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1.
Carbohydr Polym ; 345: 122551, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39227094

ABSTRACT

Even though Stellaria dichotoma L. var. lanceolate (S. dichotoma) is a well-known medicinal plant in the family Caryophyllaceae, its oligosaccharides remain unexplored in terms of their potential as bioactive agents. Here, we isolated a mixture of oligosaccharides from S. dichotoma (Yield: 12 % w/w), that are primarily non-classical raffinose family oligosaccharides (RFOs). Nine major oligosaccharides were purified and identified from the mixture, including sucrose, raffinose, 1-planteose, lychnose, stellariose, along with four new non-classical RFOs. Two of the four new oligosaccharides are linear hexose pentamers with α-galactosyl extensions on their lychnose moieties, and the other two are branched hexose hexamers with α-galactosyl extensions on their stellariose groups. Their interactions with galectin-3 (Gal-3) revealed significant binding, with the terminal galactose providing enhanced affinity for the lectin. Notably, Gal-3 residues Arg144, His158, Asn160, Arg162, Asn174, Trp181, Glu184 and Arg186 coordinate with the lychnose. In vivo studies using the dextran sulfate sodium (DSS) mouse model for colitis demonstrated the ability of these carbohydrates in mitigating ulcerative colitis (UC). Overall, our study has provided structural information and potential applications of S. dichotoma oligosaccharides, also offers new approaches for the development of medicinal oligosaccharides.


Subject(s)
Colitis , Galectin 3 , Oligosaccharides , Animals , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Mice , Galectin 3/metabolism , Galectin 3/chemistry , Colitis/drug therapy , Colitis/chemically induced , Colitis/metabolism , Caryophyllaceae/chemistry , Dextran Sulfate , Mice, Inbred C57BL , Male , Humans
2.
Food Res Int ; 195: 114976, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39277213

ABSTRACT

Changes in dietary patterns and living habits have led to an increasing number of individuals with elevated cholesterol levels. Excessive consumption of high-cholesterol foods can disrupt the body's lipid metabolism. Numerous studies have firmly established the cholesterol-lowering effects of probiotics and prebiotics, with evidence showing that the synergistic use of synbiotics is functionally more potent than using probiotics or prebiotics alone. Currently, the screening strategy involves screening prebiotics for synbiotic development with probiotics as the core. However, in comparison to probiotics, there are fewer types of prebiotics available, leading to limited resources. Consequently, the combinations of synbiotics obtained are restricted, and probiotics and prebiotics are only relatively suitable. Therefore, in this study, a novel synbiotic screening strategy with prebiotics as the core was developed. The synbiotic combination of Lactobacillus rhamnosus S_82 and xylo-oligosaccharides was screened from the intestinal tract of young people through five generations of xylo-oligosaccharides. Subsequently, the cholesterol-lowering ability of the medium was simulated, and the two carbon sources of glucose and xylo-oligosaccharides were screened out. The results showed that synbiotics may participate in cholesterol-lowering regulation by down-regulating the expression of NPC1L1 gene, down-regulating ACAT2 and increasing the expression of ABCG8 gene in vitro through cell adsorption and cell absorption in vitro, and regulating the intestinal microbiota. Synbiotics hold promise as potential candidates for the prevention of hypercholesterolemia in humans and animals, and this study providing a theoretical foundation for the development of new synbiotic products.


Subject(s)
Lacticaseibacillus rhamnosus , Oligosaccharides , Prebiotics , Synbiotics , Lacticaseibacillus rhamnosus/metabolism , Oligosaccharides/pharmacology , Humans , Hypolipidemic Agents/pharmacology , Cholesterol/metabolism , Cholesterol/blood , Gastrointestinal Microbiome/drug effects , Probiotics , Glucuronates
3.
ACS Appl Mater Interfaces ; 16(37): 49913-49925, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39240782

ABSTRACT

Renal-specific nanoparticulate drug delivery systems have shown great potential in reducing systemic side effects and improving the safety and efficacy of treatments for renal diseases. Here, stearic acid-grafted chitosan oligosaccharide (COS-SA) was synthesized as a renal-targeted carrier due to the high affinity of the 2-glucosamine moiety on COS to the megalin receptor expressed on renal proximal tubular epithelial cells. Specifically, COS-SA/CLT micelles were prepared by encapsulating celastrol (CLT) with COS-SA, and different proportions of human serum albumin (HSA) were then adsorbed onto its surface to explore the interaction between the protein corona and cationic polymeric micelles. Our results showed that a multilayered protein corona, consisting of an inner "hard" corona and an outer "soft" corona, was formed on the surface of COS-SA/CLT@HSA8, which was beneficial in preventing its recognition and phagocytosis by macrophages. The formation of HSA protein corona on COS-SA/CLT micelles also increased its accumulation in the renal tubules. Furthermore, the electropositivity of COS-SA/CLT micelles affected the conformation of adsorbed proteins to various degrees. During the adsorption process, the protein corona on the surface of COS-SA/CLT@HSA1 was partially denatured. Overall, COS-SA/CLT and COS-SA/CLT@HSA micelles demonstrated sufficient safety with renal targeting potential, providing a viable strategy for the management of ischemia/reperfusion-induced acute kidney injury.


