21 results about "Cholesterol synthesis" patented technology

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.

The application discloses application of a cholesterol synthesis enzyme in preparation of a product for enhancing killing function of CAR-T cells and derivatives thereof, wherein the cholesterol synthesis enzyme is SQLE or LSS, and the product enhances the killing function by separately knocking out SQLE or separately overexpressing LSS in the CAR-T cells and the derivatives thereof. The application significantly enhances the killing ability of the CAR-T cells and the derivatives thereof by knocking out a key enzyme SQLE in cholesterol synthesis or overexpressing LSS.

Disclosed in the invention are a type of compounds having activity of activating 5′-adenosine monophosphate-activated protein kinase (AMPK), a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for reducing fatty acid synthesis, for inhibiting triglyceride and cholesterol synthesis, for preventing and / or treating obesity and type II diabetes, for preventing and / or treating tumor, for preventing and / or treating Parkinson's disease, for preventing and / or treating Alzheimer's disease or for prolonging the lifespan of mammals:

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 provides a blood fat-reducing ganoderma lucidum spore powder pharmaceutical composition as well as a preparation method and application thereof, and belongs to the technical field of medicines. Comprising a ganoderma lucidum spore powder extract and a pharmaceutical composition, and the mass ratio of the ganoderma lucidum spore powder extract to the pharmaceutical composition is 10: (1-2); the pharmaceutical composition contains a simvastatin derivative and an apatamuron derivative. The prepared blood-fat-reducing ganoderma lucidum spore powder pharmaceutical composition adopts a mixed preparation of traditional Chinese medicine components and western medicine components, has complementary advantages, can quickly reduce cholesterol content and take effect quickly on one hand, can fundamentally inhibit cholesterol synthesis and improve metabolic disorder of hyperlipidemia on the other hand, and is small in side effect, high in patient compliance, good in effect and free of toxic and side effects on the other hand. Certain anti-inflammatory, anti-thrombotic and anti-tumor effects and the like are achieved, and the application prospect is wide.

This invention discloses a chemical-biological fusion method for cholesterol synthesis. Using plant-derived 21-hydroxy-20-methylpregn-4-en-3-one, also known as bis(2-hydroxy-2-yl)-3-one (BA), as a raw material, cholesterol is synthesized through a four-step reaction involving sulfonation, acetylation, enzymatic hydrolysis and reduction, and Grignard coupling. Addressing the drawbacks of traditional animal-derived cholesterol, which carries unpredictable risks of pathogenic bacteria and viruses, this invention uses plant-derived steroidal raw material BA to synthesize cholesterol. This method not only offers high safety, avoiding the risk of pathogenic bacteria and viral infections, but also utilizes the tandem catalysis of esterase and carbonyl reductase during synthesis, along with coenzyme regeneration, to obtain key intermediates with high stereoselectivity and in a safe and clean manner. This significantly shortens the cholesterol synthesis route, increases efficiency, simplifies operation, minimizes solvent recycling losses, reduces waste, and allows for mild reaction conditions. This method is safe, economical, and suitable for industrial production.

The present application relates to the field of organic synthesis, in particular to a kind of method for catalytic hydrogenation of cholesterols to synthesize dihydrocholesterol, with cholesterols as raw material, hydrogen donor, Pd / CuO-Al2O3 Catalyst occurs hydrogenation and generates dihydrocholesterol, the present application avoids directly using hydrogen as raw material, safety is good, meets the trend of green chemical industry, and reaction condition is mild, reaction temperature is low, reaction time is short, with good industrial production application prospect.

This invention discloses a genetically engineered strain of *Saccharomyces cerevisiae* and its application in cholesterol synthesis. The strain was obtained through multiple genetic engineering steps, starting with *Saccharomyces cerevisiae* SquP1: DHCR24 gene was integrated at the YPL062W site to achieve 7-dehydrocholesterol synthesis; the ERG6 promoter was replaced with the ERG7 promoter and the DWF5 gene was integrated to achieve cholesterol synthesis; the TGL3, TGL4, and ROX1 genes were knocked out to enhance cholesterol accumulation; the FLX1 and ZWF1 genes were integrated to strengthen cofactor supply; the HXK1 promoter was replaced and the ERG11 gene was integrated to optimize the synthesis pathway; and auxotrophic genes were reintroduced to obtain the CC37N strain. This strain achieved a maximum yield of 6.23 g / L in a 5L bioreactor fermentation, providing an excellent strain for efficient cholesterol biosynthesis.

The application discloses simvastatin-beta-cyclodextrin nanoparticles and a preparation method and application thereof, and belongs to the technical field of biological medicines, wherein the simvastatin-beta-cyclodextrin conjugate has active oxygen responsiveness, comprises an ester bond connection structure formed by a beta-cyclodextrin hydroxyl group, a thio-ketone connection unit and a simvastatin hydroxyl group, and the thio-ketone connection unit is a thio-ketone dicarboxylic acid residue formed by condensation of 3-mercaptopropionic acid and acetone; the simvastatin-beta-cyclodextrin conjugate can self-assemble to form simvastatin-beta-cyclodextrin nanoparticles. The active oxygen responsive simvastatin-beta-cyclodextrin conjugate provided by the application can dissociate in an oxidative stress related environment, realizes double-path cholesterol homeostasis regulation functions of inhibiting cholesterol synthesis and promoting cholesterol efflux, reduces the degree of macrophage foam, and further reduces the lipid load of an atherosclerotic plaque.

