75 results about "Catenin" patented technology

The invention belongs to the technical field of gene engineering, and particularly relates to a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of AML patients and application of ubiquitin specific protease 20 serving as a target spot in treating acute myelogenous leukemia. The invention provides a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of an AML patient and application of ubiquitin specific protease 20 as a target spot in treating acute myelogenous leukemia, USP20 is used as a super enhancer regulation gene, and the progress of the AML is promoted by combining with CTNNB1, ERG, ELF1 and RUNX1. The knock-down of the USP20 can significantly inhibit AML proliferation in vivo and in vitro. The wnt-beta-catenin pathway can be influenced by interfering the expression of the USP20 so as to influence the progress of AML (acute myeloid leukemia). And the inhibition effect of the inhibitor AS1517499 subjected to virtual screening on the growth of the AML cells is superior to that of a commercial inhibitor GSK2643943A of USP20.

The invention relates to an application of a nano antibody for blocking RSPO1-LGR4 effect in preparation of a medicine for treating cardiovascular diseases, the nano antibody is an NB21 nano antibody, and the NB21 nano antibody has an amino acid sequence as shown in SEQ ID No.12. The invention also relates to an application of the nano antibody for blocking RSPO1-LGR4 effect in preparation of a medicine for treating cardiovascular diseases. The antibody can specifically block a Wnt / beta-catenin pathway, effectively inhibit expression of proinflammatory factors and relieve inflammatory response of heart tissues, so that occurrence and development of cardiovascular diseases are intervened. The nano antibody has significant advantages in the aspects of intervention accuracy, conversion reliability and the like, and preclinical results show that the nano antibody can improve occurrence and development of ischemic cardiomyopathy; the pharmaceutical composition can be used for treating heart failure, myocarditis and adriamycin cardiomyopathy, can be expanded to systemic inflammatory diseases, realizes the trans-boundary application of one drug with multiple targets, fully verifies the anti-inflammatory effectiveness and safety through in-vivo and in-vitro experimental data, provides new targets, diagnostic tools and accurate intervention schemes for diagnosis and treatment of cardiovascular diseases and systemic inflammatory diseases, and has wide application prospects. The obvious scientific innovation significance and clinical transformation value are realized.

The application discloses a kind of small molecule compound combination and the method for preparing vascular endothelial cell using the small molecule compound combination induced differentiation cell.The method is directed to induce differentiated cell, and finally prepare vascular endothelial cell;The directional induction includes inhibiting the activity of lysine deacetylase, inhibiting the signal path of TGF-β, inhibiting the activity of DNA methyltransferase (DNMT), activating the signal path of WNT / β-catenin and activating the signal path of cAMP.The present application can be converted into vascular endothelial cell by small molecule compound combination induction, and each step can realize accurate quality control, which is convenient for standardized operation and large-scale production.The method provided by the present application has wide donor sources, and the patient himself can be used as a donor, so that the vascular endothelial cells required for basic research, clinical treatment or tissue engineering production can be obtained in a short time.

The present invention relates to a peptide with the activity of promoting hair growth or preventing or inhibiting alopecia. The peptide of the present invention promotes the proliferation of human follicular dermal papilla cells (HFDPC), activates cell proliferation-related signaling proteins and beta-catenin in human dermal papilla cells, enhances the expression levels of beta-catenin downstream genes, down-regulates the expression levels of the hair loss protein DKK-1, increases the expression of keratin proteins in hair outer root sheath cells (HORSC) and up-regulates the expression of transcription factors involved in cell activation in germinal matrix cells (GMC).

The invention belongs to the technical field of bioengineering, and discloses a UBXN10 active polypeptide, a carrier thereof and application of the UBXN10 active polypeptide in anti-cancer drugs. The amino acid sequence of the UBXN10 active polypeptide is as shown in SEQ ID NO: 1, and the nucleotide sequence for coding the UBXN10 active polypeptide is as shown in SEQ ID NO: 2. According to the invention, a plurality of functional means are utilized to analyze the transcriptional activity of cancer promoting beta-catenin in colorectal cancer cells and the antagonism of cancer cell proliferation and stem cell nature. The cell biology level proves that the UBXN10 active polypeptide has the potential of antagonizing beta-catenin mediated proliferation and stem cell gene expression and inhibiting colorectal cancer cell proliferation and stem cell property.

