857 results about "Signalling pathways" patented technology

The invention belongs to the technical field of biological medicine, and particularly discloses application of kaempferol in preparation of a medicine for treating chronic obstructive pulmonary disease. The invention provides application of kaempferol in preparation of a medicine for treating chronic obstructive pulmonary disease. The invention provides a medicine for treating chronic obstructive pulmonary disease. The medicine comprises kaempferol or pharmaceutically acceptable salt thereof as an active ingredient. The invention aims to provide the application of kaempferol in preparation of the medicine for treating the chronic obstructive pulmonary disease, and the chronic obstructive pulmonary disease is treated by adjusting an AMPK signal channel, a Hippo signal channel, an MAPK signal channel and a PI3K-AKT signal channel.

The present invention provides a nitrogen-containing heterocyclic compound, and a preparation method, a pharmaceutical composition and application thereof. Specifically, the present invention provides a compound as shown in the following formula I, or an optical isomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof; wherein the definition of each group is as described in the specification. The compound of formula I can be used to treat diseases related to the PD-1 / PD-L1 signaling pathway.

The invention relates to the technical field of biological medicines, in particular to rapamycin-induced extracellular vesicles and application thereof in preparation of a medicine for promoting wound repair. The rapamycin-induced extracellular vesicles can enhance the migration and tube forming ability of endothelial cells, so that angiogenesis is promoted; meanwhile, the proliferation and migration capabilities of macrophages can be inhibited, and the proportion of M1 type macrophages in a wound is reduced, so that the inflammatory response mediated by the macrophages is relieved; and the composition shows extraordinary effects in the aspect of accelerating wound repair. The biological activity of the extracellular vesicles induced by the rapamycin depends on the activation of a PI3K / Akt signal channel.

Disclosed in the present invention is a novel substituted heterocyclic compound having VAV1 target degradation activity. Specifically disclosed is a compound serving as a VAV1 target degradation agent and having the structure of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, isotopic substituent or isomer of the compound. The compound can be used for preventing or treating diseases related to VAV1 targets or signaling pathways.

The invention belongs to the technical field of microorganisms and fermentation engineering, and particularly relates to application of bifidobacterium longum subsp. Infantis Y46 in the aspects of enhancing cell defense and repair and regulating metabolic homeostasis of a host. The strain is isolated from infant feces. Animal experiments prove that living cell thalli of the bifidobacterium longum subsp. Infantis Y46, which are obtained by culturing an MRS liquid culture medium added with L-cysteine hydrochloride (0.05%, v / v), can significantly enhance the oxidative stress resistance of an organism and reduce the level of active oxygen in the organism compared with a control bacterium bifidobacterium longum subsp. Infantis 15697. Transcriptomics analysis shows that the bifidobacterium longum subsp. Infantis Y46 can enhance self-protection of cells and improve physiological imbalance caused by external pressure by regulating related signal channels of an organism. The action mechanism is closely related to signaling pathways related to cell defense, metabolic homeostasis and barrier functions. The invention provides a new strain resource and an application scheme for developing functional food or medicinal preparations for enhancing the health defense function of a human body.

The present invention relates to the field of stem cell technology. The present invention discloses a method for inducing stem cells to secrete specific factors, which includes stimulating stem cells with high-frequency waves, emitting sound waves of a specific frequency to stem cells, regulating stem cells in a hypoxic environment, culturing stem cells in a hypoxic environment, stimulating stem cells with oxidative stress, and subjecting stem cells to oxidative stimulation treatment. The present invention can significantly enhance the proliferation ability of stem cells, promote the secretion of multiple active factors, and improve cell function and adaptability. As a non-invasive physical method, high-frequency wave stimulation can activate internal cell signal pathways without introducing exogenous substances, significantly improving the proliferation ability and tissue repair potential of stem cells. Hypoxic environment regulation simulates the naturally existing microenvironmental conditions in the body, greatly promoting the secretion of active factors such as vascular endothelial growth factor, basic fibroblast growth factor, and brain-derived neurotrophic factor for tissue repair and immune regulation.

