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Frontiers in Cellular and Infection... 2022In this study we aimed to determine whether treatment with maternal TMC3115 could affect the composition of the gut microbiota and the development of the immune system...
In this study we aimed to determine whether treatment with maternal TMC3115 could affect the composition of the gut microbiota and the development of the immune system and intestinal tract of offspring, and protect the offspring from IgE-mediated allergic disease. Pregnant BALB/c mice were gavaged with TMC3115 until delivery. Offspring were sensitized with ovalbumin from postnatal days 21 to 49. After maternal treatment with TMC3115, the microbiota of the offspring's feces, intestinal contents, and stomach contents (a proxy for breast milk) at the newborn and weaning stages exhibited the most change, and levels of immunoglobulin in the sera and stomach contents and of splenic cytokines, as well as the mRNA levels of colonic intestinal development indicators were all significantly altered in offspring at different stages. After sensitization with ovalbumin, there were no significant changes in the levels of serum IgE or ovalbumin-specific IgE/IgG1 in the TMC3115 group; however, IgM, the expression of intestinal development indicators, and the production of fecal short chain fatty acid (SCFA) were significantly increased, as were the relative abundances of and the NK4A136 group. Our results suggested that maternal treatment with TMC3115 could have a profound modulatory effect on the composition of the gut microbiota and the development of the immune system and intestinal tissue in offspring at different stages of development, and may induce immune tolerance to allergens in ovalbumin-stimulated offspring by modulating the gut microbiota and SCFA production.
Topics: Animals; Mice; Female; Pregnancy; Bifidobacterium bifidum; Gastrointestinal Microbiome; Ovalbumin; Immune System; Immune Tolerance; Immunoglobulin E; Allergens
PubMed: 36452299
DOI: 10.3389/fcimb.2022.1045109 -
Scientific Reports Jul 2023Transport of interstitial fluid and solutes plays a critical role in clearing metabolic waste from the brain. Transcranial application of focused ultrasound (FUS) has...
Transport of interstitial fluid and solutes plays a critical role in clearing metabolic waste from the brain. Transcranial application of focused ultrasound (FUS) has been shown to promote localized cerebrospinal fluid solute uptake into the brain parenchyma; however, its effects on the transport and clearance of interstitial solutes remain unknown. We demonstrate that pulsed application of low-intensity FUS to the rat brain enhances the transport of intracortically injected fluorescent tracers (ovalbumin and high molecular-weight dextran), yielding greater parenchymal tracer volume distribution compared to the unsonicated control group (ovalbumin by 40.1% and dextran by 34.6%). Furthermore, FUS promoted the drainage of injected interstitial ovalbumin to both superficial and deep cervical lymph nodes (cLNs) ipsilateral to sonication, with 78.3% higher drainage observed in the superficial cLNs compared to the non-sonicated hemisphere. The application of FUS increased the level of solute transport visible from the dorsal brain surface, with ~ 43% greater area and ~ 19% higher fluorescence intensity than the unsonicated group, especially in the pial surface ipsilateral to sonication. The sonication did not elicit tissue-level neuronal excitation, measured by an electroencephalogram, nor did it alter the molecular weight of the tracers. These findings suggest that nonthermal transcranial FUS can enhance advective transport of interstitial solutes and their subsequent removal in a completely non-invasive fashion, offering its potential non-pharmacological utility in facilitating clearance of waste from the brain.
Topics: Rats; Animals; Rats, Sprague-Dawley; Ovalbumin; Dextrans; Brain; Sonication
PubMed: 37524783
DOI: 10.1038/s41598-023-39640-2 -
Journal of Basic and Clinical... Apr 2021Currently, there are several animal models for vasculitis. Ovalbumin and lipopolysaccharide (OVA, LPS) are well established for causing inflammation and used as an...
OBJECTIVES
Currently, there are several animal models for vasculitis. Ovalbumin and lipopolysaccharide (OVA, LPS) are well established for causing inflammation and used as an adjunct in the vasculitis induction. However, to date, none has established the effect of OVA and LPS in disease induction. Therefore, in the present study, an attempt has been made to develop a new animal model for vasculitis using OVA/LPS in rats.
METHODS
A total of 42 Wistar rats were divided randomly into seven groups (n=6/group), normal control, and three different doses (0.5, 1, and 5 mg/kg) of OVA and LPS treated groups. Half of the rats in each group received only intraperitoneal sensitization, while the remaining half rats were additionally subjected to a one-week intranasal challenge.