Subject(s)
Acute Kidney Injury , Chitosan , Micelles , Oligosaccharides , Protein Corona , Reperfusion Injury , Serum Albumin, Human , Chitosan/chemistry , Acute Kidney Injury/drug therapy , Acute Kidney Injury/pathology , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Animals , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Humans , Protein Corona/chemistry , Protein Corona/metabolism , Serum Albumin, Human/chemistry , Mice , Drug Delivery Systems , Male , Drug Carriers/chemistry
4.
Nutrients ; 16(17)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39275142

ABSTRACT

Immunoglobulin A (IgA) is a major gut antibody that coats commensal gut bacteria and contributes to shaping a stable gut bacterial composition. Although previous studies have shown that cyclic oligosaccharides, including cyclic nigerosyl-1,6-nigerose (CNN) and cyclodextrins (CDs, including αCD, ßCD, and γCD), alter the gut bacterial composition, it remains unclear whether cyclic oligosaccharides modify the IgA coating of gut bacteria, which relates to cyclic oligosaccharide-induced alteration of the gut bacterial composition. To address this issue, mice were maintained for 12 weeks on diets containing CNN, αCD, ßCD, or γCD; the animals' feces were evaluated for their bacterial composition and the IgA coating index (ICI), a measure of the degree of IgA coating of bacteria. We observed that the intake of each cyclic oligosaccharide altered the gut bacterial composition, with changes in the ICI found at both the phylum and genus levels. The ICI for Bacillota, Lachnospiraceae NK4A136 group, UC Lachnospiraceae, and Tuzzerella were significantly and positively correlated with the relative abundance (RA) in total bacteria for these bacteria; in contrast, significant correlations were not seen for other phyla and genera. Our observations suggest that cyclic oligosaccharide-induced modulation of the IgA coating of gut bacteria may partly relate to changes in the community structure of the gut bacteria.


Subject(s)
Feces , Gastrointestinal Microbiome , Immunoglobulin A , Oligosaccharides , Animals , Gastrointestinal Microbiome/drug effects , Oligosaccharides/pharmacology , Mice , Feces/microbiology , Bacteria/drug effects , Male , Cyclodextrins/pharmacology , Mice, Inbred C57BL
5.
Nutrients ; 16(17)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39275175

ABSTRACT

Early-life nutrition significantly impacts vaccination efficacy in infants, whose immune response to vaccines is weaker compared to adults. This study investigated vaccination efficacy in female C57Bl/6JOlaHsd mice (6 weeks old) fed diets with 0.7% galacto-oligosaccharides (GOS)/long-chain fructo-oligosaccharides (lcFOS) (9:1), 0.3% human milk oligosaccharides (HMOS), or a combination (GFH) for 14 days prior to and during vaccination. Delayed-type hypersensitivity (DTH) was measured by assessing ear swelling following an intradermal challenge. Influvac-specific IgG1 and IgG2a levels were assessed using ELISAs, while splenic T and B lymphocytes were analyzed for frequency and activation via flow cytometry. Additionally, cytokine production was evaluated using murine splenocytes co-cultured with influenza-loaded dendritic cells. Mice on the GFH diet showed a significantly enhanced DTH response (p < 0.05), increased serological IgG1 levels, and a significant rise in memory B lymphocytes (CD27+ B220+ CD19+). GFH-fed mice also exhibited more activated splenic Th1 cells (CD69+ CXCR3+ CD4+) and higher IFN-γ production after ex vivo restimulation (p < 0.05). These findings suggest that GOS/lcFOS and HMOS, particularly in combination, enhance vaccine responses by improving memory B cells, IgG production, and Th1 cell activation, supporting the potential use of these prebiotics in infant formula for better early-life immune development.


