-
American Journal of Hematology Jun 2021Intravenous (IV) iron is the therapy of choice when oral iron is ineffective or poorly tolerated, yet use has been limited by fears of hypersensitivity reactions (HSRs).... (Review)
Review
Intravenous (IV) iron is the therapy of choice when oral iron is ineffective or poorly tolerated, yet use has been limited by fears of hypersensitivity reactions (HSRs). Newer formulations that bind iron more tightly and release it more slowly have made the risk of serious or severe HSRs very low. One such formulation, ferric derisomaltose, has been approved in the United States for delivery of 1000 mg iron in a single IV infusion. Ferric derisomaltose rapidly repletes iron parameters with low rates of serious or severe HSRs. Single-infusion iron repletion offers convenience, eliminates adherence concerns, and reduces healthcare resource utilization.
Topics: Anemia, Iron-Deficiency; Biomarkers; Cardiovascular Diseases; Diagnosis, Differential; Disaccharides; Drug Costs; Drug Hypersensitivity; Fatigue; Female; Ferric Compounds; Flushing; Forecasting; Hemoglobins; Humans; Hypophosphatemia; Infusions, Intravenous; Male; Multicenter Studies as Topic; Pregnancy; Pregnancy Complications, Hematologic; Prospective Studies; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration
PubMed: 33580972
DOI: 10.1002/ajh.26124 -
Bioscience, Biotechnology, and... Jun 2022Glycosaminoglycans (GAGs) are found in various tissues and are involved in many physiological functions. Since the rhesus monkey (Macaca mulatta) is the most widely used...
Glycosaminoglycans (GAGs) are found in various tissues and are involved in many physiological functions. Since the rhesus monkey (Macaca mulatta) is the most widely used nonhuman primate in biomedical research, an understanding of the compositions of GAGs in their tissues is important. The aim of this study was to determine the content and sulfation pattern of disaccharides contained in several tissues of the rhesus monkey. The chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chain was extracted from several tissues of female and male rhesus monkeys. Compositional analysis was performed after digestion with chondroitinases ABC and ACI to reveal the sulfation pattern of the CS/DS hybrid chain. This study revealed that the major CS/DS disaccharide units present in the tissues were A and C types. The E and iE types were specifically distributed not only in the tracheal tissue but also in gastrointestinal tissues.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Disaccharides; Female; Glycosaminoglycans; Macaca mulatta; Male
PubMed: 35425970
DOI: 10.1093/bbb/zbac057 -
PloS One 2022Chondroitin sulfate (CS) and its isomeric variant, dermatan sulfate (DS), are complex glycosaminoglycans (GAGs) which are ubiquitous components of the extracellular...
Chondroitin sulfate (CS) and its isomeric variant, dermatan sulfate (DS), are complex glycosaminoglycans (GAGs) which are ubiquitous components of the extracellular matrix in various tissues including the brain. CS and/or DS are known to bind to a variety of growth factors and regulate many cellular events such as proliferation and differentiation. Although the biological activities of CS and/or DS towards neural stem/progenitor cells (NSPCs) have been well investigated, the CS and/or DS of hematopoietic stem cells (HSCs) have not been fully characterized. Here, we analyzed GAGs on mononuclear cells of rat umbilical cord blood cells (UCB-MNCs). CS was detected in vascular intima and media of rat umbilical cord at embryonic day 19 (E19) by immunohistochemistry. The stem-cell-enriched-UCBCs (SCE-UCBCs), which were expanded from rat UCB-MNCs, expressed CS. CS chains are composed of repeating disaccharide units, which are classified into several types such as O-, A-, B-, C-, D-, and E-unit according to the number and positions of sulfation. A disaccharide composition analysis revealed that CS and/or DS were abundant in rat UCB-MNCs as well as in their expanded SCE-UCBCs, while the amount of heparan sulfate (HS) was less. The degree of sulfation of CS/DS was relatively low and the major component in UCB-MNCs and SCE-UCBCs was the A-unit. A colony-forming cell assay revealed that the percentage of colony-forming cells decreased in culture with CS degradation enzyme. The CS and/or DS of UCBCs may be involved in biological activities such as stem cell proliferation and/or differentiation.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chondroitin Sulfates; Disaccharides; Female; Fetal Blood; Rats; Stem Cells
PubMed: 35077481
DOI: 10.1371/journal.pone.0262854 -
Biochemistry May 2015We have shown previously that the bleomycin (BLM) carbohydrate moiety can recapitulate the tumor cell targeting effects of the entire BLM molecule, that BLM itself is...
