58 results about "Tlr4 signaling" patented technology

The present invention relates generally to the Tlr4 signaling pathway specifically in the hematopoietic system and its contribution to insulin resistance of liver and adipose tissue. The hematopoietic component expressing Tlr4 is a principle propagator of immune signaling and results in insulin resistance. Furthermore, disclosed herein are methods and compositions for treating or preventing disorders associated with insulin resistance using a Tlr4 antagonist.

Blocking peptides comprised of the 14 amino acids that correspond to the sequences of the BB-loops of the four known TIR domain-containing adapter proteins (i.e. MyD88, TRAM, TIRAP, and TRIF) and homologous sequences of four TLRs (TLR2, TLR4, TLR1, and TLR6) are described. Adapter BB loop peptides disrupted TLR4, but not TLR2 signaling. TLR2 and TLR4 blocking peptides inhibited TLR4- and TLR2-mediated activation of ERK and cytokine induction, however, these peptides did not inhibit activation of p38. These peptides can be used to treat or prevent an immune or inflammatory response associated with a condition related to TLR4 signaling.

Disclosed herein are substituted cyclohexene TLR4 signaling pathway modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

The invention provides a research method for applying TLR4 to curing acute kidney injury caused by sepsis, and relates to the technical field of medical treatment. The method comprises the steps of mouse septic AKI model building; animal modelling judgement; specimen collection; normal and septic AKI mouse kidney cell primary culture; TLR4 determination by means of immunohistochemistry (SP method)and semi-quantitation; Real-time PCR detection of expression change of VEGF, sFLT-1, TNF-alpha and TLR4mRNA of septic AKI mouse primary kidney cells; detection of protein level expression change of VEGF, sFLT-1, TNF-alpha and TLR4 of septic AKI mouse primary kidney cells through a Western-blot method; constructing VEGF gene eukaryotic expression plasmids and optimal silence mouse VEGF gene ShRNAexpression plasmids; experimental grouping; TLR4 cell treatment; index detection; verifying TLR4 target regulation on VEGR expression; searching for protein in interaction with the VEGF; discussing molecule mechanisms which is possibly involved in TLRs signal path adjustment of the VEGF. The method speculates that the VEGF and the TLR4 signal path are in interaction for regulating the acute kidneyinjury caused by sepsis and play a part in protection.

The invention discloses an exosome and a preparing method and application thereof, and relates to the field of exosome medicines. In order to solve the problem of postoperative cognition dysfunction,mesenchymal stem cells are separated out of cornu cervi tissue; after culturing, a cell culture solution is collected, and the exosome from cornu cervi mesenchymal stem cells are extracted through separation. It is proved that CPB rat nerve function deficit and oxidative stress response can be relived, a protection effect is realized for CPB rat nerve cell apoptosis and CPB rat POCD can be relieved through a TLR2 / TLR4 signal channel. The exosome can be used for preparing medicines for improving or treating the cognition dysfunction.

Treatment of autoimmune and / or inflammatory diseases associated with overexpression of Toll-like receptor 3 (TLR3) as well as Toll-like receptor 4 (TLR4) and / or TLR3 / TLR4 signaling in nonimmune cells, monocytes, macrophages, and / or dendritic cells in association with related pathologies. The use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune and inflammatory diseases associated with TLR3 as well as TLR4 and / or TLR3 / TLR4 cellular signaling in association with related pathologies is disclosed. Methods of treating a subject having a disease or condition associated with abnormal TLR-3 as well as TLR-4 and / or TLR3 / TLR4 cellular signaling in association with related pathologies are also disclosed. The present disclosure also relates to the treatment of autoimmune-inflammatory pathologies and chemokine and cytokine-mediated diseases associated with TLR overexpression and signaling. The disclosure also relates to pharmaceutical formulations capable of inhibiting the IRF-3 / Type 1 IFN / STAT / ISRE / IRF-1 pathway associated with Toll-like receptor overexpression or signaling.

This invention relates generally to methods and compositions for diagnosing and treating disorders associated with elevated levels of Toll-like Receptor 4 (TLR4) ligands and other biomarkers. The invention also relates to methods of treating, delaying the progression of, or otherwise ameliorating a symptom of a disorder associated with elevated levels of TLR4 ligands and other biomarkers using agents that interfere with or otherwise antagonize TLR4 signaling, including neutralizing anti-TLR4 antibodies.