Subject(s)
Influenza Vaccines , Mice, Inbred C57BL , Milk, Human , Oligosaccharides , Animals , Oligosaccharides/pharmacology , Milk, Human/immunology , Milk, Human/chemistry , Female , Influenza Vaccines/immunology , Humans , Mice , Vaccination , Immunoglobulin G/blood , Galactose , B-Lymphocytes/immunology , Spleen/immunology , Cytokines/metabolism , Disease Models, Animal , Antibodies, Viral/blood
6.
Nutrients ; 16(17)2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39275204

ABSTRACT

Less than half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) respond to chemotherapy, and the prognosis of PDAC is poor, which may be mediated by the gut microbiota. We investigated the clinical improvement effects of 1-kestose, a fructooligosaccharide, on PDAC chemotherapy in this single-center, randomized, controlled pilot trial conducted at Fujita Health University Hospital, which enrolled patients with PDAC. The trial included 1-kestose administration and non-administration groups. The 1-kestose group received 9 g of 1-kestose daily for 12 weeks, and their blood markers, imaging studies, physical findings, and gut microbiota were evaluated. In the 1-kestose administration group, the cancer marker CA19-9 significantly decreased, and there was a reduction in the neutrophil-to-lymphocyte ratio (NLR). There was also suppression of the reduction of albumin levels and of an increase in C-reactive protein. Additionally, Escherichia coli, which typically increases in PDAC, significantly decreased in the 1-kestose group. Thus, 1-kestose altered the gut microbiota and improved the prognostic factors for PDAC. Large-scale, long-term trials of 1-kestose interventions for PDAC are thus warranted to improve the prognosis of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Gastrointestinal Microbiome , Pancreatic Neoplasms , Humans , Pilot Projects , Carcinoma, Pancreatic Ductal/drug therapy , Male , Female , Pancreatic Neoplasms/drug therapy , Gastrointestinal Microbiome/drug effects , Aged , Middle Aged , Dietary Supplements , Biomarkers, Tumor/blood , Prognosis , CA-19-9 Antigen/blood , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Escherichia coli/drug effects , Treatment Outcome , Neutrophils , Oligosaccharides/administration & dosage , Oligosaccharides/pharmacology
7.
Trop Anim Health Prod ; 56(7): 251, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225828

ABSTRACT

The use of antibiotics as conventional feed additives in poultry operations have proven useful, however resulted serious health concerns to consumer due to their bio-accumulation, besides rising problem of antimicrobial resistance in microbes, thus, an alternative to antibiotic growth promoter have called for. One of the aim of the experiment was to assess the lone and combined effects of feeding of chitosan oligosaccharide (COS) and blend of organic acids and short chain fatty acids in essential oils on growth performance, haematological parameters, relative lymphoid organ weight and innate immunity in early aged layer chick (male birds). A total of ninety, day-old chicks were randomly allotted into five groups: CO, Control group fed only poultry feed ; AGP, antibiotic growth promoter fed Avilomycin at the dose of 200 mg/kg of poultry feed; CH, chitosan oligosaccharide fed at the rate of 100 mg/kg feed; OE, blend of organic acids and short chain fatty acids in essential oils contained 1000 to 2000 mg/kg feed in a graded dose per week and CH + OE, chitosan oligosaccharide plus blend of organic acids and short chain fatty acids in essential oils at consistent rate and manner as followed for each of given feed additives when fed individually. Data on growth performance, samples for haematological parameters and innate immunity were measured and assayed on 7th, 21st and 42nd day post feeding (dpf) respectively. The results showed that compared with the control group; there is a marginal gain in body weight at 7th and 21st dpf in CH group and the corresponding CH + OE group. Feed conversion ratio in CH group was remarkably good at 7th and 21st dpf. No significant difference was observed in relative organ weights of thymus, spleen and Bursa of Fabricius in treatment groups as compared to control birds; however a significant rise in splenic weight index in OE fed birds at 42nd dpf noted. Haematological changes were inconsequential in treatment groups with an exception to enhancement of heterophil to lymphocyte ratio (H:L ratio) in CH group at 42nd dpf. Serum lysozyme activity proportionately elevated in CH + OE group on 21st and 42nd dpf when measured against control group; on the other hand no detectable augmentation of gut lysozyme activity observed. Both serum bactericidal and gut bactericidal activity boosted in combinatorial group at 42nd dpf. These results indicated that early age feeding of chitosan individually or combination with organic acids and short chain fatty acids in layer chick is beneficial, as it has the potential to enhance body weight gain to some extent and improves systemic and localized innate immunity to offer protection against infectious assaults thus may avoid early chick mortality in farms.


