35 results about "Cholesterol metabolism" patented technology

The invention discloses a tumor cholesterol metabolism regulation microneedle patch and a preparation method, the microneedle patch comprises a needle tip and a backing which are connected, the needle tip comprises a needle tip body and nanoparticles loaded on the needle tip body, the nanoparticle is a manganese ion-doped organic metal framework, the outer layer of the manganese ion-doped organic metal framework is modified with a targeting agent, cholesterol oxidase and superoxide dismutase are carried on the manganese ion-doped organic metal framework, the targeting agent can target a CD44 receptor, and the organic metal framework can carry drugs. The targeted drug can enter tumor cells in a targeted mode, superoxide dismutase catalyzes superoxide anions overexpressed in the tumor cells to generate H2O2 and O2, O2 needed by catalysis is provided for cholesterol oxidase, cholesterol at the tumor site is consumed by the cholesterol oxidase, accumulation of 7-DHC is reduced, meanwhile H2O2 can be generated, and the cholesterol oxidase can be used for catalyzing the tumor site. H2O2 is catalyzed by manganese ions through a Fenton-like reaction to generate OH to induce tumor cells to generate ferroptosis, so that ferroptosis-immune synergistic treatment is realized.

The invention belongs to the technical field of functional microorganisms, and provides pediococcus acidilactici MR21 and application thereof. The pediococcus acidilactici MR21 provided by the invention is preserved in the China General Microbiological Culture Collection Center (CGMCC) on December 3, 2024, and the preservation number is CGMCC NO. 32896. The pediococcus acidilactici MR21 disclosed by the invention has efficient in-vitro cholesterol removal capacity, excellent safety and remarkable probiotic characteristics, and has the effects of restoring liver functions, reducing liver fat accumulation and regulating expression of fat and cholesterol metabolism related genes by remarkably reducing the content of serum total cholesterol and low-density lipoprotein cholesterol. Therefore, the function of relieving hypercholesterolemia is achieved.

The invention relates to an SR-B1 targeted polypeptide compound and application thereof in preparation of antitumor drugs and immunotherapy sensitizers, and belongs to the technical field of biological drug manufacturing. In order to solve the problems that an existing PD-L1 inhibitor is single in action mechanism and immune system dysfunction is easily caused, the invention provides an SR-B1 targeted polypeptide compound which is composed of SR-B1 targeted polypeptide and Resiquimod. The SR-B1 targeting polypeptide comprises an SR-B1 targeting peptide fragment, a self-assembly peptide fragment and a hydrophobic molecule which are connected in sequence. The SR-B1 targeting polypeptide can recognize overexpressed SR-B1 in tumor cells, block cholesterol uptake, inhibit tumor progression and inhibit expression of PD-L1 at the same time. The polypeptide compound accurately delivers Resiquimod to a tumor site, anti-tumor immune response is activated, and sensitivity of tumor immunotherapy is greatly enhanced through combination of cholesterol metabolism regulation and immunotherapy.

The invention discloses a sweet potato vine-sourced polypeptide ST2b and application thereof, and belongs to the technical field of biological medicine, the amino acid sequence of the sweet potato vine-sourced polypeptide ST2b is GSFKMEGKR, and the polypeptide ST2b inhibits the occurrence and development of type 2 diabetes mellitus by regulating host cholesterol metabolism, so that the development of type 2 diabetes mellitus is inhibited. Experiments prove that the polypeptide ST2b treatment can inhibit expression of cholesterol synthesis related genes in a host body, so that the cholesterol level in the host body is reduced, and the characteristic of resisting type 2 diabetes mellitus is exerted; the invention provides a novel application for preparing the medicine for the type 2 diabetes mellitus.

Provided herein are compositions, methods of making the same, and methods for targeted delivery of therapeutic agents for modifying expression and function of target genes, e.g. proteins involved in lipid and cholesterol metabolism such as PCSK9.

