63 results about "TLR2" patented technology

The invention discloses lactobacillus gasseri capable of improving expression of host antibacterial peptide Cathelicidin and secretory immunoglobulin sIgA and enhancing infection resistance by oral administration and external application and a metagen thereof, and belongs to the technical field of microorganisms. The lactobacillus gasseri disclosed by the invention can be used for promoting the generation of a vaginal epithelial cell antibacterial peptide Cathelicidin; the shedding of vaginal epithelial cells is reduced, the fungal load is reduced, and the generation of vaginal tissue antibacterial peptide CRAMP is improved; the pIgR and immune globulin content of the vaginal tissue is increased; the invention also finds that the lactobacillus gasseri for external use can regulate and control TLR2 (Toll-Like Receptor 2), and further has a good balancing effect on body immunity. Therefore, the lactobacillus gasseri has a huge application prospect in a product for improving the pathogenic bacterium infection resistance of a host, enhancing the self-defense capability and inhibiting the vagina inflammation.

This immunomodulation agent contains yeast deposited to the National Institute of Technology and Evaluation under international deposition number NITE BP-04012. Preferably, the immunomodulation agent is for use in modulation of cytokine production. More preferably, the immunomodulation agent modulates the production of a cytokine in macrophage cells or dendritic cells. Further preferably, the immunomodulation agent modulates immunity via TLR2. The cytokine is preferably at least one selected from IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α.

The invention discloses periodontitis targeted sustained-release gel based on epithelial training immunization and a preparation method thereof, and relates to the technical field of biological medicine, and the preparation method comprises the following steps: modifying poloxamer, and dissolving the modified poloxamer in anhydrous acetonitrile; the preparation method comprises the following steps: dissolving RGD peptide in a PBS (Phosphate Buffer Solution), adding N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and activating to obtain an activated RGD peptide solution; adding the activated RGD peptide solution into the modified poloxamer solution, and reacting at room temperature to obtain RGD peptide modified poloxamer; the RGD peptide modified poloxamer solution is mixed with a beta-glucan solution and a TLR2 agonist solution, and the periodontitis targeted slow-release gel is obtained. The gel provided by the invention specifically targets gingival epithelial cells, reduces inflammatory response and promotes periodontal tissue regeneration, has good biocompatibility and slow release performance, and can effectively control periodontitis and prevent relapse.

The invention discloses application of ANXA2 protein in improving immunoreaction of sheep to mycoplasma pneumoniae, and finds that the ANXA2 protein is sheep mycoplasma pneumoniae receptor protein and can be combined with the sheep mycoplasma pneumoniae, meanwhile, the protein is also TLR2 receptor inhibition protein, and after expression of an ANXA2 gene is interfered and pulmonary alveolar epithelial cells are infected by the sheep mycoplasma pneumoniae, the protein can be combined with the sheep mycoplasma pneumoniae and can be combined with the TLR2 receptor inhibition protein. The autophagy response of the cells is enhanced, and the cell proliferation function is recovered; and after the ANXA2 gene is interfered, the phagocytosis and clearance of the mycoplasma by the macrophages are also enhanced. It is shown that the immune response of cells to mycoplasma can be improved by knocking out the ANXA2 gene, damage of mycoplasma pneumoniae to the cells or sheep is reduced, and the time required for variety improvement can be remarkably shortened when the ANXA2 gene is used for later disease-resistant variety breeding.

The invention relates to an application of a bioactive peptide YPFPGPIH derived from bovine casein in the aspect of anti-inflammation or immunoregulation. The peptide can be combined with TLR2 and TLR4 to inhibit the activation of NF-kappa B and MAPK signal channels, so that the levels of inflammatory factors such as IL-1beta, TNF-alpha and NO are remarkably reduced, the expression of IL-10 is up-regulated, and inflammation balance regulation is realized; the body inflammatory response is improved, and the immune organ injury is recovered. The peptide can be used for preparing anti-inflammatory drugs, immunomodulatory functional foods and nutritional supplements, and has good safety and application prospects.

This invention relates to a method for treating or preventing a disease by raising an innate immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising a TLR2 moiety in solution, wherein the TLR2 moiety comprises a TLR2 agonist and wherein the disease is not treated or prevented by a humoral or cellular immune response directed against the TLR2 moiety.

