21 results about "Cholesteryl ester" patented technology

This invention discloses a gRNA combination and its application in the preparation of drugs for the prevention of metabolic-associated fatty liver disease (MASLD). The gRNA combination, when mixed with Cas9 protein, yields an RNP complex, which, when microinjected into mouse zygotes, can breed a stable and heritable mouse strain with TMEM68 gene knockout. Combining lipidomics, transcriptomics, and primary hepatocyte functional verification, the core regulatory role of TMEM68 in hepatic lipid metabolism is revealed for the first time systematically. Experiments demonstrate that TMEM68 deficiency significantly reduces the storage of triglycerides (TAG) in the liver and hepatocytes, decreases lipid droplet formation, and reshapes the metabolic homeostasis of various lipids such as glycerophospholipids, cholesterol esters, and bile acids. Therefore, the gRNA combination of this invention, or the RNP complex obtained by mixing the gRNA combination with Cas9 protein, can be used to prepare drugs for the prevention of MASLD, providing a novel intervention strategy for MASLD prevention with broad application prospects.

A new class of synthetic cyclodextrin dimers is described. Exemplary cyclodextrin dimers are capable of treating atherosclerotic plaques by targeting various forms of cholesterol both intracellularly and extracellularly. Methods of depleting atherosclerotic plaques of cholesterol, cholesterol esters, 7-ketocholesterol, and 7-ketocholesterol esters by treatment with such cyclodextrins are also provided. A sub-class of dimers with high specificity for 7-ketocholesterol is also described.

The present invention relates to a cholesteryl ester transfer protein (CETP) inhibitor for use in the treatment of a subject suffering from or at an increased risk of cardiovascular disease, in particular hyperlipidemia or mixed dyslipidemia. Another aspect of the invention relates to a pharmaceutical composition for treating a subject suffering from or having an increased risk of cardiovascular disease, wherein the composition comprises a therapeutically effective amount of the CETP inhibitor.

The present invention relates to a cholesteryl ester transfer protein (CETP) inhibitor for use in the treatment of an individual suffering from or at increased risk of cardiovascular disease, in particular hyperlipidemia or mixed dyslipidemia. Another aspect of the invention relates to a pharmaceutical composition for use in the treatment of an individual suffering from or at increased risk of cardiovascular disease, wherein the composition comprises a therapeutically effective amount of the CETP inhibitor.

The present invention relates to a cholesteryl ester transfer protein (CETP) inhibitor:(Compound A) for use in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases, in particular hyperlipidemia or mixed dyslipidemia. A further aspect of the present invention relates to a pharmaceutical composition for use in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases, wherein the composition comprises a therapeutically effective amount of said Compound A CETP inhibitor.

The application provides a high-purity human Orai2 membrane protein preparation method based on a mammalian cell expression system. The method obtains a recombinant expression vector containing a human Orai2 gene and an affinity tag sequence; the recombinant expression vector is transfected into a host cell line for expression; a membrane dissolving buffer containing dodecyl-beta-D-maltopyranoside and cholesteryl hemisuccinate is used for lysis extraction of the host cell; after centrifugation to obtain supernatant, the supernatant is sequentially separated and purified by using an affinity chromatography medium and a gel exclusion chromatography medium, and high-purity human Orai2 protein is obtained. The application constructs a thermodynamic equilibrium micellar microenvironment, solves the conformational inactivation problem in the extraction process of multiple transmembrane proteins, and realizes efficient and high-purity enrichment of human Orai2 protein.

The application belongs to the technical field of biological medicine, and particularly relates to an N,N-dimethylethylene diamine-thiodiglycolic acid monocholesteryl ester conjugate as well as a preparation method and application thereof. The structural formula of the N,N-dimethylethylene diamine-thiodiglycolic acid monocholesteryl ester conjugate is as follows: first, cholesteryl and thiodiglycolic anhydride are dissolved together, N,N-dimethylaminopyridine is added, and a reflux reaction is performed to obtain thiodiglycolic acid monocholesteryl ester; then, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride is dissolved together, N,N-dimethylethylene diamine is added, and a reaction is performed to obtain a conjugate molecule. The conjugate is blended with lecithin to serve as a cationic liposome. By adjusting the ratio of lecithin and the conjugate, the particle size and potential of the cationic liposome can be adjusted.

