24 results about "Wnt antagonists" patented technology

Wnt signaling antagonist and agonist compositions and methods for their use are provided.

The present disclosure is directed to human protease activated receptor 4 (PAR4) binding proteins (e.g. antibodies). In particular, anti-PAR4 binding proteins which are antagonists of human PAR4, as well as methods and uses thereof.

The invention relates to a fluorescent probe for screening drug active molecules for treating cancers. Specifically, the invention relates to a construction method and application of a fluorescent probe constructed based on an SP / NK-1R mediated signal axis. Specifically, the method comprises the following steps: co-expressing TACR1 (coding NK-1R protein), beta-arrestin-1 / 2 and an ERK kinase active probe; the invention also provides a method for visually detecting the activation or inactivation of the NK-1R protein. The invention also relates to a method for guiding and screening a novel antagonist specifically targeting NK-1R by utilizing visual NK-1R inactivation. And an antagonist which is found by using a visual NK-1R inactivation screening system, is not reported or found yet, can target and block an NK-1R mediated signal channel and inhibits ERK kinase activity probe phase separation.

Methods for improving engraftment of donor cells in a subject thereof are provided. Such methods can comprise providing cells that have been modified to express a first isoform of a target protein (e.g., C-X-C motif chemokine receptor 4 (CXCR4)), administering the donor cells to the subject, and then selectively inhibiting host cells in the subject based on their expression of the second isoform of the target protein, thereby improving engraftment of donor cells in the subject. Also provided are combinations for administration to a subject in need thereof, wherein the combination comprises (1) a population of donor cells modified to express a first isoform of a target protein (e.g., CXCR4) and (2) an antagonist (e.g., anti-CXCR4 antigen-binding protein) that specifically binds to a second isoform of the target protein but does not specifically bind to the first isoform of the target protein.

The present invention relates to a method for predicting the outcome of liver transplantation for the treatment of hepatocellular carcinoma (HCC), or a method for arranging HCC patients to receive liver transplantation, comprising the following steps: determining the expression levels of indicator genes (including skin pontin, clusterin, calpain small subunit 1, F-box and WD repeat protein 7 and SproutyRTK signaling antagonist 2) selected from liver samples of patients suffering from HCC, and comparing the expression levels of the indicator genes with the expression levels of internal reference genes, and combining this with the variable total tumor volume through a linear support vector machine algorithm to predict a good prognosis for the liver transplant recipient.

The invention relates to the technical field of organoid construction and culture, and discloses a yolk sac tumor organoid culture medium and application thereof. The culture medium comprises a basic culture medium and specific addition factors, and the specific addition factors comprise L-glutamine, a TGF-BI type receptor inhibitor A83-01, nicotinamide, an N2 supplement, a vitamin A-removed B27 supplement, N-acetylcysteine, beta-estradiol, a P38MAPK inhibitor SB202190, a bone morphogenetic protein antagonist Noggin, a Wnt pathway related protein R-Spondin-1, an epidermal growth factor, an insulin-like growth factor 1, an insulin-like growth factor 2, an insulin-like growth factor 3, an insulin-like growth factor 4, an insulin-like growth factor 5 and an insulin-like growth factor 6. The medicine composition is prepared from a liver cell growth factor, a neuroregulatory protein-1, a ROCK inhibitor Y27632, activin A and interleukin-6. By adopting the culture medium disclosed by the invention, the successful construction of the egg cystic tumor organoid can be realized, and the stable passage of the egg and the stable and rapid growth after passage can be realized.

To provide a defined culture medium for isolating stratified epithelial stem cells and stably maintaining the epigenetics of the stratified epithelial stem cells during multiple passages, and to provide clonal stratified epithelial stem cells isolated using the defined culture medium.SOLUTION: And a defined culture medium comprising each of ROCK (Rho kinase) inhibitors, mitogenic growth factors, insulin or IGF, TrkA inhibitors, and Oct4 activators, and comprising at least one of VEGF inhibitors, tyrosine kinase inhibitors, and / or FGF10 or FGF10 agonists, and optionally further comprising TGF β signaling pathway inhibitors and / or bone morphogenetic proteins (BMP) antagonists, wherein the defined culture medium supports epigenetically stable growth and proliferation of stem cells of stratified epithelial tissue origin in culture.SELECTED DRAWING: Figure 1

Disclosed herein include methods, compositions, and kits suitable for use in vaccination. Provided are nucleic acid compositions (e.g., mRNA vaccines, DNA vaccines) comprising a first nucleic acid composition comprising a polynucleotide encoding one or more enveloped nanoparticle (ENP) proteins and a second nucleic acid composition comprising a polynucleotide comprising or encoding a tetherin inhibitor. An ENP protein can comprise an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD). Recruitment of one or more ESCRT proteins results in secretion of enveloped nanoparticles (ENPs) from a cell in which an ENP protein expressed. The tetherin inhibitor can increase ENP production from the cell relative to, e.g., a cell that does not express the tetherin inhibitor. There are also provided populations of ENPs in some embodiments.