The invention relates to application of lentinan in preparation of a medicine for enhancing Kukuzhou cell immune function, and belongs to the technical field of immunopharmacology. The invention discloses a mechanism and application of lentinan LNT (Lentinan) based on a TLR2 (Toll-Liver Receptor 2) signal channel for enhancing the immune function of liver cumness cells and promoting lysosome maturation. By constructing an LNT fluorescence labeling system, a Kuptake cell in-vivo tracing model and a TLR2 function intervention model, it is proved that LNT can be directly combined with TLR2 and activate a TLR2 / MyD88 / NF-kappa B signal axis, and therefore the phagocytosis and immune response capacity of Kuptake cells is enhanced. Meanwhile, TLR2 signal-induced reactive oxygen species (ROS) up-regulation can promote TFEB dephosphorylation and nuclear translocation, lysosome maturation is driven, and degradation metabolism of LNT is accelerated. The invention provides a TLR2-based immune enhancement mechanism of the LNT, and provides a theoretical basis and an application basis for developing immunomodulatory targeted drugs.

Disclosed are isolated bacteriophages having lytic activity against a broad range of mycobacterial species, as well as phage cocktails comprising different mixtures of the isolated bacteriophages. The disclosed bacteriophages include Pill582, and variants thereof, having the ability to stimulate TLR2 signaling and limit intracellular bacterial survival within macrophages through the signalosome involving NLRP3 inflammasome activation leading to the caspase 1 activation and the production of pro-inflammatory cytokine IL-1β. Also disclosed are compositions comprising the isolated bacteriophages or phage cocktails, including pharmaceutical compositions and compositions further comprising one or more non-phage therapeutic agents. The disclosed bacteriophage and phage cocktail compositions are useful in methods for treating mycobacterial infections and associated disease conditions.

The development of new immunoregulatory small molecules represents a significant advance in immunotherapy. Provided herein are compounds, such as compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and compositions, methods, uses, and kits that may be used in immunotherapy. The compounds provided herein are responsible for immunomodulatory signaling through the TLR2 receptor and are therefore useful for the treatment and / or prevention of various diseases (e.g., metabolic diseases, inflammatory diseases, immune disorders, or proliferative diseases).

The invention relates to the technical field of medicinal chemistry and pharmacology, in particular to a synthetic method of a high-activity human Toll-like Receptor 2 agonist. In the technical route, an acetal aliphatic chain in the agonist is introduced by using a method for activating dithiol acetal under an oxidation condition. By adjusting the length of an acetal aliphatic chain, a high-activity immune agonist aiming at human-derived TLR2 is created, and the EC50 aiming at TNF-alpha is equal to 116pM. The technical route is as follows: D-galactose which is low in price and easy to obtain is taken as an initial raw material, and the high-activity human TLR2 agonist is obtained in a gram-level scale through six-step chemical conversion, so that a technical route and a material basis are provided for subsequent application in vaccine adjuvants and tumor immunotherapy.

The invention belongs to the field of medicinal chemistry and pharmacology, and relates to application of a novel glycolipid TLR2 agonist 13-C in preparation of vaccine adjuvants and anti-tumor treatment. The compound is excellent in human TLR2 agonist activity, EC50 reaches 2.2 nM, and the compound is simple in structure, easy to prepare and excellent in solubility and has industrial application potential. In a B16-OVA tumor model, the antibody induction capacity of the compound is superior to that of a positive control drug Diprovocim, and the anti-tumor activity of the compound is more remarkable; in addition, PD-L1 expression of tumor tissue can be effectively down-regulated, and a synergistic anti-tumor effect is generated with a PD-L1 monoclonal antibody Atezolizumab. Besides, 13-C and a vaccine adjuvant QS-21 are combined for use, so that a synergistic enhancement effect is achieved, the antibody titer induced by a vaccine can be remarkably improved, antibody subtypes are enriched, meanwhile, cellular immunity and humoral immunity response of an organism are stimulated, and the effect of dual immune activation is achieved.

The invention discloses an inflammation regulation sequence of dairy cow mastitis and application thereof, and belongs to the technical field of biology, the inflammation regulation sequence is a regulation sequence responding to a gram-negative bacterium inflammation signal, the regulation sequence is a promoter sequence of a CXCL2 gene and is shown as SEQ ID NO: 1, and the regulation sequence is a promoter sequence of a CXCL2 gene and is shown as SEQ ID NO: 2. A regulatory sequence responding to a gram-positive bacterium inflammation signal, which is a promoter partial sequence of the NLRP3 gene and is as shown in SEQ ID NO: 2; the regulatory sequence responding to a gram-positive bacterium inflammation signal is a promoter reverse complementary sequence of the TLR2 gene and is shown as SEQ ID NO: 3; the endogenous inflammation regulation sequence provided by the invention is composed of genome elements of the dairy cow, and no exogenous coding gene is introduced, so that potential risks caused by exogenous proteins are avoided.