The application discloses a traditional Chinese medicine composition with lipid-lowering efficacy, Quling Huatu granules and a preparation method thereof, and belongs to the technical field of Chinese patent medicines. The traditional Chinese medicine composition comprises the following components in parts by weight: 5-10 parts of red yeast rice, 10-30 parts of poria cocos, 5-15 parts of atractylodes, 5-15 parts of dried ginger and 5-15 parts of costus. The atractylodes, the poria cocos and the costus in the application can dispel cold, invigorate the spleen, warm the middle and harmonize the stomach, so that the qi of the spleen and stomach runs smoothly. Meanwhile, the Quling Huatu granules contain statin components, can inhibit the synthesis of excessive cholesterol in the body, increase the synthesis of low-density protein receptors, reduce the blood cholesterol and low-density protein cholesterol levels, prevent the further development of cardiovascular diseases, and also do not cause problems such as liver and kidney function damage and gastrointestinal discomfort.

The invention discloses a Pinellinoic acid derivative shown in a general formula (I) (the specific substituent definition is shown in the specification), a pharmaceutical composition with the Pinellinoic acid derivative as an active component, a preparation method of the compound and application of the Pinellinoic acid derivative in preparation of drugs for inhibiting cholesterol synthesis activity and drugs for treating non-alcoholic fatty liver diseases. Belongs to the technical field of medicines. Pharmacological test results indicate that the Songlinolenic acid derivative has good sterol ester de novo synthesis and fatty acid de novo synthesis inhibitory activity. The compound can be used as a novel high-efficiency sterol lipid synthesis inhibitor, can be used for treating diseases related to sterol lipid metabolism, and has a good application prospect.

The invention belongs to the technical field of microorganisms, and in particular relates to lactobacillus helveticus IOB726 with an effect of reducing blood fat as well as a segmented fermentation preparation method and application of the lactobacillus helveticus IOB726. The invention discovers that the lactobacillus helveticus IOB726 has the effect of reducing blood fat for the first time. The lactobacillus helveticus IOB726 bacterial powder and the preparation thereof are prepared by adopting segmented liquid state fermentation for the first time, not only is the bacterial activity improved, but also an inulin component is added into a second-stage fermentation culture medium, so that a carbon source is provided for the growth of the lactobacillus helveticus IOB726, and the lactobacillus helveticus IOB726 is promoted to generate short-chain fatty acid in the fermentation metabolism process; the liver cholesterol synthesis can be inhibited, so that the hyperlipemia symptom can be improved. Besides, experimental results show that the lactobacillus helveticus IOB726 has an efficient blood fat reducing effect, has good acid resistance, bile salt resistance and gastrointestinal tract simulation tolerance, can play a role in human intestinal tracts, supplements strain resources of blood fat reducing probiotics, and shows a better blood fat reducing effect.

This invention discloses a genetically engineered strain of *Kluyveromyces martensii* and its applications, belonging to the field of bioengineering technology. The invention discloses a genetically engineered *Kluyveromyces martensii* strain, firstly obtained through screening a strain that produces high levels of ergosterol; based on this, it induces and isolates... Eye A haploid strain was constructed and then metabolically optimized through the introduction of heterologous DHCR24 and DWF5 genes, weakening of the competitive pathway gene ERG6, increasing the metabolic flux of the post-squalene pathway during sterol synthesis, peroxisome compartmentalization engineering of the mevalonate pathway, knockout of the hypoxia-inhibiting transcription factor ROX1, improved cofactor supply, and optimization of the yeast lipid pathway, resulting in a high-cholesterol-producing engineered strain. Through fed-batch fermentation, efficient and stable cholesterol synthesis was achieved, with a yield of 7.64 g / L, laying the foundation for cholesterol biomanufacturing.

The invention relates to the technical field of biological medicines, in particular to a medicine for synchronously improving polycystic ovarian syndrome hyperandrogenemia and lipid metabolism disorder, which takes a specific anti-ACBP neutralizing antibody as an active ingredient and plays a role by blocking two key pathological pathways mediated by ACBP: 1, blocking the interaction between ACBP and a transcription factor SREBP2 / HNF-4alpha, and 2, blocking a transcription factor SREBP2 / HNF-4alpha; the expression of a cholesterol synthesis rate-limiting enzyme HMGCR / HMGCS1 is down-regulated, and androgen synthesis substrates are reduced from the source; and secondly, the interaction between ACBP and mitochondrial transport protein TSPO / StAR is blocked, and the transport of cholesterol into mitochondria is inhibited, so that the generation of testosterone is reduced. The medicine can synchronously and remarkably reduce the serum testosterone level of a PCOS model animal, improve the polycystic form of an ovary and reduce the body weight, total cholesterol and low-density lipoprotein (LDL) level.