The application relates to the field of biological medicine, in particular to application of TDF in serum cholesterol regulation and a verification method. The application discloses that tenofovir disoproxil fumarate (TDF) can inhibit intestinal cholesterol absorption by specifically down-regulating the expression level of NPC1L1 protein in the intestinal tract, so as to reduce serum cholesterol. The regulation has tissue specificity, and TDF has no significant influence on the expression of key genes of liver cholesterol metabolism. The application also provides a method for verifying the regulation of TDF on serum cholesterol, which is evaluated by detecting blood lipid indexes and the gene and / or protein expression level of NPC1L1 in duodenal tissue. The application provides a treatment scheme with antiviral and cholesterol-lowering effects for patients with chronic hepatitis B combined with hypercholesterolemia, and provides a new idea for developing a lipid-lowering strategy targeting intestinal cholesterol absorption.

The invention relates to a brand new application of bifidobacterium longum BL21, in particular to an application of the bifidobacterium longum BL21 in preparation of a tumor treatment synergist. The BL21 strain provided by the invention can effectively improve the treatment effect of conventional tumor treatment means such as radiotherapy and / or alphaPD-L1 antibody intervention. Specifically, compared with pure radiotherapy and / or alphaPD-L1 antibody intervention, the intervention of the bifidobacterium longum BL21 can further prolong the survival time of a patient, reduce the tumor growth speed, regulate intestinal microbiota, regulate the cholesterol metabolism level and change the tumor immune microenvironment, and has a prevention effect on cancer cell proliferation.

The invention relates to the technical field of biological medicine, and particularly discloses application of nefenavir. Nefinavir is used for preparing a medicine for treating or preventing castration-resistant prostate cancer, and the medicine can specifically up-regulate expression of DHCR7, induce DNA damage of tumor cells and activate a cell cycle arrest pathway mediated by periodic protein of the cells so as to inhibit key biological processes such as proliferation of the tumor cells, cholesterol metabolism and the like; especially, formation and amplification of multinuclear giant cells in castration-resistant prostate cancer can be effectively inhibited by up-regulating expression of DHCR7, so that malignant progression of multinuclear giant cell mediated tumors and treatment of drug resistance are blocked. Finally, the castration-resistant prostate cancer is prevented and treated, and the technical bottlenecks that an existing castration-resistant prostate cancer treatment means is limited in curative effect, and the drug resistance and metastasis capability mediated by multinuclear giant cells are difficult to inhibit in a targeted manner are solved.

This application discloses the application of PLAC8 as a target in the preparation of tumor therapeutic drugs, involving the field of biomedical technology. This application clarifies that the "sympathetic nervous system-β2-AR-PLAC8-cholesterol metabolism-M2 polarization" pathway is the core driving pathway for stress-related tumor progression and chemotherapy resistance. It reveals the molecular mechanism by which PLAC8 inhibits cholesterol synthesis through phosphorylation at the S67 site, binding to the N-terminal domain of SREBP2, recruiting OGT to mediate SREBP2O-GlcNAc glycosylation. Through strategies such as gene silencing, β2-AR antagonist intervention, and targeted delivery of siPLAC8 via mannose-modified lipid nanoparticles (LNPs), the application achieved the effects of inhibiting M2 macrophage accumulation, inhibiting tumor growth, and reversing chemotherapy resistance in various tumor models, including gallbladder cancer, intrahepatic cholangiocarcinoma, and prostate cancer. Furthermore, the LNPs delivery system showed no significant toxicity. This research provides a novel therapeutic target centered on PLAC8 and a safe and effective targeted intervention strategy for stress-related tumors, highlighting its clinical translational value.

The invention discloses a sound-sensitive bionic nano-drug and a preparation method thereof, and belongs to the technical field of biological medicines. The sound-sensitive bionic nano-drug comprises porphyrin-hybridized hollow mesoporous organic silicon dioxide, a macrophage membrane and a cholesterol metabolism regulating drug, the porphyrin-hybridized hollow mesoporous organic silicon dioxide is a sound-sensitive agent and a carrier, the surface of the outer layer of the hollow mesoporous organic silicon dioxide is coated with the macrophage membrane, and the cholesterol metabolism regulating drug is coated with the macrophage membrane. Tetra (4-carboxyphenyl) porphyrin (TCPP) in a sound-sensitive agent is hybridized on a hollow mesoporous organic silicon dioxide skeleton, Ava is loaded on mesoporous and hollow structures of the TCPP, and the tumor killing effect is improved by regulating cholesterol metabolism of tumor cells and T cells and cooperating with SDT. And the sound-sensitive bionic nano-drug provides a new normal form for tumor treatment through'metabolism-sonodynamic-immunization 'multi-dimensional combination, and breaks through the limitation of traditional single treatment.