This invention relates generally to methods and compositions for diagnosing and treating disorders associated with elevated levels of Toll-like Receptor 4 (TLR4) ligands and other biomarkers. The invention also relates to methods of treating, delaying the progression of, or otherwise ameliorating a symptom of a disorder associated with elevated levels of TLR4 ligands and other biomarkers using agents that interfere with or otherwise antagonize TLR4 signaling, including neutralizing anti-TLR4 antibodies.

The invention is applicable to the technical field of biological medicines, and provides application of Paquinimod in preparation of a medicine for treating secondary lymphedema. According to the application, the S100A8 / A9 dimer small-molecule inhibitor Paquinimod is used for treating mice with lymphedema, and a result shows that the Paquinimod can be used for remarkably inhibiting secretion of inflammatory factors of the model mice, effectively relieving the edema condition and inhibiting activation of an S100A8 / A9-TLR4-CCL2 signal channel. Therefore, the inhibitor Paquinimod of the S100A8 / A9-TLR4 signal channel is applied to preparation of the medicine for treating the secondary lymphedema (SL), a new thought and a new method are developed for treatment of the SL, and the problem that the SL lacks an effective treatment means is effectively solved.

The invention belongs to the technical field of medical treatment, and discloses a new target using curcumin to inhibit DAMP (damage associated molecular pattern) molecule HSP70 and TLR4 signals to inhibit hepatic cancers and application. By establishing a cell culture and cell heat stress model, the statistical analysis is performed by CCK-8 test, scratch experiment, Transwell transfer experiment, cell cycle analysis by a flow cytometry, cell withering analysis by the flow cytometry, Western blot analysis, enzyme linked immunosorbent assay and other methods. Proofed by the statistical analysis result, the application has the advantages that the level of DAMP molecule HSP700 outside the cell and the expression of TLR4 protein are obviously increased by the heat stress, and the expression of DAMP molecule HSP700 inside the cell is obviously reduced; the proliferation, invasion and transfer of human hepatoma cell line HepG2 cells are inhibited by the curcumin, the cell withering is promoted, the cell is blocked at the S period, and the heat-stress level of the DAMP molecule HSP70 (eHSP70) outside the HepG2 cell is obviously reduced; after the curcumin is removed, the eHSP70 is increased again.

The invention discloses application of Jasurolignoside in production of a medicine for treating and / or preventing lung injuries of mammals, including humans. A structural formula of the Jasurolignoside is shown in a formula (I) as shown in the description. According to application of the Jasurolignoside in production of the medicine for treating and / or preventing the lung injuries of the mammals,including the humans, the medicine has a certain effect of preventing the lung injuries, inhibits release of proinflammatory cytokines of the lungs, and inhibits TLR4 signal channels.

The invention discloses an application of a stimulating agent CRX-675 of a Toll-like receiver 4 in resisting pulmonary fibrosis. By systematic study, the inventor discovers that a pulmonary fibrosis model is formed by injecting bleomycin (3U / Kg) into the trachea of C57BL / 6 mouse, after 7 days from model forming, CRX-675(10mg / kg / day) is injected into the abdominal cavity to the 21st day; by the histopathology and biochemical detection and other methods, when a TLR4 signal channel is activated, the death rate of the mouse injected with the bleomycin can be obviously reduced; when the TLR4 signal channel is activated, the inflammations and injuries of the lung induced by the bleomycin are obviously reduced, the pulmonary fibrosis caused by the bleomycin is reduced, the collagen deposition in the lung, the content of hydroxyproline and the expression of alpha-SMA are reduced, and the function of the lung of the mouse by pulmonary fibrosis is improved.

The invention relates to the field of medicines, and provides the application of ginsenoside GRh2 in preparing a toxoplasma gondii resisting compound preparation. GRh2 can effectively inhibit the proliferation of toxoplasma gondii when the GRh2 is separately taken as the effective ingredient to improve clinical performance of an infected mouse. The activation of microglia is inhibited by the GRh2through a TLR4 signal pathway to inhibit the overexpression of inflammatory factors, and the GRh2 has a certain protection effect on a host. In vitro pharmacodynamic tests show that the cytotoxicity of the GRh2 is small, the GRh2 has no significant difference with sulfadiazine in the proliferation inhibiting effect on the toxoplasma gondii under safety dosage and can significantly prolong the survival rate of a toxoplasma gondii infected host, the protecting effect of the GRh2 is significantly improved compared with the sulfadiazine, the GRh2 can reduce the amount of the toxoplasma gondii, thegrowth status of infected cells is almost close to that of normal cells, and the completeness of the morphology of toxoplasma gondii host cells can be effectively protected. The invention further provides the application of the ginsenoside GRh2 in preparing toxoplasma gondii vaccines.

