27 results about "Klotho" patented technology

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.

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.

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.

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.

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 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 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 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 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 application provides a culture medium for improving secretion of Klotho protein by mesenchymal stem cells and an application thereof, and particularly relates to the culture medium which comprises a basic culture medium, a statin and a ROCK inhibitor. The culture medium can effectively improve the level of the secretion of Klotho protein by the mesenchymal stem cells while not affecting the biological activity of the mesenchymal stem cells, and guarantees the biological function integrity of the mesenchymal stem cells. Meanwhile, the culture medium has simple operation, low cost and good clinical application value.

The invention discloses a Klotho mRNA lipid nanoparticle, a preparation method thereof and an application of the Klotho mRNA lipid nanoparticle in anti-aging. The method comprises the following steps: S1, respectively preparing a water phase solution containing Klotho mRNA and an organic phase solution containing a lipid mixture; s2, mixing the aqueous phase solution and the organic phase solution according to a preset flow velocity ratio by using a microfluidic mixing device, and forming a lipid nanoparticle precursor solution through self-assembly; s3, performing multi-stage dialysis treatment on the lipid nanoparticle precursor solution, replacing a buffer system and removing a residual solvent; and S4, concentrating the dialyzed solution, so as to obtain the Klotho mRNA lipid nanoparticles. According to the invention, a lipid nanoparticle (LNP) delivery platform is combined with mRNA (messenger Ribonucleic Acid) for coding secreting type Klotho protein for the first time, and a non-viral gene medicinal preparation for systemic anti-aging intervention is creatively developed.

The present application relates to the field of cosmetics, in particular to oligopeptides and application thereof. The present application provides oligopeptides, the amino acid sequence of which is shown in SEQ ID NO:1 or SEQ ID NO:2. The present application is based on a series of oligopeptides (including beta-6 and beta-683) designed based on the key role interface of beta-Klotho protein, and the calculation model predicts that the oligopeptides have good binding potential and the characteristics of maintaining activity after truncation; the series of oligopeptides act on the FGF21-FGFR signaling pathway by simulating the function of beta-Klotho, thereby promoting collagen synthesis, inhibiting collagen degradation, and ultimately achieving the beneficial effect of skin anti-aging.

The present invention provides Klotho messenger RNA (mRNA) having 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 the coding region encoding the Klotho polypeptide comprises an RNA sequence having at least 80% sequence identity with SEQ ID NO: 1, and preferably the coding region encoding the Klotho polypeptide has at least 54% GC content.

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.

Disclosed herein are methods for treating or prophylactically treating age-related cognitive decline associated with dementia by administering recombinant viral vectors designed to deliver TERT and / or KL (Klotho) genes to the patient. The TERT and / or KL genes are packaged within one or more AAV viral vectors and administered to the CNS of the patient via intranasal and / or intrathecal injection. The therapy can provide improvements in cognitive function as evidenced by improved Folstein / MMSE scores over time.

This invention relates to the field of cosmetics, and more particularly to oligopeptides and their applications. The invention provides oligopeptides with amino acid sequences as shown in SEQ ID NO:1 or SEQ ID NO:2. This invention comprises a series of oligopeptides (including β-6 and β-683) designed based on the key interface of the β-Klotho protein. Computational models predict that these oligopeptides possess excellent binding potential and retain activity even after truncation. By mimicking the function of β-Klotho, these oligopeptides act on the FGF21-FGFR signaling pathway, thereby promoting collagen synthesis, inhibiting collagen degradation, and ultimately achieving beneficial anti-aging effects on the skin.

A composition comprising citrate and carnitine which activates the production of the protein Klotho by renal tubule cells protecting them, thus reducing the oxidative stress conditions thereof, which can be used for the conservation, perfusion and reperfusion of organs for organ transplants is disclosed. Furthermore, the composition in the liquid and dietary / nutraceutical formulation can be used for reducing the nephrotoxicity induced by iodinated contrast means, antibiotics, NSAIDs 10 or agents that induce oxidative stress.