We have shown previously that the bleomycin (BLM) carbohydrate moiety can recapitulate the tumor cell targeting effects of the entire BLM molecule, that BLM itself is modular in nature consisting of a DNA-cleaving aglycone which is delivered selectively to the interior of tumor cells by its carbohydrate moiety, and that there are disaccharides structurally related to the BLM disaccharide which are more efficient than the natural disaccharide at tumor cell targeting/uptake. Because BLM sugars can deliver molecular cargoes selectively to tumor cells, and thus potentially form the basis for a novel antitumor strategy, it seemed important to consider additional structural features capable of affecting the efficiency of tumor cell recognition and delivery. These included the effects of sugar polyvalency and net charge (at physiological pH) on tumor cell recognition, internalization, and trafficking. Since these parameters have been shown to affect cell surface recognition, internalization, and distribution in other contexts, this study has sought to define the effects of these structural features on tumor cell recognition by bleomycin and its disaccharide. We demonstrate that both can have a significant effect on tumor cell binding/internalization, and present data which suggests that the metal ions normally bound by bleomycin following clinical administration may significantly contribute to the efficiency of tumor cell uptake, in addition to their characterized function in DNA cleavage. A BLM disaccharide-Cy5** conjugate incorporating the positively charged dipeptide d-Lys-d-Lys was found to associate with both the mitochondria and the nuclear envelope of DU145 cells, suggesting possible cellular targets for BLM disaccharide-cytotoxin conjugates.
Topics: Animals; Bleomycin; Cell Line; Cell Line, Tumor; Disaccharides; Humans; Microscopy, Fluorescence; Molecular Structure; Rats; Structure-Activity Relationship
PubMed: 25905565
DOI: 10.1021/acs.biochem.5b00277 -
Virologica Sinica Feb 2023Noroviruses (NoVs) are the primary cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) are receptors or attachment factors that affect the...
Noroviruses (NoVs) are the primary cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs. GII.6 NoV is one of the predominant genotypes in humans, which recognizes the type ABO secretor of HBGAs. However, the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive. In this study, we investigated the binding features of the GII.6 strain to HBGAs using saliva- and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide. We showed that the GII.6 P domain recognized some A and O secretor's saliva samples, most B secretor's saliva samples, and H disaccharide antigen, but did not bind non-secretors' saliva. Further, we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7 Å, revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs. Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs, demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity. Finally, structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup. Taken together, our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs, and shed light on NoV evolution, epidemiology, and anti-viral drug development.
Topics: Humans; Blood Group Antigens; Norovirus; Virus Attachment; Protein Binding; Polysaccharides; Disaccharides; Caliciviridae Infections; Genotype
PubMed: 36216242
DOI: 10.1016/j.virs.2022.09.010 -
The Journal of Organic Chemistry Jul 2022analysis has been applied to model the conformational properties of -acetyl side-chains in biologically important GlcNAc and ManNAc monosaccharides and in a...
analysis has been applied to model the conformational properties of -acetyl side-chains in biologically important GlcNAc and ManNAc monosaccharides and in a βGlcNAc-(1→4)-βGlcNAc disaccharide. Density functional theory calculations were conducted to obtain parameterized equations that relate the magnitudes and signs of 10 spin-coupling constants to conformations of the C2-N2 bonds of GlcNAc and ManNAc. Six of these equations were used with experimental -couplings, measured in HO/HO and DMSO- solvents in selectively C-labeled compounds, to model the C1-C2-N2-C1' torsion angle (θ) in GlcNAc and ManNAc residues. analysis gave mean values of θ of 106° for αGlcNAc and ∼116° for βGlcNAc residues, with circular standard deviations (CSDs) of 21-22° in aqueous solution, in excellent agreement with those obtained by aqueous molecular dynamics (MD) simulation. Parameter space plots revealed unique fits of the data, and root mean squared deviations (<0.2 Hz) were twofold smaller than those back-calculated from MD models, indicating that the models better fit the experimental -couplings. Context effects on both θ values were found to be small in a βGlcNAc-(1→4)-βGlcNAc disaccharide. analysis gave a mean value of θ of 249° for αManNAc in HO/HO, with a CSD of ∼19°, with both values in good agreement with MD. models of -acetyl side-chains are similar to those obtained previously for -acetyl side-chains ( 66-77). Both - and -acetylation conformationally constrain the C-O or C-N bonds relative to the same bonds in unsubstituted compounds. The present work confirms the ability of analysis to reveal relatively small changes in mean molecular torsion angles in solution and provides additional evidence of the method as an experimental tool complementary to MD simulation.
Topics: Carbohydrate Conformation; Carbohydrates; Disaccharides; Molecular Conformation; Molecular Dynamics Simulation; Monosaccharides
PubMed: 35687878
DOI: 10.1021/acs.joc.2c00189 -
Methods in Molecular Biology (Clifton,... 2023Glycosaminoglycans (GAGs) are built up of repeating disaccharide units resulting in long, linear polysaccharide chains. In most classes of GAGs, sulfation and...
Glycosaminoglycans (GAGs) are built up of repeating disaccharide units resulting in long, linear polysaccharide chains. In most classes of GAGs, sulfation and epimerization complicate the structure of the chain and influence biochemical functions. The most widespread way of their investigation by instrumental analytical techniques is to degrade them into the constituent disaccharide building blocks, followed by capillary electrophoresis or high-performance liquid chromatography (HPLC) separation. The analysis of GAG disaccharides with varying sulfation degrees poses a real challenge both from chromatographic and mass spectrometric (MS) points of view. This necessitates the constant improvement of their analytical methodology. In this chapter, an optimized workflow will be discussed for the sample preparation and subsequent HPLC-MS characterization of tissue-derived chondroitin sulfate and heparan sulfate.
