26 results about "FOXO1" patented technology

The invention relates to an N2B27 culture medium for inducing generation of bidirectional pluripotent stem cells, one of LY2090314, AS1842856 or CHIR99021 is added into an N2B27 basal culture medium, and the concentration of the CHIR99021 is 10 mu M. The invention also relates to a preparation method of the N2B27 culture medium. The weight of the LY2090314 is 10 nM, and the weight of the AS1842856 is 0.6 [mu] M. The invention also provides an application of the culture medium in induced production of bidirectional pluripotent stem cells. According to the invention, a novel stem cell culture condition for promoting co-expression of genes OCT4 and CDX2 by adding small molecules LY2090314 (LY), AS1842856 (AS) and CHIR99021 to inhibit signal channels of FOXO1 and GSK3 is screened out. The culture conditions are simple and convenient, the application range is wide, the cultured cells keep the characteristics of 16-32 cell stages of the embryos, and the development characteristics of the embryos can be efficiently reproduced. Under the condition of not depending on transcription factors, the screened bidirectional pluripotent stem cells (BPSCs) can promote efficient generation of TSC cells and establish a TSC cell line through independent differentiation of a serum culture medium or induced differentiation of a TSC culture medium. The obstacles between early embryo pedigree are broken, and the research on early embryo development is promoted.

A method to obtain more effective CAR-T cells, which are FOXO1 inhibited. The inhibition of FOXO1 potentiates the ability to induce lysis of a target cell thanks to the increased expression of TNF-α and other inflammatory cytokines, induces spontaneous cell polarization comparable to that obtained by stimulation with chemokines and thus improves the motility of the cells, induces a sharp increase of memory T cells and allows to obtain more efficient CAR-T cells to treat solid tumors than classical CAR-T cells obtained with the known protocol. An 10 ex vivo method to obtain improved CAR-T cells including the steps of (i) cultivate T cells obtained from a subject with a FOXO1 inhibitor during a time of 2 to 10 days; (ii) transducing (or transforming) the T cells into CAR-T cells thanks to a known method.

Disclosed are methods for treating congenital lymphedema or increasing lymphatic valve growth by administering a FOXO1 inhibitor. Also disclosed are methods for increasing nuclear β-catenin activity in a cell by contacting the cell with a FOXO1 inhibitor.

The invention discloses application of a YOD1 gene in preparation of a medicine for treating rhabdomyosarcoma. According to the invention, YOD1 is deeply analyzed to jointly regulate and control the protein stability of PAX3-FOXO1 and N-Myc, and after a tetracycline regulation and control system is adopted to induce and reduce the expression of YOD1, the clone formation ability of FOXO1 fusion positive rhabdomyosarcoma cells with high expression of N-Myc and the growth of xenotransplantation tumors are remarkably inhibited. Therefore, the invention not only discloses the application of the YOD1 gene, but also provides a new therapeutic target for FOXO1 fusion positive rhabdomyosarcoma cells with high expression of N-Myc.

The present application relates to the application of delta-Viniferin in the preparation of drugs for preventing or treating metabolic cardiovascular diseases. Delta-Viniferin can inhibit the expression level of aging and inflammation related genes / proteins of vascular endothelial cells, reduce endothelial dysfunction, and clarify its anti-hypertensive effect. Delta-Viniferin can inhibit the expression level of vascular smooth muscle cell phenotype conversion related genes / proteins, improve the contraction function of vascular smooth muscle, and significantly alleviate the degradation of elastic fibers of the vascular wall and the rupture of the intima of the aortic wall in vivo, and clarify its effect on preventing and treating aortic dissection. Delta-Viniferin can inhibit the expression level of myocardial fibroblast fibrosis related genes / proteins, and clarify its anti-myocardial fibrosis effect. Delta-Viniferin can promote white adipose tissue browning by targeting the SIRT1-FOXO1 axis, increase energy consumption, and clarify its effect on resisting obesity. In summary, the compound delta-Viniferin has the effect of protecting various metabolic cardiovascular diseases, and can be used to prepare drugs for preventing and treating metabolic cardiovascular diseases.

