224 results about "Signalling pathways" patented technology

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 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.

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.

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.

This invention belongs to the field of pharmaceutical technology, specifically relating to a quinazoline-azaindole compound, its preparation method, and its application in treating Alzheimer's disease. The quinazoline-azaindole compound of this invention regulates NF-κB by inhibiting DYRK1A. k B. A series of signaling pathways, including PI3k-Akt, achieve anti-neuroinflammatory effects; quinazoline-azaindole compounds can reduce the expression of inflammatory factor-related genes in an LPS-induced BV2 microglial inflammation model, thereby reducing the levels of inflammatory factors in the hippocampus and cortex, alleviating neuronal pathological damage caused by neuroinflammation, and improving cognitive impairment caused by neuroinflammation; in summary, quinazoline compounds inhibit DYRK1A and downregulate NF-κB signaling pathways. k It can reduce the expression and release of inflammatory factors, improve brain tissue pathology, and alleviate cognitive impairment through signaling pathways such as B, and has significant clinical application value.

The present invention relates to CD73 + CD44 + , CD90 + A method for generating a population of mesenchymal stromal cells (MSCs) is provided. + CD44 + , CD90 + MSCs are used in methods to generate terminally differentiated osteogenic, adipogenic, and chondrogenic cells from pluripotent stem cells (PSCs), which involve the use of a single agent, a WNT signaling pathway activator (e.g., a GSK3β inhibitor), in adherent cultures of PSCs.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

The invention belongs to the technical field of bioactive peptides, and particularly relates to a phycocyanin peptide and application thereof in preparation of a product with functions of inhibiting PTGS2 expression and regulating an Akt / GSK3beta signal channel. According to the invention, phycocyanin is taken as a raw material, active polypeptides with specific sequences are obtained through an enzymolysis separation technology, and the amino acid sequences of the active polypeptides are respectively Leuu-Ala-Ser and Leuu-Gly-Leu. Experiments prove that the phycocyanin peptide prepared by the invention can significantly inhibit the expression of PTGS2, and can play a related regulation role by activating an Akt / GSK3beta signal channel, so that the technical blank of plant active peptide targeting PTGS2 and Akt / GSK3beta signal channels is filled, and the phycocyanin peptide can be widely applied to the development of related products for regulating the abnormal expression of PTGS2 and Akt / GSK3beta signal channels.

The present invention provides ARTS mimetic compounds that act as novel antagonists for XIAP and Bcl-2. Moreover, the novel ARTS mimetic compounds of the invention induce apoptosis in premalignant and malignant cells. The invention thus provides compositions, methods and uses of said ARTS mimetic compounds in the treatment of cancer and premalignant conditions.

The present invention relates to a monoclonal antibody or an antigen-binding fragment thereof, which specifically binds to human CCR8 and is an antagonist, particularly an insurmountable antagonist, of the CCL1-CCR8 signaling pathway. The invention also relates to the antibody or antigen-binding fragment for use in therapy, particularly in the treatment of cancer.

The invention provides a method for treating AR negative TNBC through combination of quercetin and enzalutamide, the quercetin up-regulates the AR expression level by inhibiting a high-expression solute carrier SLC7A5, so that tumor cells which are not sensitive to enzalutamide originally obtain drug sensitivity again; the combined use of an AR antagonist enzalutamide (1-80 [mu] M) can cooperatively block an AR signal channel and significantly inhibit cell proliferation (the inhibition rate of drug combination is 70%, Plt, 0.01 higher than that of a single drug). In-vitro experiments prove that the scheme has a synergistic effect (the effect is optimal when the mass ratio is 1: 1-5: 1) in MDA-MB-231 cells, and an animal model shows that the tumor volume inhibition rate reaches 70% or above. Safety evaluation shows that the drug combination does not cause abnormity of serum biochemical indexes (ALT / AST / BUN / CREA) or damage of main organs and tissues. The invention further provides a preparation method of an oral preparation (tablets / capsules / nanoparticles) containing quercetin (50-500 mg / day) and enzalutamide (40-160 mg / day), and a new strategy is provided for reversing AR-TNBC drug resistance.

The invention relates to a method of differentiating pancreatic bi-potent progenitor cells into beta cells comprising cultivating pancreatic endocrine precursor cells in a medium that promotes the cAMP signalling pathway that lies downstream of apical-basal polarity in endocrine precursors, which can be used to increase the differentiation of progenitor cells into beta cells. Furthermore, the present invention relates to a method of enriching and / or isolating one or more cells expressing a marker of apical-basal polarity, thereby isolating beta cells, and to a method of producing a population of beta cells from a population of human embryonic stem cells. Furthermore, the present invention relates to a population of beta cells obtainable by the method, a pharmaceutical composition comprising the beta cells, a cell culture of progenitor cells in a medium comprising a cAMP agonist, a complex comprising a beta cell bound by the binding agents specific for CD133 and CD49a, and a use of specific binding partners for isolating beta cells.