Cholesteryl ester transfer protein inhibitors for use in the treatment or prevention of cardiovascular disease and pharmaceutical compositions containing the same. The present invention relates to cholesteryl ester transfer protein (CETP) inhibitors for use in the treatment of an individual suffering from or at increased risk of cardiovascular disease, in particular hyperlipidemia or mixed dyslipidemia. Another aspect of the invention relates to a pharmaceutical composition for use in the treatment of an individual suffering from or at increased risk of cardiovascular disease, wherein the composition comprises a therapeutically effective amount of the CETP inhibitor.

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin / kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

The present disclosure relates to gene therapy compositions and methods for the preparation and use thereof, for the treatment of Lysosomal Acid Lipase Deficiency (LAL-D) disorders, such as Wolman Disease and cholesterol ester storage disease (CESD).

The present application belongs to the technical field of medicine, and mainly relates to a conjugate of an ApoA1 short peptide and a tubulin inhibitor and a self-assembled nano preparation thereof, wherein the ApoA1 short peptide and the tubulin inhibitor are coupled through a linker. The self-assembled nano preparation comprises the following components: 1-100 parts of the conjugate of the ApoA1 short peptide and the tubulin inhibitor; 1-100 parts of phospholipid; 1-100 parts of cholesteryl ester; and 1-100 parts of water for injection or phosphate buffer. The conjugate of the ApoA1 short peptide and the tubulin inhibitor improves the targeting of the tubulin inhibitor on tumor cells and reduces the toxic side effects of the tubulin inhibitor; the self-assembled nano preparation has the advantages of low cost, few operation steps, simple process, good repeatability, can realize efficient mass production at low cost, and is conducive to storage and drug administration.

The present invention relates to a method for determining the content of omega-3 polyunsaturated fatty acids in the retina of a subject comprising the determination of the content of at least one cholesteryl ester in a blood sample from said subject, the content of omega-3 polyunsaturated fatty acids in the retina being correlated to the content of said at least one cholesteryl ester, said at least one cholesteryl ester being cholesteryl 5,8,11,14,17-eicosapentaenoate.

The present application relates to a kind of low-density extracellular vesicles and its preparation method and application, the low-density extracellular vesicles is derived from CD4 + Chimeric antigen receptor T (CD4 + CAR-T) cell culture fluid, after obtaining supernatant by ultracentrifugation, again by ultrafiltration cut-off purification is obtained.The present application is first isolated and identified from CD4 + CAR-T cell a new type of low-density extracellular vesicles (LD-EVs), the subtype is missed in traditional EV separation process, and the cognition to EV diversity is widened.The characteristics of LD-EVs are rich in sterol ester (especially cholesterin ester) by lipidomics etc., which is related to its low-density characteristics and potential membrane stability, signal transmission function, provides target for functional research and engineering modification.

This invention discloses a composite nanozyme, its preparation method, and its application. The composite nanozyme uses Prussian blue nanoparticles as a carrier, with a phospholipid bilayer formed by dimyristoylphosphatidylcholine coated on the surface of the Prussian blue nanoparticles. The phospholipid bilayer contains (2,3-dioleoyl-propyl)-trimethylamine and undecylimidazole. This invention is the first to disclose a composite nanozyme formed by modifying the surface of Prussian blue nanoparticles with DOTAP and imidazole groups. The obtained composite nanozyme can effectively catalyze ester hydrolysis, producing at least two orders of magnitude acceleration, which provides a possibility for the direct hydrolysis of cholesterol esters in atherosclerotic plaques by nanomedicines. This invention expands the enzyme-like activity of the Prussian blue nanozyme through special modification, providing a solution for simultaneously achieving multifunctional composite nanozymes with ester hydrolytic enzyme function, catalase-like properties, and superoxide dismutase-like properties.