In one aspect, methods of diagnosing a subject as having Alzheimer's disease and prognosing a subject as being at risk of progressing to Alzheimer's disease are provided. In some embodiments, the method comprises determining one or more of the level of expression of rhotekin 2 (RTKN2), the level of expression of microtubule-associated Ser / Thr kinase 4 (MAST4), the level of binding of forkhead box O1 (FOXO1) to the RTKN2 promoter, and the level of binding of amyloid precursor protein (APP) to the MAST4 promoter in a sample from the subject.

The invention relates to the technical field of biological medicines, in particular to application of HDAC7 as a target spot in diagnosis and treatment of rhabdomyosarcoma. The invention reveals for the first time that circular RNA (F-circP3F) sourced from an oncogenic fusion gene PAX3-FOXO1 is directly combined with and inhibits histone deacetylase HDAC7 to play a role through a novel mechanism, and HDAC7 can be used for early diagnosis, prognosis evaluation and curative effect monitoring of rhabdomyosarcoma as a core link of the regulation mechanism. And the method is a treatment intervention target with great potential.

Provided is a composition for inhibiting fat formation and reducing body fat, the composition including hydrangenol as an active ingredient.The composition of the present disclosure reduces fat accumulation in adipocytes, reduces phosphorylation of mammalian target of rapamycin (mTOR), and increases phosphorylation of forkhead box O1 (FoxO1), and finally, leading to reduction of an expression level of peroxisome proliferator-activated receptor gamma γ (PPAR), and as a result, the composition inhibits formation of triglyceride in adipocytes to exhibit an anti-obesity effect. Accordingly, the composition including hydrangenol disclosed herein as an active ingredient may be usefully applied to the fields of health functional foods or cosmetics for inhibiting fat formation.

The invention belongs to the technical field of biology, and relates to application of chimeric polypeptide TAT-Ae alone or in combination with an AKT inhibitor in tumor treatment. Specifically, the invention discloses application of a blocking TRIB3 / AKT inhibitor targeting tumor stemness and proliferation in preparation of drugs for preventing or treating breast cancer independently or in combination with an AKT inhibitor. The amino acid sequence table of the inhibitor for blocking TRIB3 / AKT is SEQ ID No.1, and the AKT inhibitor is Oridonin. The inhibitor for blocking TRIB < 3 > / AKT can be specifically combined with TRIB < 3 >, so that the interaction of TRIB < 3 > / AKT is blocked, the protein degradation of a transcription factor FOXO1 is promoted, and finally the expression of a dry factor SOX2 is reduced; the AKT inhibitor inhibits tumor cell proliferation by inhibiting AKT activity, so that the AKT inhibitor is applied to preparation of drugs for treating and preventing breast cancer, lymphoma, lung cancer and colon cancer. The prepared medicine has the advantages of being remarkable in curative effect, small in toxic and side effect and safe to use when being used for treating tumor diseases.

The invention relates to an application of delta-Viniferin in preparation of a medicine for preventing or treating metabolic cardiovascular diseases. Delta-Viniferin reduces endothelial dysfunction by inhibiting vascular endothelial cell senescence and inflammation related gene / protein expression level, and defines the antihypertensive effect of delta-Viniferin; delta-Viniferin improves the contraction function of vascular smooth muscle by inhibiting the expression level of gene / protein related to phenotype transformation of vascular smooth muscle cells, meanwhile, the in-vivo level remarkably relieves degradation of elastic fibers of vascular walls and rupture of intima of aortic walls, and the effect of the delta-Viniferin on preventing and treating aortic dissection is defined; delta-Viniferin defines the anti-myocardial fibrosis effect of delta-Viniferin by inhibiting the myocardial fibroblast fibrosis related gene / protein expression level; the delta-Viniferin promotes the browning of white fat by targeting an SIRT1-FOXO1 axis and increases the energy consumption, so that the effect of the delta-Viniferin on resisting obesity is defined. In conclusion, it is proved that the compound delta-Viniferin has the effect of protecting various metabolic cardiovascular diseases and can be used for preparing the medicine for preventing and treating the metabolic cardiovascular diseases.

