44 results about "Klotho" patented technology

The present invention relates to chimeric proteins that include an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion of fibroblast growth factor 21 (“FGF21”) and the C-terminus includes a C-terminal portion of fibroblast growth factor 19 (“FGF19”). The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, as well as methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, methods of treating a subject in need of increased FGF21-βKlotho-FGF receptor complex formation, methods of causing increased FGF21 receptor agonist-βKlotho-FGF receptor complex formation, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and / or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Disclosed is the use of a klotho protein or related compounds for the diagnosis and treatment of cancer, alone or together with other active pharmaceutical ingredients such as chemotherapeutic agents or hormone-regulating agents.

The invention provides hepatocellular carcinoma-related klotho gene single-nucleotide polymorphism and its construction method and use. The hepatocellular carcinoma-related klotho gene single-nucleotide polymorphism and its construction method have the advantages that 1, through a detection method provided by the invention, polymorphism of a single nucleotide located in an exon 4 area of a human klotho gene can be detected fast and simply and it is diagnosed that if an individual has susceptibility of hepatocellular carcinoma so that the hepatocellular carcinoma-susceptible population screening and hepatocellular carcinoma prevention are promoted; 2, a T allele point of rs648202 is used as a drug design target point for drug screening so that an active molecule adjusting a klotho gene expression level is selected and development of a novel antitumor drug is promoted; 3, through primer sequences and HaeIII endonuclease provided by the invention, simple, efficient and specific detection of rs648202 polymorphism is realized; and 4, according to hepatocellular carcinoma-related klotho gene single-nucleotide polymorphism, a hepatocellular carcinoma genetic diagnosis kit can be constructed.

The invention provides application of a KLOTHO protein in preparation of medicines for treating liver cancer. An amino acid sequence of the KLOTHO protein is shown in SEQ NO.1; and the invention also provides application of the KLOTHO protein in preparation of formula for diagnosing the liver cancer, and the amino acid sequence of the KLOTHO protein is shown in SEQ NO.1. The application of the KLOTHO protein has the following technical effects that: (1) the prediction occurrence of the liver cancer is reduced by detecting expressions of individual liver tissues and (or) KLOTHO proteins in blood and related composition components because the KLOTHO protein expression in the cancer tissues of a liver cancer patient is lower than para-carcinoma tissues; (2) the liver cancer is treated by improving the expression level of the KLOTHO proteins and related composition components in the liver cancer tissues because the growth of the liver cancer is inhibited by the KLOTHO proteins; and (3) because the KLOTHO participates a pathological process related to cell activities of malignant proliferation, apoptosis, invasion and the like, experience and application base is provided to deeply discuss about the relation between KLOTHO and other diseases for the future.

The invention relates to application of anti-aging gene segments and protein products of the anti-aging gene segments in treating chronic renal failure, in particular to application of secretory type Klotho genes and proteins of the Klotho genes in preparing medicine for treating chronic renal failure. According to experiments, the secretory type Klotho has remarkable effect of restraining development of kidney tissue fibrosis and chronic renal failure and has no obvious side and toxic effects, so that the secretory type Klotho can be used for preparing medicines for treating chronic renal failure and particularly used for preparing medicines capable of effectively restraining and delaying development of chronic renal failure.

The present invention relates to chimeric proteins that include an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion of fibroblast growth factor 21 (“FGF21”) and the C-terminus includes a C-terminal portion of fibroblast growth factor 19 (“FGF19”). The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, as well as methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, methods of treating a subject in need of increased FGF21-βKlotho-FGF receptor complex formation, methods of causing increased FGF21 receptor agonist-βKlotho-FGF receptor complex formation, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Disclosed are products and methods for monitoring Klotho protein levels and for stabilizing Klotho protein in a mammalian blood sample, especially at room temperature or without freezing, for a period of time. Methods of detecting and quantifying Klotho protein levels, particularly endogenous and / or exogenous soluble alpha Klotho protein levels, methods of diagnosing Klotho protein deficiency, and methods of increasing Klotho protein levels or production, particularly endogenous and / or exogenous soluble alpha Klotho protein level(s), expression, or production, in a mammalian subject, and products useful in performing the same, including diagnostic kits and compositions for treating Klotho protein deficiency, are disclosed. Compositions are configured or formulated to augment natural soluble alpha Klotho protein production, attenuate Klotho protein damage or degradation, and / or supplement Klotho protein levels with exogenous, recombinant protein. Treatment methods and uses include administration of the compositions to human or non-human mammalian subjects.

The present invention is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The Klotho fusion polypeptides of the invention include at least a Klotho protein or an active fragment thereof. The Klotho fusion proteins are useful in the treatment and preventionofa variety of age-related conditions and metabolic disorders.

