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Nature Communications May 2024The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the...
The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the major components of the mucus lining the intestine. Despite that adhesion to mucins is considered critical for the persistence of A. muciniphila in the human intestinal tract, our knowledge of how this intestinal symbiont recognizes and binds to mucins is still limited. Here, we first show that the mucin-binding properties of A. muciniphila are independent of environmental oxygen concentrations and not abolished by pasteurization. We then dissected the mucin-binding properties of pasteurized A. muciniphila by use of a recently developed cell-based mucin array that enables display of the tandem repeats of human mucins with distinct O-glycan patterns and structures. We found that A. muciniphila recognizes the unsialylated LacNAc (Galβ1-4GlcNAcβ1-R) disaccharide selectively on core2 and core3 O-glycans. This disaccharide epitope is abundantly found on human colonic mucins capped by sialic acids, and we demonstrated that endogenous A. muciniphila neuraminidase activity can uncover the epitope and promote binding. In summary, our study provides insights into the mucin-binding properties important for colonization of a key mucin-foraging bacterium.
Topics: Akkermansia; Humans; Mucins; Polysaccharides; Neuraminidase; Protein Binding; Glycosylation; Disaccharides; Verrucomicrobia; Epitopes; Bacterial Adhesion
PubMed: 38811534
DOI: 10.1038/s41467-024-48770-8 -
The Journal of International Medical... May 2024To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis.
OBJECTIVE
To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis.
METHODS
We evenly allocated 25 Sprague-Dawley rats into five groups: normal rats (control group), cirrhotic rats receiving IV normal saline (liver cirrhosis [LC] group), and cirrhotic rats receiving 20, 40, or 80 mg/kg IV ferric carboxymaltose (LC-iron20, LC-iron40, and LC-iron80 group, respectively). Biochemical parameters were compared at 0, 7, 14, 21, and 28 days. The degrees of hepatic fibrosis and iron deposition were evaluated. Inflammatory and oxidative stress markers were also compared.
RESULTS
There were no significant differences in the 28-day serum alanine aminotransferase levels among the LC-iron20, LC-iron40, and LC-iron80 groups (69 ± 7, 1003 ± 127, 1064 ± 309, 919 ± 346, and 820 ± 195 IU/L in the control, LC, LC-iron20, LC-iron40, and LC-iron80 groups, respectively). Hepatic iron accumulation increased in a dose-dependent manner, but the degree of hepatic fibrosis was comparable among the groups. The inflammatory and oxidative stress marker levels did not differ significantly according to the IV iron dose.
CONCLUSIONS
Administration of IV iron at various high doses appears safe in our rat model of cirrhosis.
Topics: Animals; Rats, Sprague-Dawley; Liver; Oxidative Stress; Male; Liver Cirrhosis; Disease Models, Animal; Rats; Ferric Compounds; Iron; Injections, Intravenous; Alanine Transaminase; Maltose; Biomarkers; Liver Function Tests; Dose-Response Relationship, Drug
PubMed: 38811356
DOI: 10.1177/03000605241253733 -
Biological & Pharmaceutical Bulletin 2024Glycosaminoglycans (GAGs), such as heparan sulfate (HS), play essential roles in living organisms. Understanding the functionality of HS and its involvement in disease...
Development of an Analytical Method for Unsaturated Disaccharides from Heparan Sulfate Using Dansylhydrazine Derivatization and High-Performance Liquid Chromatography with Fluorescence Detection.
Glycosaminoglycans (GAGs), such as heparan sulfate (HS), play essential roles in living organisms. Understanding the functionality of HS and its involvement in disease progression necessitates the sensitive and quantitative detection of HS-derived unsaturated disaccharides. Conventionally, fluorescence derivatization precedes the HPLC analysis of these disaccharides. However, the presence of excess unreacted derivatization reagents can inhibit rapid and sensitive analysis in chromatographic determinations. In this study, we describe analytical methods that use dansylhydrazine as a derivatization agent for the detection and determination of HS-derived unsaturated disaccharides using HPLC. In addition, we have developed a straightforward method for removing excess unreacted reagent using a MonoSpin NH column. This method may be employed to remove excess pre-labeling reagents, thereby facilitating the analysis of HS-derived unsaturated disaccharides with satisfactory reproducibility.
