79 results about "TLR4" patented technology

The application discloses a virtual screening method of a small-molecule compound targeting TLR4. The application screens potential compounds capable of combining with TLR4 through three-dimensional molecular docking, and preliminarily proves that three compounds, Z1410232649, F27210326 and HY-N0029, have better TLR4 inhibiting effects through experimental verification. Among them, Z1410232649 performs most outstandingly, can significantly inhibit the release of inflammatory factors IL-6, TNF-alpha and IFN-gamma induced by LPS, and can be used as a novel anti-inflammatory drug or immunotherapy drug targeting TLR4.

This invention provides the use of Yigongsan in the treatment of myelodysplastic syndrome (MDS). Specifically, this invention has found that Yigongsan improves ineffective hematopoiesis in MDS patients and significantly alleviates traditional Chinese medicine symptoms of MDS, such as fatigue, lethargy, lack of thirst, and sallow complexion. Furthermore, it has been discovered that Yigongsan regulates hematopoietic function in MDS through the S100A9-TLR4-NF-κB signaling pathway. This invention also provides a treatment method for MDS.

The invention discloses a manganese-based nano-enzyme composite material as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) preparing Mn3O4-PVP from Mn3O4 NPs and PVP10, and then loading the Mn3O4-PVP into a ZIF-8 structure in the process that Zn < 2 + > and 2-MI react to form ZIF-8, so as to obtain Mn3O4-coated ZIF-8 NPs; (2) covering the surface of the Mn3O4 ZIF-8 with HA through ion coordination, and synthesizing MZH; and (3) carrying out clathration on MZH through ES100, and synthesizing MZH coated ES100. By inhibiting a TLR4 / NF-kappa B pathway, activating an Nfr2 / Keap1 pathway and increasing expression of intestinal tight junction protein, mouse colitis induced by DSS is resisted, and symptoms of the mouse colitis are relieved.

The application discloses application of Bifidobacterium longum exopolysaccharide or a co-incubation extractive solution of the Bifidobacterium longum exopolysaccharide and probiotics in improving inflammation. The application finds that the Bifidobacterium longum exopolysaccharide and the co-incubation extractive solution of the Bifidobacterium longum exopolysaccharide and Lactobacillus acidophilus can inhibit LPS-induced TLR4 / NfkB (P65) signal path activation, inhibit the polarization of macrophages from M0 to M1, thereby inhibiting inflammatory reactions, and the inhibiting effect of the co-incubation extractive solution of the Bifidobacterium longum exopolysaccharide and Lactobacillus acidophilus is more obvious. Therefore, the Bifidobacterium longum exopolysaccharide and the co-incubation extractive solution of the Bifidobacterium longum exopolysaccharide and Lactobacillus acidophilus can be used for preparing drugs for inhibiting inflammatory reactions, and are helpful to the treatment of immune and chronic inflammatory diseases and the development of related drugs.

The application discloses an application of a TLR4 / NF-kappa B signal path inhibitor in preparation of a medicine for improving hematopoietic function of anemic inflammatory, relates to the technical field of biology and medicine, and discloses an application of the TLR4 / NF-kappa B signal path inhibitor in preparation of a medicine for improving hematopoietic function of anemic inflammatory, wherein the TLR4 / NF-kappa B signal path inhibitor is Danggui Buxue Decoction; the Danggui Buxue Decoction is composed of Astragalus and Angelica with a mass ratio of 5:1; the TLR4 / NF-kappa B signal path inhibitor is used for down-regulating expression of TLR4 protein and NF-kappa B protein in liver tissue; the improvement of hematopoietic function of anemic inflammatory includes increasing peripheral blood red blood cell count, white blood cell count, platelet count and hemoglobin level; the Danggui Buxue Decoction is used as the TLR4 / NF-kappa B inhibitor to improve anemic inflammatory, can down-regulate TLR4 / NF-kappa B expression, improve blood cells and hemoglobin, improve bone marrow pathology, reduce inflammatory factors and hepcidin, increase iron content, and provide a corresponding curative effect evaluation method, and provides a new choice for anemic inflammatory treatment.