The present invention relates to the technical field of medicine and particularly relates to an application of a traditional Chinese medicine composition for treating depression in regulating an immune inflammatory reaction and an intervention mechanism and the application of the traditional Chinese medicine composition for treating the depression, and the traditional Chinese medicine compositioncomprises radix curcumae, spina date seeds, American ginseng and fructus schizandrae. The traditional Chinese medicine composition significantly reverses up-regulated expression levels of TLR4 and MyD88 proteins in hippocampus induced by chronic restraint stress under reversal functions of interventions on chronic restraint stress-induced rat weight loss, decreased sweet water preference index, decreased horizontal motor scores and vertical motor scores, etc., and at the same time widely regulates immunoinflammatory activation mediated by a pattern recognition receptor TLR4 signaling pathway.

The invention relates to the field of medicines, and provides the application of ginsenoside GRh2 in preparing a toxoplasma gondii resisting compound preparation. GRh2 can effectively inhibit the proliferation of toxoplasma gondii when the GRh2 is separately taken as the effective ingredient to improve clinical performance of an infected mouse. The activation of microglia is inhibited by the GRh2through a TLR4 signal pathway to inhibit the overexpression of inflammatory factors, and the GRh2 has a certain protection effect on a host. In vitro pharmacodynamic tests show that the cytotoxicity of the GRh2 is small, the GRh2 has no significant difference with sulfadiazine in the proliferation inhibiting effect on the toxoplasma gondii under safety dosage and can significantly prolong the survival rate of a toxoplasma gondii infected host, the protecting effect of the GRh2 is significantly improved compared with the sulfadiazine, the GRh2 can reduce the amount of the toxoplasma gondii, thegrowth status of infected cells is almost close to that of normal cells, and the completeness of the morphology of toxoplasma gondii host cells can be effectively protected. The invention further provides the application of the ginsenoside GRh2 in preparing toxoplasma gondii vaccines.

The invention discloses a traditional Chinese medicine preparation and its preparation and application. The preparation is made from the following raw materials by weight: 20-30 parts of Astragalus root, 20-30 parts of Nansha ginseng, 20-30 parts of Beisha ginseng, and 10-30 parts of Lily Radix. 20 servings, 5-15 servings of dendrobium, 10-20 servings of aster, 10-20 servings of loquat leaves, 10-20 servings of bitter almond, 10-20 servings of Bai Bu, and 10-20 servings of angelica. It has the functions of clearing the lungs, relieving cough and relieving asthma, nourishing qi, nourishing yin and promoting blood circulation. After taking, the drug can directly act on the lesions of radiation pneumonia, inhibit the exudation of inflammatory cells in the alveolar wall, pulmonary interstitial congestion, hemorrhage, edema and alveolar structure damage, reduce the TLR4 signaling pathway signaling molecule protein and local lung. The expression of cytokines in tissue-related cells can reduce the inflammatory response of the lungs and achieve the purpose of delaying or treating radiation pneumonitis.

The invention provides application of transferrin in preparing immunosuppressant medicines and belongs to the technical field of biomedicines. Transferrin is capable of targeting at a co-receptor monocyte surface antigen CD14 of a TLR4 (toll-like receptor 4), then recognition of lipopolysaccharide (LPS) and CD14 is inhibited, LPS induced TLR4 signal path activation is also inhibited, LPS induced inflammatory factors are inhibited, LPS induced plasma inflammatory factors TNF-alpha, IL-6, IL-1beta and IFN-beta are inhibited, and LPS induced liver tissue damage and cell apoptosis can be alleviated. The transferrin has a very remarkable effect in inhibiting inflammation induced by bacterium products. The transferrin is capable of inhibiting inflammation reactions induced by bacterium productsand in addition, has the potential of preparing immunosuppressant medicines.

The invention discloses the use of Jasurolignoside in the preparation of medicines for treating and / or preventing lung injury in mammals including humans. The structural formula of Jasurolignoside is formula (I): the invention has a certain protective effect on lung injury and inhibits lung inflammation Sexual cytokine release and inhibition of TLR4 signaling pathway.