The invention discloses an application of a polypeptide of a targeted NTRK3 gene in preparation of a medicine for inhibiting the growth of PAX3-FOXO1 fusion positive rhabdomyosarcoma. The invention provides the application of the NTRK3 protein as a drug target to preparation of the drug for resisting malignant proliferation of the PAX3-FOXO1 fusion positive rhabdomyosarcoma for the first time. Furthermore, by down-regulating the expression of the NTRK3 gene, the clone formation capability of the PAX3-FOXO1 fused positive rhabdomyosarcoma cells is remarkably inhibited. Therefore, the invention not only discloses the application of the NTRK3 gene, but also provides a new therapeutic target for the PAX3-FOXO1 fusion positive rhabdomyosarcoma. The invention provides possibility for preparing a novel medicine for treating the PAX3-FOXO1 fusion positive rhabdomyosarcoma and improving the prognosis condition of a patient.

To provide compositions and methods for treating muscle atrophy and myotonic dystrophies.SOLUTION: This application discloses a polynucleic acid molecule conjugate comprising an antibody or binding fragment thereof conjugated to a polynucleic acid molecule that hybridizes to a target sequence of an atrogene, wherein the polynucleic acid molecule comprises at least one 2' modified nucleotide, at least one modified internucleotide linkage, or at least one inverted abasic moiety, and the polynucleic acid molecule conjugate mediates RNA interference against the atrogene, thereby treating muscle atrophy or myotonic dystrophy in a subject. In a certain embodiment, atrogene comprises atrogin-1 gene (FBXO32), MuRF1 gene (TRIA63), FOXO1, FOXO3, or MSTN.SELECTED DRAWING: Figure 19A

The invention discloses application of an ENDOU inhibitor in preparation of a medicine for treating airway epithelium inflammation, and belongs to the field of biological medicine. The invention provides application of a reagent for detecting the expression level of ENDOU in preparation of a kit for diagnosing and / or detecting airway epithelium inflammation or bronchial asthma, and further provides application of an ENDOU inhibitor in preparation of a medicine for treating airway epithelium inflammation or bronchial asthma. The invention proves that ENDOU affects LPS-induced inflammatory response by regulating FOXO1 and IL-17A pathways, is a key molecule for regulating airway epithelial inflammation, is expected to become a therapeutic target for airway inflammation, provides a theoretical basis for research of related drug targets, also provides a new pathophysiology mechanism for occurrence of bronchial asthma, and has a broad application prospect. The composition can be used for preventing and treating bronchial asthma.

The invention provides an application of Foxo1 in preparation of a medicine for treating hepatic fibrosis, a research result shows that the lack of Foxo1 in macrophages leads to reduction of ROS production, mitochondrial biogenesis recovery and inflammation alleviation, and from mechanism explanation, Nrf1 is directly combined with Foxo1 so as to inhibit the transcriptional activity of Foxo1. The downstream target gene KLF16 of the Foxo1 is regulated and controlled by an Nrf1-Foxo1 complex, and is of great importance to regulation of mitochondrial functions and immune response. According to the invention, the important role of the macrophage Nrf1-Foxo1 axis in controlling the mitochondrial function and the hepatic fibrosis progress is defined.

The invention discloses FoxO1 gene molecular marker primers related to tenderness of yak meat and application of the FoxO1 gene molecular marker primers, and relates to the technical field of biology, the number of the molecular marker primers is two pairs, and the nucleotide sequences of the molecular marker primers are shown as SEQ ID NO: 1-SEQ ID NO: 2 and SEQ ID NO: 3-SEQ ID NO: 4 respectively. The invention discloses the correlation between the yak FoxO1 gene mutation and the Gannan yak carcass and meat quality traits, and the FoxO1 gene mutation site can be used as a potential molecular genetic marker of the Gannan yak meat quality traits.

The present invention relates to: a composition for modulating the expression of FOXO1 and / or ETV6, the composition comprising one or more intermediate non-coding RNA modulators; a composition for attenuating splicing factor expression, the composition comprising an expression modulator of FOXO1 and / or ETV6; a composition for attenuating cell senescence and / or reentry into the cell cycle, the composition comprising FOXO1 and / or ETV6 or an expression modulator of a downstream target thereof involving splicing factor expression; or a composition capable of modulating splicing factor expression, the composition comprising one or more compounds capable of binding or inhibiting the FOXO1 and / or ETV6 gene or a downstream target thereof involving splicing factor expression. Such compositions have therapeutic benefits in preventing, managing, ameliorating or treating aging-related diseases or conditions or cancers, and also as research tools / agents.