The present disclosure relates to the use of compound (I) and any of its salts for the treatment of a neoplasm characterized by high expression of toll-like receptor 4 (TLR4) in the tumor or its microenvironment, associated with at least one of the pathophysiological complications including immunosuppression, angiogenesis, fibrosis, or metastasis.

The invention discloses a traditional Chinese medicine composition for inhibiting salmonella choleraesuis as well as a preparation and application thereof, and belongs to the technical field of traditional Chinese medicine and network pharmacology. According to the invention, traditional Chinese medicines with a good antibacterial effect on S. Choletaesuis are screened, and the compound five-plum decoction with a good antibacterial effect on S. Choletaesuis is established. The five-plum decoction can be used for effectively regulating and controlling the steady state of intestinal flora, and reducing the oxidative damage and inflammatory damage of the S. Cholera to the intestinal tract and the liver by regulating and controlling the signal channels of TLR4 / NF-kB / MyD88 and ZO-1 / Claudin-1 / Occludin. Through the multiple effects of resisting bacteria, resisting inflammation, protecting intestinal barriers and improving production performance, the five-plum decoction shows remarkable prevention and treatment effects on swine paratyphoid, and has huge value of being developed into a novel veterinary traditional Chinese medicine preparation and put into clinical application.

The invention provides a process for preparing a Biochanin A (BCA)-loaded hydroxypropyl methyl cellulose (HPMC) hydrogel aimed at promoting wound healing in diabetic patients. The hydrogel is prepared by dispersing HPMC in distilled water, followed by dissolving BCA into the mixture with continuous stirring, then storing under refrigeration. The therapeutic potential of Biochanin A (BCA) in promoting wound healing, is evaluated in rats induced with diabetes. The results showed that the BCA-loaded hydrogel accelerates diabetic wound repair by boosting antioxidant defenses via upregulating Nrf2 and related enzymes, suppressing inflammatory markers such as IL-1β, IL-6, TNF-α, COX-2, and TLR4, and stimulating angiogenesis through increased expression of TGF-β1, VEGF-A, and PDGFR. It promotes faster wound contraction, re-epithelialization, collagen deposition, granulation tissue formation, and neovascularization, potentially reducing the risk of complications like limb amputation. The invention offers a promising therapeutic approach for treating chronic diabetic wounds with improved healing outcomes.

The invention provides an application of alkaloid bicuculline in preparation of a medicine for preventing and / or treating hepatic fibrosis diseases and hepatic inflammation, and also provides an application of bicuculline in preparation of an inflammatory factor expression inhibitor and an application of bicuculline in preparation of a Toll-like receptor 4 signal channel inhibitor. 7.5 mu g / mL of bicuculline can be used for relieving the activation of hepatic stellate cells induced by TGF-beta1, remarkably reducing the expression of alpha-SMA and COL1A1, and reducing the expression of MyD88 and NF-kB as well as downstream inflammatory factors IL-6, IL-1beta and TNF-alpha in a TLR4 / MyD88 / NF-kB signal channel. By intraperitoneal injection treatment of 0.6 mg / kg of bicuculline, the liver morphology in a fibrosis model can be remarkably improved, the levels of ALT and AST in serum can be remarkably reduced, and collagen deposition and expression of alpha-SMA and COL1A1 in the liver can be remarkably reduced.

The present application relates to the technical field of biological medicine, in particular to application of aconitum brachypodum franch alcohol extract in myocardial protection, and discloses that the aconitum brachypodum franch alcohol extract mainly inhibits formation of myocardial fibrosis, reduces inflammatory reaction and reduces cell apoptosis by adjusting a TLR4 / MyD88 / NF-kappa B channel, thereby protecting ISO-induced myocardial injury of a mouse; the present application provides a theoretical basis for improving myocardial injury by the aconitum brachypodum franch, and also provides a scientific basis for development and utilization of the aconitum brachypodum franch.