Topics: Chromatography, High Pressure Liquid; Heparitin Sulfate; Disaccharides; Dansyl Compounds; Hydrazines; Spectrometry, Fluorescence; Fluorescence
PubMed: 38811191
DOI: 10.1248/bpb.b24-00194 -
Neuropharmacology Sep 2024Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and...
Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [H]raclopride on dopamine D2/3 receptors, [H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [H]UCB-J and [H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.
Topics: Animals; Swine, Miniature; Swine; Sucrose; Male; Receptor, Metabotropic Glutamate 5; Receptors, Cannabinoid; Synapses; Receptor, Cannabinoid, CB1; Receptors, Dopamine D2; Brain; Female; Receptors, Dopamine D3
PubMed: 38810925
DOI: 10.1016/j.neuropharm.2024.110018 -
Applied Microbiology and Biotechnology May 2024Galacto-oligosaccharides (GOS) are prebiotic compounds that are mainly used in infant formula to mimic bifidogenic effects of mother's milk. They are synthesized by...
Galacto-oligosaccharides (GOS) are prebiotic compounds that are mainly used in infant formula to mimic bifidogenic effects of mother's milk. They are synthesized by β-galactosidase enzymes in a trans-glycosylation reaction with lactose. Many β-galactosidase enzymes from different sources have been studied, resulting in varying GOS product compositions and yields. The in vivo role of these enzymes is in lactose hydrolysis. Therefore, the best GOS yields were achieved at high lactose concentrations up to 60%wt, which require a relatively high temperature to dissolve. Some thermostable β-glucosidase enzymes from thermophilic bacteria are also capable of using lactose or para nitrophenyl-galactose as a substrate. Here, we describe the use of the β-glucosidase BglA from Thermotoga maritima for synthesis of oligosaccharides derived from lactose and cellobiose and their detailed structural characterization. Also, the BglA enzyme kinetics and yields were determined, showing highest productivity at higher lactose and cellobiose concentrations. The BglA trans-glycosylation/hydrolysis ratio was higher with 57%wt lactose than with a nearly saturated cellobiose (20%wt) solution. The yield of GOS was very high, reaching 72.1%wt GOS from lactose. Structural elucidation of the products showed mainly β(1 → 3) and β(1 → 6) elongating activity, but also some β(1 → 4) elongation was observed. The β-glucosidase BglA from T. maritima was shown to be a very versatile enzyme, producing high yields of oligosaccharides, particularly GOS from lactose. KEY POINTS: • β-Glucosidase of Thermotoga maritima synthesizes GOS from lactose at very high yield. • Thermotoga maritima β-glucosidase has high activity and high thermostability. • Thermotoga maritima β-glucosidase GOS contains mainly (β1-3) and (β1-6) linkages.
Topics: Thermotoga maritima; Lactose; Cellobiose; beta-Glucosidase; Kinetics; Oligosaccharides; Glycosylation; Hydrolysis; Temperature; Enzyme Stability
PubMed: 38809317
DOI: 10.1007/s00253-024-13183-6 -
Laeknabladid Jun 2024High FODMAP (fermentable oligo-, di, monosaccharides and polyols) foods have been linked with worsening symptoms of IBS patients. The aim was to compare gastrointestinal... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
INTRODUCTION
High FODMAP (fermentable oligo-, di, monosaccharides and polyols) foods have been linked with worsening symptoms of IBS patients. The aim was to compare gastrointestinal symptoms and dietary intake of patients with irritable bowel syndrome following a low FODMAP diet, with or without individual nutrition therapy.
MATERIALS AND METHODS
A total of 54 patients that met Rome IV criteria for IBS were randomized into two groups, guided group (individual nutrition therapy, n=28) and self-management group (learned about low FODMAP diet online, n=26). Both groups followed low FODMAP diet for 4 weeks. Four-day food records were used to assess dietary intake. Symptoms were assessed by the IBS-severity scoring system (ISB-SSS).
