56 results about "Wnt signaling pathway" patented technology

The present invention addresses the problem of providing: a method for preparing hepatic lineage cells in a large amount and with high purity; and a method for preparing liver system cells which can achieve high graft survival rate in a living body.　The present invention provides: a hepatoblast proliferation promoter and a culture medium, each of which contains a ROCK inhibitor, a TGFβ signaling pathway inhibitor, a Wnt signaling pathway activator, and a growth factor; and a proliferation / culture method using the hepatoblast proliferation promoter or the culture medium.

The present invention provides a method of producing a population of mesenchymal stromal cells (MSC) of CD73 + CD44 +, CD90 +. The CD73 + CD44 +, CD90 + MSC is used in a method for producing terminally differentiated osteoblasts, adipoblasts and chondroblasts from pluripotent stem cells (PSCs). The differentiation methods include the use of a single agent-a WNT signaling pathway activator used on an adherent culture of PSC, such as a GSK3 [beta] inhibitor.

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 invention relates to the technical field of medicinal chemistry, and particularly discloses a compound and application thereof in preparation of a medicine with Wnt signal channel inhibition activity. The compound has a structure as shown in a formula I which is described in the specification. Researches show that the compound disclosed by the invention has the activity of inhibiting a Wnt signal channel; particularly, the IC50 value of the compound Wnt-131 is greatly smaller than that of the compound Wnt-120 and the compound Wnt-133; meanwhile, the compound is also greatly smaller than all compounds in the invention patent CN202410961646. X, and has very excellent activity of inhibiting a Wnt signal channel; therefore, the compound serving as an active ingredient has important application value in preparing the medicine for inhibiting the activity of the Wnt signal channel.

The present invention relates to a method for three-dimensional culture and induced differentiation of neural organoids and use thereof. The method for three-dimensional culture and induced differentiation of neural organoids comprises: adding a signal pathway inhibitor into an induced pluripotent stem cell three-dimensional culture, and culturing cells to obtain the neural organoids. The signal pathway inhibitor comprises a TGF-β signal pathway inhibitor, a WNT signal pathway inhibitor, and a BMP signal pathway inhibitor. Compared with a traditional method, the neural organoids obtained by the method of the present invention feature a large size, small individual difference, and short culture time. The method is simple and rapid, and has high stability and low cost, and only a common incubator is needed. The method has wide application prospects.

The invention discloses an RNF130 gene responding to a BMAA signal, an encoded protein and application, and the RNF130 gene is found to be a gene strongly responding to the BMAA signal through high-throughput screening. After the RNF130 gene is knocked out, cell proliferation inhibition caused by BMAA is reduced for mammalian cells. In addition, the RNF 130 transduction the BMAA signal to the downstream GSK-3beta protein, thereby correlating with the Wnt signaling pathway. After the activity of GSK-3beta is inhibited by using a small-molecule GSK-3beta inhibitor, the reaction of RNF130 to a BMAA signal is changed, and the influence of cell proliferation inhibition caused by BMAA can be relieved by cells. According to the present invention, the cell proliferation inhibition caused by the BMAA can be relieved by the knockout of the RNF130 gene and the inhibition of the GSK-3beta activity, such that the key response protein and the molecular mechanism of the cell proliferation toxicity caused by the algal toxin BMAA are provided so as to provide the important reference target for the research and development of the antidote for preventing or treating the BMAA toxicity or the research and development of the drug aiming at the RNF130 related structural domain in the future.