RESULTS
Results showed that both OVA/LPS in their respective groups have significantly increased circulating inflammatory cells, C-reactive protein (CRP), Inflammatory cytokines (IL-1β, IL-6, TNF-α), Kidney damage markers (BUN, Creatinine), and liver function enzymes (AST, ALT) in a dose-dependent manner.
CONCLUSIONS
OVA/LPS induced vascular inflammation in a dose-dependent manner. However, the higher (5 mg/kg) dose of ovalbumin and lipopolysaccharide has contributed to severe vascular inflammation through increasing inflammatory cytokines. These findings suggest that OVA/LPS may contribute as a possible model for vasculitis in rats.
Topics: Animals; Cytokines; Disease Models, Animal; Inflammation; Lipopolysaccharides; Ovalbumin; Rats; Rats, Wistar; Vasculitis
PubMed: 33892525
DOI: 10.1515/jbcpp-2020-0200 -
Food Research International (Ottawa,... Oct 2020Egg white was known for its excellent foaming properties, and some reports had studied the effect of polyphenol such as green tea on the foaming properties. However,...
Egg white was known for its excellent foaming properties, and some reports had studied the effect of polyphenol such as green tea on the foaming properties. However, ovalbumin, as the most abundant component of egg white protein, few literatures have reported the effects of polyphenols on its structure and foam property. In this study, ferulic acid (FA) was selected to explore the influence of polyphenol on the structure and foaming properties of ovalbumin (OVA). Results showed that hydrophobic interaction and hydrogen chemical bonds were the main driving force. FA could induce a significant decrease of free-SH content (12.76-3.72 μmol/g), a slight decline of surface hydrophobicity (716.39-577.65). Meanwhile, combined with the results of fluorescence spectroscopy and circular dichroism spectroscopy, we conclude that FA changed the structures and molecular flexibility of OVA. The increase of particle size and absolute zeta-potential showed there was a little aggregation between OVA molecules, proved FA could act as a cross-linker between OVA proteins. This behavior makes the adjacent films more firm and stable, therefore improved the foaming properties. This study suggested that FA could be a potential foaming agent to modify the foaming properties of OVA in the foam-related food industry.
Topics: Chemical Phenomena; Coumaric Acids; Food Technology; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Nanoparticles; Ovalbumin; Solubility; Sulfhydryl Compounds; Tryptophan; Tyrosine; Viscosity
PubMed: 32846520
DOI: 10.1016/j.foodres.2020.109311 -
Journal of Controlled Release :... Nov 2022The standard process for manufacturing microneedles containing API requires a way to process the API, including dissolving the API in a co-solvent and a drying process....
The standard process for manufacturing microneedles containing API requires a way to process the API, including dissolving the API in a co-solvent and a drying process. In this study, the authors introduce a novel microneedle system that involves physically attaching API particles to the biocompatible adhesive surface of the microneedles. To manufacture particle-attached microneedles, an adhesive surface was prepared by coating polydimethylsiloxane (PDMS) mixed with an elastomer base and a curing agent at a ratio of 40:1 (PDMS40) onto polylactic acid microneedles (PLA), and then attaching ovalbumin (OVA) particles with a mean diameter of 10 μm to the PDMS adhesive layer. The OVA particles were delivered for 5 min into porcine skin with a delivery efficiency of 93% ex vivo and into mouse skin with a delivery efficiency of over 90% in vivo. Finally, mouse experiments with OVA particle-attached microneedles showed a value of OVA antibody titer similar to that produced by intramuscular administration. Particle-attached microneedles are a novel microneedle system with a dry coating process and rapid API delivery into the skin. Particle-attached microneedles can provide a wide range of applications for administering drugs and vaccines.
Topics: Swine; Mice; Animals; Needles; Ovalbumin; Vaccines; Skin; Immunity, Cellular; Drug Delivery Systems; Microinjections; Administration, Cutaneous
PubMed: 36216176
DOI: 10.1016/j.jconrel.2022.10.003 -
Poultry Science Oct 2021Virus injection into EGK-X embryos is a well-defined approach in avian transgenesis. This system uses a chicken ovalbumin gene promoter to induce transgene expression in...