The invention provides a traditional Chinese medicine composition, a traditional Chinese medicine preparation, a preparation method and application, and particularly belongs to the technical field of traditional Chinese medicine preparation. The traditional Chinese medicine composition comprises the following components in parts by weight: 7-11 parts of champignon, 19-29 parts of aloe, 10-14 parts of fructus chebulae immaturus, 5-7 parts of rhizoma zingiberis, 5-7 parts of rhizoma nardostachyos, 4-6 parts of fructus chebulae and 2-4 parts of halite. The traditional Chinese medicine composition can improve the activity of SOD, inhibit the content of MDA, reduce damage of oxygen free radicals to gastric mucosa, effectively relieve inflammatory response, achieve anti-inflammation, improve ulcer surface blood flow, improve gastric mucosa damage, reduce ulcer surfaces and promote ulcer healing, and therefore the protective effect on gastric ulcer is achieved. The results of network pharmacology, molecular docking speculation and Western blot method verification show that the FMST plays an anti-inflammatory role through a TLR4 / MyD88 / NF-kappa B signal channel.

The present application relates to triterpene glycoside saponin-derived adjuvants, TLR4 agonists and antagonists, TLR9 agonists and antagonists, and combinations thereof, as well as pharmaceutical compositions comprising the foregoing and methods of making and of using the foregoing in the treatment of certain diseases.

The invention discloses application of AvBD-5 protein in resisting avian influenza virus infection, and belongs to the technical field of biology. A recombinant plasmid containing a coding sequence of the AvBD-5 protein is transformed into an escherichia coli expression system, IPTG is used for inducing expression of the AvBD-5 protein, the expressed AvBD-5 protein is purified, the high-concentration purified AvBD-5 protein is obtained through ultrafiltration and concentration, the protein can remarkably reduce the virus load of the H9N2 avian influenza virus in in-vivo and in-vitro experiments, and the virus load of the H9N2 avian influenza virus can be remarkably reduced. Meanwhile, the polypeptide has a prominent immunoregulation function, and can specifically inhibit the expression of TLR4 and block the activation of a TLR4 / NF-kappa B signal channel by regulating the immunologic function of red blood cells. The protein can be used as a novel immunomodulator or a drug candidate, and is used for preventing and treating H9N2 avian influenza virus infection.

The application discloses an application of ergothioneine in antiviral in the field of biotechnology. The ergothioneine plays an immune activation role at least by activating TLR4 and downstream NF-kappa B signal pathways. The ergothioneine is used for preparing an immunomodulator or an antiviral drug, can effectively activate immune cells and enhance antiviral capacity, to a certain extent, overcomes defects of traditional technologies, reduces problems of large side effects of current TLR4 agonists, and provides a new idea for developing a novel immunomodulator and an antiviral treatment strategy.

The present invention refers to inhibitors of the S100 calcium- binding protein A9 (S100A9) / S100A8 – Toll Like Receptor 4(TLR4) dimer-receptor axis for use in the treatment of Heart Failure with preserved Ejection Fraction (HFpEF). The present invention further refers to pharmaceutical formulations comprising the said inhibitors. The present invention's use of compounds and pharmaceutical formulations may be advantageously employed in HFpEF by attenuating the deleterious effect on endothelial function and prevention of inflammation, production of reactive oxygen species, apoptosis, senescence and pro-fibrotic phenotype.

The present invention relates to liposomes comprising a saponin, a sterol, a phospholipid and a Toll-like Receptor 4 (TLR4) agonist of formula (I), methods of preparing the liposomes, compositions comprising them and uses thereof, and immunogenic compositions comprising said liposomes as adjuvants.

A method to enhance an immune response in a mammal, and a composition comprising liposomes, a TLR4 agonist and a TLR7 agonist, are provided.

Disclosed are a composition comprising a TLR4 / MD2 pathway inhibitor and an EGFR inhibitor, a pharmaceutical composition comprising the composition, and the use of the composition / pharmaceutical composition for the treatment of cancer. The TLR4 / MD2 pathway inhibitor and the EGFR inhibitor can cooperatively kill cells of various cancers including skin melanoma, so that the TLR4 / MD2 pathway inhibitor and the EGFR inhibitor have an obvious inhibition effect on the growth of cancer cells and do not influence the weight of mice. In addition, compared with single medication, the composition disclosed by the invention can slow down the occurrence of drug resistance of tumor-bearing mice and significantly inhibit the growth of gefitinib-resistant cancer cells (such as non-small cell lung cancer tumors). Therefore, the composition disclosed by the invention can be used for preparing safe and effective antitumor drugs.