Subject(s)
Animal Feed , Chickens , Chitosan , Immunity, Innate , Animals , Chitosan/administration & dosage , Chitosan/pharmacology , Chickens/growth & development , Chickens/immunology , Male , Immunity, Innate/drug effects , Animal Feed/analysis , Diet/veterinary , Dietary Supplements/analysis , Random Allocation , Oils, Volatile/administration & dosage , Oils, Volatile/pharmacology , Organ Size/drug effects , Oligosaccharides/administration & dosage , Oligosaccharides/pharmacology
8.
Int J Biol Macromol ; 278(Pt 1): 134642, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39128745

ABSTRACT

The effect of whey protein isolate (WPI)- galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS) conjugates on RAW264.7 cells, and further the effect of WPI-GOS conjugates on CTX-induced immunosuppressed mice were investigated. Compared to WPI-FOS conjugates, WPI-GOS conjugates exhibited deeper glycation extent, more pronounced structural unfolding and helix-destabilizing, and obviously improved functional indicators of RAW264.7 macrophages. In addition, WPI-GOS conjugates also repaired immune organ and intestinal barrier and increased IL-1ß and IFN-γ levels in immunosuppressed mice. The alteration of gut microbiota induced by WPI-GOS conjugates changed the serum metabolites, causing the activation of NFκB pathway, which strengthens the immune system. The activation of NFκB pathway maybe associated with the mTOR signal pathway and ABC transporters. However, the precise mechanisms by which NFκB pathway interacts with mTOR signal pathway and ABC transporters to modulate the immune response need for further research.


Subject(s)
Cyclophosphamide , NF-kappa B , Oligosaccharides , Whey Proteins , Animals , Mice , Cyclophosphamide/pharmacology , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Whey Proteins/chemistry , Whey Proteins/pharmacology , RAW 264.7 Cells , NF-kappa B/metabolism , Immunosuppression Therapy , Gastrointestinal Microbiome/drug effects , Signal Transduction/drug effects , Male , TOR Serine-Threonine Kinases/metabolism
9.
Int J Biol Macromol ; 278(Pt 2): 134779, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39151850

ABSTRACT

Excessive iron in the liver may exacerbate Non-alcoholic fatty liver disease (NAFLD) by increasing the risk of liver cell expansion, inflammation and fibrosis. Ferroptosis in liver cells may lead the progression of simple fatty liver degeneration to steatohepatitis (NASH). More and more studies shew that ferroptosis played a crucial role in the pathological process of NAFLD. Based on the mechanism of ferroptosis, this study first synthesized a liver targeted 18-ß-Glycyrrhetinic-acid-chitosan oligosaccharide -N-acetylcysteine polymer (GCNp), and further curcumin (Cur) was used as model drug to prepare Cur loaded nanodelivery system (GCNp-Cur NPs). The particle size of GCNp-Cur NPs was 132.5 ± 9.8 nm, PDI was 0.148 ± 0.026 and the potential was 23.8 mV. GCNp-Cur NPs can regulate the GPX4/GSH pathway, inhibit lipid peroxidation, restore cellular oxidative environment, reduce free Fe2+, improve cellular lipid metabolism and iron metabolism, thereby NPs inhibited liver cell ferroptosis through multiple pathways. Additionally, GCNp-Cur NPs could also alleviate liver tissue lipid accumulation and oxidative damage, delaying disease progression, and providing a new method and theoretical basis for the treatment of NAFLD.


Subject(s)
Chitosan , Ferroptosis , Nanoparticles , Non-alcoholic Fatty Liver Disease , Oligosaccharides , Ferroptosis/drug effects , Chitosan/chemistry , Chitosan/pharmacology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Nanoparticles/chemistry , Animals , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Humans , Mice , Curcumin/pharmacology , Curcumin/chemistry , Male , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/drug effects , Liver/pathology , Iron/chemistry , Iron/metabolism , Polymers/chemistry , Polymers/pharmacology , Lipid Metabolism/drug effects
10.
Int J Biol Macromol ; 278(Pt 2): 134868, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39163965

ABSTRACT

Food allergy (FA) has increasingly attracted global attention in past decades. However, the mechanism and effect of FA are complex and varied, rendering it hard to prevention and management. Most of the allergens identified so far are macromolecular proteins in food and may have potential cross-reactions. Human milk oligosaccharides (HMOs) have been regarded as an ideal nutrient component for infants, as they can enhance the immunomodulatory capacity to inhibit the progress of FA. HMOs may intervene in the development of allergies by modifying gut microbiota and increasing specific short-chain fatty acids levels. Additionally, HMOs could improve the intestinal permeability and directly or indirectly regulate the balance of T helper cells and regulatory T cells by enhancing the inflammatory signaling pathways to combat FA. This review will discuss the influence factors of FA, key species of gut microbiota involved in FA, types of FA, and profiles of HMOs and provide evidence for future research trends to advance HMOs as potential therapeutic aids in preventing the progress of FA.


