22 results about "TLR5" patented technology

The present invention relates to a flagellin fusion protein and the use thereof, and, more specifically, to a fusion protein comprising a human IgG4 Fc variant and the use thereof using toll-like receptor 5 (TLR5) stimulation activity, wherein the human IgG4 Fc variant has mutation preventing a Fab-arm exchange.

Compositions and method of increasing levels of apoA1 and / HDL in a subject in need thereof are provided. The compositions include one or more TLR5 agonists in a pharmaceutically acceptable carrier in an effective amount to increase the level of apoA1 and / or HDL in a subject. In a preferred embodiment, the composition is an oral formulation of the one or more TLR5 agonists. The disclosed methods include administering compositions containing the one or more TLR5 agonists to a subject in need thereof, in an effective amount to increase levels of apoA1 and / or HDL in the subject. In one preferred embodiment, the subject is at risk of developing atherosclerosis and / or coronary heart disease. In some embodiments, the subject is diagnosed as having atherosclerosis. The disclosed compositions can also be administered to subjects presenting with hyperlipidemia or hypercholesterolemia.

The invention discloses a multi-epitope fusion protein based on porcine rotavirus VP7 and VP8 double targets as well as a preparation method and application of the multi-epitope fusion protein. According to the invention, salmonella typhimurium flagellin FliCS.T is taken as a skeleton, dominant neutralizing epitopes of VP7 and VP8 are accurately integrated, and the multi-epitope fusion antigen FliCS.T-VP7 + VP8 is constructed. The fusion protein has two immunological advantages: an FliCS.T skeleton has TLR5 adjuvant activity, so that innate immunity and adaptive immunity of a host can be efficiently activated; key neutralizing epitopes of porcine rotaviruses VP7 and VP8 are synchronously presented through a multi-epitope strategy, and high-titer specific neutralizing antibody and potent cellular immune response aiming at two structural proteins can be induced in vivo. The invention provides the multi-epitope fusion antigen of the porcine rotavirus, which integrates high immunogenicity and broad-spectrum neutralization protection, and a feasible technical scheme is provided for prevention and control of the porcine rotavirus.

To provide a novel cell therapeutic agent that can improve GVHD treatment efficacy by strengthening immunomodulatory activity of MSC through use of a TLR5 agonist.SOLUTION: The present invention relates to a pharmaceutical composition for prevention or treatment of graft-versus-host disease, the composition containing, as an active ingredient, mesenchymal stem cells treated with a TLR5 (Toll-like receptor 5) agonist. The composition of the present invention is excellent in ability to reduce variability under a low-grade inflammatory environment and to exert an immunomodulatory effect, and can be utilized as an MSC-based therapeutic agent for steroid-resistant graft-versus-host disease (GVHD).SELECTED DRAWING: Figure 5b

The invention discloses a product for treating radiation damage. According to the application, GP532 is subjected to random mutation, a phage mutation library is established, and the mutation library is activated and screened by using TLR5-dependent NF-kappa B, so that 9E1 is obtained. 9E1 shows dose-dependent stimulation of TLR5 dependent NF-kB activation in vitro; an effective prevention effect is shown in an in-vivo mouse radiation injury model, and a new way is provided for effective treatment of radiation injury.

The invention belongs to the technical field of gene engineering, and provides Hsp60 receptor targeted recombinant lactobacillus plantarum as well as a construction method and application thereof, lactobacillus plantarum is taken as a host, pPG612 is taken as an expression vector, and CsgB gene or CsgF gene is expressed. The two engineering probiotics can express target protein and can be stably expressed on the surfaces of thalli, the AB.9 intestinal epithelial cells can be effectively adhered, and the adhesion and invasion of the A.veronii to the AB.9 cells can be inhibited. And secondly, the engineering probiotics LP-pPG-CsgB and LP-pPG-CsgF can promote the proliferation of dendritic cells, T lymphocytes and B lymphocytes, and improve the IgT secretion of intestinal mucus. The engineering bacteria can be competitively combined with an intestinal epithelial cell Hsp60 receptor, down-regulate p65 expression, inhibit NF-kappa B signal channel activation, regulate intestinal tight junction protein redistribution and down-regulate proinflammatory factor expression through a TLR4 / TLR5 dependent NF-kappa B signal channel, and the engineering bacteria can increase the abundance of effective microbial communities in the intestinal tract of the snakeheaded fish, so that the growth of the snakeheaded fish is promoted, and the growth of the snakeheaded fish is promoted. And the flora can transfer, mediate and activate immune response through a feeding environment.

