55 results about "Klotho" patented technology

To provide a new composition for increasing expression of the Klotho gene and an application thereof.SOLUTION: The present disclosure provides, in one aspect, the following invention: a composition for enhancing expression of the human Klotho / KL gene, the composition comprising at least a portion of a protein belonging to the TNF superfamily or a nucleic acid encoding at least a portion of the protein.SELECTED DRAWING: None

The present invention relates to a compound for inducing the expression of the anti-aging gene klotho and a preparation method therefor. The compound represented by Chemical Formula 1, according to the present invention, has an excellent effect of increasing the expression level of the klotho gene which is a gene associated with aging, and thus can be useful for a pharmaceutical composition, cosmetic composition or food composition for preventing skin aging, inhibiting cellular senescence or preventing, treating alleviating a vascular aging-induced disease or a renal disease.

This invention relates to the field of cosmetics, and more particularly to active oligopeptides and their application in the preparation of anti-aging products. This invention provides an active oligopeptide with anti-aging activity, the amino acid sequence of which is shown in SEQ ID NO:1 and / or SEQ ID NO:4. This invention also provides an active oligopeptide (β1 and β1c) designed based on computational structural biology, targeting the β-Klotho FGF19 / / FGF21 and receptor-binding arm (RBA) region, and optimized for physicochemical properties, for use in skin anti-aging.

The invention provides a culture medium for improving Klotho protein secreted by mesenchymal stem cells and application of the culture medium, and particularly, the culture medium comprises a basic culture medium, statins and a ROCK inhibitor. The culture medium can effectively improve the Klotho protein secretion level of the mesenchymal stem cells, does not affect the biological activity of the mesenchymal stem cells, and ensures the biological function integrity of the mesenchymal stem cells; meanwhile, operation is easy, cost is low, and good clinical application value is achieved.

Provided are a bifunctional recombinant protein GIK for regulating the glycolipid metabolism and resisting aging, and a preparation method therefor. The recombinant protein GIK comprises an N-terminus, a middle section and a C-terminus. The N-terminus is an optimized human GLP-1 polypeptide having an amino acid sequence of SEQ ID NO: 1; the middle section is an Fc region of human IgG4 having an amino acid sequence of SEQ ID NO: 2; and the C-terminus is an s-klotho polypeptide having an amino acid sequence of SEQ ID NO: 3. The N-terminus is connected to the middle section via a connecting peptide 1 having an amino acid sequence of SEQ ID NO: 4; the middle section is connected to the C-terminus via a connecting peptide 2 having an amino acid sequence of SEQ ID NO: 5; and a signal peptide of human serum albumin having an amino acid sequence of SEQ ID NO: 7 is introduced at the N-terminus, such that a bifunctional recombinant protein that can be secreted and expressed in mammalian cells is obtained, and the bifunctional recombinant protein has an amino acid sequence of SEQ ID NO: 8.

The present invention relates to a Klotho messenger-RNA (mRNA), wherein the mRNA has a 5' CAP region, a 5' un-translated region (5'-UTR), a coding region encoding a Klotho polypeptide, a 3' untranslated region (3'-UTR) and a poly-adenosine Tail (poly-A tail), wherein the Klotho polypeptide comprises the KL1 domain of human Klotho, preferably wherein the coding region encoding the Klotho polypeptide comprises an RNA sequence having at least 80 % sequence identity to SEQ ID NO: 1, and wherein the coding region encoding the Klotho polypeptide preferably has a GC content of at least 54 %.

A genetically modified mesenchymal stem cell including an exogenous nucleic acid including a Klotho encoding region operably linked to a promoter or promoter / enhancer combination, wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell. Also disclosed are methods of treating a patient including administering a therapeutically effective number of the genetically modified mesenchymal stem cells to the patient. The methods of treatment include treating the patient for a neurodegenerative disease; cancer; organ fibrosis; renal disease; age-related changes of organs or organ systems; to slow, reverse and / or inhibit aging; arteriosclerosis; dementia; diabetes mellitus; erectile dysfunction; autoimmune diseases or autoimmune-related diseases; an inflammatory disease of the lung and sepsis.

The invention provides a polypeptide composed of a sequence SEQ ID NO: 1 or a variant of the polypeptide, the sequence of the variant has at least 85% identity with the sequence SEQ ID NO: 1, and the polypeptide is used for prolonging the life of a subject. The invention also provides a nucleic acid sequence for coding the polypeptide, a gene construct containing the nucleic acid sequence or an expression vector containing the gene construct, which are used for the application. The polypeptides, nucleic acid sequences, gene constructs or expression vectors of the invention may be administered in the form of a pharmaceutical composition with at least one pharmaceutically acceptable excipient, diluent or carrier.