The present invention provides a chimeric antigen receptor, a nucleic acid molecule, CAR-Ms, and applications thereof, and belongs to the field of biomedical engineering and peptides. The chimeric antigen receptor provided by the present invention comprises a CD8 α leader signal peptide, a single-chain variable fragment, a CD8 α hinge, a CD8 transmembrane domain, and an intracellular co-stimulatory signal transduction domain. The single-chain variable fragment can target any known antigen; the intracellular co-stimulatory signal transduction domain is any one or a combination of TLR2, TLR4, TLR7, Mincle, Dectin-1, NOD2, CD40, 4-1BB, OX40, and CD3ζ. The present invention also provides a macrophage-targeted nanogel for RNA delivery. Macrophages transfected with the nanogel system express chimeric antigen receptors, which can achieve specific targeting and phagocytosis of known antigen-positive (e.g., MUC1) tumor cells.

The present invention relates to a molecular construct comprising at least two functional entities a) and b), wherein a) is an N-formyl methionine peptide, and b) is a TLR2-ligand, wherein a) and b) are associated to one another.

The application discloses a caviar polypeptide composition with enhanced immune function, a preparation method, application and preparation, belongs to the technical field of bioactive polypeptides, and comprises at least one polypeptide with an amino acid sequence of RWFPGKPLFWRA, FWKPLRGALFPW or KWRFPGALPWFA and a molecular weight of 1400-1550 Da. The preparation method comprises caviar protein extraction, complex enzymolysis, ultrafiltration separation, chromatography purification and solid-phase synthesis. Animal experiments prove that the polypeptide can significantly enhance cell immunity, humoral immunity, monocyte-macrophage function and NK cell activity, the mechanism is related to TLR2 / TLR4 receptor activation and NF-κB / MAPK signal pathways, the safety is good, and the polypeptide is suitable for development into an immune-enhancing health food or medicine.

The present invention relates to cancer immunotherapy. In particular, the present invention provides methods, compounds, compositions and kits for treating and / or preventing cancer. Specifically, provided are methods for the treatment of cancer comprising administering a TLR2 agonist, such as a conjugate of dipalmitoyl-S-glyceryl-cysteine (Pam2Cys) and polyethylene glycol (PEG), more specifically a Pam2Cys-Ser-PEG compound, and an immunostimulatory agent, such as an anti-PD-1, anti-PDL-1, anti-PL-1, or anti-CTLA-4 immunotherapeutic agent.

The application discloses a liposome vaccine of Acinetobacter baumannii outer membrane protein and a preparation method and application thereof, and relates to the field of biological medicines. The application efficiently expresses the Acinetobacter baumannii outer membrane protein through a genetic engineering method, and obtains a liposome vaccine of Acinetobacter baumannii outer membrane protein by combining the obtained various outer membrane proteins as antigens with a lipid mixture and an adjuvant. It is verified that the vaccine can provide complete protection for mice attacked by a lethal dose of Acinetobacter baumannii. In the application, the outer membrane protein loaded in the liposome is re-folded in structure, the immunogenicity of the protein is enhanced, and the liposome can reduce the toxicity of the outer membrane protein. Omp38+BauA+FimA can be an effective antigen combination for preventing Acinetobacter baumannii infection. Pam2CSK4 as a TLR2 agonist has a strong auxiliary effect on the liposome vaccine of Acinetobacter baumannii, and can induce the activation of an innate immune response, thereby providing more comprehensive protection for a host.

The invention discloses application of an IGF2BP2-m6A-VCAN-TLR2 (Insulin-like Growth Factor 2BP2-m6A-VCAN-TLR2) signal axis in preparation of a medicine for treating lymphatic metastasis of intrahepatic cholangiocarcinoma. Aiming at the problems of unknown lymphatic metastasis mechanism and lack of effective targets of intrahepatic cholangiocarcinoma, the invention discovers and verifies that mRNA binding protein 2 of insulin-like growth factor 2 is modified by m6A to regulate and control the expression of pluripotent proteoglycan so as to activate a Toll-like receptor 2 signal, promote macrophages to secrete vascular endothelial growth factor C and drive a brand new pathway of lymphatic metastasis. Based on this, the invention provides an inhibitor targeting the signal axis, especially a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit migration, invasion and epithelial-mesenchymal transition of bile duct cancer cells, reduce macrophage secretion of vascular endothelial growth factors C, effectively inhibit tumor growth and lymphatic metastasis in a nude mouse popliteal lymph node metastasis model and a spontaneous bile duct cancer model, and present a synergistic effect when combined with gemcitabine and cis-platinum.