Virus injection into EGK-X embryos is a well-defined approach in avian transgenesis. This system uses a chicken ovalbumin gene promoter to induce transgene expression in the chicken oviduct. Although a reconstructed chicken ovalbumin promoter that links an ovalbumin promoter and estrogen-responsive enhancer element (ERE) is useful, a large viral vector containing the ovalbumin promoter and a target gene restricts viral packaging capacity and produces low-titer virus particles. We newly developed recombinant chicken promoters by linking regulatory regions of ovalbumin and other oviduct-specific genes. Putative enhancer fragments of the genes, such as ovotransferrin (TF), ovomucin alpha subunit (OVOA), and ovalbumin-related protein X (OVALX), were placed at the 5`-flanking region of the 2.8-kb ovalbumin promoter. Basal promoter fragments of the genes, namely, pTF, lysozyme (pLYZ), and ovomucoid (pOVM), were placed at the 3`-flanking region of the 1.6-kb ovalbumin ERE. The recombinant promoters cloned into each reporter vector were evaluated using a dual luciferase assay in human and chicken somatic cells, and LMH/2A cells treated with 0-1,000 nM estrogen, and cultured primary chicken oviduct cells. The recombinant promoters with linking ovalbumin and TF, OVOA, pOVM, and pLYZ regulatory regions had 2.1- to 19.5-fold (P < 0.05) higher luciferase activity than the reconstructed ovalbumin promoter in chicken oviduct cells. Therefore, recombinant promoters may be used to efficiently drive transgene expression in transgenic chickens.
Topics: Animals; Chickens; Fallopian Tubes; Female; Humans; Ovalbumin; Oviducts; Promoter Regions, Genetic; Transgenes
PubMed: 34375836
DOI: 10.1016/j.psj.2021.101365 -
Planta Medica Jul 2020is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from have shown a...
is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from have shown a variety of beneficial bioactivities. However, available data on the effects of total alkaloids against allergic asthma has not been reported. In present study, the protective effect of total alkaloids was evaluated by using an ovalbumin-induced model of asthma. The asthma model was prepared by sensitizing and challenging mice with ovalbumin, and total alkaloids (100, 200, and 400 mg/kg) were administrated to asthmatic mice by gavage. Histopathological analysis of pulmonary changes was detected by hematoxylin and eosin, and periodic acid-schiff staining. Inflammatory cell counts were determined in bronchoalveolar lavage fluid. Total immunoglobulin E and ovalbumin-specific immunoglobulin E levels in serum, and T-helper 2 cytokines and chemokine levels in bronchoalveolar lavage fluid were detected by an ELISA. Histological results demonstrated that total alkaloids significantly attenuated pulmonary inflammation in asthmatic mice. total alkaloid treatment exhibited marked effects on asthmatic mice in reducing inflammatory cell counts, decreasing interleukin-4, interleukin-5, and interleukin-13 concentrations, and downregulating TNF- and eotaxin levels in bronchoalveolar lavage fluid. In addition, total alkaloids could also inhibit the elevated serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. These findings confirmed that total alkaloids could suppress airway inflammation in ovalbumin-induced asthma through regulating the T-helper 2 response and chemokine level. total alkaloids may be a potential ethnopharmacological agent for asthmatic patients.
Topics: Alkaloids; Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Humans; Inflammation; Menispermum; Mice; Mice, Inbred BALB C; Ovalbumin
PubMed: 32365394
DOI: 10.1055/a-1151-5138 -
Inflammopharmacology Dec 2023Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction,...
OBJECTIVE
Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction, which manifests shortness of breath, cough and wheeze, etc. Histone deacetylases 8 (HDAC8) is the member of class I HDAC family and known to regulate microtubule integrity and muscle contraction. Therefore, we aimed to investigate the effects of HDAC8 inhibition in murine model of asthma using Pan-HDAC inhibitor curcumin (CUR) and HDAC8-specific inhibitor PCI-34051 (PCI), alone and in combination.
MATERIALS AND METHODS
To develop asthmatic mouse model, Balb/c mice were sensitized and challenged with ovalbumin (OVA). CUR (10 mg/kg, pre, post, alone and combined treatment) and PCI (0.5 mg/kg), were administered through intranasal (i.n) route, an hour before OVA aerosol challenge. Effects of HDAC8 inhibition by CUR and PCI pretreatments were evaluated in terms of inflammation, oxidative stress and fibrosis markers. Efficacy of curcumin post-treatment (CUR(p)) was also evaluated simultaneously.