The present invention relates to a GP-pKlotho nano-drug, its preparation method and application. A GP organic molecule is used to wrap the Klotho plasmid, and then this nano-GP-pKlotho drug is used to restore the reduction of Klotho caused by acute / chronic kidney injury and to evaluate the therapeutic effect. After intravenous injection, GP-pKlotho is passively targeted to proximal epithelial cells of the kidney, releases the DNA of Klotho in the cells, and the DNA of Klotho enters the cell nucleus. Compared with the non-injected group, the optimized DNA of Klotho translates into 5-15 times more Klotho mRNA, and the Klotho protein increases by 3-8 times, showing strong therapeutic advantages in treating hypotension in ischemic kidneys and acute and chronic kidney injuries caused by cardiovascular surgery.

This document relates to methods and materials for assessing and / or using one or more senotherapeutic agents. In some cases, methods and materials for determining the efficacy of an anti-senescence treatment in a mammal (e.g., a human) are provided. For example, a level of one or more α-Klotho polypeptides in a sample (e.g., a urine sample) from a mammal (e.g., a human) can be used to determine the efficacy of the one or more senotherapeutic agents. In some cases, methods and materials for treating a mammal (e.g., a human) having a disease or disorder characterized by a reduced level of an α-Klotho polypeptide are provided. For example, one or more senotherapeutic agents and / or one or more inhibitors of a senescence-associated secretory phenotype (SASP) polypeptide can be administered to a mammal (e.g., a human) to increase a level of α-Klotho polypeptides within the mammal.

The objective is to provide a simple and indirect method for estimating the rate of senescent immune cells (the ratio of immune cells with high SAβgal expression levels among T cells whose surface marker is CD8-positive) using a small amount of blood sample. [Solution] This method estimates the rate of senescent immune cells using the relative expression levels of one or more selected from Granzyme K, α-Klotho, GDF15, PAI-1 (SERPIN1), and ferritin in the blood.

The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising Q-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

The invention belongs to the field of medicines for treating rheumatoid arthritis, discloses application of Klotho in preparation of medicines for treating rheumatoid arthritis, and particularly relates to application of Klotho in improvement of the inflammatory state of rheumatoid arthritis by regulating a PI3K-AKT signal channel. Klotho can effectively improve clinical inflammation indexes of RA (rheumatoid arthritis). The Klotho can improve the inflammatory state of the RA by adjusting a PI3K-AKT signal channel. Animal experiments prove that Klotho can be applied to treatment of rheumatoid arthritis diseases.

This application relates to a snow tea extract, a method for preparing the snow tea extract, and its application. The method for preparing the extract includes the following steps: S1. Mixing pulverized snow tea raw materials with water at a mass ratio of 1:7-15 to obtain a first mixture; S2. Culturing Bacillus licheniformis on a culture medium to obtain a seed culture of the Bacillus licheniformis; S3. Using the seed culture as a fermentation broth, adding it to the first mixture at an inoculum of 1%-5%, and obtaining a fermented mixture after fermentation; S4. Filtering the fermented mixture, and concentrating and drying the filtrate to obtain the snow tea extract. The snow tea extract obtained in this application has an excellent promoting effect on the expression of the klotho gene in human fibroblasts and can be applied in products that improve skin health, filling a gap in the prior art.

Compositions comprising peptides and dimers thereof that exhibit anti-fibrotic activity and decrease cardiac fibrosis in patients with Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) are provided. In one embodiment the peptide is the KL1 domain of Klotho.

An albumin binding constructs that enhances the pharmacokinetic performance of therapeutic peptides and proteins, extending their half-lives and reducing administration frequency, is disclosed. The core peptide DICLPRWGCLW (SEQ ID NO: 1) is covalently linked to hydrophilic, flexible glycine-serine (Gly-Ser) linkers of the formula (ggs)xgg where X is 3 to 8 units. These linkers provide strong albumin binding (dissociation constant <20 nanomolar). Some constructs feature the GGSGGSGGSGGRLIEDICLPRGCLWEDD (SEQ ID NO: 4) peptide and allow fusion of active proteins like Klotho, maintaining biological activity and leveraging albumin's extended half-life. Constructs are produced using cellular expression systems (CHO, HEK293, Transgenic Insect Cells) for scalability. These constructs show prolonged half-lives comparable to at least 90% of native albumin. Klotho constructs using the albumin binder demonstrate FGF23 binding dissociation coefficients between 15-30 nanomolar essentially the same as natural Klotho Designed to minimize antigenicity, these constructs improve drug delivery efficacy and patient outcomes.