The invention discloses an application method of a traditional Chinese medicine composition and a clinical model establishment method in the field of medical pharmacy, and aims to overcome the difficulty in reduction of a theoretical system of a treatment mechanism of the traditional Chinese medicine composition for supporting the traditional Chinese medicine composition in the prior art, namely treatment based on syndrome differentiation of holistic concept. According to the defects which cannot be explained by current scientific biological pharmacy and chemical pharmacy, the composition is applied to a receptor TLR4 signal channel and a brain signal transduction channel radiation range of channel radiation to generate a model group, a baseline serves as a boundary of the model group, and difference data between treatment endpoint remission rate and endpoint response rate groups are filled into parameters in the model group. According to the technical scheme, the composition is applied to divided receptors, compared with analysis of effective components of a mixture by existing drug avoidance; meanwhile, the drug effect principle is explained through bioengineering, and the therapeutic dose of the optimal area is determined.

The invention discloses a fusion oligopeptide. The fusion oligopeptide is formed by fusing a cell-penetrating peptide and an oligopeptide for inhibiting combination of MD2 and CIRP. The invention also discloses an application of the fusion oligopeptide in preparation of a medicine for treating central nervous cell diseases mediated by an MD2-TLR4 signal channel. The fusion oligopeptide provided by the invention only has 15 amino acids, not only reduces immunological rejection of an organism, but also is relatively low in synthesis cost, and is used as a bioactive molecule to effectively block central nervous cell disease injury mediated by an MD2-TLR4 signal channel, relieve post-stroke nerve injury caused by nerve excitation toxicity and reduce infarct area, so that the fusion oligopeptide can be used as a biologically active molecule to effectively inhibit apoplexy. The nerve function is effectively recovered.

The invention provides a cationic liposome containing dihydroartemisinin (DHA) and HMGB1-silent siRNA, and a preparation method and an application of the cationic liposome, thereby constructing a novel drug delivery carrier. The cationic liposome not only can realize high drug loading and co-encapsulation of multiple drugs, but also can avoid liver first pass effect and improve pharmacokinetic characteristics; and the HMGB1-silent siRNA and the DHA are constructed in the same drug delivery carrier, and multiple targets act on the TLR4 signal axis, and thus a synergistic effect on LN treatmentis played, and a creative research method for treating autoimmune diseases is provided.

The invention provides an application of turnip acidic polysaccharide BRAP-2. The turnip acidic polysaccharide BRAP-2 is used for treating mouse Lewis lung cancer by activating a TLR4 signal path. Theturnip acidic polysaccharide BRAP-2 plays an important role in treating the mouse Lewis lung cancer, has a wide clinical application prospect, and provides a new target for clinical development of drugs for treating lung cancer.

The invention discloses a novel Kdo-MPLA adjuvant, and relates to the technical field of synthetic biology, the adjuvant is formed by connecting monophosphate lipid A (MPLA) and Kdo sugar through an alpha-glucosidic bond, MPLA is of a structure formed by modifying salmonella lipid A through 4 '-site monophosphorylation, and the Kdo sugar is endowed with amphipathy, so that the Kdo sugar is self-assembled into liposome nanoparticles in an aqueous solution; the rfaC and eptA genes are double knocked out through a gene editing salmonella attenuated strain, wherein the rfaC knockout blocks the synthesis of LPS core polysaccharide, and lipid A-Kdo connection is reserved; knocking out eptA to obtain a monophosphorylated lipid A; after the engineering bacteria are fermented, high-purity Kdo-MPLA is obtained by adopting a phenol-chloroform-petroleum ether extraction method, the process is simplified, and the product is uniform; the adjuvant can activate a TLR4 signal channel and induce Th1 type immune response, the levels of inflammatory factors IL-6 and IL-1beta are remarkably lower than those of natural LPS, and the adjuvant is suitable for a mixed preparation of vaccine antigens such as HPV and malaria; the method overcomes the defects of hydrolysis uncontrollability and high chemical synthesis cost of the traditional MPLA chemical extraction process.

The present inventive concepts, compositions and methods are show that the enteric glial serve to restrain the exaggerated TLR4 signaling that occurs in the premature intestinal epithelium via the release of BDNF, and that necrotizing enterocolitis (NEC) develops due to a loss of enteric glia. Compositions and methods of treatment of NEC and related enteric disease in prenatal, premature and neonatal subjects using compositions heretofore unknown for inhibition of NEC or activation of enteric glia are also provided.

The invention relates to rabdosia japonica polysaccharide as well as a preparation method and application thereof. The structure of the rabdosia japonica polysaccharide is shown in the specification, and the rabdosia japonica polysaccharide is mainly composed of arabinose, rhamnose, xylose, glucose and galactose. Experiments prove that the rabdosia japonica polysaccharide has the effects of treating inflammation-related diseases, especially chronic atrophic gastritis and acute lung injury by inhibiting an Ana-1 cell LPS induced TLR4 signal channel, so that the rabdosia japonica polysaccharide has the potential of being developed into the medicine for treating the inflammation-related diseases.