This invention proposes the application of psoralen as an Nrf2 agonist in drug preparation. This invention is the first to discover that psoralen is a specific Nrf2 agonist. Psoralen can directly target and bind to the Nrf2 protein, improving its stability, promoting its phosphorylation and nuclear translocation, thereby activating the Nrf2 signaling pathway, upregulating the expression of downstream antioxidant, anti-inflammatory, and anti-ferroptosis-related proteins, and achieving cell protection and tissue repair functions.

The invention relates to the technical field of biomedicine, and discloses an application of miR-3963 for improving insulin resistance in preparation of drugs. The invention provides application of an active component in preparation of a medicine for preventing and / or treating insulin resistance or insulin resistance related diseases. The active component comprises miR-3963 or other substances (such as miR-3963 agonists, mimics and the like) capable of increasing the content of miR-3963 in a body. Research finds that miR-3963 can respond to insulin stimulation increase, and the activity of an insulin signal channel is enhanced by targeted inhibition of expression of an SMPD1 gene, so that insulin resistance is effectively improved. According to the invention, a novel target with great potential is provided for developing a new generation of targeted drugs aiming at the root of diabetes, and a key clue is provided for the miRNA participating in the blood glucose homeostasis regulation and the generation mechanism of insulin resistance.

Provided is a novel combination therapy with PD-1 signal inhibition therapy. A pharmaceutical composition of the present invention contains a substance that can enhance a T cell receptor (TCR) signal, and is administered before, after, or simultaneously with administration of a PD-1 signal inhibitor. An enhancer of PD-1 signal inhibitory activity of the present invention contains a CD45 inhibitor and / or cells. A TCR signal enhancer of the present invention contains a CD45 inhibitor and / or cells.

The invention discloses a Ruditapes philippinarum miR-263b inhibitor and application thereof, and finds that Ruditapes philippinarum miR-263b can regulate and control innate immune response of a host by targeting RpSC2, negatively regulates activation of an immune-related signal channel in a vibrio infection process, and further, on the basis of a molecular regulation and control mechanism, the Ruditapes philippinarum miR-263b inhibitor can be used for inhibiting the infection of vibrio. The invention discloses a specific inhibitor which is completely complementary with a miR-263b mature body sequence. Experimental data show that after Ruditapes philippinarum is injected with the miR-263b inhibitor, the expression level of miR-263b in vivo is reduced, and the inhibition effect of miR-263b on RpSC2 is effectively relieved, so that the expression level of a target gene RpSC2 is up-regulated, an NF-kappa B immune signal channel is activated, the immune defense capability of the Ruditapes philippinarum on vibrio anguillarum is enhanced, the death rate after infection is remarkably reduced, and the Ruditapes philippinarum is prevented from being infected. The in-vivo bacterium loading amount is obviously reduced, and the pathological injury of hepatopancreas tissue is obviously relieved.

The invention relates to the technical field of bioengineering, in particular to application of reticular structure collagen with an ECM (extracellular matrix) regulation function in tissue filling and / or compatibilization. The recombinant III-type humanized collagen provided by the invention can be self-crosslinked to form a net structure, and has good mechanical strength. The collagen has short-term and long-term effects at the same time, can be directly used as a filling agent in a short term, and can activate a plurality of signal channels and promote expression of various collagens in an extracellular matrix in a long term, jointly construct and maintain a net structure of the extracellular matrix, improve an extracellular matrix environment and improve the extracellular matrix activity. The cell morphology and the cell adhesion, migration and multiplication capacity are improved, the lasting filling and repairing effects are achieved, and good application prospects are achieved in the field of tissue filling and repairing.

The invention relates to the field of biological medicines, relates to a treatment technology for early abortion, and in particular relates to an application of Clostridium prausnitzii (Faecalibacterium prausnitzii) in preparation of a medicine for treating early abortion. An experiment of a Poly (I: C) induced early-stage abortion mouse model proves that the clostridium praeparatum can obviously reduce the embryo loss rate and improve placenta development through oral intragastric administration. The action mechanism is that maternal immune balance is regulated by increasing the proportion of regulatory T cells (Treg) and inhibiting excessive activation of an IL-17 signal channel. As human intestinal symbiotic bacteria, the clostridium praeparatum is high in safety and can be used for intervention of early abortion, especially recurrent abortion, and a new strategy is provided for clinic.