The present invention relates to the use of a STING agonist, of a TLR5 agonist or of a TLR7 agonist for enhancing the number of p16high immune cells in vitro or in a patient in need thereof, in particular to extend health span and protect tissues against aging. It is also herein reported that p16high immune cells surprisingly play a key role in establishing disease tolerance, and can be useful for counteracting different lethal conditions, including LPS-induced sepsis, acute lethal SARS-CoV-2 infection, cancer and ionizing irradiation. The present invention thus relates to a pharmaceutical composition comprising autologous or heterologous p16high immune cells such as p16high CAR-T cells, and its use for various therapeutic purposes. These cells are preferably obtained by contacting them with a STING agonist, a TLR5 agonist and / or a TLR7 agonist.

The application belongs to the technical field of biology, and discloses a preparation method of a Salmonella typhimurium flagellin and Senecavirus antigen fusion protein. The application selects Escherichia coli Rosetta (DE3) as a host, fuses a Salmonella typhimurium flagellin gene and a Senecavirus antigen gene, optimizes codons, and then clones the fusion protein into a pET-28a (+) vector, so that the obtained fusion protein can keep the adjuvant activity of the flagellin, improve the solubility and expression level of VP2, and the yield can reach 40 mg / L, thereby greatly reducing the expression and purification process cost. The fusion protein provided by the application can activate the TLR5 path and activate mouse macrophages, and the production process is simple and low in cost, so that the application has important significance for the research and production of Senecavirus subunit vaccines.

The present invention relates to the manufacture and application of flagellin immunopotentiating derivatives with TLR5 activity using an eukaryotic cell expression system. The flagellin derivative according to the present invention has a high immunostimulatory effect and can be used in various vaccine and immunotherapy compositions.

The present invention relates to a Toll-like receptor 5 gene conditional overexpression animal model. Specifically, the present invention provides a method for preparing a non-human model animal with conditional overexpression of the TLR5 gene, wherein Cas9mRNA and gRNA are obtained by in vitro transcription; a homologous recombination vector (donor vector) is constructed, wherein the vector comprises a 5' homology arm, a TLR5 gene expression cassette and a 3' homology arm, wherein the TLR5 gene expression cassette is a silent expression cassette, and under induction conditions, the silent expression cassette is converted into an activated TLR5 gene expression cassette. Cas9mRNA, gRNA and the homologous recombination vector are injected into a fertilized egg in vitro to obtain an injected fertilized egg. The injected fertilized egg is regenerated into a TLR5 gene conditional overexpression animal model. The animal model of the present invention has broad application prospects in antiviral, antibacterial immunity, antitumor immunity, diagnosis and treatment of inflammatory bowel disease, etc.

The invention belongs to the technical field of biology, and particularly relates to a flagellin mutant capable of enhancing TLR5 ligand activity and application of the flagellin mutant. An amino acid mutation site of salmonella typhimurium flagellin is selected, recombinant protein is expressed by using an escherichia coli system through a site-specific mutagenesis technology, in-vitro experiments prove that the recombinant protein shows good biological activity, and compared with a wild flagellin mutant, the recombinant protein can better activate the activity of a TLR5 ligand and can be used for preparing a TLR5 mutant. And a good foundation is provided for enhancing the activity of flagellin adjuvants and vaccines.

The application belongs to the technical field of biology, and discloses a Salmonella typhimurium flagellin derivative and Senecavirus antigen fusion protein and application thereof. The Salmonella typhimurium flagellin derivative gene and the Senecavirus antigen gene are fused, and after codon optimization, the fusion protein is cloned into a pET-28a(+) vector, and the fusion protein is expressed by using an Escherichia coli system. In-vivo experiment verification shows that the fusion protein has good biological activity, can activate TLR5 ligand activity, and promote macrophage activation, and lays a foundation for development of a Senecavirus subunit vaccine.

