33 results about "TLR2" patented technology

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 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 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.

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 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 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.

The application discloses a periodontitis targeted sustained-release gel based on epithelial training immunity and a preparation method thereof, relates to the technical field of biological medicine, and the preparation process is as follows: poloxamer is modified and then dissolved in anhydrous acetonitrile; RGD peptide is dissolved in a PBS buffer solution, N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide are added for activation to obtain an activated RGD peptide solution; the activated RGD peptide solution is added into the modified poloxamer solution, and reaction is carried out 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 to obtain the periodontitis targeted sustained-release gel. The gel provided in the application can specifically target gingival epithelial cells, reduce inflammatory reactions, promote periodontal tissue regeneration, has good biocompatibility and sustained-release performance, and can effectively control periodontitis and prevent recurrence.

The present invention pertains to a new method for the diagnosis, prognosis, stratification and / or monitoring of a therapy, of a pulmonary dysfunction in a subject. The method is based on the determination of the level of a panel of biomarkers selected from TM4SF18, TRGV9, ADORA2A, H963, IRF2, TNFSF14, TRIB1, SMAD3, TSLP, SLAMF8, THBS1, SOD1, HAS2, TLR2, THBD, TRA, TFEC, SPHK1, COL3A1, Elastin, IL6R, SN, TEK, SOX7, CXCL9, CXCL10, SLC38A6, SLC15A3, TGFA, SLPI, VWF, TLR8, TGFB1, CXCR6, CCL24, PD1, PLA1A, TRD, CTLA4, MMP9, CD301, PDL1, PDL2, TGFB1, CXCR6, CCL24, PD1, PLA1A, TRD, CTLA4, MMP9, and CD301. The new biomarker panels of this invention allow diagnosing and even stratifying various pulmonary dysfunctions in a subject, and even allow early detection of Chronic lung allograft dysfunction (CLAD). Furthermore provided are diagnostic kits for performing the methods of the invention.

This invention belongs to the field of biotechnology, specifically relating to a highly immunomodulatory peptide derived from silkworm pupa protein, its preparation method, and its applications. The invention provides a silkworm pupa protein immunomodulatory peptide, the amino acid sequence of which is shown in SEQ ID NO.2, SEQ ID NO.3, and / or SEQ ID NO.8. This silkworm pupa protein immunomodulatory peptide is prepared by hydrolyzing silkworm pupa protein with alkaline protease, followed by purification of the enzymatic hydrolysis product through ultrafiltration and gel filtration. The most immunomodulatory peptide is screened by determining the immunomodulatory activity index, and identified by LC-MS / MS to obtain a highly immunomodulatory peptide derived from silkworm pupa protein. This immunomodulatory peptide strongly binds to TLR2 and TLR4 / MD-2 receptors through hydrogen bonds and hydrophobic interactions, activating immunity and effectively promoting macrophage proliferation and phagocytosis. This immunomodulatory peptide exhibits good immunomodulatory activity and can be used as a potential functional food ingredient.

The application discloses a bifidobacterium that can significantly improve the expression of BDNF of a host and an application thereof, and belongs to the technical field of microorganisms. The bifidobacterium CCFM1359 provided by the application can effectively improve the levels of BDNF and its specific receptor TrkB in the colon of a mouse, can also increase the number of enteric glial cells, improve the content of excitatory neurotransmitter Ach in the colon, down-regulate the content of inhibitory neurotransmitter NO, and repair the enteric nervous system. Moreover, the bacteria can down-regulate the gene expression levels of TLR2 and TNF-alpha, up-regulate the gene expression level of IL-10, reduce the inflammation level in the colon, and regulate the intestinal motility. Therefore, in the future, a more personalized treatment scheme can be adopted for patients with damaged enteric nerves (including but not limited to intestinal motility disorders), and the application prospect is very considerable.

