-
International Journal of Surgery... Nov 2015Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the... (Review)
Review
Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.
Topics: Animals; Animals, Genetically Modified; Antibodies; Disaccharides; Genetic Engineering; Graft Rejection; Humans; N-Acetylneuraminic Acid; Polysaccharides; Primates; Swine; Transplantation, Heterologous; Transplants
PubMed: 26306769
DOI: 10.1016/j.ijsu.2015.07.724 -
Gut Microbes Sep 2020Trehalose is a disaccharide and fasting-mimetic that has been both canonized and vilified for its putative cardiometabolic and microbial effects. Trehalose analogues are...
Trehalose is a disaccharide and fasting-mimetic that has been both canonized and vilified for its putative cardiometabolic and microbial effects. Trehalose analogues are currently under development to extend the key metabolic therapeutic actions of trehalose without adversely affecting host microbial communities. In the current study, we contrast the extent to which trehalose and its degradation-resistant analogue, lactotrehalose (LT), modulate microbial communities and host transcriptomic profiles. We demonstrate that trehalose and LT each exert adaptive metabolic and microbial effects that both overlap and diverge. We postulate that these effects depend both upon compound stability and bioavailability, and on stereospecific signal transduction. In context, the data suggest that trehalose is unlikely to be harmful, and yet it harbors unique effects that are not yet fully replicated by its analogues. These compounds are thus valuable probes to better define trehalose structure-function, and to offer as therapeutic metabolic agents.
Topics: Animals; Clostridioides difficile; Clostridium Infections; Dietary Sugars; Gastrointestinal Microbiome; Humans; Mice; Ribotyping; Stereoisomerism; Transcriptome; Trehalose
PubMed: 32329657
DOI: 10.1080/19490976.2020.1750273 -
Gut and Liver Jul 2016Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without... (Review)
Review
Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy.
Topics: Anti-Bacterial Agents; Cost of Illness; Disaccharides; Forecasting; Hepatic Encephalopathy; Humans; Patient Acceptance of Health Care
PubMed: 27377741
DOI: 10.5009/gnl15419 -
Marine Drugs Oct 2022Fucosylated chondroitin sulfate (FCS) from the sea cucumber (FCS) is the first one that was reported to be branched by disaccharide GalNAc-(α1,2)-Fuc (15%) and...
Fucosylated chondroitin sulfate (FCS) from the sea cucumber (FCS) is the first one that was reported to be branched by disaccharide GalNAc-(α1,2)-Fuc (15%) and sulfated Fuc (85%). Here, four size-homogenous fractions, and seven oligosaccharides, were separated from its β-eliminative depolymerized products. Detailed NMR spectroscopic and MS analyses revealed the oligomers as hexa-, hepta-, octa-, and nonasaccharide, which further confirmed the precise structure of native FCS: it was composed of the CS-E-like backbone with a full content of sulfation at O-4 and O-6 of GalNAc in the disaccharide repeating unit, and the branches consisting of sulfated fucose (Fuc and Fuc) and heterodisaccharide [GalNAc-(α1,2)-Fuc]. Pharmacologically, FCS and its depolymerized derivatives, including fractions and oligosaccharides, showed potent neurite outgrowth-promoting activity in a chain length-dependent manner. A comparison of analyses among oligosaccharides revealed that the sulfate pattern of the Fuc branches, instead of the heterodisaccharide, could affect the promotion intensity. Fuc and the saccharide length endowed the neurite outgrowth stimulation activity most.
Topics: Animals; Sea Cucumbers; Chondroitin Sulfates; Fucose; Oligosaccharides; Disaccharides; Neuronal Outgrowth; Sulfates
PubMed: 36286476
DOI: 10.3390/md20100653 -
Frontiers in Immunology 2022Type-I and Type-II LacNAc are Gal-GlcNAc disaccharides bearing a β1,3- or β1,4-linkage respectively. They exist as the backbones of Lewis antigens that are highly... (Review)
Review
Type-I and Type-II LacNAc are Gal-GlcNAc disaccharides bearing a β1,3- or β1,4-linkage respectively. They exist as the backbones of Lewis antigens that are highly expressed in several cancers. Owing to the promise of developing carbohydrate-based anti-cancer vaccines, glycan synthesis at a large scale is indeed an important task. Synthesis of Type-I and Type-II tandem repeat oligomers has been hampered by the presence of GlcNAc residues. Particularly, -protecting group plays a determining role in affecting glycosyl donor's reactivity and acceptor's nucleophilicity. This review discusses several representative studies that assembled desirable glycans in an efficient manner, such as chemoselective one-pot synthesis and chemoenzymatic methods. Additionally, we also highlight solutions that have been offered to tackle long-lasting problems, e.g., prevention of the oxazoline formation and change of donor/acceptor reactivity. In retrospect of scientific achievements, we present the current restrictions and remaining challenges in this less explored frontier.
