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Journal of Hazardous Materials Sep 2023Nitrogen dioxide (NO) is a widespread air pollutant. Epidemiological evidence indicates that NO is associated with an increase of incidence rate and mortality of asthma,...
Nitrogen dioxide (NO) is a widespread air pollutant. Epidemiological evidence indicates that NO is associated with an increase of incidence rate and mortality of asthma, but its mechanism is still unclear. In this study, we exposed mice to NO (5 ppm, 4 h per day for 30 days) intermittently to investigate the development and potential toxicological mechanisms of allergic asthma. We randomly assigned 60 male Balb/c mice to four groups: saline control, ovalbumin (OVA) sensitization, NO alone, and OVA+NO groups. The involved mechanisms were found from the perspective of airway inflammation and oxidative stress. The results showed that NO exposure could aggravate lung inflammation in asthmatic mice, and airway remodeling was characterized by significant thickening of the airway wall and infiltration of inflammatory cells. Moreover, NO would aggravate the airway hyperresponsiveness (AHR), which is characterized by significantly elevated inspiratory resistance (Ri) and expiratory resistance (Re), as well as decreased dynamic lung compliance (Cldyn). In addition, NO exposure promoted pro-inflammatory cytokines (IL-6 and TNF-α) and serum immunoglobulin (IgE) production. The imbalance of Th1/Th2 cell differentiation (IL-4 increased, IFN-γ reduced, IL-4/IFN-γ significantly increased) played a key role in the inflammatory response of asthma under NO exposure. In a nutshell, NO exposure could promote allergic airway inflammation and increase asthma susceptibility. The levels of ROS and MDA among asthmatic mice exposed to NO increased significantly, while GSH levels sharply decreased. These findings may provide better toxicological evidence for the mechanisms of allergic asthma risk due to NO exposure.
Topics: Mice; Male; Animals; Nitrogen Dioxide; Interleukin-4; Asthma; Inflammation; Ovalbumin; Oxidative Stress
PubMed: 37295329
DOI: 10.1016/j.jhazmat.2023.131787 -
International Journal of Pharmaceutics Aug 2023In recent years, protein drug development has gained momentum, and simple and facile controlled-release systems without loss of activity are required. Herein, we...
In recent years, protein drug development has gained momentum, and simple and facile controlled-release systems without loss of activity are required. Herein, we developed a sustained-release system for protein drugs by exploiting the "astringency" mechanism, namely insoluble precipitate formation by interacting with tannic acid. Tannic acid formed insoluble precipitates with various protein drugs, such as nisin, insulin, lysozyme, ovalbumin, hyaluronidase, and human immunoglobulin G, through hydrophobic interactions and hydrogen bonds. The lysozyme/tannic acid complex retained in vitro lytic activity. Precipitates of the insulin/tannic acid complex prolonged hypoglycemic effects without loss of activity after subcutaneous administration. The ovalbumin/tannic acid complex enhanced anti-ovalbumin antibody production induced by ovalbumin, which may be attributed to its sustained-release profile. Accordingly, tannic acid is useful as a simple and user-friendly drug delivery system for protein drugs.
Topics: Humans; Muramidase; Delayed-Action Preparations; Tannins; Ovalbumin; Insulins
PubMed: 37454828
DOI: 10.1016/j.ijpharm.2023.123229 -
Food Chemistry Sep 2022This study aimed to establish binary protein system on egg white ovalbumin (OVA) -lysozyme (LYS), and investigated the relationship between co-aggregation and...
This study aimed to establish binary protein system on egg white ovalbumin (OVA) -lysozyme (LYS), and investigated the relationship between co-aggregation and co-gelation. We focused on the formation of OVA-LYS complex, the typical thermo-dynamically favored coacervation process, in terms of gelling properties, microstructure and thermodynamics. Benefited from synergistic effects during co-gelation, the thermally induced gels of OVA-LYS complex formed at extremely low protein concentration (18 mg/mL) and showed higher storage modulus with increasing LYS concentration. Moreover, the rising particle size, reduced zeta potential, unordered secondary structure and strengthened protein chain were observed with the addition of LYS. Remarkably, the divalent ions enhanced thermodynamic stability of OVA-LYS complex, although the growth of aggregates units were prevented by ions at room temperature. ITC and molecular docking analyses revealed the binding affinity stoichiometry and combination phase, which were closely related to the decrease of minimum energy resulted from the formation of hydrogen bond.
Topics: Antiviral Agents; Egg White; Gels; Molecular Docking Simulation; Muramidase; Ovalbumin; Thermodynamics
PubMed: 35483286
DOI: 10.1016/j.foodchem.2022.133030 -
Methods in Molecular Biology (Clifton,... 2022Aeroallergens are common inducers of asthma in humans and are widely used in experimental research to generate animal models of this disease. In this chapter, we...