The invention discloses an application of cholesterol synthetase in preparation of a product for enhancing the killing function of CAR-T cells and derivatives thereof, the cholesterol synthetase is SQLE or LSS, and the product enhances the killing function by separately knocking out the SQLE or separately overexpressing the LSS in the CAR-T cells and the derivatives thereof. According to the application, a cholesterol synthesis key enzyme SQLE is knocked out or LSS is overexpressed, so that the killing ability of CAR-T cells and derivatives thereof is remarkably enhanced.

The invention relates to the technical field of organic synthetic chemistry, in particular to a method for synthesizing 7-dehydrocholesterol from cholesterol. Comprising the following steps: dissolving cholesterol in a first solvent, adding cyclohexanone and aluminum isopropoxide, and carrying out an Oppenauer oxidation reaction to obtain an intermediate 1; dissolving the intermediate 1 in a second solvent, sequentially adding isopropenyl acetate and p-toluenesulfonic acid, and carrying out first acetylation reaction to obtain an intermediate 2; dissolving the intermediate 2 in a third solvent, and carrying out an upper debromination reaction to obtain an intermediate 3; and dissolving the intermediate 3 in a fourth solvent, then adding 2, 4, 6-trimethylpyridine and acetyl chloride as reaction accelerators, carrying out a second acetylation reaction to obtain an intermediate 4, and carrying out a reduction reaction and purification on the intermediate 4 to obtain the 7-dehydrocholesterol. The 7-dehydrocholesterol is synthesized by the method, the total synthesis yield exceeds 60%, the product purity is 98% or above, and the method is easy to amplify for industrial synthesis.

The invention relates to the field of organic synthesis, in particular to a method for synthesizing dihydrocholesterol by catalytically hydrogenating cholesterol, cholesterol is used as a raw material, hydrogenation reaction is performed in the presence of a hydrogen donor and a Pd / CuO-Al2O3 catalyst to generate dihydrocholesterol, direct use of hydrogen as the raw material is avoided, safety is good, the green chemical industry trend is met, reaction conditions are mild, and the method is suitable for industrial production. The reaction temperature is low, the reaction time is short, and the industrial production application prospect is good.

The invention discloses a construction method and application of a fetal-derived hypercholesterolemia animal model. The fetal-derived hypercholesteremia animal model is characterized in that 20 mg / kg of aspirin with a clinical dose is given to rodents (such as Kunming mice) through oral intragastric administration in the middle and late pregnancy periods (such as 9-18 pregnancy), and typical hypercholesteremia appears after high-fat diet is given to male filial generations 8-12 weeks after the male filial generations are born. Based on mice exposed by aspirin during pregnancy, ascorbic acid is externally supplemented to maternal bodies during pregnancy, so that the liver cholesterol synthesis function and the blood cholesterol level of offspring can be effectively reduced. Therefore, the established fetal hypercholesterolemia animal model has the characteristics of novelty, reliability and simplicity and convenience in operation, meanwhile, the effect of reversing the susceptibility of offspring hypercholesterolemia by supplementing ascorbic acid to the maternal body is found, and a new thought and a new technology are provided for early prevention and treatment of fetal hypercholesterolemia.

The present invention has been made in view of the conventional demand for clear elucidation of the mechanism of action as to whether or not the total cholesterol amount in the plasma and liver is reduced, and the present invention produces inhibitors containing 3, 5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient, and provides inhibitors that exhibit an excellent effect of acting on HMGCR via SREBP2 and suppressing and inhibiting the cholesterol synthesis pathway itself.SOLUTION: The present invention is characterized by containing 3, 5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient, which acts on HMGCR via SREBP2 to suppress and inhibit the cholesterol synthesis pathway.SELECTED DRAWING: Figure 1

[Problem] The present invention has been made in response to the need to elucidate the mechanism of action underlying a previously confirmed reduction in plasma and liver total cholesterol levels. The present invention relates to producing and providing an inhibitor that contains 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient and is highly effective for directly suppressing and inhibiting a cholesterol synthesis pathway by acting on HMGCR via SREBP2. [Solution] The present invention is characterized by having suppressive and inhibitory effects on a cholesterol synthesis pathway on the basis of the action of 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient on HMGCR via SREBP2.

The invention relates to an application of a signal regulation method based on non-classical Hippo in diseases caused by RIPK4 inactivation mutation. YAP / TAZ is activated in a manner of knocking out RIPK4, phenotypes of diseases caused by RIPK4 inactivation mutation are successfully simulated, expression or activity of YAP / TAZ is respectively inhibited in a manner of knocking down, knocking out YAP / TAZ or overexpressing RIPK4, and drugs for treating or relieving diseases caused by RIPK4 inactivation mutation are developed by aiming at inhibiting YAP / TAZ gene expression or activity. In addition, abnormal expression of a group of cholesterol synthesis genes (Fdft1, Mvd, Cyp51 and Nsdhl) is found; therefore, YAP / TAZ with deregulated activity and cholesterol synthesis genes with abnormal expression can be used as diagnostic markers, and the YAP / TAZ gene can also be used as a therapeutic target.