The invention provides an application of 2-indolecarboxylic acid in preparation of a tumor targeted therapy drug. Through computer-aided drug design and molecular docking optimization, 2-indolecarboxylic acid shows high binding energy to an HER2 kinase structural domain. In HER2 positive NCI-N87 gastric cancer cells, the 2-indolecarboxylic acid significantly inhibits cell proliferation and induces G0 / G1 phase arrest and apoptosis. The mechanism research shows that the 2-indoleformic acid can play a role by regulating and controlling the HER2 / Akt / beta-catenin pathway (Western blot verification). In an NCI-N87 cell tumor-bearing nude mouse model, 2-indolecarboxylic acid (15 mg / kg) significantly inhibits tumor growth, and does not cause obvious weight loss or organ toxicity. Immunohistochemical analysis shows that the positive rate of a tumor tissue proliferation marker Ki-67 in a treatment group is remarkably reduced, and apoptosis detection shows that the proportion of TUNEL positive cells is remarkably increased, which indicates that 2-indolecarboxylic acid inhibits tumor cell proliferation and promotes apoptosis at the same time. The invention provides a lead compound with clinical transformation potential for HER2 targeted therapy.

The invention provides a high-transparency and high-simulation bacterial engineering biological cornea as well as a preparation method and application thereof, and belongs to the technical field of tissue engineering cornea materials. According to the method, a bacterial synthetic biology method is adopted, a curvature customization model and an hydroformylation system are combined, and the high-transparency bionic cornea (DBC-L-Cel) which is customized in curvature and shape and has a nanofiber network structure is constructed. The light transmittance of the bionic cornea reaches 91.91%, the light transmittance and the mechanical property of the bionic cornea are matched with those of a natural cornea, and meanwhile the bionic cornea has excellent biocompatibility, adhesiveness and scar resistance. In-vitro experiments show that DBC (at) L-Cel can reduce matrix fibrosis by inhibiting AGE / RAGE / NF [kappa] B and PI3K / AKT pathways and up-regulate Wnt / beta-catenin pathway to activate proliferation, and corneal epithelium is repaired by an adhesion function. In-vivo experiments show that the high-simulation biological cornea DBC-L-Cel is transplanted to a rabbit model with large-scale corneal defects, repair and regeneration of corneal stroma and epithelium can be remarkably promoted, and rapid scar-free repair and reconstruction of the damaged cornea are achieved.

The invention provides a polypeptide for enhancing T cell function and application thereof, and belongs to the technical field of biological medicine. The amino acid sequence of the polypeptide disclosed by the invention is as shown in SEQ ID NO. 1. According to the invention, an interaction interface of CLDN18.2 and beta-catenin is targeted for the first time, the full D-type functional polypeptide is designed to realize high-stability and high-affinity protein-protein interaction blocking, and the problem that the interaction site is difficult to target by the traditional antibody drug or small molecule drug is broken through; the used polypeptide PC18.1 has good in-vitro stability and is suitable for subsequent clinical development; the polypeptide is easy to prepare on a large scale through a synthesis means, has the purity of more than or equal to 98%, is low in cost and convenient to modify, and can be flexibly applied to immune combined treatment schemes such as nano-carrier loading and local delivery.

The application provides a kind of nasal mucosa in vitro culture method and culture fluid, the composition of the culture fluid includes Wnt / β-catenin signal pathway activator 0.1-20 μg / ml, fibroblast growth factor 10-150 ng / ml, TGF-β inhibitor 0.02-3 μg / ml, ROCK inhibitor 0.1-100 μmol / L, P38 MAPK inhibitor 0.1-1 μmol / L, serum-free additive 1X, N-acetyl cysteine 1-10 mmol / L, nicotinamide 1-20 mmol / L, GlutaMax additive 1X, antibiotic, DMEM / F12 culture medium 1X.The application can carry out in vitro culture to nasal mucosa, can keep at least 2 weeks of activity, and have complete epithelial barrier and immune system, can realize ex vivo nasal mucosa virus infection experiment.

This invention provides the application of the IFI16 gene as a target in the preparation of bortezomib-resistant drugs for the treatment of multiple myeloma, involving drug targets, related diagnostic reagents, and treatment strategies for the diagnosis and treatment of multiple myeloma (MM). This invention reveals for the first time the core driving role of IFI16 in bortezomib resistance in MM and its novel mechanism of action through the Wnt / β-catenin pathway; more importantly, it provides novel biomarkers, drug targets, and highly feasible combination therapy regimens for accurate prognostic assessment of MM and overcoming the clinically challenging problem of bortezomib resistance, possessing significant theoretical implications and broad clinical application prospects.

