-
Nature Sep 2019Fibrosis is observed in nearly every form of myocardial disease. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess...
Fibrosis is observed in nearly every form of myocardial disease. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure. However, clinical interventions and therapies that target fibrosis remain limited. Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8 T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts-fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease.
Topics: Animals; Antigens, Surface; CD8-Positive T-Lymphocytes; Endomyocardial Fibrosis; Fibroblasts; Humans; Immunotherapy, Adoptive; Male; Mice; Ovalbumin; Wound Healing
PubMed: 31511695
DOI: 10.1038/s41586-019-1546-z -
Nature Nanotechnology Dec 2020Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate...
Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis.
Topics: Animals; Cancer Vaccines; Cells, Cultured; Female; Fluorocarbon Polymers; Immunotherapy; Melanoma, Experimental; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles; Ovalbumin; Polyethyleneimine
PubMed: 33139933
DOI: 10.1038/s41565-020-00781-4 -
Frontiers in Immunology 2022Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut-lung axis in asthma development....
The Ability of Resveratrol to Attenuate Ovalbumin-Mediated Allergic Asthma Is Associated With Changes in Microbiota Involving the Gut-Lung Axis, Enhanced Barrier Function and Decreased Inflammation in the Lungs.
Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut-lung axis in asthma development. In the current study, we investigated if Resveratrol (RES), a plant-based polyphenol, can attenuate ovalbumin (OVA)-induced murine allergic asthma, and if so, the role of microbiome in the gut-lung axis in this process. We found that RES attenuated allergic asthma with significant improvements in pulmonary functions in OVA-exposed mice when tested using plethysmography for frequency (F), mean volume (MV), specific airway resistance (sRaw), and delay time(dT). RES treatment also suppressed inflammatory cytokines in the lungs. RES modulated lung microbiota and caused an abundance of A accompanied by a reduction of LPS biosynthesis in OVA-treated mice. Furthermore, RES also altered gut microbiota and induced enrichment of significantly in the colon accompanied by an increase in butyric acid concentration in the colonic contents from OVA-treated mice. Additionally, RES caused significant increases in tight junction proteins and decreased mucin (Muc5ac) in the pulmonary epithelium of OVA-treated mice. Our results demonstrated that RES may attenuate asthma by inducing beneficial microbiota in the gut-lung axis and through the promotion of normal barrier functions of the lung.
Topics: Animals; Asthma; Disease Models, Animal; Inflammation; Lung; Mice; Microbiota; Ovalbumin; Resveratrol
PubMed: 35265071
DOI: 10.3389/fimmu.2022.805770 -
Talanta Apr 2021SARS-COV-2 is a novel coronavirus discovered in Wuhan in December 30, 2019, and is a family of SARS-COV (severe acute respiratory syndrome coronavirus), that is,... (Review)
Review
SARS-COV-2 is a novel coronavirus discovered in Wuhan in December 30, 2019, and is a family of SARS-COV (severe acute respiratory syndrome coronavirus), that is, coronavirus family. After infection with SARS-COV-2, patients often experience fever, cough, gas prostration, dyspnea and other symptoms, which can lead to severe acute respiratory syndrome (SARS), kidney failure and even death. The SARS-COV-2 virus is particularly infectious and has led to a global infection crisis, with an explosion in the number of infections. Therefore, rapid and accurate detection of the virus plays a vital role. At present, many detection methods are limited in their wide application due to their defects such as high preparation cost, poor stability and complex operation process. Moreover, some methods need to be operated by professional medical staff, which can easily lead to infection. In order to overcome these problems, a Surface molecular imprinting technology (SM-MIT) is proposed for the first time to detect SARS-COV-2 virus. For this SM-MIT method, this review provides detailed detection principles and steps. In addition, this method not only has the advantages of low cost, high stability and good specificity, but also can detect whether it is infected at designated points. Therefore, we think SM-MIT may have great potential in the detection of SARS-COV-2 virus.
Topics: COVID-19; Humans; Magnetite Nanoparticles; Microspheres; Molecular Imprinting; Ovalbumin; Polymers; SARS-CoV-2; Sensitivity and Specificity; Viral Proteins
PubMed: 33592725
DOI: 10.1016/j.talanta.2020.121977 -
Food Chemistry May 2024When subjected to dry-heating, egg white ovalbumin, a phosphoglycoprotein, undergoes fragmentation and forms soluble aggregates. We investigated the mechanisms of...
