20 results about "Lipotoxicity" patented technology

The invention discloses application of rutin hydrate in preventing and treating repeated embryo planting failure, and belongs to the technical field of assisted reproduction. It is found for the first time that CD36 is a key membrane protein for lipid transport and uptake of EECs, rutin hydrate competitively inhibits combination of CD36 and natural ligands of CD36, abnormal lipid excessive uptake is remarkably blocked, lipid accumulation and lipid toxicity damage in cells are effectively relieved, and the effect of inhibiting EECs lipid transport and uptake is achieved. And finally, the endometrial receptivity defect related to RIF is reversed, and the embryo adhesion and implantation capability is remarkably improved. Therefore, rutin hydrate provides a brand new strategy for developing targeted therapy drugs for RIF, especially for lipid metabolism disorder type endometrial receptivity badness, and has remarkable clinical application and transformation prospects.

The present invention relates to a composition for preventing, alleviating or treating metabolic diseases, the composition comprising a rosuvastatin and ursodeoxycholic acid conjugate or a pharmaceutically acceptable salt thereof, in which the statin conjugates to an ursodeoxycholic acid transporter and has the effects of function inhibition, cholesterol level reduction, antilipid toxicity, body weight reduction, blood lipid reduction, fatty liver alleviation, inflammation alleviation, and kidney damage alleviation. The composition, in the form of a single formulation, has the characteristics of maintaining the therapeutic effects of rosuvastatin and ursodeoxycholic acid while reducing the side effects of existing statins, and thus can be widely used as a substitute for complex formulations in the treatment of metabolic diseases.

The present disclosure relates to the use of an isolated or artificial ribonucleic acid sequence in any condition susceptible of being improved or prevented by modulating glucolipotoxicity, namely diabetes and obesity. The present disclosure further relates to a vector or a construct, a host cell, a pharmaceutical composition and / or a kit comprising said isolated or artificial ribonucleic acid sequence. The present disclosure further relates to an in vitro or ex vivo method for diagnosis or prognosis of diabetes.

The invention provides a culture medium for culturing heart tissue, a method for inducing diabetic cardiomyopathy disease phenotype in heart tissue, diseased heart tissue and a kit. An exemplary culture medium for culturing cardiac tissue comprises 100 to 300 M of palmitic acid / salt / ester, 100 to 300 M of oleic acid / salt / ester, and 0.5 to 15 nM of endothelin-1.

The invention provides a lipid nanoparticle. The lipid nanoparticle comprises a distearoyl phosphatidyl ethanolamine-polyethylene glycol derivative and a saturated fatty acid dimer as shown in a formula (I), wherein the mass ratio of the distearoyl phosphatidyl ethanolamine-polyethylene glycol derivative to the saturated fatty acid dimer is (10-30): (1-10). The saturated fatty acid dimer as shown in the formula (I) is delivered by adopting the distearoyl phosphatidyl ethanolamine-polyethylene glycol derivative, so that intracellular lipid accumulation and lipotoxicity effect can be induced, pyroptosis of tumor cells is promoted, systematic anti-tumor immune response is stimulated, and tumor growth is inhibited. More importantly, the lipid nanoparticles can enhance the sensitivity of liver cancer to PD-1 blocking treatment and significantly improve the combined treatment effect, no obvious toxic or side effect is observed, and the lipid nanoparticles show good clinical application prospects. (I).

The invention discloses a pancreatic cancer immunotherapy drug based on a DGAT1 target spot and application, and belongs to the technical field of biological medicine. The invention discloses an application mechanism of the DGAT1 as an inhibition target in immunotherapy of the drug-resistant pancreatic cancer for the first time, an immunosuppressive tumor microenvironment can be reversed by inhibiting the DGAT1, on the basis, a new pharmaceutical application of the DGAT1 inhibitor in preparation of pancreatic cancer immunotherapy drugs or immune checkpoint inhibitor sensitization drugs is provided, and the application of the DGAT1 inhibitor in immunotherapy of the pancreatic cancer is promoted. And efficient clinical transformation can be realized by new use of old medicines. The invention further provides a metabolism-immune dual-channel activation combined scheme, the DGAT1 inhibitor relieves TME lipid toxicity, the immune checkpoint therapeutic agent blocks T cell depletion signals, and the synergistic inhibition effect on tumor growth is achieved. The invention further provides a precise diagnosis and treatment integrated strategy, beneficial crowds are screened based on the DGAT1 expression level, and the objective remission rate can be remarkably increased by drug combination for the crowds.

The application discloses a method for relieving obesity cardiomyopathy lipid toxicity by Chemerin and belongs to the technical field of pharmacological research. Mice are selected to establish an obesity mouse model, and are equally divided into a control group, a high-fat diet group, an AAV CMKLR1 virus group, and a high-fat + AAV CMKLR1 virus group. In succession, mouse heart ultrasound, TSE system detection, glucose tolerance test, and insulin tolerance test are carried out, and mouse blood glucose is measured at intervals. Then, tissue protein is extracted for protein immunoblotting, and tissue RNA is extracted for reverse transcription, and then qPCR is used to detect the expression of related genes. After paraffin embedding and slicing of mouse tissues, HE, WGA, immunofluorescence and other pathological staining are carried out. MTBE method is used for lipid extraction and detection of lipid content. ELISA method is used to measure serum Chemerin, and Acyl-RAC method is used to detect protein palmitoylation. Finally, the experimental results are analyzed to draw a conclusion. The present application proves by clinical data and mouse models that Chemerin compensatorily increases in the process of obesity, and Chemerin can relieve cardiac lipid toxicity caused by obesity and protect cardiac function.