This invention discloses a recombinant plasmid pULK for treating renal fibrosis, its preparation method, and its applications. The recombinant plasmid pULK carries a Klotho-specific ligand peptide, a GGGGS flexible linker peptide, and a USP2 coding sequence tandemly in a 5'→3' configuration. The amino acid sequences are MASDPLGVVR, GGGGS, and the corresponding USP2 sequence, respectively. The preparation method includes fusion gene design and synthesis, vector linearization, recombinant construction and transformation, and positive clone verification. This plasmid can target and stabilize the Klotho protein, avoiding off-target risks, and can be used to prepare anti-renal fibrosis drugs. It is applicable to various chronic kidney diseases with renal fibrosis, filling a technological gap and demonstrating strong feasibility for clinical translation.

The present invention provides a polypeptide consisting of the sequence of SEQ ID NO: 1, or a variant thereof consisting of a sequence at least 85% identical to SEQ ID NO: 1, for use in the prevention and / or treatment of a muscle disease or disorder. The present invention also provides a nucleic acid sequence encoding the polypeptide, a gene construct comprising the nucleic acid sequence, or an expression vector comprising the gene construct, for said use. The polypeptide, nucleic acid sequence, gene construct, or expression vector of the present invention may be administered in the form of a pharmaceutical composition, together with at least one pharmaceutically acceptable excipient, diluent, or carrier. The present invention also provides non-therapeutic methods for improving muscle function and / or increasing muscle mass in a subject.

This invention relates to the field of cosmetics, and more particularly to oligopeptides and their application in the preparation of anti-aging products. This invention provides an oligopeptide with anti-aging activity, the amino acid sequence of which is shown in any of SEQ ID NO:1 to SEQ ID NO:3. This invention rationally designs and optimizes three α-Klotho-derived oligopeptides (RBA-1, RBA-1d, and RBA-1e) with a clear structural basis and optimized physicochemical properties through high-resolution crystal structure information of the FGF23-FGFR1c-αKlotho ternary complex, systematic truncation screening of the receptor binding arm (RBA), and conformation prediction, for use in skin anti-aging.

A fusion protein and a use thereof. The fusion protein comprises an FGF21 mutant protein. The FGF21 mutant protein comprises modifications based on a wild-type human FGF21 sequence, the modifications being: deletion of a proline residue at position 171, or formation of a pair of disulfide bonds before and after the proline residue at position 171 by means of substitution, deletion, or addition of one or more amino acid residues. The FGF21 mutant protein is resistant to enzymatic degradation at the C-terminus thereof by a fibroblast activation protein (FAP), maintains C-terminus activity for binding to a β-klotho receptor, thereby extending an in vivo half-life and the pharmacological effect. The fusion protein enhances the therapeutic efficacy thereof in weight loss, blood glucose reduction, and non-alcoholic steatohepatitis (NASH) by fusing the FGF21 mutant protein with other molecules, such as GLP-1.

This invention relates to compositions for the prevention or treatment of degenerative neurological diseases, comprising a compound that induces the expression of the anti-aging gene klotho as an active ingredient. The compound of this invention, expressed by chemical formula 1, exhibits excellent efficacy in increasing the expression level of the Klotho gene, a gene related to aging, and can be effectively used as a pharmaceutical composition or food composition for the prevention, improvement, or treatment of degenerative neurological diseases.

Provided herein are klotho polypeptide compositions and methods for improving cognitive function in an individual, including treatment with a klotho polypeptide.

This disclosure provides engineered α-klotho polypeptides and methods for their production and use. The soluble α-klotho polypeptides disclosed herein comprise an α-klotho moiety having one or more mutations relative to human α-klotho for enhanced activity, productivity, and / or stability. This disclosure further provides pharmaceutical compositions comprising the engineered α-klotho polypeptide, and methods for using the engineered α-klotho polypeptide in treatments, including the treatment of age-related conditions and kidney disease. Also disclosed are nucleic acids encoding the engineered α-klotho polypeptide, recombinant cells expressing the engineered α-klotho polypeptide, and methods for producing the engineered α-klotho polypeptide.

The invention belongs to the technical field of biological medicines, and particularly relates to a long-acting non-insulin dependent double-target recombinant protein and application thereof in diabetes treatment. According to the present invention, the double-target recombinant protein is obtained by connecting the polypeptide of the targeted activation beta-Klotho / FGFR1c compound with the polypeptide of the targeted activation GLP-1 receptor through the linker; the double-target recombinant protein provided by the invention has a hypoglycemic effect, reduces the inflammation level of diabetes mellitus, effectively improves the blood sugar of diabetes mellitus, and can be used as a drug for treating and / or preventing diabetes mellitus and related diseases, protecting the structural integrity of liver cells of diabetes mellitus and reversing liver injury related to diabetes mellitus; the double-target recombinant protein provided by the invention is independent in hypoglycemic mechanism, different from insulin and non-insulin dependent hypoglycemic mechanism.