The present application relates to the technical field of drug synthesis, and particularly relates to a compound or derivative thereof used as a TLR2 antagonist, and a preparation method and application thereof. A specific technical scheme is as follows: a compound or derivative thereof used as a TLR2 antagonist, as shown in the following formula I: wherein, n=0, 1 or 2; R1 is selected from hydrogen, halogen, non-substituted or substituted alkyl, halogenated alkyl, alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated heterocycloalkyl, aryl and heteroaryl. The compound and the derivative thereof provided by the present application can inhibit the release of TNF-alpha caused by TLR2 / 1 and TLR2 / 6 activation at a cell level, and have no obvious cytotoxicity. Meanwhile, the compound or the derivative thereof has good physicochemical properties and in-vivo and in-vitro metabolic properties.

The application discloses a lactobacillus paracasei for repairing intestinal nerves and an application thereof, and belongs to the field of microorganisms. The lactobacillus paracasei CCFM1321 provided by the application can significantly increase the number of intestinal nerve glial cells, improve the level of glial cell-derived neurotrophic factor GDNF and the expression of its receptor GFR alpha 1 / RET, and repair the damaged intestinal nervous system of mice. The lactobacillus paracasei can down-regulate the over-activation of Toll-like receptor 2 (TLR2), reduce the expression of inhibitory neurotransmitters, increase the expression of serotonin 5-HT and its receptor 5-HT 2B , and has the effect of protecting the intestinal nervous system. Moreover, the lactobacillus paracasei can reduce the inflammation level in the colon tissue caused by the damage of intestinal nerves, improve the pathological damage of the colon tissue, and relieve the intestinal motility disorder. Therefore, a more personalized treatment scheme can be adopted for gastrointestinal diseases caused by the abnormal intestinal nervous system, and the application prospect is considerable.

The invention discloses application of a CSF2RA gene, an acute myelogenous leukemia marker, a prognosis effect analysis model and a construction method thereof, and relates to the technical field of biology. Mainly relates to application of a reagent for detecting the expression quantity of a CSF2RA gene or a Hub gene related to the CSF2RA gene in preparation of a product for predicting the prognosis effect of acute myelogenous leukemia. Meanwhile, the invention also discloses an acute myelogenous leukemia marker which is one or more of CD4, ITGAM, TLR4, TLR2, FCGR3A, IL10, CD86, TLR8, ITGAX and FCGR2B genes. The invention provides a new target CSF2RA for predicting the prognosis effect of the acute myelogenous leukemia, and provides a prognosis effect analysis model, and the result shows that the high expression of the CSF2RA gene or the Hub gene related to the CSF2RA gene is related to the poor prognosis of a patient with the acute myelogenous leukemia.

The invention relates to the technical field of biology, in particular to application of a yeast culture in relieving growth inhibition and liver and intestine injury of pseudobagrus ussuriensis induced by vegetable protein feed. The feed formula disclosed by the invention comprises 48% of vegetable protein (soybean meal, cottonseed meal and corn protein powder), 1-3% of yeast culture and the like. 1-2% of yeast culture is added into the feed containing 30% of soybean meal, 11% of cottonseed meal and 7% of corn protein powder, so that the growth performance of the pseudobagrus ussuriensis can be remarkably improved, and through mechanisms such as a TLR2-MyD88-NF-kappa B pathway and the like, the oxidation resistance is improved, and inflammatory response and liver and intestine injury induced by plant protein antinutritional factors are relieved. The feed disclosed by the invention is simple in formula components, easily available in raw materials, safe and harmless, and beneficial to development of novel green additives and promotion of healthy breeding of the pseudobagrus ussuriensis.

The present invention belongs to the technical field of biomedicine, and specifically relates to an intracellular signaling domain of a chimeric antigen receptor and the use thereof. The intracellular signaling domain comprises at least two of a1)-a7): a1) FCE or a portion thereof; a2) CD3ζ or a portion thereof; a3) CD40 or a portion thereof; a4) TLR2 or a portion thereof; a5) TLR4 or a portion thereof; a6) IFNgR or a portion thereof; and a7) PI3Krecruit or a portion thereof. The chimeric antigen receptor comprising the intracellular domain can maintain a CAR-positive rate while ensuring the viability and recovery yield of immune cells, thereby better ensuring the activity of CAR-immune cells. Immune cells expressing the chimeric antigen receptor comprising the intracellular domain exhibit significantly enhanced phagocytic, cytotoxic and anti-exhaustion capacities in addition to T cell activation level, thereby achieving more potent antitumor activity and enhanced tumor infiltration.