The invention relates to an application of an intervention SNRK-MTA1 signal channel axis in preparation of a non-small cell lung cancer targeted therapy drug. The nucleotide sequences of the mRNA of the SNRK gene and the mRNA of the MTA1 gene are respectively as shown in SEQ ID NO.1-2. The invention innovatively provides a strategy for treating the non-small cell lung cancer through double-target combined intervention. According to the strategy, SNRK gene expression is improved through exogenous gene overexpression plasmids, and meanwhile MTA1 gene expression is silenced through the siRNA technology. In a non-small cell lung cancer model, the strategy of combined application of the SNRK-OE plasmid and siMTA1 can specifically up-regulate the SNRK mRNA level and knock down the MTA1 mRNA level at the same time, and the combined strategy shows a better anti-tumor effect than single intervention, and can more effectively inhibit the growth and migration of tumor cells. Based on the discovery, the SNRK-MTA1 signal pathway axis can be developed into a novel therapeutic target for non-small cell lung cancer, and is used for designing a drug combination scheme or a composite targeted drug.

Provided is a novel heterocyclic compound having a regulatory effect on CB1 signaling pathway abnormalities. Specifically provided is a compound having a structure as shown in formula (I) or a pharmaceutically acceptable salt, a solvate, a hydrate, an isotope substituent or an isomer thereof as a CB1 target regulator.

The invention relates to a cyclopeptide inhibitor aiming at human STING (stimulating interferon gene) and application of the cyclopeptide inhibitor. The cyclic peptide can specifically bind to and inhibit activation of human STING. The invention also provides a nanoparticle delivery system for loading the cyclopeptide on a cationic polymer PBAE and an amphiphilic polymer pDMA-pEPEMA, and a preparation method of the nanoparticle delivery system. The cyclic peptide and the nanoparticles thereof can be used for preparing medicines for treating autoimmune diseases (such as systemic lupus erythematosus and the like) caused by excessive activation of the cGAS-STING signal pathway. Compared with the existing small molecule STING inhibitor, the cyclopeptide inhibitor provided by the invention has higher specificity, stability and inhibition effect.

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 provides an application of a spleen T lymphocyte exosome in construction of a depression animal model, a stress rat spleen T lymphocyte exosome is injected into a mouse body to construct the depression animal model, and the depression animal model can be used for depression drug screening, drug efficacy evaluation or diagnosis, and can be used for treating depression. And the method can also be used for researching and revealing pathogenesis of depression. The invention also proves that the IL4 / IL4R alpha signal channel and the BDNF signal channel play an important role in depression through experiments. The invention has important significance for clinical research of depression.

The invention discloses design and synthesis of a series of brain-targeted ginsenoside Rg1 derivatives and application of the brain-targeted ginsenoside Rg1 derivatives in treatment of Alzheimer's disease. According to the invention, ginsenoside Rg1 and polyethylene glycol with a specific chain length are covalently linked to successfully construct the derivative capable of enhancing the penetrating power of the blood-brain barrier. The series of derivatives provided by the invention not only solve the problems of poor brain targeting and insufficient stability of natural Rg1, but also can inhibit neuroinflammation by regulating and controlling an NLRP3 / caspase-1 signal channel in an LPS-induced neuroinflammation model, and finally, the learning and memory ability is remarkably improved. The product is simple and convenient in preparation process and good in biological safety, and a new candidate compound is provided for developing a new generation of Alzheimer disease treatment medicines.

Disclosed herein are small molecule compounds, compositions, formulations, and methods of modulating gpl30. Compounds, compositions, and formulations described herein are capable of modulating pro-inflammatory, fibrotic and / or regenerative responses. The disclosure also provides methods for treating or ameliorating disease, disorders and conditions associated with gp130 activity, particularly those associated with inflammatory and degenerative disorders, or combination thereof.

