21 results about "LGR5" patented technology

The invention provides a method for purifying ovarian progenitor cells and application of the ovarian progenitor cells to in-vitro generation of steroid secretion cells, and belongs to the technical field of biology. The method for purifying the ovarian progenitor cells comprises the following steps: digesting, filtering and washing an ovary, purifying through a magnetic bead or flow cytometry sorting procedure, and screening to obtain the ovarian progenitor cells, a marker used in the purification process is LY6A, LGR5 or PDGFRA (Platelet Derived Growth Factor Receptor A). Experimental results show that the PDGFRA < + > progenitor cells and the LY6A < + > progenitor cells can form androgen synthetic cells for expressing CYP11A1 and CYP17A1; and the LGR5 < + > progenitor cells can only form progestational hormone synthetic cells which express CYP11A1 but do not express CYP17A1.

The invention belongs to the technical field of biomedical detection, and relates to a colon cancer stem cell marker detection kit. The kit comprises a processing assembly, a detection assembly, a reading assembly and a shell, a detection strip is arranged in the detection assembly, and three markers of CD133, LGR5 and ALDH1 are simultaneously detected by adopting a lateral flow immunochromatography technology; the treatment assembly comprises a sample collector, a cracking buffer solution storage cavity and a mixing cavity, and can automatically complete sample pretreatment; the reading assembly comprises an optical detection module and a signal processing module and can quantitatively analyze the detection result. The kit has the advantages of simplicity and convenience in operation, rapidness in detection, high precision, high portability and the like, the detection time is 15-30 minutes, the detection limit can reach the ng / mL level, and the kit is suitable for clinical rapid detection and basic medical institutions and provides technical support for early diagnosis and treatment monitoring of colon cancer.

The invention relates to the technical field of biomedicine, and particularly discloses application of an exosome overexpressing a CAP gene and an LGR5 gene in preparation of a medicine for treating cartilage inflammation. The exosome for overexpressing the CAP gene and the LGR5 gene has targeting and cartilage protection functions, can be swallowed by cartilage cells and targeted to the cartilage cells, can improve the levels of a gene Col2a1 for cartilage generation and a gene Sox9 for regulating cartilage development, and can reduce the level of a gene Mmp13 for cartilage degradation, so that the exosome can be applied to cartilage protection of cartilage cells. The cartilage abrasion of osteoarthritis mice is relieved, and knee joints are protected, so that cartilage generation can be promoted, cartilage aging is relieved, and cartilage degradation is reduced in a complex inflammation environment. Furthermore, the invention provides the mesenchymal stem cell exocrine for over-expression of CAP / LGR5, a new technical scheme is provided for targeted therapy based on stem cell engineering, and the mesenchymal stem cell exocrine has a wide application prospect.

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.

The application provides a multi-specific antibody monomer having a light chain (LC) and a heavy chain (HC), each having a N-terminal and a C-terminal, comprising, a first scFv domain having a binding affinity to a tumor-associated antigen (TAA) at the N-terminal of the HC (Position 1, or P1), a Fab domain having a binding affinity to CD3, and a second scFv domain having a binding affinity to PD-L1 at the C-terminal of the LC (Position 5, or P5) or the N-terminal of the LC (Position 6, or P6). In some embodiments, the TAA comprises EGFR, HER3, DLL3, HER2, GPC3, HLA-G, uPAR, Nectin4, Fra, Tissue Factor, B7-H4, VEGFR2, B7-H3, Muc16, CEACAM6, Claudin6, CLDN18.2, LGR5, GCC, CD20, CD19, Integrin β6, Muc1, CDH6, FAP, CAIX, Integrin β4, CDH17, Lewis B / Y, GPRC5D, CEACAM5, ROR1, or EGFR vIII.

The application discloses application of an Rps14 gene, a medicine and a construction method of a mouse model, belongs to the technical field of biotechnology, and the nucleotide sequence of the Rps14 gene is shown as SEQ NO. 1; compared with the prior art, the specific Rps14 transgenic mouse with a loxp site provided in the application can be used for specifically studying functions and effects of Rps14 overexpression at different sites. Specific overexpression of Rps14 in Lgr5 positive inner ear stem cells can promote significant increase of ectopic hair cells, and effective effects can be used for promoting structural and functional repair after hair cell damage and for improving hearing loss. Rps14 can be synergistically regulated with other reported inner ear genes, for example, Atoh1, Gfi1, Pou3f4 and the like, and effectively promote more ectopic hair cell proliferation and functional maturation.

The present disclosure relates to means and methods in the treatment of cancer. In particular, the present disclosure relates to methods of treating cancer in an individual with antibodies that bind to LGR5 and EGFR. The present invention further relates to combinations for use in such methods, and to combinations for use in the manufacture of a medicament for the treatment of head and neck cancer.