When subjected to dry-heating, egg white ovalbumin, a phosphoglycoprotein, undergoes fragmentation and forms soluble aggregates. We investigated the mechanisms of dry-heat-induced fragmentation of ovalbumin. SDS-PAGE analysis showed that ovalbumin fragmented into five polypeptides, and their amount increased over 6 h of dry-heat treatment at 120 °C. The fragments contained fewer or no phosphoserine, compared with that in crude ovalbumin. Liquid chromatography-tandem mass spectrometry analysis of tryptic digests revealed that the fragmentation sites were located on phosphoserine residues, S and S. During fragmentation, the phosphoserine residues underwent conversion into dehydroalanine residues, which were subsequently hydrolyzed. The nitrogen from the dehydroalanine became a newly formed terminal amide group on the N-terminal fragment, while the remaining molecule predominantly formed a new terminal pyruvoyl group. Furthermore, the fragments were incorporated into monomers or soluble aggregates of ovalbumin via covalent and non-covalent bonds. This study demonstrated a novel mechanism for dry-heat-induced fragmentation of phosphoproteins.
Topics: Ovalbumin; Phosphoserine; Hot Temperature; Peptides; Egg White
PubMed: 38159316
DOI: 10.1016/j.foodchem.2023.138263 -
Analytical Biochemistry Jan 2022Ovalbumin particles are reduced to nano size using heat treatment techniques. Their structural patterns in their native state and in their pH denatured state were...
Ovalbumin particles are reduced to nano size using heat treatment techniques. Their structural patterns in their native state and in their pH denatured state were attempted. Denaturation is also a part of conformation and hence conformations due to pH and glucose were analyzed using FTIR spectroscopy. The interactions behind these conformations are unraveled and the role of glucose as cosolvent in restricting the denaturation is also revealed from the observed secondary structures of ovalbumin. Further, the characterization of these synthesized nano particles reveals the extent of their applications. The obtained results indicate that consideration of ovalbumin nanoparticles seems to favor a very clear trend of protein denaturation and the observed structural modifications are the result of development of non-covalent interactions by the cosolvent molecules.
Topics: Nanoparticles; Ovalbumin; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared
PubMed: 34774535
DOI: 10.1016/j.ab.2021.114456 -
The Journal of Allergy and Clinical... Apr 2023Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12 to C16 to those with...
BACKGROUND
Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12 to C16 to those with C18, has been recently indicated to affect various immune and inflammatory responses; however, the precise process by which ELOVL6-related lipid dysregulation affects allergic airway inflammation is unclear.
OBJECTIVES
This study sought to evaluate the biological roles of ELOVL6 in allergic airway responses and investigate whether regulating lipid composition in the airways could be an alternative treatment for asthma.
METHODS
Expressions of ELOVL6 and other isoforms were examined in the airways of patients who are severely asthmatic and in mouse models of asthma. Wild-type and ELOVL6-deficient (Elovl6) mice were analyzed for ovalbumin-induced, and also for house dust mite-induced, allergic airway inflammation by cell biological and biochemical approaches.
RESULTS
ELOVL6 expression was downregulated in the bronchial epithelium of patients who are severely asthmatic compared with controls. In asthmatic mice, ELOVL6 deficiency led to enhanced airway inflammation in which lymphocyte egress from lymph nodes was increased, and both type 2 and non-type 2 immune responses were upregulated. Lipidomic profiling revealed that the levels of palmitic acid, ceramides, and sphingosine-1-phosphate were higher in the lungs of ovalbumin-immunized Elovl6 mice compared with those of wild-type mice, while the aggravated airway inflammation was ameliorated by treatment with fumonisin B1 or DL-threo-dihydrosphingosine, inhibitors of ceramide synthase and sphingosine kinase, respectively.
CONCLUSIONS
This study illustrates a crucial role for ELOVL6 in controlling allergic airway inflammation via regulation of fatty acid composition and ceramide-sphingosine-1-phosphate biosynthesis and indicates that ELOVL6 may be a novel therapeutic target for asthma.
Topics: Animals; Mice; Asthma; Ceramides; Disease Models, Animal; Inflammation; Ovalbumin
PubMed: 36592705
DOI: 10.1016/j.jaci.2022.12.808 -
ACS Biomaterials Science & Engineering Dec 2022Osteosarcoma is a malignant osteogenic tumor with a high metastatic rate commonly occurring in adolescents. Although radiotherapy is applied to treat unresectable...