The present invention provides a method for preparing retinal pigment epithelial cells, comprising (1) a first step of subjecting pluripotent stem cells to suspension culture in a serum-free medium to form aggregates of the pluripotent stem cells, (2) a second step of subjecting the aggregates of the pluripotent stem cells to suspension culture in a serum-free medium to form aggregates of the pluripotent stem cells. (1) a third step in which the aggregate formed in step (1) is subjected to suspension culture in a serum-free medium or a serum-containing medium, each of which does not contain a substance acting on the Sonic hedgehog signal transduction pathway and contains a substance acting on the BMP signal transduction pathway, to obtain an aggregate containing retinal progenitor cells; the aggregate formed in step (2) is subjected to suspension culture in a serum-free medium or a serum-containing medium that does not contain a substance that acts on the Sonic hedgehog signal transduction pathway and a substance that acts on the BMP signal transduction pathway, but contains a substance that acts on the Wnt signal pathway, thereby obtaining an aggregate containing retinal pigment epithelium cells.

Provided are peptoid-peptide macrocycles. The peptoid-peptide macrocycles may have inhibitory activity towards the Wnt signaling pathway. The Wnt signaling pathway is associated with cancer and other diseases and conditions. Such diseases include, for example, pulmonary fibrosis. Also described are methods of making the peptoid-peptide macrocycles, compositions containing the peptoid-peptide macrocycles, and methods of using the peptoid-peptide macrocycles.

The invention belongs to the technical field of biological medicines, and particularly relates to a tetrahedral framework nucleic acid carrying a small molecule drug as well as a preparation method and application of the tetrahedral framework nucleic acid. According to the invention, good cell entry performance, editability, anti-inflammatory and anti-oxidation capability of tetrahedral framework nucleic acid and anti-inflammatory and osteogenesis promoting effects of a JAK inhibitor are combined, and the JAK inhibitor Upatinib (UPA) is successfully loaded onto the tetrahedral framework nucleic acid (tFNA) to obtain a tFNA / UPA compound (TUC); the TUC can significantly inhibit inflammatory reaction by inhibiting a JAK / STAT pathway on the premise of reducing the drug dosage, enhances a WNT signal pathway, promotes an osteogenesis function, more effectively treats rheumatoid arthritis, and has a wide application prospect.

Described herein are methods to affect binding by a multivalent binding molecule to a FZD receptor and a Wnt co-receptor on a cell wherein binding by the multivalent binding molecule to both FZD receptor and co-receptor on the cell activates a Wnt signaling pathway. Also described herein are multivalent binding molecules comprising a FZD receptor binding domain and a Wnt co-receptor biding domain on either end of an Fc domain that activate a Wnt signaling pathway and methods for their use.

The application discloses a lactococcus lactis GL-1 and application of the lactococcus lactis GL-1 in Apostichopus japonicus breeding, and belongs to the field of aquatic beneficial microorganisms and application technologies thereof. The lactococcus lactis GL-1 is preserved in the China General Microbiological Culture Collection Center on September 16, 2025, and the preservation number is CGMCC No. 35938, and the lactococcus lactis GL-1 is isolated from traditional fermented food doubansauce. The strain can well adapt to different environments, and can be used for preparing an Apostichopus japonicus feed additive. When the number of viable lactococcus lactis GL-1 in the feed is greater than or equal to 1x10 8 CFU / g, the low-salt stress resistance of the Apostichopus japonicus can be significantly enhanced, the survival rate and growth performance are improved, the intestinal flora structure is improved, the colonization of beneficial bacteria is promoted, and immune-related pathways such as the Wnt signal pathway are activated, so that the health level of the Apostichopus japonicus is improved from multiple aspects. A safe and effective microbial solution is provided for solving the low-salt stress problem in the Apostichopus japonicus breeding.

Disclosed is the use of a hulless barley grass extract containing polyphenol in controlling colorectal cancer and ulcerative colitis. In terms of the ulcerative colitis, the drug ameliorates a weight loss of colitis mice, reduces an oxidative stress level of colitis mice, reduces relative mRNA expression levels of inflammatory factors TNF-α, IL-6, and IL-1β, and effectively improves a pathological damage caused by inflammatory response in the colon tissue of ulcerative colitis model mice. In terms of the colorectal cancer, the drug is shown to prevent and / or inhibit the occurrence and development of ulcerative colitis and associated colorectal cancer thereof by inhibiting the overexpression of a Wnt signaling pathway and reducing the inflammatory response and oxidative stress damage. The raw materials of the extract are derived from natural products, which are easy to collect and highly safe.