The present invention provides the use of a FoXO1 inhibitor in the preparation of a drug for the prevention and treatment of lymphoma. The present invention selected AS1842856 for experiments in a NOD SCID mouse lymphoma tumor model. Administration via intraperitoneal injection effectively prevented and treated the occurrence of PEL (Pelvic Encephalopathy). Dissection of the mice revealed no symptoms of the drug affecting any of the mouse's internal organs. When AS1842856 was used to directly inhibit FoXO1 and FoXO3 in latently KSHV-infected lymphoma cells, it was found that the cells' antioxidant capacity was weakened, thereby increasing intracellular ROS levels, leading to KSHV reactivation and ultimately massive PEL cell death. Inducing oncolytic reactivation of endogenous viruses from latently infected tumor cells is a very attractive cancer treatment option, and inhibitors of FoXOs will have promising application prospects in the prevention and treatment of lymphoma.

The invention discloses application of periplocin in anti-hepatocellular carcinoma drugs and a target screening method, and in-vitro experiment discussion verification is adopted. Through network pharmacology, a TCMSP database is used for screening key bioactive components of cortex periplocae, hepatocellular carcinoma related targets are screened in combination with transcriptomics sequencing data, an intersection is taken, and a network is constructed to screen out an FOXO1 key target. The cell activity and cell proliferation are detected through an MTT method and a clone formation experiment, cell cycle apoptosis is detected through flow cytometry, and it is further determined that the FOXO1 is low in expression in hepatocellular carcinoma tissue and is related to the survival time of a patient. The cortex periplocae component is analyzed, network pharmacology and cell experiments are combined to verify the anti-hepatocellular carcinoma active component and possible action mechanism of periplocin, a scientific basis is expected to be provided for fundamental research of anti-hepatocellular carcinoma pharmacodynamic substances of periplocin, and a novel hepatocellular carcinoma targeted therapeutic drug is found from the scientific basis.

The invention discloses an application of a low molecular weight protein GRAB-L as a PI3K signal channel activator. An in-vivo experiment shows that the protein GRAB-L serving as an effective component in the bitter gourd-derived extracellular vesicles can obviously reduce fasting blood glucose and postprandial blood glucose of mice, obviously reduce blood fat, relieve fatty degeneration of livers, improve the insulin secretion level and reduce the content of autoantibodies in serum of type 1 diabetes mellitus (T1DM) mice to a certain extent; as a PI3K activator, the compound can activate PI3K phosphorylation and PI3K / AKT / FOXO1 / GSK3beta signal channels, inhibit liver glycogen synthesis and gluconeogenesis, increase glycogen decomposition, glycolysis and the like to improve liver dysfunction and maintain glucose homeostasis, and has great significance in treatment of diabetes mellitus.

The invention discloses an application of an LRP1-beta chain 2AAAA oligopeptide accelerant in a medicine for preventing and / or treating insulin resistance or diabetes mellitus. The invention finds that the liver overexpression improved LRP1-beta chain 2AAAA oligopeptide can treat insulin resistance and type 2 diabetes induced by high fat diet, and has a better treatment effect than the LRP1-beta chain oligopeptide found by previous researches, thereby providing a new target and a treatment strategy for the treatment of insulin resistance and type 2 diabetes. The invention verifies that the LRP1-beta chain 2AAAA oligopeptide reduces hepatic gluconeogenesis and improves glycometabolism of high-fat induced hepatic insulin resistance mice and db / db diabetic mice by inhibiting expression of glucose-6-phosphatase (G6PC) down-regulated by a FoxO1 / G6PC axis, and can quickly reduce fasting blood sugar level of the mice in a short time, so that glycometabolism of the mice is recovered to be normal, and the LRP1-beta chain 2AAAA oligopeptide can be used for preventing and treating hepatic ischemia. And no obvious adverse reaction or side effect is found.