RESULTS
Inflammatory cell recruitment, oxidative stress (reactive oxygen species, nitric oxide), histamine and Immunoglobulin E (IgE) levels and expression of fibrosis markers including hydroxyproline, matrix metalloproteinases-9 and alpha smooth muscle actin (MMP-9 and α-SMA) were significantly reduced by CUR, CUR(p), PCI-alone and combined treatments. Protein expressions of HDAC8, Nuclear factor-κB (NF-κB) accompanied by MAPKs (mitogen-activated protein kinases) were significantly reduced by the treatments. Structural alterations were examined by histopathological analysis and linked with the fibrotic changes.
CONCLUSIONS
Present study indicates protective effects of HDAC8 inhibition in asthma using HDAC8 using CUR and PCI alone or in combination, attenuates airway inflammation, fibrosis and remodeling; hence, bronchoconstriction was accompanied through modulation of MAP kinase pathway.
Topics: Animals; Mice; Curcumin; Asthma; Lung; Inflammation; Mitogen-Activated Protein Kinases; Fibrosis; Mice, Inbred BALB C; Ovalbumin; Disease Models, Animal
PubMed: 37934384
DOI: 10.1007/s10787-023-01371-1 -
Advanced Healthcare Materials Nov 2022Here, antigen and adjuvant encapsulated dendritic cell-targeted nanoparticles for immune activation in the small intestinal lymphatic system to inhibit melanoma...
Here, antigen and adjuvant encapsulated dendritic cell-targeted nanoparticles for immune activation in the small intestinal lymphatic system to inhibit melanoma development are described. This strategy is demonstrated using chondroitin sulfate-coated nanoparticles (OPGMN) grafted with glycocholic acid and mannose for cationic liposomes encapsulated with ovalbumin as an antigen and polyinosine-polycytidylic acid as a cancer-specific adjuvant. OPGMN is absorbed in the gastrointestinal tract and delivered to the lymph nodes when orally administered. Oral delivery of OPGMN induces increased dendritic cell maturation compared to the intradermal route in the lymph node and induces T helper type 1 and type 2 responses, such as immunoglobulin G1 and G2c, interferon-gamma, and interleukin-2, in the blood. Repeated oral administration of OPGMN increases the population of CD3 CD8 T cells, CD44 CD62L memory T cells, and CD11b CD27 natural killer cells in the blood. OPGMN completely prevents melanoma development in the B16F10-bearing C57BL/6 mouse model by reducing the population of CD4 CD25 Foxp3 regulatory T cells in the blood. This strategy is expected to prevent the recurrence of tumors after various cancer treatments.
Topics: Mice; Animals; Ovalbumin; Poly I-C; CD8-Positive T-Lymphocytes; Mice, Inbred C57BL; Dendritic Cells; Nanoparticles; Antigens; Adjuvants, Immunologic; Lymph Nodes; Melanoma
PubMed: 35835068
DOI: 10.1002/adhm.202200909 -
International Immunopharmacology Jul 2022As a ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in allergic inflammation. Recently, the...
As a ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in allergic inflammation. Recently, the nuclear factor kappa B (NF-κB) pathway and PAK1 have been indicated to be associated with allergic diseases. However, the effect of PPAR-γ on NF-κB and PAK1 production in food allergies is not known. This study aims to 1) systematically validate that the activation of PPAR-γ attenuates allergic reactions and 2) elucidate the mechanism by which PPAR-γ regulates mast cell degranulation. Brown Norway rats were separated into control, ovalbumin, ovalbumin + rosiglitazone, and ovalbumin + GW9662 groups. In vivo experiments demonstrated that rosiglitazone administration markedly inhibited the clinical symptoms and the serum levels of immunoglobulins E and G1. In addition, cytokine release was regulated by activated PPAR-γ and characterized by increased levels of IFN-γ and decreased levels of IL-4, IL-5, and TNF-α. Our data showed that activated PPAR-γ has the potential to alleviate food allergies by enhancing intestinal mucosal integrity and tight junctions. Moreover, we found that PPAR-γ activation inhibited mast cell degranulation both in vivo and in vitro. Our in vitro findings also showed that the activated PPAR-γ signal could inhibit PAK1 phosphorylation and the expression of p65. Furthermore, the interaction between p65 and p-PAK1 during ovalbumin treatment was attenuated after PPAR-γ activation. Collectively, these results demonstrate that PPAR-γ is an important regulator of mast cell degranulation and the Th2-type response, which sheds new light on the importance of PPAR-γ in food allergies.
Topics: Animals; Down-Regulation; Inflammation; Mast Cells; NF-kappa B; Ovalbumin; PPAR gamma; Rats; Rosiglitazone; p21-Activated Kinases
PubMed: 35636075
DOI: 10.1016/j.intimp.2022.108692