40 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.

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 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.

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.

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.

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 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%.

The invention develops a Klotho protein delivery system based on recombinant lactic acid bacteria. The Klotho protein delivery system is characterized in that optimized Klotho genes are integrated into a food-grade carrier pNZ8149 through genetic engineering, and the food-grade carrier pNZ8149 is introduced into lactococcus lactis NZ3900 to construct a recombinant strain for expressing Klotho protein; and the functional Klotho protein can be efficiently secreted through Nisin induction. The preparation is orally taken in the form of viable bacteria to feed chicks, targeted release of Klotho protein is realized through intestinal colonization, and experiments prove that the preparation can synergistically activate growth and metabolism pathways (the weight of 21-day-old chicks is increased, and the feed conversion ratio is reduced) and improve intestinal health. The technology breaks through the limitation that traditional probiotics are lack of functional protein delivery capacity, an antibiotic / hormone growth promoter is replaced by a green scheme without resistance and zero residue, and a new safe and efficient growth regulation strategy is provided for livestock and poultry breeding.

The present disclosure relates to use of a multitargeted polypeptide in the treatment of organ fibrosis, in particular to use of a polypeptide mini-klotho and its gene therapy vectors and methods for the treatment of renal fibrosis, hepatic fibrosis, pulmonary fibrosis and other organ fibrosis. The present disclosure provides the use of mini-klotho in the treatment of renal, hepatic and pulmonary fibrosis models, with significant therapeutic effects and without obvious toxic or side effects. Therefore, the mini-klotho of the present disclosure can be prepared into a pharmaceutical preparation for the treatment of organ fibrosis.

The invention discloses a biomarker composition and application thereof, and belongs to the field of biomarker analysis and detection. The invention firstly provides a group of biomarker compositions, wherein the biomarker compositions comprise a Klotho protein and a neutrophil gelatinase associated lipocalin (NGAL); the combined detection biomarker composition can be used for early assessment of the risk of hypertensive disorder in pregnancy complicated with acute kidney injury. When the marker composition is used for predicting the risk of hypertensive disorder in pregnancy complicated with acute kidney injury, the risk of acute kidney injury can be recognized in advance in the early pregnancy stage.

The present invention describes a nutritional supplement for increasing klotho gene expression. The nutritional supplement comprises salmon milt DNA, dried sturgeon eggs and algal oil and is formulated for oral delivery. Endogenic levels of the klotho protein have been shown to increase through the consumption of the Klotho nutritional supplement.

The present 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 human Klotho KL1 domain, preferably wherein the coding region encoding the Klotho polypeptide comprises an RNA sequence having at least 80% sequence identity with SEQ ID NO: 1, and wherein the coding region encoding the Klotho polypeptide preferably has a GC content of at least 54%.

The present disclosure relates to compositions and methods for increasing the level of Klotho in a cell or in a subject and in particular to compositions and methods for treating diseases or conditions associated with Klotho. The methods described herein involve supplementing the level of Klotho protein in a cell by administering to the cell a nucleic acid encoding the Klotho protein.

The invention relates to a thamnolia vermicularia extract and a preparation method and application of the thamnolia vermicularia extract, and the preparation method of the thamnolia vermicularia extract comprises the following steps: S1, mixing a crushed thamnolia vermicularia raw material with water according to a mass ratio of 1: (7-15) to obtain a first mixture; s2, culturing bacillus licheniformis on a culture medium to obtain a seed solution of the bacillus licheniformis; s3, using the seed solution as a zymophyte solution, adding the zymophyte solution into the first mixture according to an inoculum size of 1%-5%, and performing fermentation to obtain a fermentation mixture; and S4, filtering the fermentation mixture, and concentrating and drying the filtrate to obtain a product, namely the thamnolia vermicularia extract. The thamnolia vermicularia extract obtained in the invention has an excellent promotion effect on expression of klotho genes in human fibroblasts, can be applied to products for improving skin health, and fills the blank in the prior art.

The present invention relates to a novel compound that induces the expression of the anti-aging gene klotho. The compound according to the present invention is not only excellent in the effect of increasing the expression level of the klotho gene, which is an aging-related gene, but also has a protective effect against oxidative stress in retinal pigment epithelial cells (RPE), and therefore can be usefully used as a pharmaceutical composition for preventing or treating macular degeneration, or a functional health food composition.

The present disclosure relates to monoclonal antibodies and antigen-binding fragments thereof that bind to human β-klotho, and pharmaceutical compositions and methods of treatment comprising the same.