The application belongs to the field of nanomaterials and biomedicine, and provides a X03 phage-cerium oxide nanoscale enzyme composite treatment platform based on chemical cross-linking of polyethylene glycol, a synergistic treatment platform integrating bactericidal and detoxification functions, namely X03@CeO2, is constructed by covalently coupling phage X03 targeting pseudomonas aeruginosa and CeO2 nanoscale enzyme with phosphatase activity, which solves the problem that antibiotic and phage therapy exacerbate systemic inflammatory storm due to massive release of lipopolysaccharide caused by bacterial lysis when killing multiple drug-resistant gram-negative bacteria. In vitro and in vivo experiments show that the complex can efficiently remove bacteria and biofilm, simultaneously degrade released LPS, significantly inhibit the production of inflammatory factors, active oxygen burst and TLR4 pathway activation, greatly improve the survival rate in a lethal sepsis mouse model and reverse multiple organ damage. The application is suitable for treating sepsis caused by drug-resistant gram-negative bacteria.

The present invention provides a pharmaceutical composition comprising solid particles comprising at least one toll-like receptor 4 (TLR4) agonist and micelles comprising at least one toll-like receptor 7 (TLR7) agonistfor use as a medicament or for use in the treatment of cancer, an antibiotic resistance, an inflammatory condition or disease, an autoimmune disease or an infectious disease and at least one amphiphilic micelle-forming agent. Also provided is a method of preparing the pharmaceutical composition and a kit or kit of parts comprising the pharmaceutical composition for use.

The invention relates to application of Chinese yam protein, in particular to application of Chinese yam active protein in preparation of medicine for regulating blood testis barrier to treat testis dysfunction. L-YP has unique fluorescence characteristics and remarkable antioxidant activity, and can effectively improve testis immune microenvironment disorder by repairing blood testis barriers and inhibiting NLRP3 and TLR4 / MyD88 / NF-kappa B inflammatory pathways. In combination with a molecular docking technology, a molecular mechanism that key components such as YP2 (mitochondrial ornithine aminotransferase) and the like realize immunoregulation through high-affinity binding is clarified for the first time. According to the application disclosed by the invention, a molecular docking technology is creatively combined with system experimental analysis, and a molecular mechanism of improving testis injury by the Chinese yam protein is illuminated from the perspective of a'structure-function-target 'synergistic effect, so that a novel dietary intervention strategy is provided for preventing reproductive toxicity caused by chemotherapy; the application potential of medicinal and edible components in the field of male reproductive health is highlighted.

The present application provides novel compounds or pharmaceutically acceptable salts thereof having TLR4 activating effects, and useful as immunostimulants or adjuvants in vaccine or allergen immunotherapy. The present application provides a compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof. In the formula (I), X, Y, Z and n are each as defined in the specification.[Formula 1]

Preparation method and application of diterpenoid, relate to the application technical field of diterpenoid.The present application separates two new compounds of diterpenoid A and diterpenoid B from a strain of Hericium fermentation extract, and discloses chemical structural formula of the two compounds, and corresponding nuclear magnetic, mass spectrum, infrared and ultraviolet data, and its function of significantly inhibiting the production of inflammatory BV2 cell NO.Diterpenoid B has 24% of the promotion rate of axon growth of PC-12 cell, and simultaneously has significant inhibition of TLR4 / NF-κB signal path to inhibit downstream inflammatory proteins of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and diterpenoid A and diterpenoid B both show significant anti-neuroinflammatory activity.The present application can obtain the preparation method and application of diterpenoid.