This invention belongs to the fields of biomedical materials and colloid chemistry, and discloses a structurally remodeled egg yolk low-density lipoprotein biomimetic liposome and its application in regulating cholesterol metabolism. The method includes extracting and purifying natural egg yolk low-density lipoprotein; selectively removing endogenous cholesterol by adding β-cyclodextrin under alkaline conditions; adding a phytosterol ethanol solution to the cholesterol-removed low-density lipoprotein dispersion, followed by incubation and dialysis purification to obtain the biomimetic liposome. The obtained biomimetic liposome uses partially cholesterol-removed egg yolk low-density lipoprotein as its structural framework, with phytosterols embedded in its phospholipid monolayer and lipid core interface. This biomimetic liposome can inhibit cholesterol micelle formation, reduce cholesterol absorption, promote macrophage cholesterol efflux, and inhibit macrophage foam formation. It can be used to prepare cholesterol metabolism regulating materials, functional delivery systems, and dietary supplement products.

The present invention provides an application of a DHCR7 down-regulator in attenuating alcohol-induced liver tumors. The present invention reveals that DHCR7 plays a role in regulating liver tumors (alcohol-induced liver tumors), analyzes the important mechanism of action of the cholesterol metabolism pathway regulated by DHCR7 in the development of liver tumors, and provides a drug target and theoretical basis for the development of a new generation of anti-cancer drugs. Taking DHCR7 as a target, drugs for inhibiting (including alleviating or treating) liver tumors can be developed, as well as for diagnosing and prognosticating liver tumors or symptoms.

The invention belongs to the field of gene engineering, and particularly relates to application of an SQLE gene in inhibition of PEDV virus replication. The invention provides shRNA (short hairpin Ribonucleic Acid) of a specific targeting SQLE gene, the shRNA can specifically target the SQLE gene, the knock-down of the SQLE gene is realized, and an LLC-PK1 cell line of the knock-down cholesterol metabolism gene SQLE is obtained. The cell line has resistance phenotype to PEDV virus, can significantly inhibit PEDV virus, and is expected to enhance immunogenicity and induce a body to generate stronger immune response, so that PEDV infection is effectively resisted, and the problem of poor immune effect of a traditional vaccine is solved.

The present invention addresses the problem of providing a test substance evaluation method and a test substance evaluation kit with which it is possible to distinguish between damage caused by suppression or deletion of a function of a gene product and damage caused by stimulation in human-derived pluripotent stem cells in which a function of a gene product involved in cholesterol metabolism regulation has been suppressed or deleted or cells differentiated from said human-derived pluripotent stem cells, and to evaluate the effect of the test substance only on damage caused by stimulation. The present invention provides a test substance evaluation method, the method comprising: a step (a) for culturing human-derived pluripotent stem cells in which a function of a gene product involved in cholesterol metabolism regulation has been suppressed or deleted or cells differentiated from said human-derived pluripotent stem cells in a culture medium substantially free of serum and containing sterols; and a step (b) for bringing the human-derived pluripotent stem cells or cells differentiated from the human-derived pluripotent stem cells into contact with a test substance.

The invention provides application of SPPARMs in treatment of atherosclerosis, and belongs to the technical field of biological medicine. An ApoE gene knockout mouse is subjected to high-fat feeding to construct an atherosclerotic mouse model, THP-1 macrophages are exposed to oxidized low-density lipoprotein to construct a macrophage foaming model, INT131 is used for drug administration to an animal model and a cell model, and results show that INT131 can effectively relieve formation of atherosclerotic plaques, and can be used for treating atherosclerotic plaques. The content of AS mouse serum total cholesterol and low-density lipoprotein cholesterol is obviously reduced, and the content of high-density lipoprotein cholesterol is increased. In addition, INT131 can reduce intake of lipid in macrophages, promote cholesterol excretion and cholesterol metabolism, and inhibit formation of foam cells by inhibiting inflammatory response.