RESULTS
The number of subjects who did not complete the study was 13, thereof five in the nutrition therapy and eight in the self-management group, leaving 23 and 18 subjects available for analysis, respectively. Symptoms declined from baseline to endpoint in both groups, by 183±101 points on average in the group receiving nutrition therapy (p< 0.001) and 132±110 points in the self-management group (p< 0.001), with no difference between groups. At baseline, about 80% of meals in both groups contained food high in FODMAP's. The corresponding proportion was 9% and 36% in week 3 in the nutrition therapy and self-management group, respectively (p< 0.001).
CONCLUSION
Both groups experienced relieve of symptoms, but compliance to the low FODMAP diet was better in the group receiving individual nutrition therapy compared with the group who only received instructions on how to learn about low FODMAP diet online.
Topics: Humans; Irritable Bowel Syndrome; Treatment Outcome; Fermentation; Monosaccharides; Time Factors; Middle Aged; Polymers; Diet, Carbohydrate-Restricted; Adult; Disaccharides; Severity of Illness Index; Male; Female; Dietary Carbohydrates; Oligosaccharides; Nutrition Therapy; Nutritive Value; FODMAP Diet
PubMed: 38809220
DOI: 10.17992/lbl.2024.05.796 -
RSC Advances May 2024Deep eutectic solvents (DESs), characterized by their low volatility, non-toxicity, and biodegradability, have gained attention as green solvents due to their minimal...
Deep eutectic solvents (DESs), characterized by their low volatility, non-toxicity, and biodegradability, have gained attention as green solvents due to their minimal environmental impact and sustainability. The choline chloride/glucose DES, composed solely of biomass, is notable for its high biocompatibility and ability to be prepared at low cost. However, it is also known for its low thermal stability and tendency to denature when heated. In this study, we approached the choline chloride/glucose DES, with its thermal denaturation properties, as a unique chemical conversion medium entirely constituted from biomass. We investigated the thermal denaturation and reaction behaviors of the DES when subjected to prolonged heating. It was found that the choline chloride/glucose DES was relatively thermally stable at around 100 °C, but underwent thermal denaturation at 130 °C, enabling the production of 5-HMF and seven types of rare sugars derived from glucose. The yield of disaccharides containing seven types of rare sugars and 5-HMF relative to the weight of glucose was as high as approximately 70% and 5%, respectively. This study thus reveals that simply heating a liquid composed exclusively of biomass under mild conditions can generate a range of high-value compounds.
PubMed: 38808234
DOI: 10.1039/d4ra02546f -
ENeuro Jun 2024Amylin, a pancreatic hormone that is cosecreted with insulin, has been highlighted as a potential treatment target for obesity. Amylin receptors are distributed widely...
Amylin, a pancreatic hormone that is cosecreted with insulin, has been highlighted as a potential treatment target for obesity. Amylin receptors are distributed widely throughout the brain and are coexpressed on mesolimbic dopamine neurons. Activation of amylin receptors is known to reduce food intake, but the neurochemical mechanisms behind this remain to be elucidated. Amylin receptor activation in the ventral tegmental area (VTA), a key dopaminergic nucleus in the mesolimbic reward system, has a potent ability to suppress intake of palatable fat and sugar solutions. Although previous work has demonstrated that VTA amylin receptor activation can dampen mesolimbic dopamine signaling elicited by random delivery of sucrose, whether this is also the case for fat remains unknown. Herein we tested the hypothesis that amylin receptor activation in the VTA of male rats would attenuate dopamine signaling in the nucleus accumbens core in response to random intraoral delivery of either fat or sugar solutions. Results show that fat solution produces a greater potentiation of accumbens dopamine than an isocaloric sucrose solution. Moreover, activation of VTA amylin receptors elicits a more robust suppression of accumbens dopamine signaling in response to fat solution than to sucrose. Taken together these results shed new light on the amylin system as a therapeutic target for obesity and emphasize the reinforcing nature of high-fat/high-sugar diets.