The invention discloses a mutated fibroblast growth factor (FGF) 1 and methods of use. The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a [Beta]-Klotho-binding protein, an FGFRlc-binding protein, a [Beta]-Klotho-binding protein and a FGFRlc-binding protein, a C-terminal region from FGF 19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

The invention relates to a biological artificial blood vessel able to realize in vivo self-reconstruction. The artificial blood vessel is prepared by the method of: 1. weaving a natural biological material or artificial synthetic material into a blood vessel scaffold by electrospinning or 3D printing, or using antigen removed decellularized homologous and heterologous blood vessel; and 2. representing Klotho protein or GDNF on the blood vessel scaffold. The biological artificial blood vessel obtained in the invention has excellent mechanical performance, anticoagulation performance and biodegradability. The biological artificial blood vessel can be constructed into artificial biological blood vessels with arbitrary caliber, induces circulating endothelial progenitor cell homing in vivo, at the same time converts the blood vessel to a bioreactor sustainedly releasing adenosine, optimizes local microenvironment, achieves artificial blood vessel self-reconstruction, and ultimately forms a completely self-replaced mature blood vessel.

The invention relates to the technical field of diabetic nephropathy, in particular to a medicine for treating and preventing diabetic nephropathy, which comprises 10 to 100 mg of tianagliflozin and 10 to 50 mg of DPP24 inhibitor. The medicine prepared by the invention can remarkably reduce the content or expression quantity of blood urea nitrogen, blood creatinine, 24h urine protein, urine protein quantification and transforming growth factor-beta1, remarkably improves the expression quantity of the klotho protein, has a better effect of treating and preventing diabetic nephropathy, can be stored for a long time, and has small toxic and side effects.

The invention discloses using secreted splicing variant of mammal Klotho (s- KL) as an agent for the prevention and / or treatment of cognitive and / or behaviour impairments. It also refers to gene constructs and expression vectors useful in gene therapy for the delivery of said s-KL variant to the central nervous system of a mammal, in particular a rodent or a human. Pharmaceutical compositions comprising either the protein s-KL or any gene construct for expressing the protein in the CNS are also disclosed.

The invention discloses a method for screening and constructing primary hepatocyte klotho gene transduction stem cells in the technical field of gene transduction stem cell screening and constructing methods. Drugs are screened by taking a T allelic site of rs648202 as a drug design target on the basis of a polymorphic DNA sequence of a klotho gene exon 4 region obtained by PCR (Polymerase Chain Reaction) amplification; and active molecules capable of adjusting the expression level of a klotho gene are screened out, polymorphic typing DNA fragment transduction is adopted based on human hepatocytes, and vector transduction is performed by sequentially adopting hTERT and pLXSN dual vectors, so that transduction of a pLXSN-hTERT expression vector for efficiently expressing hTERT is achieved, and the effect of constructing stem cells for efficiently expressing the klotho gene is achieved. In a low-solubility hygromycin double-screening culture system, the survival ability of the mesenchymal stem cells for tranducing the exogenous klotho gene is improved.

The invention discloses a fusion gene for modifying mesenchymal stem cells, a plasmid, stem cells obtained through modification and a preparation method. The fusion gene comprises a Klotho nucleic acid artificial sequence, a self-shearing polypeptide T2A nucleic acid artificial sequence and an FGF23 nucleic acid artificial sequence, and the Klotho nucleic acid artificial sequence, the self-shearing polypeptide T2A nucleic acid artificial sequence and the FGF23 nucleic acid artificial sequence are sequentially connected in series. The mesenchymal stem cells modified by the fusion gene prepared by the invention are obviously higher than normal stem cells Klotho and FGF23 in expression quantity, and the continuous expression effect on the Klotho and the FGF23 can be realized.

A method of producing Klotho protein includes preparing a Klotho plasmid DNA vector, culturing cells, transfecting the cells with the Klotho plasmid DNA vector in a cell culture medium, growing the transfected cells, and harvesting the cell culture supernatant by removing the transfected cells. The Klotho plasmid DNA vector has a mammalian selection marker and a Klotho open reading frame. The cells are primary fibroblast cells and / or mesenchymal stromal cells. A method of manufacturing a cosmetic composition includes combining Klotho protein or the cell culture supernatant with a cosmetically acceptable vehicle. A method of treating a patient to improve the condition and appearance of aging skin includes topically administering the cosmetic composition to the patient. By upregulating the Klotho gene in vitro and incorporating the Klotho protein and growth factors into a composition, transepidermal water loss, skin atrophy, and free radical damage to the skin may be addressed.

The present invention relates in one aspect to the discovery that β-Klotho is the primary cell-surface receptor for FGF21, with FGFR1c functioning as a catalytic subunit that ultimately mediates intracellular signaling. In one aspect, the invention provides compositions and methods that are useful in treating or preventing endocrine FGF-related diseases or disorders.

The invention discloses a method for analyzing the effect of Rab8 on regulating the expression of Klotho in non-small cell lung cancer, including analyzing the effect of Rab8 on regulating the expression of Klotho on the membrane surface through the post-translation link, analyzing the Wnt signaling pathway and the regulation of the expression of Klotho on the membrane surface by Rab8. The role in EMT and analysis of the role of Rab8 in regulating Klotho membrane surface expression in non-small cell lung cancer cell function. The present invention finds for the first time that Rab8 binds to Klotho, promotes its transport to the membrane surface through the pathway after protein biosynthesis, improves the distribution level of Klotho membrane surface, inhibits Wnt / β-catenin signal activation, and inhibits epithelial-mesenchymal transition of cells, thereby inhibiting Lung cancer cell migration and invasion. Therefore, Rab8 has the function of actively regulating Klotho.