Subject(s)
Food Hypersensitivity , Gastrointestinal Microbiome , Milk, Human , Oligosaccharides , Humans , Gastrointestinal Microbiome/drug effects , Oligosaccharides/pharmacology , Oligosaccharides/therapeutic use , Milk, Human/immunology , Milk, Human/chemistry , Food Hypersensitivity/prevention & control , Food Hypersensitivity/immunology , Food Hypersensitivity/microbiology , Immunomodulation/drug effects , Animals
11.
Int J Biol Macromol ; 278(Pt 3): 134844, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39168191

ABSTRACT

Stachyose (STA) is a prebiotic with poor oral bioavailability. In this study, we developed stachyose caproate (C6-STA), as a novel STA derivative, to demonstrate its high adsorption rate via oral administration. Pharmacokinetic analysis reveals that after absorption, the STA derived from C6-STA reaches its highest peak in the blood, liver, and kidney at 20 min, 30 min, and 12-24 h, with approximate levels of 1200 µg/mL, 0.14 µg/mL, and 0.2-0.3 µg/mL, respectively. In addition, the accumulation of STA in prostate tissues of mice with castration-resistant prostate cancer (CRPC) (1.75 µg/mg) is 10-fold higher than that in normal prostate tissues (0.14 µg/mg). The analysis also reveals that C6-STA has t1/2 of 12.8 h and Tmax of 0.25 h, indicating that it has the potential to be used as a promising drug in clinical practice. The toxicological evaluation shows no obvious side effects of C6-STA in mice administered with a 0.2 g/kg intragastric dose. Pharmacodynamic analysis and mechanism investigation of C6-STA show its ability to inhibit peroxiredoxin 5 (PRDX5) enzyme activity, disrupt PRDX5-nuclear factor erythroid 2-related factor 2 (NRF2) interaction, and decrease NAD(P)H quinone dehydrogenase 1 (NQO1) levels. NQO1 decrease further causes the accumulation of quinone radicals, which ultimately leads to the apoptosis of LNCaP cell-derived drug-tolerant persister (DTP) cells and slows CRPC progression. Our study discovered the anti-tumor activity of stachyose and shows that prebiotics have biological functions in vivo besides in the gut. Further investigation of C6-STA, especially in CRPC patients, is warranted.


Subject(s)
Peroxiredoxins , Prebiotics , Prostatic Neoplasms, Castration-Resistant , Male , Animals , Mice , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/metabolism , Peroxiredoxins/metabolism , Humans , Cell Line, Tumor , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , NAD(P)H Dehydrogenase (Quinone)/metabolism , NF-E2-Related Factor 2/metabolism
12.
Int J Biol Macromol ; 278(Pt 3): 134910, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39173792

ABSTRACT

Chitin, an N-acetyl-D-glucosamine polymer, has multiple functions in living organisms, including the induction of disease resistance and growth promotion in plants. In addition, chitin oligosaccharides (COs) are used as the backbone of the signaling molecule Nod factor secreted by soil bacteria rhizobia to establish a mutual symbiosis with leguminous plants. Nod factor perception triggers host plant responses for rhizobial symbiosis. In this study, the effects of chitins on rhizobial symbiosis were examined in the leguminous plants Lotus japonicus and soybean. Chitin nanofiber (CNF), retained with polymeric structures, and COs elicited calcium spiking in L. japonicus roots expressing a nuclear-localized cameleon reporter. Shoot growth and symbiotic nitrogen fixation were significantly increased by CNF but not COs in L.japonicus and soybean. However, treatments with chitin and cellulose nanofiber, structurally similar polymers to CNF, did not affect shoot growth and nitrogen fixation in L.japonicus. Transcriptome analysis also supported the specific effects of CNF on rhizobial symbiosis in L.japonicus. Although chitins comprise the same monosaccharides and nanofibers share similar physical properties, only CNF can promote rhizobial nitrogen fixation in leguminous plants. Taking the advantages on physical properties, CNF could be a promising material for improving legume yield by enhancing rhizobial symbiosis.