The invention discloses a compound lactic acid bacteria composition and application thereof, and belongs to the technical field of microbial medicine. The compound lactic acid bacteria composition is prepared from lactobacillus plantarum (Lactobacillus plantarum) HMPM1006C and lactobacillus curvatus (Lactobacillus curvatus) HMPM1403C, and the ratio of the viable count of the lactobacillus plantarum (Lactobacillus plantarum) HMPM1006C to the viable count of the lactobacillus curvatus (Lactobacillus curvatus) HMPM1403C to the viable count of the lactobacillus plantarum (Lactobacillus plantarum) HMPM1403C is 1 to (0.1 to 3). Through the synergistic effect of multiple target points, absorption of carbohydrates in the intestinal tract can be delayed, insulin sensitivity can be improved, cholesterol metabolism can be promoted, meanwhile, intestinal flora balance is adjusted, inflammatory response is relieved, improvement on type 2 diabetes mellitus and related metabolic diseases is achieved, and the effect is remarkably superior to that of a single strain; a safe and effective new strategy is provided for prevention and adjuvant treatment of metabolic syndrome, type 2 diabetes and obesity.

The invention discloses an application of ABCA1 as a steady-state regulation target of lung cholesterol. By constructing a CYP27A1 gene knockout mouse model and combining molecular biology and RNA (Ribonucleic Acid) sequencing technologies, the invention further discloses a potential relationship between down-regulation of ABCA1 in liver tissues and specific up-regulation of ABCA1 in lung tissues and cholesterol. The research of the invention not only helps to deepen the understanding of the role of the ABCA1 in the lung cholesterol homeostasis, but also provides theoretical support for the prevention and treatment of cholesterol metabolism related diseases, and defines that the ABCA1 can be used as a target spot for regulating and controlling the lung cholesterol homeostasis.

The present invention discloses a tetravalent platinum complex for inhibiting cholesterol metabolism, a preparation method and an application thereof, and belongs to the field of medical technology. The tetravalent platinum complex of the present invention is obtained by connecting and coordinating a cholesterol metabolism inhibitor with a platinum anticancer drug; the platinum anticancer drug includes a cisplatin derivative or an oxaliplatin derivative. The present invention achieves the anti-tumor purpose by introducing a cholesterol regulator into the structure of a platinum drug, and destroying the material and energy basis required for the growth and reproduction of tumor cells by regulating cholesterol metabolism. In the process of regulating cholesterol metabolism, the immune cells in the tumor microenvironment are affected, and the anti-tumor immune response is activated, thereby achieving the purpose of synergistic anti-tumor, while overcoming the drug resistance and systemic toxicity of traditional platinum drugs.

The present application discloses novel compounds, and compositions comprising said compounds, that are effective small-molecule agonists that stimulate overproduction of cytosolic cyclic AMP (cAMP) in Mycobacterium tuberculosis (Mtb) which inhibits cholesterol metabolism. These small-molecule agonists demonstrate potentiation of current tuberculosis (TB) therapeutics, exhibiting potential as a promising new class of agents for the treatment of TB. The application further discloses methods of treatment of TB using compositions comprising the disclosed novel compounds in combination therapy with current TB therapeutics.

Described herein are methods and kits for the use of ANGPTL3, ANGPTL4, ANGPTL8, and / or ANGPTL3 / 8 inhibitors in the field of severe hypertriglyceridemia, particularly for distinguishing complete or partial lipoprotein lipase (LPL) deficiency and assessing LPL bioavailability in subjects. As described, these inhibitors can be used to distinguish subjects with significant basal LPL activity from controls with no or little LPL activity. The inhibitors can also be used to distinguish recurrent from persistent chylomicronemia in subjects with severe hypertriglyceridemia or chylomicronemia. Administration of the inhibitors can also replace post-heparin LPL activity measurement or genotyping in identifying disorders of triglyceride and HDL-cholesterol metabolism.