This application relates to a peptide targeting LGR5, a PET molecular probe, its preparation method, and its application. The peptide is any one of the following: (1) its amino acid sequence is YLASRVH; (2) a derived peptide formed by substituting one or more amino acids into the amino acid sequence shown in (1), wherein the derived peptide has the same or substantially the same function as the peptide with the sequence shown in (1); (3) a derived peptide after chemical or genetic modification of the peptide in (1) or (2). The PET molecular probe targeting LGR5 includes a peptide targeting LGR5, a chelating agent, and a radionuclide. The probe of the present invention has good stability, high affinity and specificity for LGR5, and can sensitively monitor the LGR5 expression level at the tumor site; it is also rapidly metabolized in vivo and provides fast imaging. In LGR5-positive tumor models, it can reach the tumor site in a short time and obtain high-contrast PET imaging effects.

The invention discloses a fusion polypeptide for preventing alopecia, a modified exosome and a composition thereof. A Wnt3a active peptide and an LGR5 targeting peptide are connected in series through a flexible connecting peptide to obtain a fusion polypeptide, and the fusion polypeptide has a specific targeting effect on hair follicle stem cells and can activate a Wnt pathway; an exosome is modified by the fusion polypeptide to prepare a fusion polypeptide-exosome (FP-Exo), and the fusion polypeptide-exosome (FP-Exo) is mixed with an anti-DKK1 monoclonal antibody to prepare the anti-hair loss composition. An in-vitro experiment shows that the composition can remarkably promote hair follicle stem cell proliferation, an in-vivo experiment proves that the composition can effectively promote hair follicle regeneration of mice with androgenetic alopecia, and compared with common exosomes and minoxidil, the composition is better in key indexes such as hair follicle density, hair follicle growth period proportion and cell proliferation, and the composition has good application prospects. And a new effective means is provided for alopecia treatment.

This invention relates to a therapeutic target for metabolic dysfunction-related fatty liver disease (MAFLD) and hepatitis, and its application, belonging to the field of biomedical technology. This invention is the first to discover that the expression level of DPF2 in Lgr5-positive hepatocytes can specifically determine the severity of MAFLD and MASH. Based on this finding, this invention significantly improves the pathological structure of MASH by overexpressing DPF2 in Lgr5-positive hepatocytes, demonstrating that targeting Lgr5-positive hepatocytes in the liver can be a therapeutic strategy for metabolic-related fatty liver disease. This invention provides a novel therapeutic target for the treatment of MAFLD / MASH, which has good specificity and broad application prospects.

Familial adenomatous polyposis (FAP) patients harbor mutations in the APC gene and will develop adenoma and early colorectal cancer. Taking biopsies from non-adenomatous (NA) and adenomatous (A) colonic mucosa of FAP patients, we investigated the early events associated with FAP using the intestinal organoid model. In addition to their high proliferative capacity, NA- and A-organoids were characterized by cysts and cysts with buds, respectively, suggesting abnormal maturation. A-organoids were enriched in the stem cell marker LGR5 and dependent on EGF and TGFβ for their growth. Downstream of EGFR, AKT, β-catenin and YAP were found to be activated in A-organoids. While the p110β isoform of PI3K was predominant in A-organoids and essential for their growth, p110α was associated with the immature state of NA-organoids. Accordingly, the present invention relates to a method of treating Familial Adenomatous Polyposis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a PI3K inhibitor.

The invention discloses application of a Dkk3 gene, a drug and a construction method of a mouse model, and belongs to the field of biomedicine. The invention relates to a gene editing tool, which can insert loxP sites on two sides of exon 5 and 6 sequences of a Dkk3 gene based on a CRISPR / Cas9 gene editing technology. The amino acid sequence of the Dkk3 gene is as shown in SEQNO.1; compared with the prior art, the loxp site inserted specific Dkk3 transgenic mouse provided by the invention can be used for specifically researching the regulation and control functions and effects after Dkk3 knockout at different sites. Specific knockout of Dkk3 in Lgr5 positive inner ear stem cells can promote significant increase of ectopic hair cells, and the Dkk3 can be effectively used for promoting structure and function repair after hair cell injury and improving hearing loss. The Dkk3 and other reported inner ear genes, such as Atoh1, Gfi1, Pou3f4 and the like, can be synergistically regulated and controlled, so that the proliferation and functional maturation of more ectopic hair cells are effectively promoted.

The WNT-ACTIVATED ADIPOSE-DERIVED STEM CELL APPARATUSES, METHODS AND SYSTEMS (hereinafter “WAADSC”) disclosed herein in various embodiments provide for production of an isolated and enriched population of mesenchymal stem cells that have an active Wnt signaling demonstrated by the elevated expression of Lgr5 marker and / or Nestin in more than 50% of the population. Such an autologous cell population may, in embodiments, be injected into cerebral ventricles of patients with neurodegenerative diseases to yield therapeutic results, such as halting the progression of certain conditions and / or ameliorating specific symptoms thereof.

