Thus we have conducted a survey on the state of the sialidase family in metazoan. Using an in silico approach, we identified and characterized sialidase orthologs from 21 different organisms distributed among the evolutionary tree: Metazoa relative (Monosiga brevicollis), early Deuterostomia, precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles, avians and early and recent mammals). We were able to reconstruct the evolution of the sialidase protein family from the ancestral sialidase NEU1 and identify a new form of the enzyme, NEU5, representing an intermediate step in the evolution leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the mechanisms that shaped the substrate specificity and other peculiar properties of the modern mammalian sialidases. Moreover, we further confirm findings on the catalytic residues and identified enzyme loop portions that behave as rapidly diverging regions and may be involved in the evolution of specific properties of sialidases.