The invention provides a method of producing a population of CD34+ hematopoietic precursor cells. The CD34+ hematopoietic precursor cells are used in methods of producing natural killer (NK), methods of inducing NK cell differentiation from pluripotent stem cells (PSCs), and methods of generating terminally differentiated hematopoietic cells from PSCs. The differentiation of immune cells such as NK cells from PSCs includes the use of a hemogenic endothelium induction cocktail that includes a WNT signaling pathway activator, a bone morphogenetic protein and / or a vascular endothelial growth factor. Also provided is a method of producing hematopoietic stem cells from pluripotent stem cells.

The present invention relates to a composition comprising a TAF10 inhibitor for preventing or treating colorectal cancer. The inhibition of TAF10 was found to lead to suppressing the growth and proliferation of colorectal cancer cells, reducing vascularization, and inhibiting the WNT signaling pathway, and increase the survival rate of patients as analyzed with a large-scale cancer database. In particular, reversal of the cancerization process, which is the differentiation of colorectal cancer cells into normal cells, was confirmed. Unlike conventional anticancer agents that simply induce the death of cancer cells, the present invention can thus be advantageously utilized as a treatment method for converting colorectal cancer cells into normal cells while excluding side effects of normal cell death that may occur during anticancer treatment.

The present invention discloses a method for substantially expanding the population of natural killer (NK) cells through the use of modified cellular culture conditions. By employing a targeted induction cocktail, including a WNT signaling pathway activator and bone morphogenetic protein (BMP), this technique facilitates the differentiation of pluripotent stem cells (PSCs) into NK cells. The core innovation lies in optimizing culture conditions, which significantly enhances the proliferation of NK cells. This approach streamlines the production of NK cells for therapeutic uses, emphasizing the expansion phase within the culture environment.

The invention relates to a cyclic peptide comprising the amino acid sequence N-terminal-X4X3X2X1-a-Y1Y2Y3Y4-C-terminal, wherein -a- represents a linker, and wherein the peptide comprises a linker -c- between the N-terminal amino acid and C-terminal amino acid, and / or wherein the two amino acids of one or two of the following amino acid pairs form a side chain-to-side chain bridged di-amino acid forming a bridge -b-: X1 and X1; X2 and Y2; X3 and Y3; and X4 and Y4. The invention further relates to the use of said cyclic peptide as a medicament, especially for inhibiting or preventing a Wingless / integrase-1 (Wnt)-dependent disease in an individual in need thereof.

Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclosure describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for disease modeling and drug screening.

This invention discloses a composition for the differentiation of mesenchymal stem cells (ADSCs) into keratinocytes and its application. The composition comprises: a Wnt signaling pathway activator, a TGF-β signaling pathway inhibitor, a bone morphogenetic protein pathway activator, and at least one of retinoic acid and a retinoic acid agonist. The small molecule composition provided by this invention is meticulously designed to gradually guide the fate transition of ADSCs by mimicking key signaling events during embryonic development. This strategy is not a simple compound screening, but a rational design based on a deep understanding of developmental biology, achieving precise regulation of cell lineages in vitro by reproducing the natural developmental process. The composition of this invention is not a simple superposition of components, but rather achieves cell fate transition by precisely regulating the balance of signaling pathway networks.

Current treatments for corneal disorders, also known as keratopathy, depend on the stage of the keratopathy. In mild cases of keratopathy, supportive care such as saline eye drops may be sufficient to improve symptoms. The present disclosure provides a method for treating corneal disorders with a modulator of the WNT signaling pathway. More specifically, treatments are provided for corneal epithelial and / or endothelial damage, defects, deficiencies, and dystrophy. Dosage methods and pharmaceutical compositions for treating corneal disorders are also provided.