The present invention relates to a cholesteryl ester transfer protein (CETP) inhibitor for use in the treatment of an individual suffering from or at increased risk of cardiovascular disease, in particular hyperlipidemia or mixed dyslipidemia. Another aspect of the invention relates to a pharmaceutical composition for use in the treatment of an individual suffering from or at increased risk of cardiovascular disease, wherein the composition comprises a therapeutically effective amount of the CETP inhibitor.

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin / kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

The invention relates to the technical field related to biological medicine, in particular to a method for inhibiting cholesterol esterification of macrophages, through targeted regulation of a PPAR-gamma / LXR-alpha signal channel by means of palmatine (PAL), foam cell formation can be effectively reduced, and accordingly atherosclerosis (AS) can be improved. Oxidized low-density lipoprotein (ox-LDL) is used for inducing foaming, then 25-100 [mu] g / ml palmatine is used for intervening for 48 hours, and experiments show that the palmatine remarkably reduces the cholesterol esterification rate (from 52.17% to 41.88%, Plt; according to the present invention, with the application of the palmatine in the preparation of the medicine, the expression of cholesterol efflux genes such as ABCA1, ABCG1 and the like is up-regulated, the release of inflammatory factors IL-6 and TNF-alpha is inhibited (reduced by more than 60%), and the molecular docking proves that the combination of the palmatine and the PPAR-V is stable (the combination energy is-8.482 kcal / mol), and is superior to the traditional medicine; the invention provides a new strategy for natural, safe and multi-target intervention of AS, and has significant clinical application potential.

An integrated wound dressing device for treatment of an insertion site of percutaneous and drug delivery devices has a transparent film layer with a bottom side, a top side and a perimeter. The bottom side is coated with an adhesive impregnated with an antimicrobial agent. The transparent film has a radius cutout between a central opening and the perimeter. A liquid crystal temperature sensitive film with an adhesive placed on the top side of the transparent film layer is preferably near and around the central opening. The dressing also has a layer of double folded release paper below the bottom side of the transparent film layer. The preferred TLCs used are cholesteryl esters with a preferable temperature detection range of 35-40° C. The preferred antimicrobial agent is chlorohexidine gluconate (CHG).

The invention belongs to the technical field of cancer treatment, and discloses a method for inducing mitochondrial apoptosis and remodeling an immunosuppressive tumor microenvironment to inhibit CRPC by targeting DHCR7 and cooperating with enzalutamide. It is found that drug-resistant cells show remarkable cholesterol accumulation and cholesterol ester reduction, meanwhile, 7-DHC depletion is accompanied, the level of 7-DHC can be recovered through drug treatment, mitochondrial damage dependent on reactive oxygen species (ROS) is caused, and tumors are sensitive to enzalutamide again. Calcitriol and enzalutamide act synergistically to overcome drug resistance and activate anti-tumor immunity, associating epidemiological observations about the association between vitamin D deficiency and invasive prostate cancer over tens of years with viable treatment strategies. The results not only expand the understanding of metabolic heterogeneity in castration resistant prostate cancer (CRPC), but also provide a biomarker-based framework for using existing therapies to resist fatal treatment drug resistance.

According to the present invention, it is possible to provide a drug carrier having excellent bioavailability and improved drug encapsulation efficiency by preparing lipoprotein-mimicking solid lipid nanoparticles having a core-shell structure consisting of albumin-conjugated cholesterol, a fusogenic lipid, a cationic lipid, a triglyceride and a cholesteryl ester.

The present invention relates to a cholesteryl ester transfer protein (CETP) inhibitor for use in the treatment of a subject suffering from or at an increased risk of cardiovascular disease, in particular hyperlipidemia or mixed dyslipidemia. Another aspect of the invention relates to a pharmaceutical composition for treating a subject suffering from or having an increased risk of cardiovascular disease, wherein the composition comprises a therapeutically effective amount of the CETP inhibitor.