The invention relates to the field of infant food, in particular to an anti-oxidative stress composition and application thereof to improvement of neonatal necrotizing enterocolitis. The composition is prepared from the following components: neutral oligosaccharide and sialylated oligosaccharide. The neutral oligosaccharide is 3-fucosyllactose, and the sialylated oligosaccharide is 3 '-sialic acid lactose. The invention provides a composition capable of relieving neonatal necrotizing enterocolitis. Through combination of the 3-fucosyllactose and the 3 '-sialic acid lactose, related symptoms of the neonatal necrotizing enterocolitis can be improved by inhibiting a TLR4 / NF-kappa B inflammation pathway, improving cell oxidative stress, protecting cell barriers and reducing cell apoptosis, and the 3-fucosyllactose and the 3'-sialic acid lactose have important application value in the field of functional foods or formula foods.

The invention relates to the field of medical health care products, in particular to a medicinal and edible composition with an immune regulation function and a preparation method of the medicinal and edible composition. The composition is prepared from raw materials in percentage by mass as follows: 30%-40% of a hericium erinaceus extract, 15%-25% of a sparassis crispa extract, 10%-12% of chickpea powder, 5%-8% of low-acid smoked plum powder, 3%-5% of lily powder, 2%-3% of microencapsulated fingered citron powder, 8%-10% of an okra extract, 0.5%-1.5% of calcium chloride, 1%-2% of beta-cyclodextrin, 3%-5% of rice protein and the balance of filling auxiliary materials. The composition has the advantages that: (1) the cellular immunity is enhanced by directly activating a TLR4 / NF-kappa B pathway; (2) regulating a flora-mucous membrane barrier and optimizing an immune response environment; (3) the cyclodextrin embedding and ion coating technology breaks through the absorption barrier; and the triple mechanisms are linked with one another, so that the exponential-level improvement of the immune regulation effect is finally realized.

A method of inhibiting phosphorylation of the tau protein and / or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

The application belongs to the technical field of biology and specifically relates to application of fibrinogen alpha chain in chimeric antigen receptor T cell (CAR-T) therapeutic drugs, wherein the fibrinogen alpha chain plays a direct role in maintaining tumor cell population stemness by activating a TLR4-NF-kappa B signal pathway. Meanwhile, the fibrinogen alpha chain promotes a significant increase in expression level and proportion of TROP2 in triple-negative breast cancer (TNBC) by activating the TLR4-NF-kappa B signal pathway, and shows enhanced sensitivity to targeted TROP2-CAR-T therapy. Therefore, through exogenous regulation of the fibrinogen alpha chain, up-regulation of tumor cell TROP2 expression and homogenization among tumor cell subpopulations are induced, thereby providing an important scheme for tumor stem cell targeted therapy of TNBC.

The invention relates to a kit for screening dilated cardiomyopathy. The kit comprises a reagent for detecting one or more of genes of TP53, TNF, IL1beta, JUN, CD8A, TLR4, UBB, CTLA4, CXCL8 and NFKBIA. The kit provided by the invention is high in detection efficiency and low in detection cost, provides important reference basis for diagnosis and prognosis judgment of patients with dilated cardiomyopathy, and can remarkably improve the survival rate of the patients.

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 the field of immunology, in particular to preparation of a mucous membrane adjuvant for recruiting pre-DC and application of the mucous membrane adjuvant in influenza vaccines. Tridecafluoroheptyl ethylene oxide and mannose are grafted on polyethyleneimine, the polyethyleneimine and structural protein hemagglutinin of influenza viruses are adsorbed to form a nano vaccine MF25PEI / HA, secretion of CCL2 is promoted by activating a TLR4 pathway of nasal cavity cDC, pre-DC is recruited and differentiated into cDC, and the network steady state of the nasal cavity cDC is maintained. HA uptake is increased by targeting cDC, cDC maturation is stimulated, and high-level immune response is induced. After intranasal immunization of MF25PEI / HA, secretion of high-level IgA and IgG is caused, activation of B cells, T cells and Tfh cells is promoted, and differentiation of memory B cells and memory T cells is induced. Effective protection can be provided for the influenza H1N1 virus, and a new thought is provided for research and development of respiratory mucosa vaccines.