The invention belongs to the technical field of biology, and particularly relates to salmonella typhimurium flagellin capable of enhancing human TLR5 binding affinity and application of the salmonella typhimurium flagellin. A key amino acid mutation site of flagellin is screened and determined, and recombinant expression is realized in an escherichia coli system by adopting a site-directed mutagenesis technology. In-vitro experiments prove that the derivative can significantly activate the function of a TLR5 ligand. The invention solves the problem that the existing flagellin has a limited effect on activating the activity of the human TLR5, and provides a new technical scheme and theoretical basis for the application of the flagellin in the fields of vaccines, immunotherapeutic agents and radioprotectants.

The application belongs to the technical field of genetic engineering, and provides Hsp60 receptor targeted recombinant plant lactobacillus, a construction method and application. The plant lactobacillus is used as a host, pPG612 is used as an expression vector, and CsgB genes or CsgF genes are expressed. Two strains of engineering probiotics can express target proteins and can stably express on the surface of the bacterial body, effectively adhere to AB.9 intestinal epithelial cells, and can inhibit the adhesion and invasion of AB.9 cells. A. veronii Secondly, the engineering probiotics LP-pPG-CsgB and LP-pPG-CsgF can promote the proliferation of dendritic cells, T lymphocytes and B lymphocytes, and improve the secretion of intestinal mucus IgT. The engineering bacteria can also competitively bind to the Hsp60 receptor of intestinal epithelial cells, down-regulate the expression of p65 through the TLR4 / TLR5 dependent NF-κB signal pathway, inhibit the activation of the NF-κB signal pathway, regulate the redistribution of intestinal tight junction proteins, and down-regulate the expression of pro-inflammatory factors. Furthermore, the engineering bacteria can increase the abundance of intestinal beneficial flora of the snakehead, and the flora can mediate and activate the immune response through the feeding environment.

The invention relates to bacillus flagellin FlgE serving as a specific ligand of animal intestinal tracts TLR5 and application of the bacillus flagellin FlgE in replacement of feed antibiotics, and belongs to the technical field of microbial engineering, FlgE interacts with the animal intestinal tracts TLR5 to promote colonization of probiotics in the animal intestinal tracts and competitively inhibit colonization and growth of harmful bacteria in the animal intestinal tracts, the animal is a pig or a chicken. According to the invention, in-vitro interaction between bacillus flagellin FlgE and pig source TLR5 as well as between bacillus flagellin FlgE and chicken source TLR5 is verified, and a novel TLR5 specific ligand protein is found, so that a novel thought and a novel direction are provided for researching a colonization mechanism of probiotic bacillus in intestinal tracts; related test results also provide theoretical and practical basis for development of safer and more efficient animal feed antibiotic substitutes based on probiotic bacillus.

The application discloses a multi-epitope fusion protein based on porcine rotavirus VP7 and VP8 double targets and a preparation method and application thereof. S.T As a skeleton, the advantages of precisely integrating VP7 and VP8 neutralizing epitopes are constructed into multi-epitope fusion antigen FliC S.T -VP7+VP8. The fusion protein has two immunological advantages: FliC S.T The skeleton has TLR5 adjuvant activity, can efficiently activate the innate immunity and adaptive immunity of a host, and can synchronously present key neutralizing epitopes of porcine rotavirus VP7 and VP8 through a multi-epitope strategy, so that high-titer specific neutralizing antibodies and strong cellular immune responses against the two structural proteins can be induced in the body. The application provides a multi-epitope fusion antigen of porcine rotavirus which integrates high immunogenicity and broad-spectrum neutralization protection, and provides a feasible technical scheme for the prevention and control of porcine rotavirus.

The present invention relates to the manufacture and application of flagellin immunopotentiating derivatives with TLR5 activity using an eukaryotic cell expression system. The flagellin derivative according to the present invention has a high immunostimulatory effect and can be used in various vaccine and immunotherapy compositions.

