383 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 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 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.

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.

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 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.

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.

The present invention relates to methods and uses of CGRP signaling pathway activators for promoting antibody generation and vaccine protection, and related pharmaceutical compositions and vaccine compositions.

The invention belongs to the technical field of biological medicine and molecular biology, and provides application of GJB6 in preparation of an esophageal squamous cell carcinoma prognosis evaluation reagent and screening of drugs for targeted treatment of esophageal squamous cell carcinoma. The low expression of the GJB6 is applied to preparation of an esophageal squamous cell carcinoma prognosis evaluation reagent. GJB6 is low in expression in ESCC patients, and ESCC prognosis is poor. And the prognosis of patients with high expression of GJB6 is better. Overexpression of GJB6 inhibits ESCC cell proliferation, migration and invasion and in-vivo tumor enlargement. The GJB6 plays a role of a cancer suppressor gene in ESCC and inhibits cell proliferation, migration and invasion. The AKT signal channel is one of downstream channels for GJB6 to regulate the occurrence and development of ESCC. The AKT inhibitor effectively inhibits GJB6 low-expression ESCC malignant phenotypes, including enhancement of cell proliferation and migration invasion ability and in-vivo tumor enlargement. The AKT is a key therapeutic target of the GJB6 low expression type ESCC.

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 combination therapies for modulating the tumor microenvironment and enhancing infiltration of immune cells into the tumor microenvironment with a bispecific anti-EGFR / c-Met antibody in combination with a PD-(L) 1 axis inhibitor. The invention also relates to combination therapies for inhibiting EGFR and MET signaling pathways in tumor cells, and targeting tumor cells expressing EGFR and MET to be disrupted by immune effector cells such as natural killer cells and macrophages by antibody dependent cytotoxicity (ADCC) and cell gnawing mechanisms, respectively.

The invention discloses application of ganoderma lucidum exosomes in preparation of corneal injury repair preparations, and belongs to the technical field of biological medicines. The ganoderma lucidum exosome realizes corneal injury repair by promoting corneal endothelial cell proliferation and migration ability, promotes corneal endothelial proliferation and cell migration and accelerates corneal endothelial injury repair through an EGFR / ERK signal channel, can be used for treatment of corneal epithelium defect related ocular surface diseases, corneal lesion and other diseases, and has a wide application prospect. And a new thought is provided for treatment of corneal endothelial diseases.

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.

This invention discloses the application of the inflammasome NLRP6 as a target in screening drugs for treating epilepsy, and the application of NLRP6 expression inhibitors in the preparation of drugs for treating epilepsy. This invention reveals for the first time the role of the inflammasome NLRP6 in epileptic neuroinflammation. This invention identifies NLRP6 as a key regulator of neuroinflammation in epilepsy and investigates its role in activating the caspase-1 / IL-1β / IL-18 signaling pathway. Knockdown of NLRP6 can improve the damaging effects of epilepsy on neurons, thereby improving seizures; overexpression of NLRP6 may exacerbate seizures, neuronal damage, and neuroinflammatory responses. This invention provides a new potential target for epilepsy treatment, offering new research ideas and directions.

The invention is based on the surprising finding that SIK3 is associated with resistance against anti-tumour immune responses. In particular, the invention provides methods for treating proliferative diseases using inhibitors of SIK3, especially nucleic acid or small molecule inhibitors of SIK3. Also provided are methods of sensitising cells involved with a proliferative disorder against the cytotoxic effect of certain pro-inflammatory signalling pathways, and / or to kill such cells and / or methods for treating proliferative diseases, using a SIK3 inhibitor together with ligands or agonists of such signalling pathways. Other methods provided by the invention include those involving SIK3 inhibitors to enhance or overcome certain side effects associated with treatments that utilise such signalling pathways, as well as diagnostic, prognostic and monitoring methods and kits based on the detection of SIK3 in a sample obtained from a subject, and screening methods useful for identifying or characterising inhibitors of SIK3.

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.

Disclosed herein are analogues of itraconazole that are potent hedgehog signaling pathway inhibitors. The compounds are expected to be useful in the treatment of cell proliferation disorders such as cancer, particularly cancers that are dependent upon the hedgehog signaling pathway such as basal cell carcinoma and medulloblastoma.

The invention discloses an epigenetics method for improving the cryopreservation efficiency of sheep semen. The method comprises the following steps: extracting seminal fluid of Donflilien and Hu sheep hybrid F1-generation sheep, dividing the seminal fluid into a fresh group and a frozen group, carrying out somatic cell removal and small non-coding RNA extraction, screening out differentially expressed microRNAs by utilizing a Pandorah sequencing technology, analyzing a target gene and a signal channel of the microRNAs, and determining the seminal fluid of the Donflilien and Hu sheep hybrid F1-generation sheep. The small non-coding RNA related to sperm cryopreservation is found to mainly relate to key biological processes such as oxidative stress response and cell surface receptor signal channels. The screened differentially expressed small non-coding RNA is added into the frozen semen through methods such as in vitro chemical synthesis, so that the artificial fertilization conception rate of the frozen semen is remarkably increased.

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.