The invention discloses an antibody fusion protein which simultaneously targets CD24, IL4R and an integrin receptor. In-vitro determination shows that the antibody fusion protein disclosed by the invention remarkably inhibits proliferation, migration, invasion, colony formation and adhesion of kidney cancer cells, shows a comprehensive and remarkable anti-tumor effect on gastric cancer, colon cancer and breast cancer, and has an effect of inhibiting angiogenesis. The result of an MC38-hPDL1C57BL6 / J mouse subcutaneous transplantation tumor model shows that the antibody fusion protein disclosed by the invention is combined with a PDL1 antagonist azolizumab, so that the growth of tumors can be remarkably inhibited. The antibody fusion protein can be used as a potential candidate drug for treating metastatic renal cell carcinoma, PDL1 overexpression cancer, ophthalmic diseases and inflammation or autoimmune diseases.

Methods of improving donor cell implantation in a subject thereof are provided. The methods may include providing a donor cell modified to express a first subtype of a target protein (e.g., interleukin-2 receptor subunit gamma (IL2RG)), the first subtype being functionally indistinguishable, but immunological distinguishable, from a second subtype of the target protein, administering the donor cell to a subject, and administering the donor cell to the subject. The host cells in the subject are then selectively inhibited based on expression of the second subtype of the target protein, thereby improving implantation of the donor cells in the subject. Also provided are combinations for administration to a subject in need thereof, where the combination comprises (1) a population of cells modified to express a first subtype of a target protein (e.g., IL2RG), and (2) an antagonist that specifically binds to a second subtype of the target protein but does not specifically bind to the first subtype of the target protein (e.g., an anti-IL2RG antigen binding protein).

The invention relates to the technical field of biological medicines, in particular to a method for inducing neural stem cells to differentiate into dopaminergic neurons by a small molecule compound. A magnetic mesoporous silica-phase change liposome composite system is constructed, wherein the surface of a three-dimensional porous bioglass substrate is modified with bifunctional peptide, and a glycogen synthase kinase inhibitor, a transmembrane protease inhibitor and a bone morphogenetic protein receptor antagonist are loaded on the three-dimensional porous bioglass substrate. A response mechanism of a photosensitive cyclic adenylate analogue and a dopamine synthesis precursor is activated through blue light pulses, and finally targeted sorting is completed by a fluorescent tracing substrate, so that a high-purity functional dopaminergic neuron population is obtained. Through physical microenvironment optimization, chemical signal channel regulation and control and multi-dimensional integration of a light-operated maturation mechanism, efficient and controllable differentiation of neural stem cells to dopaminergic neurons is realized, and a standardized preparation scheme is provided for Parkinson's disease cell therapy.

The invention discloses an IL-11 long-acting protein antagonist compound and application thereof, according to the sequence characteristics (SEQ ID NO.1) and receptor binding characteristics of human IL11 mutein, Cys mutation is introduced at a specific site by using site-specific mutagenesis, and an activity maintenance mutant is screened by means of cell activity. By utilizing a chemical reaction, fatty acids with different lengths of side chains C16-C22 are introduced into a Cys side chain for modification, and a long-acting product with kept activity is screened by virtue of cell activity again.

Provided herein are, inter alia, peptides capable of binding viral proteins and thereby preventing viral infection, replication and spread (e.g., SARS CoV-2). The conjugates provided herein include a trimerizing domain (e.g., a collagen 18 trimerizing domain) attached through a peptide linker to a viral protein binding domain (e.g., a spike binding domain). The peptides and trimeric compositions provided herein exhibit a unique trimeric symmetry which results in superior binding affinities and low binding entropies providing for desirable compositions inhibit viral entry and treating viral infection.

Disclosed herein are methods and kits for producing ligated peptides. The methods comprise culturing a cell comprising a first and second peptide sequences and an AEP catalytic domain construct, such that the AEP catalytic domain construct hydrolyses an Asn-containing recognition sequence of the first peptide sequence and ligates the resulting Asn-containing sequence to the N-terminus of the second peptide sequence such that the first peptide sequence is ligated to the second peptide sequence. The methods and kits find application, for example, in the identification of transcription factor antagonists.

The invention relates to a nucleic acid aptamer for specifically recognizing fibroblast growth factor 10 (FGF10) protein as well as a screening method and application of the nucleic acid aptamer. The nucleic acid aptamer is at least one of FAS-1, FAS-4, FAS-9, FAS-10 and FAS-12, and is obtained by screening through a magnetic bead-SELEX (systematic evolution of ligands by exponential enrichment) technology. The aptamer can be combined with FGF10 protein with high affinity, the equilibrium dissociation constant (Kd) of the aptamer is within the range of 5-20 nM, and the aptamer has good recognition specificity. By means of the excellent performance, the nucleic acid aptamer has wide application prospects in construction of an efficient detection method of the FGF10 protein and research and development of an FGF10 antagonist.