The application provides a kind of chimeric flagellin and its application.The chimeric flagellin is formed by the chimeric of A type Seneca virus VP2 fragment and Escherichia coli Nissle 1917 flagellin FliC through Linker (GGGGS) 3, which realizes the soluble expression of chimeric flagellin in Escherichia coli system, and the yield can reach 200 mg / L at most. And through the detection of in vitro Caco2 and Raw264.7 cell models, the recombinant chimeric flagellin shows good TLR5 receptor activity, which can effectively activate TLR5 signal pathway.

The application discloses a kind of chimeric antigen receptor macrophages and preparation method thereof.To the problem that traditional T cell costimulatory domain is not matched with macrophage signal pathway, the application provides a CAR structure specially designed for the biological characteristics of macrophage.The chimeric antigen receptor expressed by the CAR-M cell includes at least one costimulatory domain selected from Ncr1, TLR5, Rage and Tim4, and the CAR structure is composed of CD22 scFv extracellular antigen recognition region, CD8 alpha hinge region, transmembrane region, the costimulatory domain and CD3 zeta intracellular signal domain in sequence.By constructing the recombinant expression plasmid of pB vector skeleton and inserting P2A-EGFP expression monitoring element, RAW264.7 macrophages are transfected by using Zeta life transfection reagent, and the CAR positive rate can reach more than 97% by flow cytometry or confocal microscopy verification.The application realizes the efficient activation of phagocytosis, antigen presentation and microenvironment remodeling functions specific to macrophages, and significantly improves the application potential of CAR-M in solid tumor treatment.

The invention discloses an epirubicin drug sensitive marker, a detection reagent and related application thereof. The epirubicin drug sensitive marker is an epirubicin drug-resistant marker or / and an epirubicin sensitive marker, and the epirubicin drug-resistant marker is one or more of SRD5A2, ATOH8, DCPS, DAPK2, PON1, TLR5 and NPTX1, and the epirubicin drug-sensitive marker is one or more of SRD5A2, ATOH8, DCPS, DAPK2, PON1, TLR5 and NPTX1. The epirubicin star sensitive marker is one or more of IGFBP3, CCZ1, TRIAP1, LSR, CCNE1, PCSK1N, NUDT5, CDKL2, LRRC73, RAC3 and DNAAF3 (deoxyribonucleic acid-associated protein 3). The epirubicin drug sensitive marker can be used for predicting the drug effect of epirubicin. According to the present invention, the expression of the related molecules is detected by sequencing the transcriptome of the tissue of the urothelium carcinoma patient, or by using the PC R, the gene chip, the tissue chip, the NanoString technology, the immunohistochemistry and the ELISA method, such that the clue can be provided for the medication of the epirubicin and the precise treatment of the bladder cancer.

The invention relates to the field of biomedicine, and discloses application of a reagent for detecting a biomarker in preparation of a product for early diagnosis or prognosis of sepsis. And the biomarker is any one or a combination of more of TLR5, HMGB2, C19orf59, TXK and DGKA. The ability and reliability of the five biomarkers for distinguishing healthy individuals and sepsis patients in two queues are verified through an ROC curve and a PR curve, and candidate biomarkers are further verified through a CLP mouse model.

The application belongs to the field of aquatic organism breeding, and particularly relates to a SNP site of grass carp TLR5 related to grass carp hemorrhagic disease resistance, a SNP site combination and application thereof. The application successfully screens the SNP site of grass carp TLR5 related to grass carp hemorrhagic disease resistance through PCR-RFLP sequencing and correlation analysis, which is located at the 30969284th and 30958638th base of chromosome 20. In view of the two SNP sites, a SNP site combination of TLR5 related to grass carp hemorrhagic disease resistance is further developed, and the grass carp hemorrhagic disease resistance individual can be screened through detection of the SNP site combination. Therefore, the SNP molecular marker provided by the application can be used for grass carp molecular marker assisted breeding, and accelerate the breeding of disease-resistant grass carp varieties, and provide a reference basis for the disease-resistant breeding of grass carp.