Provided herein are methods for treating acute alcohol toxicity using an agonist for a Fibroblast Growth Factor Receptor (FGFR) andβKlotho complex such as Fibroblast Growth Factor 21 (GFF21). Also provided are compositions and kits comprising these agonists (e.g., FGF21 (for administration to a subject in need.

The present invention relates to novel albumin binding constructs that enhance the pharmacokinetic performance of therapeutic peptides and proteins, extend their half-life and reduce the frequency of administration. The core peptide DICLPRWGCLW (SEQ ID NO: 1) is covalently linked to a hydrophilic and flexible glycine-serine (Gly-Ser) linker of the formula (ggs) xg, wherein x is from 3 to 8 units. The linkers provide a strong binding force (dissociation constant lt; 20 nanomoles) to albumin. Some constructs have a GGSGGSGGSGGRLIEDICLPRGCLWEDD (SEQ ID NO: 4) peptide, allowing fusion of active proteins, such as Klotho, maintaining biological activity, and utilizing the long half-life of albumin. In some embodiments, constructs are produced using cellular expression systems (CHO cells, HEK293 cells, transgenic insect cells) to ensure scalability. Upon administration, these constructs exhibit an extended half-life up to at least 90% of the half-life of native albumin. The novel Klotho constructs using the novel albumin conjugates show a FGF23 binding dissociation constant of from 15 to 30 nanomoles, substantially the same as that of natural Klotho. These constructs are designed to minimize antigenicity, thereby enhancing drug delivery effectiveness and improving patient prognosis.

The invention provides a fusion protein and application thereof. The fusion protein comprises an FGF21 mutant protein, and the FGF21 mutant protein has some changes on the basis of a wild-type human FGF21 sequence: deletion of a proline residue at a 171 site, or substitution, deletion or addition of one or more amino acid residues to form a pair of disulfide bonds before and after the proline residue at the 171 site. The FGF21 mutant protein can resist enzyme digestion degradation of fibroblast activated protease (FAP) on a C terminal of the FGF21 mutant protein and maintain the binding activity of the C terminal and a beta-klotho receptor, so that the in-vivo half-life period of the FGF21 mutant protein can be prolonged, and the drug effect of the FGF21 mutant protein can be improved. According to the fusion protein disclosed by the invention, the FGF21 mutant protein is fused with other molecules, such as GLP-1 and the like, so that the treatment effects of the fusion protein on the aspects of losing weight, reducing blood sugar and non-alcoholic steatohepatitis (NASH) are further enhanced.

The disclosure provides a complex comprising (a) a first monomer comprising an Fc domain fused to two FGF21 domains comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4, which may be the same or different, and (b) a second monomer comprising an Fc domain fused to at least one FGF21 domain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4, wherein at least two of the FGF21 domains of the complex comprise a free beta-klotho binding region.

The present invention discloses a parallel silk scaffold with anti-inflammatory activity, a preparation method and an application thereof, belonging to the field of biomedicine technology. The method comprises the following steps: using mulberry silk as a raw material, degumming, dissolving, dialysis and centrifuging to obtain a silk fibroin solution; mixing polyvinyl alcohol and the silk fibroin solution, adding Klotho protein, then ultrasonicating, drying, water-dissolving and centrifuging the mixed solution to obtain silk fibroin nanospheres loaded with Klotho protein; mixing the Klotho protein-loaded silk fibroin nanospheres with the silk fibroin solution in proportion, and subjecting the mixture to directionally freezing, freeze-drying, cross-linking and re-freeze-drying to obtain a Klotho protein-loaded nanosphere-combined parallel silk sponge scaffold. The composite scaffold constructed by the present invention has a parallel topological structure and excellent mechanical strength; and has nanospheres with drug loading and continuous drug release properties, providing a drug sustained-release system for damaged tissue areas, and has a certain effect on alleviating inflammatory reactions and promoting the repair of tissues such as tendons and ligaments.

The invention relates to a Klotho messenger RNA (mRNA). Wherein the mRNA has a 5'cap region, a 5 'untranslated region (5'-UTR), a coding region encoding a Klotho polypeptide, a 3 'untranslated region (3'-UTR) and a polyadenosine tail (poly A tail) wherein the Klotho polypeptide comprises the KL1 domain of human Klotho, preferably wherein the coding region encoding the Klotho polypeptide comprises an RNA sequence having at least 80% sequence identity to SEQ ID NO: 1, and wherein the coding region encoding the Klotho polypeptide preferably has a GC content of at least 54%.