The invention relates to the field of oncology, in particular to application of a cancer immunotherapy target and a diagnosis and prognosis prediction biomarker. Wherein at least one marker in the EGFR / Wnt / beta-catenin-LINC00973-miRNA-CD55 / CD59 pathway can be used for evaluating the sensitivity or the prognosis of the cancer immunotherapy.

The present invention provides a method for administering a β-catenin peptide antagonist, and a method for treating solid tumors by administering a β-catenin peptide antagonist.

This specification provides peptides that bind to β-catenin and compositions comprising such peptides. Agents utilizing peptides that directly bind to β-catenin can be used for imaging, diagnosis, and treatment of diseases caused by β-catenin dysfunction. This specification also provides methods for using such peptides and compositions in imaging, diagnosis, and treatment of tissue-invasive diseases, including endometriosis.

Provided herein are compounds that are useful for or methods of inhibiting β-catenin or disrupting the interaction between β-catenin and T-cell factor 4, which are useful in the treatment of diseases or health conditions, such as cancer, neurodegenerative, a metabolic disease, a cardiovascular disease, fibrosis, and a bone disease. In one aspect, the compounds have Formula 1 wherein R1 is —(CR42)mXR5; R2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aralkyl, heteroaralkyl, or heteroaryl; and R3 is —(CR62)nR7.

The invention provides an application of USP7 (ubiquitin-specific protease 7) as a target spot in preparation of drugs for treating vascular abnormal leakage diseases, and relates to the technical field of biomedicine, USP7 (ubiquitin-specific protease 7) as a deubiquitination enzyme not only regulates tumor, nerve and immune related diseases, but also is closely related to vascular endothelial cell functions. In the vascular homeostasis, the USP7 can maintain the integrity of a vascular barrier and inhibit pathological leakage by stabilizing endothelial connexin such as VE-cadherin and beta-catenin; under the inflammation or hypoxia condition, through deubiquitination of HIF-1alpha or NF-kappa B pathway components (such as I kappa B alpha), vascular endothelial cell activation can be promoted, VEGF signal-driven abnormal angiogenesis or release of inflammatory factors can be aggravated, and diabetic retinopathy, tumor vascular hyperplasia and sepsis-related vascular leakage can be participated. According to the application, verification experiments prove that USP7 has a certain protection effect on vascular permeability, and a treatment strategy is provided for vascular abnormal leakage diseases clinically.

Compounds and compositions are provided as inhibitors of the Wnt / β-catenin pathway for the treatment of diseases that implicate the same.

This invention discloses the application of angeloylgomisin H and its composition in the preparation of anti-hair loss products. Angeloylgomisin H has the effect of preventing hair loss, and the anti-hair loss composition contains angeloylgomisin H and evening primrose oil B. The two can synergistically upregulate the expression levels of VEGF and β-catenin, thereby playing a synergistic role in preventing hair loss.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of LGR5 in diagnosis and treatment of vascular calcification. Experiments prove that the key effect of the LGR5 in aortic smooth muscle calcification is found for the first time, it is indicated that the LGR5 is a new target spot for regulating and controlling vascular calcification, meanwhile, vascular calcification can be accurately inhibited through knockdown / knockout of the specific Lgr5 gene of vascular smooth muscle, and meanwhile, vascular calcification can be accurately inhibited through knockout / knockout of the specific Lgr5 gene of the vascular smooth muscle. According to the application disclosed by the invention, the mechanism that the Lgr5 regulates and controls the osteogenic differentiation of the vascular smooth muscle cells through the Wnt / beta-catenin signal channel is preliminarily clarified, and a clear action target and a theoretical basis are provided for drug research and development; the invention provides a new strategy for treatment of diseases such as atherosclerosis and the like, and has a wide clinical application prospect.

This invention discloses the application of LGK974 in the preparation of drugs for the prevention and / or treatment of dry eye syndrome, relating to the field of biomedical technology. The application of LGK974 in the preparation of drugs for the prevention and / or treatment of dry eye syndrome. This invention is the first to discover the application of the Wnt-β-catenin pathway inhibitor LGK974 in the treatment of dry eye syndrome. LGK974, by inhibiting the Wnt-β-catenin pathway, can effectively protect meibomian gland acini and ducts, restoring normal lipid metabolism and secretion. In a NOD (Normally Ophthalmic Disorder) Sjögren's syndrome model, oral administration of 200-400 μg / kg / day of LGK974 significantly improved dry eye symptoms, including reduced corneal defects and increased tear secretion, alleviating morphological and functional damage to the meibomian glands. LGK974 provides a new targeted strategy for the treatment of dry eye syndrome, especially Sjögren's syndrome-related dry eye syndrome and meibomian gland dysfunction-related dry eye syndrome, and may become a potent and effective drug for the clinical treatment of dry eye in the future.