Subject(s)
Chitin , Lotus , Nanofibers , Nitrogen Fixation , Rhizobium , Symbiosis , Lotus/microbiology , Chitin/chemistry , Chitin/pharmacology , Chitin/metabolism , Nanofibers/chemistry , Rhizobium/physiology , Plant Roots/microbiology , Plant Roots/drug effects , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Gene Expression Regulation, Plant/drug effects , Glycine max/microbiology , Glycine max/drug effects , Glycine max/growth & development
13.
Int J Biol Macromol ; 278(Pt 4): 134957, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39182881

ABSTRACT

The receptor-binding domain (RBD) is crucial for understanding how severe acute respiratory syndrome coronavirus (SARS-CoV-2) recognizes and infects host cells. Chitooligosaccharide (CS) exhibits diverse antiviral activities, with its derivatives showing remarkable efficacy in blocking SARS-CoV-2 infection. Thus, this study employed spectroscopy, virus-infected cell experiments, and molecular simulation to investigate the molecular interactions between CS and SARS-CoV-2 RBD, as well as their mechanisms. In spectroscopic experiments, all four CS variants with different molecular weights formed interactions with the RBD. These variants increased the resistance of HEK293ACE2 cells to SARS-CoV-2 invasion. Molecular docking revealed that the four CS variants could bind to the RBD through hydrogen bonding or salt-bridge interactions, forming stable complexes. Chitotetraose provided stronger protection to HEK293ACE2 cells compared to other CS variants and displayed higher molecular docking scores. Further investigation into the optimal docking conformation of chitotetraose was conducted through molecular dynamics simulation methods. This study lays a solid theoretical foundation and provides a scientific basis for the development of targeted RBD inhibitors, as well as drug screening and application against novel coronaviruses.


Subject(s)
Chitosan , Molecular Docking Simulation , Molecular Dynamics Simulation , Oligosaccharides , Protein Binding , SARS-CoV-2 , Humans , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , SARS-CoV-2/drug effects , HEK293 Cells , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , COVID-19/virology , Binding Sites , Chitin/analogs & derivatives , Chitin/chemistry , Chitin/pharmacology , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Protein Domains , COVID-19 Drug Treatment
14.
Int J Biol Macromol ; 277(Pt 2): 134346, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39094883

ABSTRACT

To date, although the high-carbohydrate (HC) feed has been extensively adopted in the aquaculture industry, its effects on the intestinal function and development of aquatic animals still remain unclear. In addition, the corresponding nutritional intervention is still barely reported. This study aimed to evaluate the influence of xylooligosaccharides (XOS) on the intestinal health of Megalobrama amblycephala subjected to a HC feeding. Fish (average weight: 44.55 ± 0.15 g) were randomly offered 3 diets, including a control one (29 % carbohydrate), a HC one (41 % carbohydrate), and a XOS supplemented one (HC + 1.0 % XOS, HCX) respectively for 12 weeks. The HC feeding caused morphological abnormalities of intestine, an increased intestinal permeability, and the intestinal immunosuppression, all of which were markedly reversed by XOS administration. In addition, compared with the HC group, HCX feeding remarkably promoted the intestinal activities of digestive and brush border enzymes, and the expressions of cell proliferation-related proteins (Wnt10b and Cyclin D1). The 16s rDNA sequencing also revealed that XOS administration increased the abundance of beneficial bacteria, and decreased that of pathogenic ones. In conclusion, dietary supplementation of XOS improved the intestinal histomorphology, barrier function, cell proliferation and bacterial communities of carbohydrate-overloaded fish Megalobrama amblycephala.


Subject(s)
Carps , Gastrointestinal Microbiome , Glucuronates , Intestines , Oligosaccharides , Animals , Gastrointestinal Microbiome/drug effects , Oligosaccharides/pharmacology , Glucuronates/pharmacology , Carps/microbiology , Carps/growth & development , Intestines/drug effects , Intestines/pathology , Intestines/microbiology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Animal Feed , Dietary Carbohydrates/pharmacology , Dietary Carbohydrates/adverse effects , Dietary Supplements
15.
Int J Biol Macromol ; 277(Pt 3): 134492, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39106929

ABSTRACT

Alginate is the general term of a polysaccharide which is widely used in the area of pharmaceutics and the food industry and is known for its unique biological activities. However, due to the low water solubility and large viscosity of alginate, its development and utilization in the agricultural field are limited. Alginate oligosaccharide (AOS) is a degradable product derived from alginate and has attracted much attention in recent years because of its specific characteristics such as a low molecular weight, high water solubility, and non-toxicity. Boar semen quality, which is affected by various factors, is an important indicator for measuring reproductive performance of boars. With the development of artificial insemination technology, high quality semen has been more and more important. Therefore, increasing semen quality is an important means to improve the reproductive performance in swine industry. In this research review, we used the PubMed database and Google Scholar and web of science to search for relevant literature on the topic of AOS in relation to boar semen quality. Key words used were alginate oligosaccharide, boars, semen quality, microbiota and metabolites. The purpose of this review article was to describe the current knowledge on the relationship between AOS and boar semen quality, and provide an overview of solutions for the decline in the boar semen quality in specific conditions. Based on the existing literature, it is evident that AOS can be used as a new type of food additive. This review paper provides a theoretical basis for the production of high-quality boar sperm and, suggests that, in the future, AOS can even aid in treating human infertility.