Aeroallergens are common inducers of asthma in humans and are widely used in experimental research to generate animal models of this disease. In this chapter, we describe four mouse models of aeroallergen-induced asthma. These models differ in type and number of allergens used, route and duration of allergen exposure, and utilization of an adjuvant, representing different mechanistic variants of asthma. In addition, we describe several basic methods that are commonly used in mechanistic studies of asthma in mice. These methods include tracheotomy and bronchoalveolar lavage, cytospin and morphologic analysis of bronchoalveolar lavage cells, and lung harvest and digestion for generation of single-cell suspension.
Topics: Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Lung; Mice; Mice, Inbred BALB C; Ovalbumin
PubMed: 35771460
DOI: 10.1007/978-1-0716-2364-0_1 -
Nano Letters Nov 2023Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier...
Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier remains a major challenge in the development of intranasal vaccines. Herein, a transmucosal nanovaccine based on cationic fluorocarbon modified chitosan (FCS) is developed to induce mucosal immunity. In our system, FCS can self-assemble with the model antigen ovalbumin and TLR9 agonist CpG, effectively promoting the maturation and cross-presentation of dendritic cells. More importantly, it can enhance the production of secretory immunoglobin A (sIgA) at mucosal surfaces for those intranasally vaccinated mice, which in the meantime showed effective production of immunoglobulin G (IgG) systemically. As a proof-of-concept study, such a mucosal vaccine inhibits ovalbumin-expressing B16-OVA melanoma, especially its lung metastases. Our work presents a unique intranasal delivery system to deliver antigen across mucosal epithelia and promote mucosal and systemic immunity.
Topics: Mice; Animals; Ovalbumin; Immunity, Mucosal; Adjuvants, Immunologic; Antigens; Mucous Membrane; Vaccines; Mice, Inbred BALB C
PubMed: 37943583
DOI: 10.1021/acs.nanolett.3c03419 -
International Journal of Biological... Jun 2023The polymeric materials formed by proteins and polysaccharides through molecular interactions have attracted public attention. In this study, a novel binary complex...
The polymeric materials formed by proteins and polysaccharides through molecular interactions have attracted public attention. In this study, a novel binary complex consisting of ovalbumin (OVA) and fucoidan (FUC) was obtained by electrostatic self-assembly. The self-assembly properties and the formation mechanism of the OVA-FUC binary complex were investigated by changing the charging degree and density of complex through altering pH value and polysaccharides proportion. Structural changes during the OVA-FUC electrostatic self-assembly process were investigated by a phase diagram, ζ-potential, and particle size. The optimal conditions for preparing soluble OVA-FUC binary complex were determined by the protein retention rate and insoluble solids content. Results showed that the soluble OVA-FUC binary complex could be obtained at the pH of 3.5 to 5, and the insoluble OVA-FUC binary complex was generated at the pH of 2.5 to 3.5. The OVA-FUC binary complex (19 ± 0.29 mN/m) possessed a medium ability to reduce interfacial tension of the water-oil interface compared with OVA (15 ± 1.13 mN/m) and FUC (24 ± 0.3 mN/m), indicating that OVA-FUC binary complex has good amphiphilicity and can be applied as a potential pH-controlled emulsifier in function food systems for delivering bioactive substances.
Topics: Ovalbumin; Polysaccharides; Emulsifying Agents
PubMed: 37121411
DOI: 10.1016/j.ijbiomac.2023.124644 -
Methods in Molecular Biology (Clifton,... 2022Spherical or discoidal lipid polymer nanostructures bearing cationic charges successfully adsorb a variety of oppositely charged antigens (Ag) such as proteins,...
Spherical or discoidal lipid polymer nanostructures bearing cationic charges successfully adsorb a variety of oppositely charged antigens (Ag) such as proteins, peptides, nucleic acids, or oligonucleotides. This report provides instructions for the preparation and physical characterization of four different cationic nanostructures able to combine and deliver antigens to the immune system: (1) dioctadecyl dimethylammonium bromide (DODAB) bilayer fragments (DODAB BF); (2) polystyrene sulfate (PSS) nanoparticles (NPs) covered with one cationic dioctadecyl dimethylammonium bromide bilayer (DODAB) named (PSS/DODAB); (3) cationic NPs of biocompatible polymer poly(methyl methacrylate) (PMMA) prepared by emulsion polymerization of the methyl methacrylate (MMA) monomer in the presence of DODAB BF (PMMA/DODAB NPs); (4) antigen NPs (NPs) where the cationic polymer poly(diallyl dimethyl ammonium chloride) (PDDA) directly combined at nontoxic and low dose with the antigen (Ag); when the oppositely charged model antigen is ovalbumin (OVA), NPs are named PDDA/OVA. These nanostructures provide adequate microenvironments for carrying and delivering antigens to the antigen-presenting cells of the immune system.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Cations; Nanoparticles; Ovalbumin; Polymers; Polymethyl Methacrylate; Quaternary Ammonium Compounds; Vaccines
PubMed: 34918247
DOI: 10.1007/978-1-0716-1892-9_10 -
Investigative Ophthalmology & Visual... Apr 2023Allergic conjunctivitis (AC) is a common allergic condition worldwide that requires accurate screening and early diagnosis. We found that gp130 is essential for AC, as...