The present application relates to the technical field of adoptive cell transfer therapy, and particularly, to a cholesterol metabolite-based TCR-T cell preparation and an immunotherapy. In the present application, 7-hydroxy-hydroxylated cholesterol is used for treating T cells, the level of TCR signals is reduced, the memory function of T cells is enhanced, the memory cell proportion of T cells is increased, and therefore, the continuity of killing tumors is improved.

This invention belongs to the field of pharmaceutical technology, and particularly relates to a silicon-based preparation for regulating intestinal flora to improve cholesterol metabolism and its preparation method. The method includes: S1, providing pharmaceutical-grade water-soluble silica raw material; S2, diluting the water-soluble silica raw material with sterile deionized water, stirring at 100-200 r / min for 10-20 min at 20-25°C, and preparing low-dose and high-dose silicon-based preparations respectively. This invention addresses the shortcomings of existing cholesterol-lowering drugs, such as muscle toxicity and new-onset diabetes, caused by long-term use, by providing a silicon-based preparation using pharmaceutical-grade water-soluble silica as a raw material. By limiting the content of metasilicic acid and silica in the raw material, controlling the heavy metal impurity content to ≤10 ppm, and combining sterile deionized water dilution with precise stirring conditions and pH control, the high purity and stability of the preparation are ensured.

Methods and uses of compositions (e.g. comprising one or more microbial strains, one or more components (e.g. microbial components), one or more metabolites (e.g. microbial metabolites), or any combination thereof) for prevention, reduction of risk, treatment, and / or improvement of metabolism (e.g. lipid and cholesterol metabolism) associated diseases, disorders, and conditions are disclosed.

The present application relates to a gene for regulating cholesterol metabolism and a micropeptide MP19 encoded thereby, and a use thereof, and also relates to a use of the micropeptide in the preparation of a drug or pharmaceutical composition for detecting, preventing, alleviating or treating diseases associated with abnormal cholesterol metabolism, said diseases comprising atherosclerosis, age-related macular degeneration, hyperlipidemia, non-alcoholic hepatitis, hepatocellular carcinoma, coronary heart disease, ischemic stroke, and obesity. By means of endogenous overexpression or exogenous synthesis of the micropeptide, diseases associated with abnormal cholesterol metabolism can be effectively prevented, alleviated, or treated.

The invention provides an application of PLAC8 as a detection target in preparation of a tumor diagnosis product, and relates to the technical field of biomedicine, the technical key points are as follows: the application of the PLAC8 as the detection target in preparation of the tumor diagnosis product and a tumor prognosis condition inspection product integrates three gallbladder cancer clinical queues, and has the advantages of high accuracy, high sensitivity and high reliability. By combining a cross-species model and technologies of multiple immunofluorescence, single cell RNA sequencing and the like, the PLAC8 is found to be a cross-species conservative M2 macrophage gene with significant difference. PLAC8 is abnormally enriched in gallbladder cancer tissues, and normal gallbladder epithelium is almost not expressed and can be stably detected through tumor tissues and peripheral blood. Expression of the gene is limited to a macrophage cluster, the gene is in positive correlation with M2 markers CD206 and CD163, and M2 polarization is promoted by regulating cholesterol metabolism. Clinical verifications show that increase of PLAC8 + CD163 + macrophages in tumors is an independent prognosis factor, high expression is closely related to short lifetime of patients and increase of chemotherapy non-response rate, and PLAC8 can be used as a potential biomarker for evaluating drug resistance of gallbladder cancer chemotherapy and tumor progression.