Provided herein are methods and compositions for obtaining hepatocytes. Provided herein is a kit or cell culture medium composition for inducing hepatocytes from pluripotent stem cells, the composition comprising the following inducers: (1) Activin A, (2) a modulator of the BMP signaling pathway, (3) a modulator of the FGF signaling pathway, (4) a modulator of the Wnt signaling pathway, (5) a growth factor, (6) a TGFβ receptor / ALK5 inhibitor. Also provided herein are methods for preparing hepatocytes by the kit or cell culture medium composition, hepatocytes obtained by the methods, artificial liver devices containing the hepatocytes and / or use of the hepatocytes for preparing artificial liver devices, and methods for large scale culture of hepatocytes.

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions / disorders / diseases due to mutations or dysregulation of the Wnt pathway and / or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

The present application relates to the technical field of nanobiomaterials, and particularly relates to a nano-polypeptide material for double inhibition of a tumor Wnt signal pathway, a preparation method and application thereof, the nano-polypeptide material for double inhibition of the tumor Wnt signal pathway comprising a polypeptide with an amino acid sequence as shown in SEQ ID NO:1, and a hydrophobic fluorescent group connected to a terminal lysine of the polypeptide through an amide bond. After the nano-polypeptide material targets FZD7 proteins highly expressed on a tumor cell membrane surface, the nano-polypeptide material is deformed into a nano-fiber network structure in situ, long-term retention and direct blocking of a binding site of a Wnt ligand and the FZD7 protein are achieved, and signal activation is inhibited from an upstream of the pathway. Meanwhile, the dense fiber network indirectly limits a self-secretion and paracrine process of mature modified Wnt proteins mediated by vesicles or exosomes, signal cascade amplification conduction between adjacent cells is inhibited, key protein expression and downstream target protein transcription levels in the Wnt signal pathway are double down-regulated in the inside and outside, and finally the treatment effect of the tumor is enhanced.

The present invention pertains to a pharmaceutical composition for preventing or treating squamous cell carcinoma, the pharmaceutical composition containing a highly expressed lncRNAs in esophageal squamous cell carcinoma (HERES) expression inhibitor. More specifically, the present invention pertains to a pharmaceutical composition which uses a HERES expression inhibitor to reduce the expression of HERES and affect Wnt signaling pathways, and thereby prevent or treat squamous cell carcinoma.The present inventors discovered that the expression pattern of HERES is related to the onset of squamous cell carcinoma, and found that HERES can be a target for treating squamous cell carcinoma. Accordingly, the pharmaceutical composition according to the present invention was determined to have the effect of inhibiting the proliferation, metastasis, and the like of squamous cell carcinoma by containing the HERES expression inhibitor, and is thus expected to be advantageously used for preventing and treating or ameliorating squamous cell carcinoma.

The invention discloses a stomach body three-dimensional organoid culture medium as well as a preparation method and a culture method thereof, and belongs to the technical field of organoid culture. The stomach body three-dimensional organoid culture medium comprises a basic culture medium and a stomach body organoid growth supplement, the stomach body organoid growth supplement comprises a Wnt signaling pathway agonist, an FGF (Fibroblast Growth Factor) family member, a TGF-beta signaling pathway inhibitor, hyaluronic acid and retinoic acid. The invention further discloses a preparation method of the gastric body three-dimensional organoid culture medium and a gastric body three-dimensional organoid culture method. The method can solve the problems that the existing organoid culture technology is difficult to effectively maintain and amplify the stomach organoid with the functional oxyntocytes, and the existing organoid culture technology has unstable pedigree and incomplete structure.