Subject(s)
Alginates , Oligosaccharides , Semen Analysis , Alginates/chemistry , Alginates/pharmacology , Animals , Swine , Male , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Semen/drug effects , Semen/metabolism , Semen/chemistry , Sperm Motility/drug effects
16.
Int J Biol Macromol ; 277(Pt 3): 134489, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111493

ABSTRACT

Chitooligosaccharides (COS) has attracted increasing attention due to the various promising bioactivities, tremendous potential in agricultural, environmental nutritional and functional food fields. COS as the major degradation product from chitosan or chitin is prepared via enzymatic, chemical and physical methods. Further obtained COS generally possesses different structural characteristics, such as molecular weight, degree of acetylation and degree of polymerization. Innovations into COS modification has also broadened application of COS in nutrition as well as in agricultural safety. Due to the affinity between structure and bioactivity, diversity of structural characteristics endows COS with various bioactivities like antitumor, antioxidant and anti-inflammatory effects, especially hepatoprotective activity. Therefore, the present review narrates the recent developments in COS physicochemical properties, while paying considerable attention to preparation strategies of COS and their advantages and disadvantages. Moreover, the modification of COS is also discussed including alkylation, quaternization and sulfation, herein the structure-activity relationship of COS was highlighted. Additionally, we summarize the latest research on hepatoprotective activity and mechanisms of COS. Eventually, the future directions of research on COS were discussed, which would provide a new appreciation for the future use of COS.


Subject(s)
Chitin , Chitosan , Oligosaccharides , Chitosan/chemistry , Chitosan/pharmacology , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Chitin/chemistry , Chitin/analogs & derivatives , Chitin/pharmacology , Humans , Animals , Protective Agents/pharmacology , Protective Agents/chemistry , Liver/drug effects , Liver/metabolism , Structure-Activity Relationship , Antioxidants/chemistry , Antioxidants/pharmacology
17.
ACS Appl Mater Interfaces ; 16(34): 44409-44427, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39162197

ABSTRACT

Cancer presents a significant health threat, necessitating the development of more precise, efficient, and less damaging treatment approaches. To address this challenge, we employed the 1-ethyl-(3-dimethyl aminopropyl) carbodiimide/N-hydroxy succinimide (EDC/NHS) catalytic system and utilized quaternized chitosan oligosaccharide (HTCOSC) as a drug carrier to construct a nanoparticle delivery system termed HTCOSC-cRGD-ES2-MTX (CREM). This system specifically targets integrin αvß3 on tumor cell surfaces and enables simultaneous loading of the antiangiogenic agent ES2 (IVRRADRAAVP) and the chemotherapy drug methotrexate (MTX). Due to its amphiphilic properties, CREM self-assembles into nanoparticles in aqueous solution, exhibiting an average diameter of 179.47 nm. Comparative studies demonstrated that CREM, in contrast to free ES2 and MTX-free nanoparticles (CRE), significantly suppressed the proliferation of EAhy926 endothelial cells and B16 melanoma cells in vitro, resulting in inhibition rates of 71.18 and 82.25%, respectively. Furthermore, CREM exhibited a hemolysis rate below 2%, indicating excellent in vitro antiangiogenic and antitumor activity as well as favorable blood compatibility. Additionally, both CRE and CREM demonstrated favorable tumor targeting capabilities through the specific binding action of cyclic RGD (cRGD) to integrin αvß3. Further in vivo investigations revealed that CREM induced apoptosis in tumor cells via the mitochondrial apoptotic pathway and reduced the expression of angiogenic factors such as vascular endothelial growth factor (VEGF), thereby inhibiting tumor angiogenesis. This potent antitumor effect was evident through a tumor suppression rate of 80.19%. Importantly, histopathological staining (HE staining) demonstrated the absence of significant toxic side effects of CREM on various organs compared to MTX. In conclusion, the CREM nano drug delivery system synergistically enhances the therapeutic efficacy of antiangiogenic drugs and chemotherapeutic agents, thus offering a novel targeted approach for cancer treatment.