Topics: Antigens, Neoplasm; Disaccharides; Lewis Blood Group Antigens; Oligosaccharides; Polysaccharides
PubMed: 35281035
DOI: 10.3389/fimmu.2022.858894 -
Sports Medicine (Auckland, N.Z.) Feb 2019Exercise-associated physiological disturbances alter gastrointestinal function and integrity. These alterations may increase susceptibility to dietary triggers, namely... (Review)
Review
Exercise-associated physiological disturbances alter gastrointestinal function and integrity. These alterations may increase susceptibility to dietary triggers, namely gluten and a family of short-chain carbohydrates known as FODMAPs (fermentable oligo-, di-, monosaccharides and polyols). A recent surge in the popularity of gluten-free diets (GFDs) among athletes without celiac disease has been exacerbated by unsubstantiated commercial health claims and high-profile athletes citing this diet to be the secret to their success. Up to 41% of athletes at least partially adhere to a GFD diet, with the belief that gluten avoidance improves exercise performance and parameters influencing performance, particularly gastrointestinal symptoms (GIS). In contrast to these beliefs, seminal work investigating the effects of a GFD in athletes without celiac disease has demonstrated no beneficial effect of a GFD versus a gluten-containing diet on performance, gastrointestinal health, inflammation, or perceptual wellbeing. Interestingly, the subsequent reduction in FODMAPs concurrent with the elimination of gluten-containing grains may actually be the factors affecting GIS improvement, not gluten. Pre-existent in the gastrointestinal tract or ingested during exercise, the osmotic and gas-producing effects of variably absorbed FODMAPs may trigger or increase the magnitude of exercise-associated GIS. Research using FODMAP reduction to address gastrointestinal issues in clinically healthy athletes is emerging as a promising strategy to reduce exercise-associated GIS. Applied research and practitioners merging clinical and sports nutrition methods will be essential for the effective use of a low FODMAP approach to tackle the multifactorial nature of gastrointestinal disturbances in athletes.
Topics: Athletes; Diet; Diet, Gluten-Free; Disaccharides; Gastrointestinal Diseases; Glutens; Humans; Irritable Bowel Syndrome; Monosaccharides; Nutritional Requirements; Oligosaccharides
PubMed: 30671907
DOI: 10.1007/s40279-018-01034-0 -
Nutrients Nov 2020Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its... (Review)
Review
Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its therapy mainly relies on symptomatic treatments. Changes in lifestyle and dietary behavior are usually the first step, but unfortunately, there is little high-quality scientific evidence regarding a dietary approach. This is due to the difficulty in setting up randomized double-blind controlled trials which objectively evaluate efficacy without the risk of a placebo effect. However, a Low Fermentable Oligo-, Di- and Mono-saccharides And Polyols (FODMAP) Diet (LFD) and Gluten Free Diet (GFD) are among the most frequently suggested diets. This paper aims to evaluate their possible role in IBS management. A GFD is less restrictive and easier to implement in everyday life and can be suggested for patients who clearly recognize gluten as a trigger of their symptoms. An LFD, being more restrictive and less easy to learn and to follow, needs the close supervision of a skilled nutritionist and should be reserved for patients who recognize that the trigger of their symptoms is not, or not only, gluten. Even if the evidence is of very low-quality for both diets, the LFD is the most effective among the dietary interventions suggested for treating IBS, and it is included in the most updated guidelines.