In some aspects, provided herein are antibodies or antigen-binding fragments that bind to the glycoprotein receptor CD200R present on the surface of a cell. In some cases, the antibodies or antigen binding fragments provided herein agonize the CD200R signaling pathway that inhibits inflammatory and immune responses. In other aspects, provided herein are compositions, methods of use, methods of preparation, polynucleotides, vectors, host cells, and kits related to antibodies or antigen-binding fragments that bind to CD200R.

The invention provides a novel chimeric flagellin and application thereof. The novel chimeric flagellin is formed by chimeric combination of a Senecavirus A VP2 fragment and an escherichia coli Nissle 1917 flagellin FliC through Linker (GGGGS) 3, soluble expression of the novel chimeric flagellin in an escherichia coli system is achieved, and the highest yield can reach 200 mg / L. In addition, through detection of in-vitro Caco2 and Raw264.7 cell models, the recombinant novel chimeric flagellin shows good TLR5 receptor activity, and can effectively activate a TLR5 signal channel.

The invention relates to an anti-human HHLA2 nano antibody and application thereof, a variable region of the nano antibody comprises CDR1, CDR2 and CDR3, an amino acid sequence of the CDR1 comprises any one of sequences as shown in SEQ ID NO: 29-36 or a mutation thereof, an amino acid sequence of the CDR2 comprises any one of sequences as shown in SEQ ID NO: 37-46 or a mutation thereof, an amino acid sequence of the CDR3 comprises any one of sequences as shown in SEQ ID NO: 47-56 or a mutation thereof, and the variable region of the nano antibody comprises CDR1, CDR2 and CDR3. The mutation is the substitution, insertion or deletion of 1, 2, 3 or 4 amino acids in the amino acid sequence. The nano antibody disclosed by the invention can be specifically combined with tumor cells expressing human HHLA2, and the killing effect of immune cells on the tumor cells can be improved by blocking a signal channel between the HHLA2 and KIR3DL3.

The current invention relates to agonist molecules of the Wnt7 signaling pathway, wherein the agonist comprises one or more LRP binding domains such as one or more LRP5 and / or one or more LRP6 binding domains and one or more Gpr124 or Reck binding domains. The agonists are developed to be deployed in medical treatments, more particularly in the treatment of neurological and / or ophthalmological diseases and / or disorders.

The invention provides application of G3BP1 in preparation of a medicine for protecting barrier function integrity of vascular endothelial cells, and belongs to the technical field of biological medicine manufacturing. The invention provides application of G3BP1 in preparation of a medicine for protecting barrier function integrity of vascular endothelial cells. The present invention relates to G3BP1 that ensures the sustained expression of key adherent junction proteins (VE-cadherin, p120) by directly binding to and stabilizing the mRNA of these proteins; meanwhile, the G3BP1 is combined with the MYD88mRNA to promote the degradation of the MYD88mRNA, so that a permeability-promoting MYD88-ARNO-ARF6 signal channel is inhibited, especially under the condition of an inflammation period. Therefore, the G3BP1 regulates and maintains the integrity of the vascular barrier through double transcription, and a new treatment strategy is provided for damage repair of the functional integrity of the vascular endothelial cell barrier.

To provide an anti-mutant calreticulin (mutCALR) antibody.SOLUTION: An anti-mutant calreticulin (mutCALR) antibody is provided. The antibody comprises a heavy chain variable region (VH) comprising a VH CDR1, a VH CDR2 and a VH CDR3. The antibody comprises a light chain variable region (VL) comprising a VL CDR1, a VL CDR2 and a VL CDR3. The antibody is configured to: inhibit one or more signaling pathways downstream of a thrombopoietin receptor (MPL) in a cell expressing human mutant CALR; inhibit oncogenic cell proliferation in a cell expressing human mutant CALR; inhibit dimerization of the MPL in a cell expressing human mutant CALR; and / or inhibit binding of the MPL to human mutant CALR.SELECTED DRAWING: Figure 6