Disclosed herein are modified soluble α-Klotho proteins and isolated fragments of wildtype soluble α-Klotho protein. Also disclosed are pharmaceutical compositions including the modified soluble α-Klotho proteins and / or isolated fragments of soluble α-Klotho protein and methods of their use in treating a subject.

Described is a low voltage, pulsed electrical stimulation device for controlling expression of klotho, a useful protein, by tissues. Also described are methods of enhancing expression of klotho in cells and treating a subject's kidneys.

The invention discloses an antibody capable of being specifically combined with human beta-Klotho receptor and application of the antibody. The antibody can be specifically combined with a co-receptor beta-Klotho of a fibroblast growth factor 21, is used for activating a human beta-Klotho / FGFR1c (Fibroblast Growth Factor Receptor 1c) complex receptor and can be used for treating or preventing type II diabetes mellitus and related diseases in mammals.

Described is a low voltage, pulsed electrical stimulation device for controlling expression of klotho, a useful protein, by tissues. Also described are methods of enhancing expression of klotho in cells and treating a subject's kidneys.

The invention provides an anti-aging composition. The anti-aging composition comprises chlamydomonas extract and acetyl hexapeptide-8 in a mass ratio of (1: 2000)-(5: 2). The invention also provides an application of the anti-aging composition, and a skin care product and a cosmetic containing the anti-aging composition. According to the application, the chlamydomonas extract and the acetyl hexapeptide-8 are creatively compounded for use, especially the Rheoolique and the Aci-Klotho, so that inflammatory response can be inhibited, cell autophagy can be promoted, and collagen degradation can be inhibited; the composition can continuously promote the generation of collagen, reduce the secretion of destructive protease and inflammatory factors, and finally realize the increment of collagen, thereby fundamentally improving the aging skin state.

This document provides methods and materials for treating aging. For example, a mammal having, or at risk for developing, an age-related impairment (e.g., age-related cognitive decline) can be treated by increasing the level of one or more myokine polypeptides (e.g., one or more Klotho polypeptides) within cells within the mammal. This document also provides methods and materials for increasing the ability of muscle progenitor cells to regenerate muscle cells by increasing the level(s) of one or more myokine polypeptides (e.g., an α-Klotho polypeptide) within a muscle progenitor cell.

Methods and compositions for treating a severe acute respiratory syndrome-related coronavirus (SARS-CoV) infection in a subject in need are provided. In some aspects, a therapeutically effective amount of a Klotho polypeptide and / or a Klotho polynucleotide encoding a Klotho polypeptide is administered to the subject. In some other aspects, the subject is treated with a first therapy when the subject has diminished Klotho activity, and with a second therapy when the subject does not have diminished Klotho activity. Diminished Klotho activity is determined by comparing the amount of Klotho protein in a blood sample from the subject to a predetermined threshold. In particular, methods and compositions for treating SARS-CoV-2 infection are provided.

The invention provides application of Epitalon in preparation of a medicine for relieving cisplatin-induced acute kidney injury, belongs to the field of biological medicine, and proves that the Epitalon improves the cisplatin-induced acute kidney injury by up-regulating expression of klotho protein in kidney tissues for the first time, so that a possibly effective prevention and treatment medicine is provided for the cisplatin-induced acute kidney injury. At present, an effective medicine for treating the acute kidney injury caused by the cis-platinum is still lacked clinically, so that it is possible for the invention to provide the effective clinical medicine for preventing and treating the acute kidney injury caused by the cis-platinum.

Disclosed is the use of a klotho protein or related compounds (especially KL1 or KL1 analogue) for treatment, and especially treatment of cancer, alone or together with other active pharmaceutical ingredients such as chemotherapeutic agents.

Nanoparticles coated with extracellular matrix (ECM) are provided, in some aspects, for the delivery of a therapeutic protein, nucleic acid, or drug. In some embodiments, the nanoparticles are delivered to a subject via inhalation or aerosol delivery. Also provided, in some aspects, are methods for treating acute lung injury comprising administering α-Klotho (αKlotho) protein or DNA to a subject.

Disclosed are products and methods for monitoring Klotho protein levels and for stabilizing Klotho protein in a mammalian blood sample, especially at room temperature or without freezing, for a period of time. Methods of detecting and quantifying Klotho protein levels, particularly endogenous and / or exogenous soluble alpha Klotho protein levels, methods of diagnosing Klotho protein deficiency, and methods of increasing Klotho protein levels or production, particularly endogenous and / or exogenous soluble alpha Klotho protein level(s), expression, or production, in a mammalian subject, and products useful in performing the same, including diagnostic kits and compositions for treating Klotho protein deficiency, are disclosed. Compositions are configured or formulated to augment natural soluble alpha Klotho protein production, attenuate Klotho protein damage or degradation, and / or supplement Klotho protein levels with exogenous, recombinant protein. Treatment methods and uses include administration of the compositions to human or non-human mammalian subjects.