Topics: Clinical Trials as Topic; Diet, Carbohydrate-Restricted; Diet, Gluten-Free; Disaccharides; Fermentation; Humans; Irritable Bowel Syndrome; Monosaccharides; Oligosaccharides; Polymers; Treatment Outcome
PubMed: 33139629
DOI: 10.3390/nu12113368 -
Biosynthesis and Biological Significances of LacdiNAc Group on - and -Glycans in Human Cancer Cells.Biomolecules Jan 2022An increasing number of studies have shown that the disaccharide GalNAcβ1→4GlcNAc (LacdiNAc) group bound to - and -glycans in glycoproteins is expressed in a variety... (Review)
Review
An increasing number of studies have shown that the disaccharide GalNAcβ1→4GlcNAc (LacdiNAc) group bound to - and -glycans in glycoproteins is expressed in a variety of mammalian cells. Biosynthesis of the LacdiNAc group was well studied, and two β4--acetylgalactosaminyltransferases, β4GalNAcT3 and β4GalNAcT4, have been shown to transfer -acetylgalactosamine (GalNAc) to -acetylglucosamine (GlcNAc) of - and -glycans in a β-1,4-linkage. The LacdiNAc group is often sialylated, sulfated, and/or fucosylated, and the LacdiNAc group, with or without these modifications, is recognized by receptors and lectins and is thus involved in the regulation of several biological phenomena, such as cell differentiation. The occurrences of the LacdiNAc group and the β4GalNAcTs appear to be tissue specific and are closely associated with the tumor progression or regression, indicating that they will be potent diagnostic markers of particular cancers, such as prostate cancer. It has been demonstrated that the expression of the LacdiNAc group on -glycans of cell surface glycoproteins including β1-integrin is involved in the modulation of their protein functions, thus affecting cellular invasion and other malignant properties of cancer cells. The biological roles of the LacdiNAc group in cancer cells have not been fully understood. However, the re-expression of the LacdiNAc group on -glycans, which is lost in breast cancer cells by transfection of the β4GalNAcT4 gene, brings about the partial restoration of normal properties and subsequent suppression of malignant phenotypes of the cells. Therefore, elucidation of the biological roles of the LacdiNAc group in glycoproteins will lead to the suppression of breast cancers.
Topics: Animals; Breast Neoplasms; Female; Humans; Lactose; Mammals; N-Acetylgalactosaminyltransferases; Polysaccharides
PubMed: 35204696
DOI: 10.3390/biom12020195 -
Journal of Animal Science Feb 2022A completely randomized design employing a 2 × 2 factorial experiment was designed in this study to evaluate the effects of in ovo injection of disaccharide (DS)...
A completely randomized design employing a 2 × 2 factorial experiment was designed in this study to evaluate the effects of in ovo injection of disaccharide (DS) and/or methionine (Met) on hatchability, growth performance, blood hematology, and serum antioxidant parameters in geese. A total of 600 fertilized geese's eggs containing live embryo were randomly assigned into 4 groups with 6 replicates and 25 eggs per replicate. Factors in four groups comprised noninjection, DS injection (25 g/L maltose + 25 g/L sucrose + 7.5 g/L NaCl), Met injection (5 g/L Met + 7.5 g/L NaCl), or DS plus Met injection (25 g/L maltose + 25 g/L sucrose + 5 g/L Met + 7.5 g/L NaCl), respectively. We found that the administration of DS in embryo increased hatching time, yolk sac-free carcass weight, yolk sac-free carcass indexes and decreased assisted hatching ratio, yolk sac weight, yolk sac indexes, but did not affect hatchability and mortality. Moreover, higher body weight and serum glucose concentrations in DS injection group compared with noninjection group were observed on day of hatching. The body weight and average daily gain (ADG) of geese in DS injection group were higher than noninjection group after incubation. In ovo injection of Met increased hatching time and yolk sac-free carcass indexes, but decreased yolk sac indexes. In addition, the strategy of in ovo feeding of Met led to higher body weight, ADG, serum uric acid, glutathione (GSH), and glutathione peroxidase concentrations, as well as lower GSSG/GSH ratio, serum glutathione disulfide (GSSG), and malondialdehyde (MDA) concentrations than the noninjection group on day of hatching. The post-hatching body weight, ADG, serum total protein, albumin, and uric acid concentrations increased, whereas post-hatching serum GSSG and MDA concentrations and GSSG/GSH ratio decreased when injected with Met. In addition, synergistic effects of in ovo injection of DS plus Met on hatching time as well as post-hatching body weight and ADG were observed. Therefore, in ovo injection of DS plus Met was demonstrated to be a way to improve the development of geese during early incubation stages.
Topics: Animals; Antioxidants; Chickens; Disaccharides; Geese; Hematology; Methionine; Ovum; Uric Acid
PubMed: 35094079
DOI: 10.1093/jas/skac014 -
The Cochrane Database of Systematic... Jan 2021Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial.
OBJECTIVES
The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials.
SELECTION CRITERIA
Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.
MAIN RESULTS
We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision).
AUTHORS' CONCLUSIONS
Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.
Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Colitis, Ulcerative; Crohn Disease; Disaccharides; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Fumarates; Hematinics; Humans; Iron Compounds; Maltose; Middle Aged; Placebos; Pyrones; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33471939
DOI: 10.1002/14651858.CD013529.pub2