This invention discloses the application of 12S-HHT in the preparation of drugs for the prevention and / or treatment of cardiovascular diseases. The study found that after administration, 12S-HHT acts as a signaling molecule in vivo, activating the PPARδ signaling pathway and regulating the expression of a series of downstream genes related to energy metabolism and mitochondrial function, thereby achieving a therapeutic effect. Mechanism of action: By binding to and activating PPARδ, it upregulates its downstream target genes. ANGPTL1 It promotes fatty acid oxidation and enhances the "metabolic flexibility" of myocardial cells.

The invention discloses a SbASR4 gene for regulating and controlling plant salt stress tolerance as well as an encoding protein and application thereof. The SbASR4 gene is derived from Sorghum baicola, and the encoded protein is simultaneously positioned in a cell membrane and a cell nucleus, does not have transcriptional activation activity, and is a negative regulation factor of plant salt stress response. The overexpression of the gene can significantly increase the sensitivity of the plant to salt and ABA, and the silence or knockout of the gene can greatly improve the salt tolerance of the plant. Mechanism research shows that the SbASR4 protein directly interacts with an SOS signal channel core kinase SOS2 in a plant body, and the SOS channel is negatively regulated through the interaction, so that the expression of a downstream ion transport gene is inhibited. The invention provides a method for improving the salt tolerance of plants by reducing the expression of SbASR4 or destroying the interaction of SbASR4 and SOS2, related genetic materials and products, and a brand new target and an effective strategy are provided for salt-resistant breeding of crops.

The present invention relates to a biomarker for diagnosing pediatric atopic dermatitis and use thereof. As result of comparing immune phenotypes of a healthy control group with those of pediatric atopic dermatitis patients, it has been identified that Th1, Th2, Th17 and Th22 cells or expression of STAT1, CD6 and ALCAM genes are increased or decreased. In addition, in the present invention, it has been identified that the frequencies of monocytes, plasmacytoid dendritic cells, CD4 central memory T cells, and CD4 effector memory T cells are related to the severity of pediatric atopic dermatitis. Therefore, the present invention can ensure an efficient treatment strategy for pediatric atopic dermatitis by accurately diagnosing pediatric atopic dermatitis and the severity thereof.

The present application belongs to the technical field of coordination chemistry and biomedical science, and provides a multifunctional iridium (III) complex, a preparation method and application thereof. The multifunctional iridium (III) complex (Mito-Ir) is composed of an iridium (III) complex cation and a coordination anion shown in the following formula. Mito-Ir can efficiently target mitochondria, and also has the abilities of phosphorescence imaging, type I and type II active oxygen generation, and photocatalytic oxidation of nicotinamide adenine dinucleotide. Under light irradiation, Mito-Ir triggers severe mitochondrial dysfunction through the above synergistic effect, and then specifically activates the caspase-3 / GSDME signaling pathway, and significantly induces pyroptosis; this pyroptosis-based cell death mechanism can effectively overcome the apoptosis tolerance of tumor cells, and is accompanied by the release of a large amount of inflammatory factors and damage-associated molecular patterns, stimulates immunogenic cell death, and activates the body's anti-tumor immune response.

Provided are an anti-ST2 antibody and a pharmaceutical composition. Specifically provided is an anti-ST2 antibody or an antigen-binding fragment thereof. The anti-ST2 antibody comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region comprises HCDR1 to HCDR3, and the light chain variable region comprises LCDR1 to LCDR3, wherein the amino acid sequence of HCDR1 is as shown in SEQ ID NO: 1, the amino acid sequence of HCDR2 is as shown in SEQ ID NO: 2, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO: 3; and the amino acid sequence of LCDR1 is as shown in SEQ ID NO: 4, the amino acid sequence of LCDR2 is as shown in SEQ ID NO: 5, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO: 6. The antibody can bind to human ST2, block the binding of human IL-33 to ST2, and inhibit the activation of downstream signaling pathways of a human IL-33 / ST2 pathway.

The invention relates to the technical field of biological medicines, and particularly provides a hair follicle regeneration nano activator as well as a preparation method and application thereof. The activator comprises a first coupling monomer and a second coupling monomer, an oligonucleotide sequence of the first coupling monomer and an oligonucleotide sequence of the second coupling monomer are at least partially complementary and form a double-chain structure through base pairing, the first coupling monomer is formed by coupling a first polypeptide and a first ssDNA, and the second coupling monomer is formed by coupling a second polypeptide and a second ssDNA. The second coupling monomer is formed by coupling a second polypeptide and a second ssDNA; wherein the first polypeptide and the second polypeptide are both specifically targeted to beta-catenin protein. The polypeptide-DNA-polypeptide dimer has a polypeptide-DNA-polypeptide sandwich-type dimer structure, can be specifically combined with beta-catenin in stem cells, only regulates and controls a Wnt / beta-catenin pathway, does not generate non-specific influence on other pathways, and can efficiently activate a hair follicle regeneration related signal pathway and promote a hair follicle development biological process.