Provided herein are Toll-like receptor 2 (TLR2) agonists for use in enhancing human immune response and / or as adjuvants in vaccines. The TLR2 agonists include thiophenes, imidazoles, or phenyl-containing compounds, which may be compounds of Formulae (I), (II), (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein are used as enhancers of an immune response (e.g., innate and / or adaptive immune response), and are useful in treating and / or preventing a disease, as adjuvants in a vaccine for the disease, (e.g., proliferative disease, inflammatory disease, autoimmune disease, infectious disease, or chronic disease). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

The application discloses a targeted acne-removing composition suitable for sensitive skin and a preparation method and application thereof. The targeted acne-removing composition comprises lysozyme, a first extract and a second extract in a mass ratio of 1:(0.1-10):(0.1-5). The first extract comprises guaiacum extract and myrtle fruit extract. The second extract comprises sophora flavescens extract and angelica sinensis extract. The targeted acne-removing composition containing lysozyme, the first extract and the second extract in specific mass ratios can inhibit the activity of propionibacterium acnes, down-regulate the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), and achieve efficient acne removal, and has the mild property and can be suitable for sensitive skin.

The present invention contemplates new members of the diprovocim family of compounds that exhibit improvements in both potency and efficacy in the murine system, permitting more effective use in vivo in animal models while maintaining the remarkable activity agonist towards human TLR1 / TLR2. The prototypical new agonist called diprovocim-X exhibits the same excellent potency and efficacy of diprovocim-1 in human THP-1 cells (EC50 of 140 pM vs 110 pM with efficacy 100% that of diprovocim-1 and Pam3CSK4), and displays a superb EC50 of 750 pM in mouse macrophages with an efficacy 550% that of diprovocim-1. Diprovocim-X served as an adjuvant in vivo in mice when co-administrated with a non-immunogenic antigen (OVA), indicating stimulation of the adaptive immune response. These the new diprovocim family compounds are now functionalized for linkage to antigenic, targeting, or delivery moieties, properties to enable precision activation of coordinated innate and adaptive immune responses in target tissues.

The application belongs to the field of tea polysaccharide research, and discloses a Zijuan tea polysaccharide ZTPW with immunoregulatory activity, and a preparation method and application thereof. The ZTPW is a uniform polysaccharide obtained by hot water extraction and alcohol precipitation of Zijuan tea leaves, and separation and purification through an ion exchange column and a gel column, the main repeating unit structure of which is shown in the following, and the weight average molecular weight thereof is 7.73 kDa. Through in vitro immunoregulatory activity research, the ZTPW can be recognized by pattern recognition receptors TLR2 and TLR4 to activate macrophages, significantly enhance the activity of mouse monocyte macrophage RAW264.7 cells, and mediate the production of NO and cytokines of mouse monocyte macrophage RAW264.7 through MAPKs and NF-kappa B signal pathway, so as to play an immunoregulatory role. The polysaccharide can be used as a potential immunoregulator for the development of functional food or medicine.

The invention relates to application of SAA1 as a biomarker in preparation of an ovarian cancer diagnostic kit. The invention further provides application of a reagent for detecting the content of SAA1 protein in preparation of the ovarian cancer diagnostic kit and application of an SAA1 inhibitor in preparation of a medicine for treating ovarian cancer. A series of experiments show that myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues of an ovarian cancer patient are obviously gathered; sAA1 is elevated in an ovarian epithelial cancer (EOC) patient and is associated with a poor prognosis; sAA1 promotes proliferation of ovarian cancer cells in vitro; sAA1 released by ovarian cancer cells recruits MDSCs through a TLR2 / 4 receptor and promotes differentiation of the MDSCs. The invention innovatively provides a new treatment thought by deeply revealing the key effect of the SAA1-MDSCs in the ovarian cancer immunosuppression process, which undoubtedly has extremely important scientific significance and also shows huge value in clinical application.

The invention discloses three potential bovine colostrum protein peptides with immunoregulatory activity and a preparation method of the three potential bovine colostrum protein peptides. The amino acid sequences of the active peptide are KTTMPLW, RDMPIQAF and SRYPSYGL respectively, and the active peptide has high affinity binding with a TLR2 / TLR4-MD-2 receptor through molecular docking verification. The method comprises the following steps: screening optimal protease on the basis of a virtual enzyme digestion technology and a quantitative structure-activity relationship (QSAR) model, carrying out enzymolysis on bovine colostrum protein by adopting alkaline protease, and carrying out ultrafiltration to obtain lt; and finally, carrying out LC-MS / MS (liquid chromatography-mass spectrometry / mass spectrometry) identification and bioinformatics screening to obtain a target peptide fragment. The invention provides a new technical scheme for high-value utilization of bovine coloctrum and development of functional immunoregulation food.