Topics: Chondroitin Sulfates; Chromatography, High Pressure Liquid; Heparitin Sulfate; Glycosaminoglycans; Disaccharides
PubMed: 36662463
DOI: 10.1007/978-1-0716-2946-8_6 -
Journal of Agricultural and Food... Apr 2023Trehalose is a disaccharide and is often foliar applied by farmers aiming at increasing stress resistance or crop production. However, the physiological effect of...
Trehalose is a disaccharide and is often foliar applied by farmers aiming at increasing stress resistance or crop production. However, the physiological effect of exogenously applied trehalose on crops remains obscure. Here, we explored the effect of foliar trehalose application on style length of solanaceous crops, and . Trehalose application promotes pistil to stamen ratio by gaining style length. Another disaccharide consisting of two glucose molecules, maltose, showed the same effect on style length of , while monosaccharide glucose did not. Trehalose is found to affect style length through uptake via roots or interaction with rhizosphere but not through absorption by shoots in . Our study suggests that yield improvement of solanaceous crops by trehalose application under stressed conditions is brought about by suppression of the occurrence of short-styled flowers. This study suggests that trehalose holds potential to act as a plant biostimulant in preventing short-styled flowers in solanaceous crops.
Topics: Trehalose; Disaccharides; Crops, Agricultural; Glucose; Flowers
PubMed: 37011406
DOI: 10.1021/acs.jafc.2c08479 -
Polski Merkuriusz Lekarski : Organ... Aug 2020Disaccharidases are a group of enzymes of the small intestinal brush border, that are essential for degradation of disaccharides (sucrose, lactose, maltose, isomaltose,... (Review)
Review
Disaccharidases are a group of enzymes of the small intestinal brush border, that are essential for degradation of disaccharides (sucrose, lactose, maltose, isomaltose, trehalose) into monosaccharides, which are then absorbed from the gastrointestinal tract. Their deficiency may occur at any stage of human life and have a genetic basis or be a secondary to ongoing gastrointestinal disease. Disaccharidase deficiencies cause disorders of digestion and absorption leading to occurrence of clinical symptoms such as abdominal pain, flatulence, diarrhea. For more than fifty years disaccharidase activity (DA) measurements in the small intestine biopsy samples are still considered the "gold standard" in the diagnostics for disaccharide deficiency. The aim of this review was to emphasize the role of disaccharidases in the digestion. Moreover, the significance of their deficiency in children and adults based on the current knowledge was described. It was showed that deficiency or inactivity of disaccharidases may lead to gastrointestinal intolerance symptoms. Early diagnostics allows the initiation of appropriate treatment, which contribute to reduction or complete resolution of clinical symptoms.
Topics: Adult; Child; Diarrhea; Disaccharidases; Humans; Intestine, Small; Intestines; Sucrose
PubMed: 32827425
DOI: No ID Found -
Organic & Biomolecular Chemistry Apr 2022Many children suffering from autism spectrum disorder (ASD) experience gastrointestinal (GI) conditions. has been regularly detected in the stool of individuals...
Many children suffering from autism spectrum disorder (ASD) experience gastrointestinal (GI) conditions. has been regularly detected in the stool of individuals suffering from GI symptoms and autism. Literature has suggested that strains WAL 16351 and WAL 14578 produce an immunogenic capsular polysaccharide (CPS) comprised of disaccharide repeating units: α-D-Man-(1 → 4)-β-Rha-(1 → 3) that could be used for the development of an immunotherapeutic vaccine. Ambiguity in the configuration of rhamnose led to the synthesis of tri- and disaccharide analogues containing D-rhamnose and L-rhamnose, respectively. ROESY-NMR spectra showed that CH-6 of rhamnose and H-2 of mannose in the L-Rha containing disaccharide gave correlation. No such correlation was seen between the CH-6 of rhamnose and the H-2 of mannose in the D-Rha containing trisaccharide. Molecular dynamics studies on hexasaccharide containing L-Rha or D-Rha confirmed that these structures adopt conformations resulting in different distances between the C6-rhamnose and the H-2 mannose of the preceding residue. We also demonstrate that assignment of the absolute configuration of the rhamnosyl residue in the β-Rha-(1 → 3)-D-Man linkage can be determined using the C chemical shift of C-2 in of D-Mannose. While β-D-Rha will lead to an upfield shift of C-2 due to γ- interaction between H-1 Rha and H-2 Man, β-L-Rha will not. Our results provide insights to distinguish between D- and L-rhamnose in the α-D-Man-(1 → 4)-β-Rha-(1 → 3) repeating motif.
Topics: Autism Spectrum Disorder; Child; Disaccharides; Humans; Magnetic Resonance Spectroscopy; Mannose; Rhamnose
PubMed: 35333269
DOI: 10.1039/d2ob00131d