Subject(s)
Chitosan , Methotrexate , Oligosaccharides , Methotrexate/chemistry , Methotrexate/pharmacology , Methotrexate/therapeutic use , Chitosan/chemistry , Animals , Humans , Mice , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Drug Carriers/chemistry , Cell Line, Tumor , Nanoparticles/chemistry , Cell Proliferation/drug effects , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Integrin alphaVbeta3/metabolism , Oligopeptides/chemistry , Oligopeptides/pharmacology
18.
Mar Drugs ; 22(8)2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39195483

ABSTRACT

Red seaweed carrageenans are frequently used in industry for its texturizing properties and have demonstrated antiviral activities that can be used in human medicine. However, their high viscosity, high molecular weight, and low skin penetration limit their use. Low-weight carrageenans have a reduced viscosity and molecular weight, enhancing their biological properties. In this study, ι-carrageenan from Solieria chordalis, extracted using hot water and dialyzed, was depolymerized using hydrogen peroxide and ultrasound. Ultrasonic depolymerization yielded fractions of average molecular weight (50 kDa) that were rich in sulfate groups (16% and 33%) compared to those from the hydrogen peroxide treatment (7 kDa, 6% and 9%). The potential bioactivity of the polysaccharides and low-molecular-weight (LMW) fractions were assessed using WST-1 and LDH assays for human fibroblast viability, proliferation, and cytotoxicity. The depolymerized fractions did not affect cell proliferation and were not cytotoxic. This research highlights the diversity in the biochemical composition and lack of cytotoxicity of Solieria chordalis polysaccharides and LMW fractions produced by a green (ultrasound) depolymerization method.


Subject(s)
Carrageenan , Molecular Weight , Rhodophyta , Humans , Rhodophyta/chemistry , Carrageenan/pharmacology , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Oligosaccharides/isolation & purification , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Fibroblasts/drug effects , Hydrogen Peroxide , Cell Survival/drug effects , Cell Proliferation/drug effects , Polymerization , Ultrasonic Waves , Viscosity
19.
Ecotoxicol Environ Saf ; 283: 116802, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39106567

ABSTRACT

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.


Subject(s)
Chitosan , Oligosaccharides , Testis , Male , Animals , Testis/drug effects , Chitosan/pharmacology , Oligosaccharides/pharmacology , Mice , Metabolomics , Oligospermia , Gastrointestinal Microbiome/drug effects , Signal Transduction/drug effects , Spermatogenesis/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , Phosphatidylinositol 3-Kinases/metabolism
20.
J Clin Psychopharmacol ; 44(5): 457-461, 2024.
Article in English | MEDLINE | ID: mdl-39146178

ABSTRACT

BACKGROUND: Preliminary evidence suggests that people with schizophrenia have decreased relative abundance of butyrate-producing bacteria in the gut microbiota. Butyrate plays a critical role in maintaining the integrity of the gut-blood barrier and has a number of anti-inflammatory effects. This proof-of-concept study was designed to assess whether the addition of the oligofructose-enriched inulin (OEI) prebiotic: Prebiotin could increase the production of butyrate. METHODS: Twenty-seven people who met the criteria for either Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, schizophrenia or schizoaffective disorder were entered into a 10-day, double-blind, placebo-controlled, randomized clinical trial. The study was conducted on an inpatient unit to standardize the participant diet and environment. Participants were randomized to either OEI (4 g, 3 times a day) or a placebo (4 g of maltodextrin, 3 times a day). In order to assess the effect of OEI treatment on butyrate levels, participants underwent pretreatment and posttreatment OEI challenges. The primary outcome measure was relative change in postchallenge plasma butyrate levels after 10 days of OEI treatment. RESULTS: In both the intent-to-treat and completer analyses, OEI treatment was associated with a greater number of participants who met the OEI challenge responder criteria than those treated with placebo. OEI treatment was also associated with an increase in baseline butyrate levels (effect size for the group difference in the change of baseline butyrate levels was 0.58). CONCLUSIONS: We were able to demonstrate that treatment with the prebiotic OEI selectively increased the level of plasma butyrate in people with schizophrenia.Trial registration:ClinicalTrials.gov identifier NCT03617783.


Subject(s)
Butyrates , Oligosaccharides , Prebiotics , Schizophrenia , Humans , Schizophrenia/drug therapy , Schizophrenia/blood , Prebiotics/administration & dosage , Double-Blind Method , Male , Female , Adult , Middle Aged , Oligosaccharides/administration & dosage , Oligosaccharides/pharmacology , Inulin/administration & dosage , Inulin/pharmacology , Gastrointestinal Microbiome/drug effects , Proof of Concept Study , Psychotic Disorders/drug therapy , Psychotic Disorders/diet therapy , Psychotic Disorders/blood , Young Adult
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