The invention belongs to the technical field of biological medicines, and particularly relates to a targeted beta-catenin palmitoylation small-molecule inhibitor and application thereof in treatment of colorectal cancer. The application of beta-cat-Oxazole in preparation of the medicine for treating the colorectal cancer is provided for the first time, the beta-cat-Oxazole can specifically target an interaction interface (residues near C466) of ZDHHC5 and beta-catenin, and other functions or normal physiological signal channels of the beta-catenin are not affected. Due to the accuracy, the miss-target risk is remarkably reduced, and a treatment window is wider. The compound can be used as a single drug in a preclinical model to significantly inhibit tumor growth; in an AOM / DSS induced colorectal cancer model, the tumor load is reduced by about 50%. In addition, the invention discloses a core mechanism of a targeted ZDHHC5-beta-catenin interaction interface, and a new structural basis is provided for subsequent drug target design.

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a sperm-nourishing seed jade decoction and application thereof to improvement of endometrial receptivity, the sperm-nourishing seed jade decoction is composed of 30 g of radix rehmanniae preparata, 15 g of cornus officinalis, 15 g of radix paeoniae alba and 15 g of angelica sinensis, by inhibiting the epithelial-mesenchymal transition (EMT) process, the expression of E-cadherin and beta-catenin is up-regulated, the expression of Vimentin is down-regulated, and the endometrial receptivity is improved. Therefore, the stability and integrity of endometrial epithelium are maintained, intimal thickening, gland hyperplasia and angiogenesis are promoted, and an effective treatment strategy can be provided for infertility caused by thin endometrium.

The application belongs to the technical field of protein engineering, and discloses a humanized collagen type ⅩⅦ polypeptide and a preparation method and application thereof. The amino acid sequence of the humanized collagen type ⅩⅦ polypeptide is shown as SEQ ID NO. 1, and the polynucleotide sequence encoding the humanized collagen type ⅩⅦ polypeptide is shown as SEQ ID NO. 2. The application also provides application of the polypeptide in preparation of a protein product with the functions of preventing hair loss, repairing, anti-wrinkle and skin tightening. The efficacy detection at the cell level proves that the prepared humanized collagen type ⅩⅦ polypeptide can promote the proliferation of hair papilla cells, keratinocytes and fibroblasts, and promote the up-regulation of the expression of the β-Catenin signal pathway protein closely related to hair growth in the hair papilla cells, thereby proving that the humanized collagen type ⅩⅦ polypeptide has the efficacy of preventing hair loss and / or repairing, anti-wrinkle and skin tightening.

The present disclosure relates to methods of treating, preventing, and / or ameliorating a disease or disorder involving excessive Wnt signaling in a subject in need thereof, the method comprising administering to the subject an inhibitor of β-catenin nuclear transport. In certain embodiments, the disease or disorder involving excessive Wnt signaling is cancer. The present disclosure further relates to pharmaceutical compositions comprising at least one inhibitor of β-catenin nuclear transport and a pharmaceutically acceptable carrier.

The invention relates to the technical field of deep processing of black chenopodium quinoa, in particular to a black chenopodium quinoa active peptide capable of promoting hair follicle cell growth and hair growth and care activity and a preparation method and application of the black chenopodium quinoa active peptide. The black chenopodium quinoa active peptide is prepared by the following steps: crushing, pretreating with amylase, performing alkali extraction and acid precipitation, performing double-enzyme step-by-step hydrolysis with alkaline protease and pepsase, and performing ultrafiltration to cut off a fragment with the molecular weight of less than 5000Da, thereby obtaining the black chenopodium quinoa active peptide. In addition, seven brand-new non-toxic characteristic peptide fragments are further screened out, the 5 alpha-reductase and a GSK-3beta receptor can be efficiently combined, and hair follicle cell proliferation is promoted and oxidative damage is relieved by inhibiting the 5 alpha-reductase and activating Wnt / beta-catenin and Nrf2 / HO-1 signal channels. The peptide is natural and safe, the process is simple, the black quinoa peptide is expanded to the field of hair growth and hair care for the first time, the market gap related to grain peptide is filled, and high-value utilization of black quinoa is achieved.