The invention relates to a diatomic iron-iron site nano-enzyme constructed by relieving oxidative stress and cartilage degeneration and used for targeted osteoarthritis treatment. According to the invention, a nitrogen-doped porous carbon anchored diatomic iron nano enzyme catalyst (Fe2-NCs) with Fe-Fe dimer coordination is developed by using a'subject-object 'strategy. The Fe2-NCs protect cartilage cells from oxidative stress induced apoptosis by modulating ROS and active nitrogen species (RNS) and promoting O2 release. In addition, Fe2-NCs restores mitochondrial function by inhibiting NOX4 expression, improving ATP production, and normalizing COXIV levels. In an in-vivo OA model, the Fe2-NCs can reduce the expression of a pro-inflammatory medium COX-2 through an NF-kappa B signal channel, inhibit the up-regulation of MMP-13 and delay the degradation of type II collagen. The invention provides a new theoretical framework and methodological approach for the treatment of osteoarthritis, and has important clinical and scientific significance.

The invention provides a nerve growth factor functionalized exosome as well as a preparation method and application thereof. The functionalized exosome can activate a Wnt / beta-catenin signal channel to maintain dryness of corneal limbal stem cells (LSCs) so as to promote corneal epithelium repair, can activate a cAMP signal channel to relieve inflammatory response and promote corneal nerve regeneration, and can be used for treating or relieving corneal chemical burns, including relieving inflammatory response, reducing stromal scar formation and inhibiting corneal neovascularization. Corneal epithelium repair and nerve regeneration are promoted.

The invention discloses application of sodium butyrate in preparation of a medicine for relieving brain injury caused by gas explosion, the sodium butyrate regulates nerve cell ferroptosis through a JNK / P38 MAPK pathway to relieve the brain injury caused by gas explosion, firstly, an animal model of rat brain injury caused by gas explosion is established, and the relation between NaB and brain tissue neuron injury is intervened and observed by applying NaB; secondly, a shock wave physiotherapy instrument is used for impacting a co-culture system of three cells of CTX, H19-7 and GMI-R to simulate explosion to construct an in-vitro experimental model, P38, ERK and Fer-1 inhibitors are adopted for intervention, iron metabolism, ferroptosis and MAPK signal channel factor changes are observed from the cell and molecular level, a mechanism for inhibiting ferroptosis through a related cascade signal channel mediated by NaB-mediated intestinal-brain axis regulation and control is clarified, and the effect of inhibiting ferroptosis is achieved. And a theoretical basis is provided for further explaining the action mechanism of the gas explosion brain injury.

This document provides methods and materials involved in treating cancer. For example, methods and materials for modulating (e.g., increasing or decreasing) an interleukin-1 (IL-1) signaling pathway (e.g., an IL-1βsignaling pathway) during an adoptive cell therapy (e.g., a chimeric antigen receptor (CAR) T cell therapy) are provided. In some cases, one or more inhibitors of an interleukin-1 receptor antagonist (IL-1RA) polypeptide can be used to increasing IL-1 signaling (e.g., to reduce immunosuppression of the administered cells). In some cases, CAR T cells having a reduced level of an interleukin 1 receptor, type I (IL-1R1) polypeptide can have decreased IL-1 signaling (e.g., to reduce T cell toxicity associated with the administered cells).

The invention belongs to the field of biological medicines, and particularly discloses application of uridine in preparation of medicines for preventing and treating ulcerative colitis, including application of uridine in preparation of medicines for preventing and treating ulcerative colitis in acute stage, application of uridine in preparation of medicines for preventing and treating ulcerative colitis in remission stage and the like. Uridine can improve the symptoms of DSS-induced acute experimental colitis model mice, has a good treatment effect, and improves the weight of the model mice; experimental results indicate that a high-dose group of uridine has a good treatment effect, the mechanism and specificity of uridine up-regulate expression and activity of colon local SIRT1 protein, further inhibit phosphorylation activation of an NF-kappa B signal channel, regulate secretion of inflammatory factors and expression of tight junction protein, repair intestinal mucosal barrier while moderately regulating immunity, and improve the immunity of a human body. The systemic inflammatory response is effectively relieved.