PURPOSE
Allergic conjunctivitis (AC) is a common allergic condition worldwide that requires accurate screening and early diagnosis. We found that gp130 is essential for AC, as gp130 levels are elevated in AC. Therefore, this study aimed to elucidate the functions and the possible underlying mechanisms of gp130 in AC.
METHODS
To compare mRNA expression profiles, the conjunctival tissues of BALB/c mice with ovalbumin (OVA)-induced AC were subjected to RNA-sequencing (RNA-seq) analysis followed by bioinformatic analysis. A nonrandomized study involving 57 patients with AC and 24 sex- and age-matched healthy individuals was conducted. A protein chip was used to detect cytokine levels in patient tears. Differentially expressed proteins in patient serum were detected using label-free quantitative mass spectrometry. Histamine-stimulated conjunctival epithelial cells (HConEpiCs) were used to construct a cell model. LMT-28 which can inhibit gp130 phosphorylation was dropped onto the murine ocular surface, and the resulting symptoms were observed.
RESULTS
Gp130 is upregulated in the conjunctival tissues of OVA-induced mice, the serum and tears of patients, and the histamine-stimulated HConEpiCs. Signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2) were upregulated in the conjunctival tissues of mice with OVA-induced AC and in HConEpiCs. Ocular surface inflammation was significantly relieved in LMT-28-treated mice. The expression of IgE, IL-4, IL-5, and IL-13 in serum of LMT-28-treated mice decreased. The number of mast cells in conjunctival tissue was decreased compared with OVA-induced mice.
CONCLUSIONS
Gp130 may play an important role in AC via the gp130/JAK2/STAT3 pathway. Inhibiting gp130 phosphorylation alleviates ocular surface inflammation in mice, presenting a potential treatment approach for AC.
Topics: Animals; Mice; Conjunctivitis, Allergic; Janus Kinase 2; Cytokine Receptor gp130; Ovalbumin; Histamine; STAT3 Transcription Factor; Inflammation
PubMed: 37022703
DOI: 10.1167/iovs.64.4.5 -
Food Chemistry Oct 2022In this study, ovalbumin (OVA) formed a complex with neohesperidin (NH) via a pH-shifting method. The NH-OVA complex self-assembled into NH-OVA nano-particles, which...
In this study, ovalbumin (OVA) formed a complex with neohesperidin (NH) via a pH-shifting method. The NH-OVA complex self-assembled into NH-OVA nano-particles, which were then characterized and whose binding mechanism was evaluated by using multi-spectroscopic, thermodynamics, and molecular docking simulation methods. Fluorescence intensity decreased after OVA was complexed with NH. The binding constant of the OVA-NH complex was in the order of 6.32 × 10 M suggesting that the complex is stable. Circular dichroism (CD) analysis showed that α -helix content increased, β-folding, β -turning, and irregular crimp content decreased after OVA and NH binding. Isothermal titration calorimetry results showed that hydrophobic interactions and hydrogen bonds made an important impact in the complex formation. The molecular docking results revealed that Van der Waals forces and hydrogen bonds contributed to the free binding energy of the complex. There were multiple possible surface binding sites between OVA with NH. The obtained results provide new insights into the interaction mechanism of OVA and NH, and as a vehicle for NH, the OVA has shown promising applications in functional foods.
Topics: Binding Sites; Circular Dichroism; Hesperidin; Hydrogen-Ion Concentration; Molecular Docking Simulation; Ovalbumin; Protein Binding; Spectrometry, Fluorescence; Thermodynamics
PubMed: 35561507
DOI: 10.1016/j.foodchem.2022.133104 -
Journal of the American Chemical Society Sep 2021Herein, a method for synthesizing and utilizing DNA dendrons to deliver biomolecules to living cells is reported. Inspired by high-density nucleic acid nanostructures,...
Herein, a method for synthesizing and utilizing DNA dendrons to deliver biomolecules to living cells is reported. Inspired by high-density nucleic acid nanostructures, such as spherical nucleic acids, we hypothesized that small clusters of nucleic acids, in the form of DNA dendrons, could be conjugated to biomolecules and facilitate their cellular uptake. We show that DNA dendrons are internalized by 90% of dendritic cells after just 1 h of treatment, with a >20-fold increase in DNA delivery per cell compared with their linear counterparts. This effect is due to the interaction of the DNA dendrons with scavenger receptor-A on cell surfaces, which results in their rapid endocytosis. Moreover, when conjugated to peptides at a single attachment site, dendrons enhance the cellular delivery and activity of both the model ovalbumin 1 peptide and the therapeutically relevant thymosin alpha 1 peptide. These findings show that high-density, multivalent DNA ligands play a significant role in dictating cellular uptake of biomolecules and consequently will expand the scope of deliverable biomolecules to cells. Indeed, DNA dendrons are poised to become agents for the cellular delivery of many molecular and nanoscale materials.
Topics: Animals; Cell Line; DNA; Dendrimers; Endocytosis; Mice; Ovalbumin; Peptides; Thymalfasin
PubMed: 34410116
DOI: 10.1021/jacs.1c07240