The application discloses a genetically engineered probiotic preparation and its use in tumor immunotherapy. The genetically engineered probiotic contains an expression cassette regulated by an inflammation-responsive promoter, which can encode a novel trifunctional fusion protein. The fusion protein contains a secretion signal peptide, a human IL-1 receptor antagonist, a flexible linker, an anti-human GM-CSF nanobody, a second flexible linker, and an anti-human PD-L1 nanobody in sequence. In vitro experiments confirm that the fusion protein has complete biological activity, can simultaneously neutralize GM-CSF, block PD-1 / PD-L1 binding, and inhibit the IL-1 signaling pathway. Animal experiments show that oral administration of the probiotic can significantly enhance the anti-tumor efficacy of CAR-T cells, effectively prevent and alleviate cytokine release syndrome, and provide a safe and effective adjuvant therapy strategy for CAR-T therapy.

The present disclosure is directed to human protease activated receptor 4 (PAR4) binding proteins (e.g. antibodies). In particular, anti-PAR4 binding proteins which are antagonists of human PAR4, as well as methods and uses thereof.

The present disclosure is directed to human protease activated receptor 4 (PAR4) binding proteins (e.g. antibodies). In particular, anti-PAR4 binding proteins which are antagonists of human PAR4, as well as methods and uses thereof.

The invention discloses a puffer fish TRPV1 inhibitory peptide, a preparation method and application, and belongs to the field of polypeptides, and the amino acid sequence of the puffer fish TRPV1 inhibitory peptide is RLF. According to the puffer fish skin TRPV1 inhibitory peptide, the preparation method and the application, the puffer fish skin is used as a starting raw material, and the amino acid sequence of the puffer fish skin TRPV1 inhibitory peptide is successfully obtained through a specific process. Experiments prove that the prepared puffer fish TRPV1 inhibitory peptide shows an excellent inhibitory effect on TRPV1. The inhibitory peptide can be used for preparing a TRPV1 antagonist, and the antagonist can play an anti-inflammatory regulation role through multiple pathways and effectively lower the high reactivity of skin microvessels.

This invention discloses the application of PACAP peptides as plant immunomodulators, belonging to the field of plant immunology technology. This invention is the first to apply PACAP to a plant system, discovering that it can act as a novel plant immunomodulator to regulate plant immune responses, thereby enhancing plant resistance to pathogenic microorganisms. Experimental results show that PACAP can rapidly induce intracellular calcium ion influx in Arabidopsis thaliana cells, activate the MAPK signaling pathway, and upregulate the expression of early immune marker genes such as FRK1. Furthermore, PACAP treatment significantly improves plant resistance to pathogens such as *Pseudomonas syringae* and *Ralstonia solanacearum*. This invention also confirms that not only does the full-length PACAP (1-38) possess plant immune-promoting activity, but its N-terminal truncated peptide (1-27) and receptor antagonist fragment (6-38) also have plant immune-inducing functions. This invention provides a new technical solution for the development of plant immune inducers.

The invention belongs to the technical field of microorganisms, and discloses an NTase protein, a screening method thereof and application of the NTase protein in preparation of an anti-phage signal system antagonist and / or an antibacterial preparation. The NTase protein provided by the invention specifically comprises an amino acid fragment with a sequence as shown in SEQ ID NO: 1 or a variant fragment with at least 70% sequence identity with the sequence as shown in SEQ ID NO: 1, the NTase protein has an excellent antagonistic effect on a CBASS system of prokaryotes, and the infection efficiency of viruses on prokaryotic cells can be improved by inhibiting the CBASS system; therefore, a better antibacterial effect is achieved, and the compound has a very excellent application prospect in research and development of novel antibacterial drugs.

The invention provides an application of a composition containing an mCCL6 / hCCL15-CCR1 signal channel blocking agent in preparation of a medicine for treating diseases related to inflammatory bowel diseases. According to the application, the mechanism that expression of mCCL6 / hCCL15 in intestinal fibrosis is increased, intestinal fibroblast activation and collagen generation are promoted, and then intestinal fibrosis progress can be promoted is found for the first time. In a mouse intestinal fibrosis model, the intestinal fibrosis can be effectively relieved by blocking a CCL6-CCR1 signal transduction pathway by using an mCCL6 neutralizing antibody and a CCR1 small molecule antagonist. According to the application, the specific target spot is found, the CCL6-CCR1 signal channel is inhibited, and the intestinal fibrosis is specifically treated, so that the application has breakthrough significance on health improvement of patients with the intestinal fibrosis and even intestinal stenosis, and a new idea is provided for treatment of the intestinal fibrosis.

The invention relates to a heterocyclic compound with hedgehog pathway antagonist activity, in particular to a compound with a structure shown in a formula A or pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer and prodrug thereof. The compound can effectively block a Shh signal pathway, and meanwhile, can down-regulate expression of pulmonary fibrosis related protein alpha-SMA protein; the lung fibrosis lesion process can be obviously inhibited.