The invention discloses an RSPO monoclonal antibody for resisting tumors and inhibiting tissue fibrosis and application of the RSPO monoclonal antibody. The heavy chain variable region of the RSPO monoclonal antibody comprises HCDR1, HCDR2 and HCDR3, and the amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 are respectively shown as SEQ ID NO.1, SEQ ID NO.2 and SEQ ID NO.3; the light chain variable region of the RSPO monoclonal antibody comprises LCDR1, LCDR2 and LCDR3, and the amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 are shown as SEQ ID NO.4, SEQ ID NO.5 and SEQ ID NO.6 respectively. The anti-human RSPO antibody disclosed by the invention can inhibit a beta-catenin signal channel, destroy LGR protein signal transduction and inhibit solid tumor growth and tissue fibrosis development by inhibiting combination of RSPO3 protein and LGR5 protein. Compared with the prior art, the RSPO-3 monoclonal antibody provided by the invention, aiming at a single antigen, namely RSPO-3, can be combined with RSPO-3 with high specificity and inhibit the combination of RSPO-3 protein and LGR protein, and has high specificity.

LGR5 binding agents, in particular antibodies or fragments thereof which bind to human LGR5, and the use of such binding agents in the treatment of disease, such as cancer and inflammatory disease, and the detection of LGR5.

The use of an aqueous extract from Linderae Radix for the preparation of a medicament for preventing and treating ulcerative colitis is provided, which belongs to the technical field of prevention and treatment of ulcerative colitis. The present disclosure proposes for the first time that an aqueous extract from Linderae Radix has the effects of preventing and treating ulcerative colitis, wherein the aqueous extract from Linderae Radix can effectively alleviate the symptoms of ulcerative colitis, mainly including improving the clinical symptoms and pathological changes in mice with dextran sodium sulfate-induced ulcerative colitis. In addition, the present disclosure proposes for the first time that the aqueous extract from Linderae Radix has the effects of: maintaining the number and function of goblet cells; increasing the number of mitochondria; activating “bile acid-mitochondrial” signaling to enhance Lgr5+ ISC activity to further promote the regeneration of intestinal epithelial cells.

The invention provides a new medicine for treating gastric cancer, opens up a brand new application field of an alpha-glucosidase inhibitor, and provides a potential effective, safe and economical new treatment scheme for patients with gastric cancer; the invention also discloses a brand new anti-gastric cancer action mechanism of the alpha-glucosidase inhibitor, phosphorylation of PPP1CA at a T320 site is inhibited by down-regulating expression of a tumor inhibition factor RASAL2, and finally inactivation of a downstream p38 MAPK signal channel and a downstream Smad signal channel (a key medium of a TGF-beta channel) is caused. Expression of key genes related to tumor stem cell characteristics (LGR5, CD44 and SOX9), transcription factors (BACH1) and immune escape (PD-L1) is reduced through inhibition of the pathways, so that the effects of inhibiting proliferation of gastric cancer cells and reducing the malignancy degree of the gastric cancer cells are achieved.

The invention discloses application of myricetin in proliferation and differentiation of intestinal stem cells, and belongs to the field of organoid culture. After the organ-like model is treated by myricetin, the relative expression quantity of Lgr5 mRNA is remarkably increased, which indicates that the model can respond to intervention of myricetin, up-regulate expression of an intestinal stem cell marker Lgr5, and contribute to proliferation and tissue repair of intestinal stem cells. Immunofluorescence detection shows that the protein expression intensity of the myricetin group MUC2 is enhanced, which proves that the model can verify the promotion effect of myricetin on goblet cell differentiation and mucus secretion and improve the intestinal barrier function. QPCR detection proves that after myricetin treatment, the relative expression quantity of mRNA closely connected with related genes ZO-1, Occludin and Claudin-1 is remarkably increased, which indicates that the organ model can evaluate the protection and strengthening effects of myricetin on intestinal epithelium close connection, and has potential application value in treatment of intestinal barrier injury related diseases.

The application relates to the field of biomedical technology, and particularly discloses application of an exosome overexpressing CAP and LGR5 genes in preparation of a drug for treating cartilage inflammation. The exosome overexpressing the CAP and LGR5 genes has both targeting property and cartilage protection function, the exosome can be more phagocytosed by cartilage cells, is targeted to the cartilage cells, can improve the levels of a cartilage generation gene Col2a1 and a cartilage development regulating gene Sox9, can reduce the level of a cartilage degradation gene Mmp13, can relieve cartilage abrasion of osteoarthritis mice, and can protect knee joints, so that the exosome can promote cartilage generation, relieve cartilage aging and reduce cartilage degradation under a complex inflammation environment. Further, the application provides a mesenchymal stem cell exosome overexpressing CAP / LGR5, provides a new technical scheme for targeted treatment based on stem cell engineering, and has a wide application prospect.

This invention provides a pharmaceutical composition that can maintain the activity of a bispecific antibody that binds to both EGFR and LGR5, as well as its analog variants. [Solution] A pharmaceutical composition is provided comprising a polyspecific antibody having a first binding domain that binds to EGFR and a second binding domain that binds to LGR5, a functional portion or derivative thereof, a buffer system including histidine buffer and / or citrate buffer, a sugar component, and a nonionic surfactant.