The invention discloses a TRIM31-targeted platelet delivery system. The platelet delivery system is formed by entrapment of sh-TRIM31 plasmids by platelets; the entrapment concentration of the sh-TRIM31 plasmid is 1.5 to 2.5 [mu] g / 109 blood platelets. According to the invention, tumor specific targeting is realized through a platelet drug delivery system, sh-TRIM31 plasmids are accurately delivered into cytoplasm for release, a treatment concentration is reached, TRIM31 silencing is realized, intranuclear c-MYC inhibition is realized through an ROS / beta-catenin axis, and finally, cooperation with radiotherapy is realized, tumor radiosensitivity is remarkably enhanced, and radiotherapy resistance is reversed.

The present invention belongs to the technical field of cellular anti-aging, and specifically relates to a small-molecule compound composition capable of reversing the senescence of an adult stem cell and restoring the regeneration activity thereof, and a method for reversing cellular senescence by means of using a chemical small-molecule composition and the use thereof. The composition capable of reversing cellular senescence comprises a WNT / β-catenin agonist, a TGF-β receptor inhibitor, an RAR agonist, a Smoothened receptor agonist, a multi-target inhibitor of the VEGFR and PDGFR families, a histone methyltransferase inhibitor, and a JAK1 / 2 inhibitor. The composition effectively solves the problem of the weak proliferation and regeneration potential of senescent adult stem cells, effectively reverses the senescence of the adult stem cells and maintains the intrinsic biological characteristics of the cells, and can thus improve and enhance the efficacy of clinical autologous cell transplantation therapy and cell derivative therapy.

The invention relates to the technical field of bioengineering, and particularly discloses a construction method and application of a mixed type liver cancer mouse model, pCMV-Cre, pT3-EF1 alphaH-c-Met, pT3-EF1 alphaH-N90-beta-catenin plasmids and pCMV (CAT) T7-SB100 transposase are mixed to prepare an injection, and the injection is injected into a C57BL / 6-MFN1flox / flox mouse at the age of 6 weeks in a caudal vein mode to obtain the mixed type liver cancer mouse model. The construction method of the mixed type liver cancer mouse model is stable, reliable, efficient and easy to implement, and the constructed mixed type liver cancer mouse model can be used for exploring the generation and development mechanism of the mixed type liver cancer and researching treatment targets and can also be used for screening drugs for treating the mixed type liver cancer.

The invention provides application of an AGGF1 expression inhibitor in preparation of a medicine for preventing and / or treating prostatic cancer. Through cell test and animal test analysis, it is determined that the preparation for inhibiting AGGF1 expression inhibits proliferation of prostate cancer cells by inhibiting expression of Wnt / beta-catenin pathway key protein beta-catenin and phosphorylation of GSK3B and / or by inhibiting oxidative stress, and therefore growth of tumors is effectively controlled.

This invention discloses a combination of type 17 collagen and chlorogenic acid and its application. The composition consists of type 17 collagen and chlorogenic acid, with a mass ratio of type 17 collagen to chlorogenic acid of (11~18):1. This invention found that the combined use of chlorogenic acid and type 17 collagen in a certain ratio has a significantly better effect on upregulating β-catenin in hair papilla cells than either type 17 collagen or chlorogenic acid alone, exhibiting a synergistic effect and can be applied in anti-hair loss products.

The invention provides application of ANKRD13A in preparation of drugs and diagnostic reagents for intestinal cancer, relates to the technical field of biomedicine, and is technically characterized by providing application of ANKRD13A as a therapeutic target in preparation of drugs for preventing and / or treating intestinal cancer. Close association between ANKRD13A and occurrence and development of the intestinal cancer is defined through a series of verification experiments. Clinical sample analysis shows that transcript abundance and protein expression level of ANKRD13A in a colon cancer tissue are remarkably lower than those in a normal colon tissue; the cell level verification proves that the mRNA and protein expression of ANKRD13A in the colon cancer cell line is obviously reduced compared with that of a normal colon epithelial cell line; animal experiments show that an Ankrd13a gene-deficient mouse is induced by AOM / DSS, the occurrence rate of colorectal tumors is higher, the number of the tumors is larger, and tumor tissues have medium-high-grade canceration characteristics along with abnormal expression of beta-Catenin, nuclear ectopic, increase of Ki67 positive cells and other malignant pathological expressions. The experimental results jointly prove that expression deletion or down-regulation of ANKRD13A is closely related to occurrence risk increase of intestinal cancer.