The invention discloses the application of Toll-like receptor 4 agonist CRX-675 in resisting pulmonary fibrosis. The inventor found through systematic research that for C57BL / 6 mice, the pulmonary fibrosis model was caused by intratracheal injection of bleomycin (3U / Kg). After 7 days of modeling, intraperitoneal injection of CRX-675 (10mg / kg / day) to the 21st day; through histopathological and biochemical detection methods, it was found that activating the TLR4 signaling pathway can significantly reduce the mortality of bleomycin-infused mice; activating the TLR4 signaling pathway can significantly reduce the lung inflammation induced by bleomycin and damage, reduce bleomycin-induced pulmonary fibrosis, including reducing lung collagen deposition, hydroxyproline content and expression of α-SMA, and improve lung function in mice with pulmonary fibrosis.

The invention discloses application of a reagent for inhibiting pyroptosis of platelets in preparation of a medicine for preventing and / or treating sepsis, and the sepsis is severe sepsis or septic shock. In the invention, the inventor finds out the close relevance between severe sepsis and pyroptosis of platelets for the first time, reveals the pathological process of GSDMD-dependent pyroptosis of platelets, and finds that pyroptosis of platelets is generated based on induction of abnormally increased S100A8 / A9 in plasma through up-regulation of a TLR4 signal channel. Therefore, a theoretical basis is provided for development of targeted treatment targets of severe sepsis. Moreover, specific GSDMD knockout platelets and TLR4 knockout platelets are successfully constructed, the treatment effect of the specific GSDMD knockout platelets and the specific TLR4 knockout platelets on severe sepsis is proved through platelet replacement or infusion and other modes, and a new treatment strategy is provided for excessive inflammatory response of severe sepsis and platelet infusion.

The present invention is applicable to the field of biomedical technology, and provides the use of Paquinimod in the preparation of a drug for treating secondary lymphedema. The present invention uses Paquinimod, a small molecule inhibitor of S100A8 / A9 dimer, to treat lymphedema mice. The results show that Paquinimod can significantly inhibit the secretion of inflammatory factors in model mice, effectively alleviate edema, and inhibit the activation of the S100A8 / A9-TLR4-CCL2 signaling pathway. Therefore, the present invention uses Paquinimod, an inhibitor of the S100A8 / A9-TLR4 signaling pathway, in the preparation of a drug for treating secondary lymphedema (SL), which opens up new ideas and methods for the treatment of SL and effectively solves the problem of the lack of effective treatment methods for SL.

The invention provides application of plant lactobacillus in prevention and / or treatment of acute inflammation caused by LPS, and relates to the technical field of microorganisms, for mice with acute inflammation caused by LPS, plant lactobacillus DY6 can inhibit immune system transition activation and lymphocyte abnormal proliferation by adjusting blood routine indexes and visceral organ indexes; the anti-inflammatory effect is achieved by down-regulating inflammatory factors and neutrophil infiltration markers and inhibiting a TLR4 signal channel; redox balance is adjusted, intestinal flora unbalance is improved, and the effect of preventing and / or treating acute inflammation caused by LPS is achieved.

The application discloses a novel Kdo-MPLA adjuvant, relates to the technical field of synthetic biology, and discloses that the adjuvant is composed of monophosphoryl lipid A (MPLA) and Kdo sugar through an alpha-glycosidic bond, the MPLA is a structure of Salmonella lipid A modified by monophosphorylation at a 4' position, and the Kdo sugar is endowed with amphiphilicity, so that the Kdo sugar is self-assembled into a liposome nanoparticle in an aqueous solution; the attenuated strain of Salmonella is edited by double knockout of rfaC and eptA genes: the rfaC knockout blocks the synthesis of LPS core polysaccharide and retains the lipid A-Kdo connection; the eptA knockout obtains monophosphorylated lipid A; after fermentation of the engineering bacteria, high-purity Kdo-MPLA is obtained by using a phenol-chloroform-petroleum ether extraction method, the process is simplified, and the product is uniform; the adjuvant can activate a TLR4 signal pathway and induce a Th1 type immune response, and the levels of inflammatory factors IL-6 and IL-1beta are significantly lower than those of natural LPS, so that the adjuvant is suitable for a mixed preparation of HPV, malaria and other vaccine antigens; and the application overcomes the uncontrollability of hydrolysis and the high cost defect of chemical synthesis of a traditional MPLA chemical extraction process.