Methods and compositions for enhancing Wnt signaling pathway activities in a tissue of a subject have been developed for the treatment of cancer, in particular cancers with one or more mutations in the APC (adenomatous polyposis coli) gene. Preferably, the amount of the compositions for enhancing Wnt signaling does not reduce or inhibit proliferation or viability of normal healthy cells in the subject. In some embodiments, pharmaceutical compositions including an effective amount of one or more GSK-3 inhibitors are administered to reduce cancer cell proliferation or viability in a subject. A preferred GSK-3 inhibitor is LY2090314 encapsulated within, or associated with nanoparticles. Dosage forms of LY2090314 encapsulated within, or associated with nanoparticles for administration are also described.

The invention relates to the technical field of nano biological materials, in particular to a nano polypeptide material for dual inhibition of tumor Wnt signal pathways as well as a preparation method and application of the nano polypeptide material for dual inhibition of tumor Wnt signal pathways, and the nano polypeptide material for dual inhibition of tumor Wnt signal pathways comprises polypeptide with an amino acid sequence as shown in SEQ ID NO: 1, the hydrophobic fluorophore is connected with the last lysine of the polypeptide through an amido bond. The nano polypeptide material deforms into a nano fiber network structure in situ after targeting FZD7 protein highly expressed on the surface of a tumor cell membrane, is retained for a long time and directly blocks a binding site of a Wnt ligand and the FZD7 protein, and inhibits signal activation from the upstream of a pathway. Meanwhile, the dense fiber network indirectly limits autosecretion and paracrine processes mediated by vesicles or exosomes of mature modified Wnt protein and inhibits signal cascade amplification conduction between adjacent cells, so that key protein expression and downstream target protein transcription level in a Wnt signal channel are doubly down-regulated in internal and external aspects, and finally, the tumor treatment effect is enhanced.

The application provides a fusion protein for inhibiting a Wnt signal path and application thereof, and relates to the field of biological medicines, and comprises the following: a first peptide segment, wherein the first peptide segment comprises a FU1 fragment; a second peptide segment, wherein the second peptide segment comprises a DRPB fragment; and the first peptide segment is connected with the second peptide segment. The prepared fusion protein can effectively inhibit the Wnt signal path, can inhibit excessive proliferation of cells under a pathological condition of abnormal activation of Wnt, and can effectively regulate the Wnt signal path.

The invention discloses an application of juglans regia polysaccharide in preparation of a product for relieving neurotoxicity caused by ochratoxin A. The monosaccharide composition of the mangnolia mandshurica polysaccharide (WGP) comprises nine monosaccharides including fucose, rhamnose, arabinose, galactose, glucose and the like, and the main chain structure is formed by alternately connecting alpha-D-GalpA and alpha-L-Rhap. The WGP can significantly improve the neural behavior, effectively regulate the expression of a TLR4 / MYD88 pathway, a Wnt signal pathway and a neurotransmitter receptor gene, especially reverse the abnormal expression of AQP1, effectively relieve nerve injury, and open up a new direction for further application of the WGP.

The invention relates to the field of biological medicines, and discloses a targeted inhibitor capable of effectively inhibiting the progress of gallbladder cancer and remarkably improving the lifetime and prognosis of a patient. Through single-cell transcriptome data of a gallbladder cancer patient, single-cell transcriptome data of gallbladder cancer organoid, multiple immunofluorescence experiments, real-time quantitative PCR of gallbladder cancer cell lines, immunohistochemistry of gallbladder cancer tissues and organoid, gallbladder cancer whole exon data and inhibitor agonist experiments, it is found that compared with para-carcinoma, the single-cell transcriptome data of the gallbladder cancer patient, the single-cell transcriptome data of the gallbladder cancer organoid, the single-cell Differential genes of gallbladder cancer epithelial cells in cancer tissues are enriched to a WNT pathway, crosstalk is generated between the gallbladder cancer epithelial cells mainly through a WNT7A-FZD6 ligand and receptor pair in a WNT signal pathway, and inflammatory fibroblasts and epithelial cells can perform intercellular communication through a WNT5A-FZD6 ligand and receptor pair in an ncWNT signal pathway.