The invention belongs to the technical field of biology, and particularly relates to an anti-hair-loss fish collagen peptide composition with a hair follicle signal channel regulating and controlling function and application of the anti-hair-loss fish collagen peptide composition. The composition can activate a Wnt / beta-catenin signal channel, inhibit a BMP channel, promote hair follicle growth period conversion and hair papilla cell proliferation, repair hair quality and improve the scalp microenvironment at the same time. The composition can be prepared into an oral preparation or an external scalp care product, has the advantages of safety, high efficiency and multi-target regulation, and is suitable for alopecia prevention and hair quality repair.

The invention belongs to the field of medicinal chemistry, and relates to an indole acrylic acid amide derivative as well as a preparation method and application thereof. Functional activity screening of G protein dependent signaling pathways is carried out on all synthesized compounds, and it is found that the new derivatives can be used as allosteric antagonism regulators of beta2-adrenergic receptors. Trans-indole acrylic acid with different substituent groups is used as a raw material, amide coupling is performed to obtain the novel indole acrylic acid amide derivative, and R1 is a hydrogen atom, a halogen atom, a methyl group or a methoxyl group; r2 is any one of phenyl, m-bromophenyl, m-chlorphenyl, m-fluorophenyl, m-cyanophenyl, m-methoxyphenyl, cyclohexyl and piperidyl. A biological activity test result shows that the indole acrylic acid amide derivative disclosed by the invention has relatively good antagonistic activity on beta2AR and can be used for carrying out negative allosteric regulation on the functional activity of isoproterenol.

The present invention relates to a method for preparing organ-specific mesenchymal cells from pluripotent stem cell-derived intestinal organoid stromal cells. By using cells derived from stromal cell layers adjacent to intestinal organoids for differentiation into organ-specific mesenchymal cells, the present invention can greatly increase the efficiency of differentiation into stromal cells through the regulation of retinoic acid (RA) and hedgehog (HH) signaling pathways, and can increase the expression of organ-specific markers without exhibiting undifferentiated state cell characteristics, and thus mesenchymal cells having well-simulated biological characteristics can be prepared.

The invention relates to an application of a small molecule medicine STK000311 in a medicine for treating a cGAS-STING pathway abnormal activation disease, and belongs to the technical field of biological medicines. According to the application disclosed by the invention, the small-molecular medicine STK000311 or the pharmaceutically acceptable salt of the small-molecular medicine STK000311 serving as the cGAS-STING signaling pathway inhibitor has an obvious treatment effect on the cGAS-STING pathway abnormal activation diseases for the first time, and verification experiments show that the small-molecular medicine STK000311 can be used for obviously inhibiting the activity of human cGAS protein in a targeted manner and inhibiting cGAS-mediated antiviral immune response; the transcription level of ISGs in PBMCs (peripheral blood mononuclear cells) of an SLE (systemic lupus erythematosus) patient is inhibited, the fact that the small-molecule medicine STK000311 has huge potential of developing cGAS activity related diseases is fully proved, a novel treatment medicine is provided for clinic, and the small-molecule medicine STK000311 has good clinical application value and wide application prospect.

The invention discloses a heterocyclic aryl or heteroaryl-heteroaryl derivative and application of the heterocyclic aryl or heteroaryl-heteroaryl derivative. The heterocyclic aryl or heteroaryl-heteroaryl derivative of the present invention is a compound of formula (I), a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a pharmaceutically acceptable salt of an isomer thereof, a solvate thereof or a pharmaceutically acceptable salt of a solvate thereof. The compound disclosed by the invention has good inhibitory activity on a 20-hydroxyeicosatetraenoic acid (20-HETE) signal channel, and has a good medicinal prospect. # imgabs0 #

Disclosed are in vitro methods for the differentiation of precursor cells into a neural crest cell (NCC) primed to a neurogenic lineage. The methods may include, for example, the steps of activating a Hedgehog signaling pathway (“HH signaling pathway”) in a precursor cell, wherein the precursor cell may be contacted with a neural crest cell induction medium for differentiation of the precursor cell into a neural crest cell. Compositions for carrying out the disclosed methods are also disclosed.