The application provides an E. coli outer membrane vesicle targeting TLR2 receptor and a construction method thereof, and relates to the technical field of biological medicine. The application first constructs a ClyA-HLYV fusion protein, and successfully obtains a recombinant plasmid ClyA-HLYV-pGEX-6P-1 stably expressing the fusion protein through genetic engineering technology, and induces endogenous expression of the fusion protein in an E. coli W3110 strain, to prepare a targeted bacterial outer membrane vesicle (HLYV-OMVs) expressing the ClyA-HLYV fusion protein on the surface. The HLYV-OMVs prepared by the application not only retain the specific recognition ability of HLYV to the surface TLR2 receptor of breast cancer cells, but also have the potential to encapsulate drugs, realizing the dual functions of targeted recognition and drug delivery. In addition, the HLYV-OMVs effectively solve the key problem of long-acting time of HLYV single peptide in targeted application, have good stability, significantly accelerate the effect starting speed after HLYV combines with the receptor, and lay an important foundation for efficient targeted treatment of tumors.

The invention relates to the technical field of biological deep processing and extraction, and discloses a directional preparation method of intestinal immunity-enhanced sea cucumber peptide, which comprises the following steps: (1) sea cucumber pretreatment; (2) carrying out deep penetration wall breaking on the supercritical CO2 / deep eutectic solvent; (3) performing enzymolysis treatment; (4) peptomics analysis; (5) performing molecular docking and virtual screening on the sea cucumber peptide and the TLR2 receptor; (6) membrane separation targeted enrichment; and (7) performing rotary evaporation, concentration and drying to obtain the sea cucumber peptide. Supercritical CO2 with strong permeation and diffusion characteristics is used as a carrier and cooperates with the deep-eutectic solvent to penetrate through a compact cuticle structure of sea cucumbers. The SC-CO2 acts on a stratum corneum lipid phase, a remarkable micropore expansion effect is initiated, and the pore density is greatly improved; functional ions in the deep eutectic solvent accurately destroy a salt bridge cross-linked network of cuticle key structure protein, and solvent components induce deep swelling of collagen through hydrogen-bond interaction, so that effective disintegration of the cuticle structure is realized.

The application discloses an IGF2BP2-m6A-VCAN-TLR2 signal axis in the preparation of a drug for treating intrahepatic cholangiocarcinoma lymphatic metastasis. In view of the problems of unknown intrahepatic cholangiocarcinoma lymphatic metastasis mechanism and lack of effective target, the application finds and verifies a new pathway that from insulin-like growth factor 2 mRNA binding protein 2, m6A modification regulates the expression of multi-functional proteoglycan, and then activates Toll-like receptor 2 signal, promotes macrophage secretion of vascular endothelial growth factor C and drives lymphatic metastasis. Based on this, the application provides an inhibitor targeting the signal axis, in particular, a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit cholangiocarcinoma cell migration, invasion and epithelial mesenchymal transition, reduce macrophage secretion of vascular endothelial growth factor C, and effectively inhibit tumor growth and lymphatic metastasis in a naked mouse popliteal lymph node metastasis model and a spontaneous cholangiocarcinoma model. The compound presents a synergistic effect in combination with gemcitabine and cisplatin.

Provided is a chimeric antigen receptor (CAR) having a ligand-binding domain, a transmembrane domain, and a cytoplasmic portion (e.g., a cytoplasmic portion that includes a toll-like receptor 2 (TLR2) signaling domain, and a CD3 zeta (CD3ζ) signaling domain). Further provided is a cell (e.g., a pluripotent cell, or a NK cell derived from a pluripotent cell) comprising the CAR, and methods for making and using such cells in immunotherapy for cancer. The CAR-NK cells may be CISH- / - iPSC-NK cells.

The quinoline sulfur-containing derivative compound with a brand new structure is designed on the basis of an ATM-P53 signal and a TLR2 pathway, has the characteristics of high efficiency, low toxicity, prevention and treatment, stable quality, convenience in taking, effectiveness in oral injection and the like, can directly resist multi-system injury caused by radiation, effectively relieves symptoms of acute radiation sickness, and has a good application prospect. The precious opportunity is won for subsequent comprehensive treatment, and a new thought and direction are provided for developing efficient and safe radiation protection medicines.