Osteosarcoma is a malignant osteogenic tumor with a high metastatic rate commonly occurring in adolescents. Although radiotherapy is applied to treat unresectable osteosarcoma with radiation resistance, a high dose of radiotherapy is required, which may weaken the immune microenvironment. Therefore, there is an urgent need to develop novel agents to maximize the radiotherapeutic effects by eliciting immune activation effects. In this study, we synthesized therapeutic gadolinium-based metal-bisphosphonate nanoparticles (NPs) for osteosarcoma treatment that can be combined with radiotherapy. The gadolinium ion (Gd) was chelated with zoledronic acid (Zol), a commonly used drug to prevent/treat osteoporosis or bone metastases from advanced cancers, and stabilized by ovalbumin (OVA) to produce OVA-GdZol NPs. OVA-GdZol NPs were internalized into K7M2 osteosarcoma cells, showing a high sensitization effect under X-ray irradiation. Cell pretreatment of OVA-GdZol NPs significantly enhanced the radiation therapeutic effect in vitro by reducing the cell colonies and increased the signal of γH2AX-positive cells. More importantly, OVA-GdZol NPs promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and M1 polarization of macrophages. The inhibitory effect on K7M2 osteosarcoma of OVA-GdZol NPs and X-ray radiation was evident, indicated by a significantly reduced tumor volume, high survival rate, and decreased lung metastasis. Meanwhile, both innate and adaptive immune systems were activated to exert a strong antitumor effect. The above results highly suggest that OVA-GdZol NPs serve as both radiosensitizers and immune adjuvants, suitable for the sequential combination of vaccination and radiotherapy.
Topics: Humans; Adolescent; Gadolinium; Diphosphonates; Nanoparticles; Ovalbumin; Neoplasms; Tumor Microenvironment
PubMed: 36383732
DOI: 10.1021/acsbiomaterials.2c00880 -
Food Chemistry Sep 2022The effect of ovalbumin-flavonoids (naringenin, genistein, naringin, puerarin, and daidzein) interactions on the formation and properties of ovalbumin hydrogels was...
The effect of ovalbumin-flavonoids (naringenin, genistein, naringin, puerarin, and daidzein) interactions on the formation and properties of ovalbumin hydrogels was investigated. The results suggested that flavonoids were able to promote the gelation of low concentration ovalbumin solution, which was not able to form hydrogel upon heating. All hydrogels formed by flavonoids and ovalbumin were more elastic than viscous. The hydrogels formed by naringenin and ovalbumin showed the strongest gel hardness, springiness, and water holding capacity. Fluorescence spectroscopy and molecular docking analysis revealed that the main interactions between ovalbumin and naringenin, genistein, puerarin, naringin were hydrogen bond, while the main interaction between ovalbumin and daidzein was hydrophobic force. Flavonoids, which have a structure with more phenolic hydroxyl groups, a C2 = C3 double bond and dehydrogenated glycosides, possessed higher affinity to ovalbumin. This research provides new insights into mechanism of ovalbumin-flavonoids interactions and its influence on the formation and property of hydrogel.
Topics: Flavonoids; Genistein; Hydrogels; Molecular Docking Simulation; Ovalbumin
PubMed: 35405558
DOI: 10.1016/j.foodchem.2022.132892 -
Advanced Healthcare Materials Mar 2021Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower- and middle-income countries, including the...
Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower- and middle-income countries, including the costly requirements for cold-chain distribution and trained medical personnel to administer the vaccines. A heat-stable and highly porous tablet vaccine that can be administered sublingually via simple dissolution under the tongue is described. SIMPL tablet vaccines (Supramolecular IMmunization with Peptides subLingually) are produced by freeze-drying a mixture of self-assembling peptide-polymer nanofibers, sugars, and adjuvant. Sublingual immunization with SIMPL tablets raises antibody responses against both a model epitope from ovalbumin and a clinically relevant epitope from Mycobacterium tuberculosis. Further, sublingual antibody responses are not diminished after heating the tablets for 1 week at 45 °C, in contrast to a more conventional carrier vaccine (KLH). This approach directly addresses the need for a heat-stable and easily deliverable vaccine to improve equity in global vaccine coverage.
Topics: Administration, Sublingual; Epitopes; Immunization; Ovalbumin; Peptides
PubMed: 33634607
DOI: 10.1002/adhm.202001614