Topics: Animals; Ventral Tegmental Area; Male; Dopamine; Nucleus Accumbens; Receptors, Islet Amyloid Polypeptide; Rats, Sprague-Dawley; Dietary Fats; Signal Transduction; Amylin Receptor Agonists; Rats; Sucrose
PubMed: 38806231
DOI: 10.1523/ENEURO.0133-24.2024 -
PeerJ 2024The burgeoning issue of landfill leachate, exacerbated by urbanization, necessitates evaluating its biological impact, traditionally overshadowed by physical and...
The burgeoning issue of landfill leachate, exacerbated by urbanization, necessitates evaluating its biological impact, traditionally overshadowed by physical and chemical assessments. This study harnesses , a model organism, to elucidate the physiological toxicity of landfill leachate subjected to different treatment processes: nanofiltration reverse osmosis tail water (NFRO), membrane bioreactor (MBR), and raw leachate (RAW). Our investigation focuses on the modulation of sugar metabolism, particularly trehalose-a disaccharide serving dual functions as an energy source and an anti-adversity molecule in invertebrates. Upon exposure, showcased a 60-70% reduction in glucose and glycogen levels alongside a significant trehalose increase, highlighting an adaptive response to environmental stress by augmenting trehalose synthesis. Notably, trehalose-related genes in the NFRO group were up-regulated, contrasting with the MBR and RAW groups, where trehalose synthesis genes outpaced decomposition genes by 20-30 times. These findings suggest that predominantly counters landfill leachate-induced stress through trehalose accumulation. This research not only provides insights into the differential impact of leachate treatment methods on but also proposes a molecular framework for assessing the environmental repercussions of landfill leachate, contributing to the development of novel strategies for pollution mitigation and environmental preservation.
Topics: Animals; Caenorhabditis elegans; Trehalose; Water Pollutants, Chemical; Stress, Physiological
PubMed: 38799059
DOI: 10.7717/peerj.17332 -
Veterinary World Apr 2024Stingless bees are generally found in tropical countries, including Indonesia. In West Sumatra, stingless bees are known as , consist of several species with different...
BACKGROUND AND AIM
Stingless bees are generally found in tropical countries, including Indonesia. In West Sumatra, stingless bees are known as , consist of several species with different characteristics; however, the properties of honey produced by stingless bees have not yet been explored. This study aimed to determine the physicochemical, antioxidant, and antimicrobial activities as well as the microbiota profile of stingless bee honey from the bee species , , , and that are intensively developed in West Sumatra, Indonesia.
MATERIALS AND METHODS
Honey produced by the stingless bee species , . , , and originating in West Sumatra was examined in the present study. The physicochemical properties (Association of Official Analytical Chemists), antioxidant activity (2,2-diphenyl-1-picrylhydrazyl technique), total phenols (Folin-Ciocalteu method), antimicrobial activity (Agar-Well diffusion test), total lactic acid bacteria, and microbiota diversity were measured in stingless bee honey samples.
RESULTS
Stingless bee species significantly affected the physicochemical properties, antioxidant activity, total phenolic content, antimicrobial activity, and total lactic acid bacteria (p = 0.05), except for the crude fiber content. The carbohydrate profiles of honey produced by and were dominated by monosaccharides, whereas those of honey from and were dominated by disaccharides. In terms of antioxidant activity (half maximal inhibitory concentration [IC] value), there were no significant differences (p > 0.05) between honey from , , and , but there were significant differences (p > 0.05) between honey from . The honey of and had the highest total phenolic content (65.65 ± 14.00 and 69.78 ± 8.06, respectively). In addition, honey from the four stingless bee species showed antimicrobial activity against the pathogenic bacteria , , , and . From the principal co-ordinate analysis (PCoA) results, it can be concluded that the microbiota profiles of the four stingless bee honey samples differed.
CONCLUSION
The results showed that honey from , , , and has different physicochemical characteristics, antioxidant activity, antimicrobial activity, and microbiota diversity. By knowing the content of this stingless bee honey, the results of this study can be used as information that this stingless bee honey has the potential as a functional food that is beneficial for health.
PubMed: 38798299
DOI: 10.14202/vetworld.2024.785-795