The invention discloses a germinated brown rice extract capable of remarkably improving cholesterol metabolism of liver as well as a preparation method and application of the germinated brown rice extract. The method comprises the following steps: soaking cleaned and disinfected brown rice in an inositol aqueous solution, and spraying the inositol aqueous solution with the same concentration during germination. And after germination is finished, drying and crushing the brown rice, adding a methanol aqueous solution, adding ascorbic acid with a certain concentration, performing ultrasonic extraction, centrifuging, and taking supernate to obtain a target extract. Compared with a conventional germinated brown rice alcohol extract, the prepared germinated brown rice extract has the advantages that the polyphenol enrichment effect is better, the polyphenol retention rate in the ultrasonic extraction process is higher, and the prepared extract can remarkably regulate liver cholesterol metabolism.

The invention relates to the field of adoptive immune cell therapy, in particular to a TCR-T cell preparation based on cholesterol metabolites and an immunotherapy. The invention provides application of 7-hydroxy-hydroxylated cholesterol in preparation of a product. The product at least has one of the following functions: 1) reducing the TCR signal level; 2) improving the memory cell proportion of T cells; 3) the tumor killing persistence of the T cells is improved; and 4) a cell preparation as TCR-T. The cholesterol natural metabolite 7a-HC is used for treating the T cells, the TCR signal level is reduced, and therefore the memory function of the T cells is enhanced, and the 7a-HC is an autometabolite and is safe and harmless. The 7a-HC is found to be capable of improving the memory cell proportion of T cells, so that the persistence of killing tumors is improved. The 7a-HC is used for further improving the solid tumor treatment effect in HBV antigen positive tumor treatment, and the 7a-HC can be widely applied to TCR-T cells by regulating the TCR signal level.

The invention discloses a production method and application of a bile acid and Chinese herbal medicine combined feed additive. The additive is prepared from the following raw materials in parts by weight: 30-50 parts of rhizoma alismatis, 15-25 parts of hawthorn, 10-20 parts of radix bupleuri, 5-15 parts of an artemisia apiacea extract, 2-8 parts of berberine, 5-15 parts of pericarpium citri reticulatae, 10-20 parts of poria cocos and 5-10 parts of liquorice. Based on the compatibility theory of'monarch, minister, assistant and guide 'of traditional Chinese medicine, various Chinese herbal medicine active ingredients such as rhizoma alismatis, hawthorn, radix bupleuri, artemisia apiacea extract, berberine, pericarpium citri reticulatae, poria cocos and liquorice are selected and scientifically formulated, all the ingredients are clear in division of labor and have a synergistic effect, the rhizoma alismatis serves as the monarch, and cholesterol metabolism is directly regulated and controlled; multi-target synergistic interaction of promoting bile acid synthesis, inhibiting inflammatory response, remodeling intestinal microecology, repairing intestinal liver circulation steady state and the like is realized, the action mechanism is clear, and the effect is superior to that of a single component or a simple mixture.

The invention discloses application of CH25H in treating intestinal cancer, and belongs to the field of disease treatment. The invention focuses on cholesterol metabolite 25-hydroxycholesterol (25HC), and aims to systematically clarify the key action mechanism of the cholesterol metabolite in macrophage metabolism reprogramming, TME remodeling and immunotherapy sensitization. The research not only clings to the leading edge of international tumor immunometabolism, but also provides a clear transformation direction for breaking through the bottleneck of colorectal cancer immunotherapy.

The invention belongs to the technical field of cholesterol metabolism model establishment, and particularly relates to a method for establishing a high-glucose induced loach cholesterol metabolism disorder model. According to the loach cholesterol metabolism disorder model establishing method, young loaches are domesticated with basal feed, and healthy loaches are obtained. The healthy loaches are fed with high-glucose induction feed every 8: 30-9: 30 and 15: 30-16: 30, breeding management is carried out, and the model loaches with the cholesterol metabolism disorder are obtained. Wherein the mass fraction of digestible carbohydrates in the high-glucose induction feed is 34%-40%. The content of AST, ALT, TBA, TG, CHOL, HDL-C and LDL-C in serum of a cholesterol metabolism disorder model loach and the content of TG and CHOL in liver of the loach have at least 16% difference compared with healthy loaches. The establishment method of the high-glucose-induced loach cholesterol metabolism disorder model is simple and convenient, has good repeatability and has important application significance.