The invention relates to an application of a milk-derived peptide KEMPFPK in the aspects of immune balance regulation and inflammation relief. The peptide can effectively inhibit the activation of downstream NF-kB and MAPK signal channels by targeting a TLR2 / 4 receptor on the surface of a macrophage, significantly relieve immune organ structure damage caused by cyclophosphamide, systematically down-regulate the levels of IL-6, IL-1beta, TNF-alpha, IgA and IgM in serum, and increase IL-10 at the same time, so that the multi-level anti-inflammatory and immunoregulation effects are achieved. The peptide can be used for preparing anti-inflammatory drugs, immunomodulatory functional foods and nutritional supplements, and has good safety and application prospects.

Methods, compounds, compositions, and kits for the treatment of cancer, comprising TLR2 agonists, particularly dipalmitoyl-S- glyceryl-cysteine (Pam2Cys) derivatives and conjugates, are provided. In one aspect, methods of treating, preventing or minimizing the progression of cancer comprising the administration of a compound comprising a Pam2Cys moiety and a polyethylene glycol (PEG) are provided.

The invention provides a nasal mucosa vaccine adjuvant, a nasal mucosa vaccine, a preparation method and application, and belongs to the technical field of vaccine adjuvants. The invention provides a virus bionic nasal mucosa vaccine adjuvant, which takes nanoparticles as a carrier, a nucleic acid-like TLR agonist is loaded in the virus bionic nasal mucosa vaccine adjuvant, and a polysaccharide adjuvant is modified on the outer surface of the virus bionic nasal mucosa vaccine adjuvant; raw materials for preparing the nanoparticles comprise an amphiphilic polymer material and cationic lipid. From the structure, a shell of a nanoparticle of the nasal mucosa vaccine adjuvant simulates a virus envelope, a nucleic acid-like TLR agonist simulates virus nucleic acid, and the outer surface of the nanoparticle is modified with a polysaccharide adjuvant simulative virus glycoprotein; from the perspective of functions, the nasal mucosa vaccine adjuvant reengraves a virus infection time sequence, firstly activates a TLR2 / 4 pathway through a polysaccharide adjuvant to start mucosa immunity, and then activates an intracellular TLR3 pathway through a nucleic acid-like TLR agonist, so that dual-pathway synergistic interaction is realized, and the problem that mucosa and system immunity are disjointed by a traditional adjuvant is solved.

The invention provides a method for improving the transfer developmental capacity of a frozen bovine IVF (in-vitro fertilization) embryo, which is characterized in that in the processes of freezing and unfreezing the bovine IVF embryo, culturing the embryo in a later period and the like, high-concentration sodium pyruvate, insulin, TLR2 (toll-like receptor 2) and a Cytosporone B are independently or jointly added, so that the survival rate and developmental capacity of the frozen embryo, the pregnancy rate after transplantation and the like are improved. Experiments show that the embryo survival rate, the hatching rate and the embryo transfer pregnancy rate of a group which is jointly added with sodium pyruvate, insulin, TLR2 and Nur77 agonist B are obviously higher than those of a double-substance adding group, a single-substance adding group and a control group. The method lays a foundation for production and related scientific research of in-vitro fertilized embryos in the future, provides an effective, safe and feasible strategy for improving in-vitro embryo production efficiency and embryo quality, and has great popularization value.

An example of a composition for promoting metabolic health can include a combination of cyanidin and delphinidin in an amount sufficient to treat metabolic disorders.Furthermore, an example of a method for treating a condition or disorder related to metabolic health in a subject can include reducing endotoxin levels compared to baseline endotoxin levels, and adjusting cardiometabolic biomarkers related to lipid or glucose metabolism from abnormal cardiometabolic baseline levels to normal levels.Exemplary methods can also include reducing liver inflammation, treating high-fat diet-induced colon dysfunction, reducing the expression of toll-like receptors TLR4 and TLR2, reducing plasma endotoxin levels, reducing the expression of NADPH oxidase NOX1, and increasing tight junction proteins in the colon of a subject.