This invention discloses a nanodecoy receptor that blocks the IL-17 signaling pathway, including IL-17RA-CMVs carrying a fusion sequence of PDGFR-TMD and IL-17RA. This invention also provides a method for preparing the aforementioned nanodecoy receptor that blocks the IL-17 signaling pathway, comprising the following steps: S1. Using genetic engineering, IL-17RA and PDGFR-TMD are fused and designed, and a lentivirus carrying the IL-17RA and PDGFR-TMD fusion sequence is coated onto mammalian cells. A cell line stably expressing the IL-17RA and PDGFR-TMD fusion sequence is established in mammalian cells through lentivirus transfection; S2. The cell line from step S1 is taken, and cell membrane vesicles are prepared by ultrasonic disruption and permeabilization extrusion until the fusion sequence of IL-17RA carrying PDGFR-TMD is displayed at high density and correctly oriented on the outer surface of the cell membrane vesicles, forming IL-17RA-CMVs. The nano-decoy receptor of the present invention can efficiently and broadly block the interaction between IL-17 and IL-17RA, avoid such systemic side effects, and achieve treatment only through local minimally invasive delivery, thus solving the side effects problem caused by existing systemic drug administration.

This invention discloses a method for inducing pluripotent stem cells to differentiate into skin keratinocytes and its culture medium, solving problems such as long differentiation cycles, low yields, insufficient purity, and animal-derived contamination in existing technologies. The first stage uses medium I containing FGF2 and tanshinone IIA to promote mesodermal differentiation. The second stage uses medium II containing BMP4, EGF, dexamethasone, and PVA to regulate and synergistically induce the BMP / ERK signaling pathway. The final stage uses medium III for expansion culture, obtaining fibroblasts with a purity >99% within 20 days. This method is non-invasive, simple, and low-cost, with potential for large-scale production. The obtained cells can be used for skin regeneration, disease modeling, drug screening, and clinical treatment, demonstrating significant medical application and industrial transformation value.

The invention relates to the technical field of traditional Chinese medicine and health food processing, and discloses a preparation process and application of a black ginseng extract lozenge, and the preparation process comprises the following steps: crushing starch, powdered sugar and polyethylene glycol in parts by weight, and sieving for later use; performing ultrasonic extraction and vacuum concentration on the black ginseng to obtain a black ginseng concentrated solution; slowly adding a pre-prepared black ginseng concentrated solution into the sieved starch and powdered sugar, and stirring to prepare a soft material; granulating, drying and finishing the soft material to obtain dry granules; and adding sieved polyethylene glycol into the dry particles, uniformly mixing, tabletting, forming, and sterilizing by ultraviolet radiation to obtain the buccal tablets. According to the method, ultrasonic-assisted extraction is adopted, so that degradation of heat-sensitive rare saponin is avoided; the concentrated solution is directly granulated, so that the difficulty that the extract absorbs moisture and is sticky is overcome, and the forming rate is increased; the prepared lozenge can activate a PI3K-Akt signal channel and regulate release of 5-HT, and can be used for preparing products for relieving chronic fatigue syndrome and improving spatial cognitive impairment.

This invention discloses butylphthalide nanoparticles, comprising: a layered double hydroxide and butylphthalide, wherein the butylphthalide is loaded onto the layered double hydroxide. This invention also discloses a method for preparing the above-mentioned butylphthalide nanoparticles, comprising the following steps: mixing the layered double hydroxide, butylphthalide, and water, adsorbing, separating the solid and liquid phases, and drying to obtain butylphthalide nanoparticles. This invention further discloses the application of the above-mentioned butylphthalide nanoparticles in the preparation of drugs for treating acute renal ischemia-reperfusion injury. This invention also discloses a drug for treating acute renal ischemia-reperfusion injury, comprising: the above-mentioned butylphthalide nanoparticles and pharmaceutically acceptable excipients. The butylphthalide nanoparticles of this invention have high drug loading capacity, good stability, and can target and activate the PI3K-AKT signaling pathway, effectively inhibit HK-2 cell apoptosis and oxidative stress, restore mitochondrial function, and improve renal ischemia-reperfusion injury.