The present invention discloses the application of the YOD1 gene in the preparation of a drug for treating rhabdomyosarcoma. The present invention deeply analyzes how YOD1 co-regulates the stability of PAX3-FOXO1 and N-Myc proteins. After inducing and reducing YOD1 expression using a tetracycline regulatory system, the cloning ability and xenograft tumor growth of rhabdomyosarcoma cells that are FOXO1 fusion-positive and accompanied by high N-Myc expression are significantly inhibited. Therefore, the present invention not only discloses the application of the YOD1 gene, but also provides a new therapeutic target for rhabdomyosarcoma cells that are FOXO1 fusion-positive and accompanied by high N-Myc expression.

Compounds comprising a PAX3::FOXO1 fusion protein binding moiety, a bivalent linker, and an E3 ubiquitin ligase binding moiety. The compounds can be used to reduce PAX3::FOXO1 protein levels in a subject with fusion-positive rhabdomyosarcoma (FP-RMS), to ubiquitinate a PAX3::FOXO1 fusion protein in a cell, to treat FP-RMS in a subject in need thereof, and / or to treat a disease caused by the overexpression of PAX3::FOXO1 protein in a subject in need thereof.

The invention belongs to the technical field of biological medicine, and discloses a hirudin chitosan microsphere for repairing endometrial injury through in-situ injection as well as a preparation method and application of the hirudin chitosan microsphere, non-toxic chitosan microspheres are adopted as a slow-release carrier, and controllable slow release of hirudin is realized by optimizing a preparation process. The chitosan microsphere loaded hirudin is locally injected into an injured uterine cavity of a mouse, experiments prove that the uterine tissue structure of an injured region of the mouse uterus is remarkably improved, cell proliferation, muscular layer reconstruction and endometrial angiogenesis of the injured region are promoted through an FOXO1-ERK1 / 2 pathway, intrauterine inflammation is inhibited, the pregnancy rate is increased, and the curative effect is improved. The traditional Chinese medicine composition has a good treatment effect and can be applied to a treatment method of severe uterine injury. The core innovation of the hirudin-chitosan microsphere delivery system is to construct the hirudin-chitosan microsphere delivery system with the targeted slow release characteristic, and a novel material is provided for treating severe uterine injury.

The present application relates to the technical field of brain amyloid angiopathy drugs, and specifically discloses application of dendrobium alkaloid in preparation of a drug for preventing and treating brain amyloid angiopathy, wherein the drug for preventing and treating brain amyloid angiopathy comprises a FOXO1 expression upregulation / autophagy-lysosome activator, and the FOXO1 expression upregulation / autophagy-lysosome activator is dendrobium alkaloid. The drug of the present application increases clearance of Aβ while resisting inflammation and oxidation, reduces damage to cerebral blood vessels, and thus delays or improves cognitive impairment of patients with brain amyloid angiopathy; and through regulation of activation of vascular endothelial transcription factor FOXO1, toxicity of astrocytes is inhibited, and part of autophagy lysosome function is recovered.

Provided herein are compositions, systems, kits, and methods for treating a patient with cancer (e.g., Ewing's Sarcoma) by treating the patient with at least one of the following compositions: a) a composition comprising at least a portion of at least one fusion neoantigen selected from: EWSR1-FLi1, EWS-FEV, EWSR1-ERG, EWS-ATF, EWS-WT1, PAX7-FOXO1, CCNB3-BCOR, CIC-DVX, SS18-SSX2; b) a composition comprising a nucleic acid sequence encoding said at least a portion of said at least one fusion neoantigen; c) a composition comprising an antibody, or antigen-binding fragment, the specifically binds said at least a portion of said at least one fusion neoantigen; and / or d) a composition comprising a chimeric antigen receptor T-cell (CAR T cell) that expresses a chimeric antigen receptor that is specific for said at least a portion of said at least one fusion neoantigen.

Provided herein are compositions comprising T cells modified to overexpress FOXO1 and methods of use thereof. Methods are provided to treat a disease or disorder in a subject comprising administration of the modified T cells. Also provided are methods for preventing exhaustion of engineered T cells comprising introducing a nucleic acid that overexpresses FOXO1 into the T cells.