The invention relates to application of a lotus plumule extract in preparation of drugs for activating Rab5a / PPARalpha signal axis, promoting fatty acid oxidation and reducing myocardial lipid toxicity injury. Animal experiments verify that the plumula nelumbinis extract effectively inhibits abnormal weight growth, reduces fat deposition, reconstructs fatty acid oxidative metabolism steady state, improves myocardial lipid toxicity injury and maintains cardiac functions by activating Rab5a / PPARalpha signal axis, and the plumula nelumbinis extract is stable in extraction process, clear in mechanism, small in toxic and side effects and easy to popularize. The problem that existing lipid metabolism abnormity intervention medicine targets and components are single can be solved, and a new scheme is provided for medicine research and development of metabolic diseases.

This invention discloses the application of sodium mannoside in the preparation of drugs for treating obesity and non-alcoholic fatty liver disease (NAFLD). Studies in this invention show that sodium mannoside has the effects of controlling body weight, improving glucose and lipid metabolism, enhancing insulin sensitivity, improving glucose tolerance, and preventing NAFLD. It can be used to prepare therapeutic drugs for metabolic diseases such as obesity caused by a long-term high-fat diet. Sodium mannoside can protect obese mice from liver lipotoxicity caused by a high-fat diet, providing more effective drugs for the prevention and treatment of obesity and NAFLD.

The invention provides an application of dihydroberberine in preparation of a medicine for treating lipotoxic myocardial injury. The application proves that dihydroberberine can reduce inflammatory cell infiltration and / or fibrosis in heart tissues caused by myocardial cell lipid accumulation and lipotoxicity, and reduce myocardial cell death; and a novel medicine is provided for treating the lipotoxic myocardial injury.

The invention relates to the technical field of medicines, in particular to application of a carnitine and / or TGR5 inhibitor in preparation of a medicine for treating fatty liver diseases related to metabolic dysfunction. It is found that activation of TGR5 causes inhibition of carnitine biosynthesis, and then lipid metabolism of hepatocytes is affected. The expression of the BBOX1 protein is recovered through exogenous supplement of carnitine and a TGR5 inhibitor or gene therapy, lipid metabolism of liver cells can be effectively improved, and lipid toxicity and inflammatory response are reduced. A new thought is provided for the treatment of MASH, that is, the progress of diseases is prevented by recovering the lipid metabolism capability of hepatocytes instead of depending on anti-inflammatory or anti-fibrosis drugs.

The invention relates to a coumarin alkaloid compound extracted from fine-base pill roots as well as a preparation method and application of the coumarin alkaloid compound, and belongs to the technical field of medicines. The invention relates to five coumarin alkaloids which are extracted and separated from roots of Annonacea plant fine base pills ((Roxb.) Benth.et Hook.f.ex Bedd.), the structural mother nucleus of the compounds is 5H-chromeno [4, 3-b] pyridin-5-one, and the 7, 8, 9 and 10 sites of the ring are substituted by methoxy groups or hydroxyl groups, and the structural mother nucleus of the compounds is 5H-chromeno [4, 3-b] pyridin-5-one, the structural mother nucleus of the compounds is 5H-chromeno [4, 3-b] pyridin-5-one, and the structural mother nucleus of the compounds is 5H-chromeno [4, 3-b] pyridin-5-one. The method comprises the following steps: sequentially carrying out MCI column chromatography, silica gel column chromatography, ODS column chromatography and HPLC separation chromatographic methods on a fine-base pill root crude extract for separation and purification so as to finally obtain five coumarin alkaloids, and further relates to applications of the compounds in resisting metabolic disorder related fatty liver diseases (MASLD), resisting lipotoxicity and improving lipid accumulation.

The invention discloses schizochytrium limacinum polypeptide with a lipid metabolism regulating effect as well as a separation and purification method and application. The separation and purification method comprises the following steps: S1, preparing a schizochytrium limacinum protein suspension; s2, adjusting the schizochytrium limacinum protein suspension obtained in the step S1 to be neutral, adding neutral protease for hydrolysis, cooling after boiling, and hydrolyzing to obtain schizochytrium limacinum protein hydrolysate; s3, the schizochytrium limacinum protein enzymatic hydrolysate obtained in the step S2 is filtered through a membrane, polypeptide with the molecular weight being smaller than 3 kDa and the amino acid sequence being SEQ ID NO.1 is obtained, and the schizochytrium limacinum polypeptide with the lipid metabolism adjusting effect is obtained. According to the invention, accumulation of triglyceride (TG) and cholesterol (TC) in cells is effectively reduced, lipotoxicity stress is relieved, and efficient and low-toxicity candidate active molecules are provided for development of drugs for resisting fatty liver, reducing blood fat or treating metabolic syndrome.

This invention discloses a steroidal compound with anti-lipotoxicity and antioxidant activity, its preparation method, and its applications. The steroidal compound is β-sitosterol-3-β-O-glucopyranoside-6′-O-palmitate, with the structural formula shown below. The steroidal compound BSBD of this invention exhibits significant anti-lipotoxicity and antioxidant activity in a HepG2 cell model induced by the combined effects of free fatty acids and hydrogen peroxide, showing great promise for application in the preparation of drugs for the prevention or treatment of non-alcoholic steatohepatitis.

The invention provides a cell model based on palmitic acid induced hepatic lipid toxicity injury and a construction method thereof, and the construction method comprises the following steps: 1, carrying out cell culture, and culturing a HepG2 human liver cancer cell line to a logarithmic phase; 2, performing cell activity determination and palmitic acid (PA) treatment, and performing induction treatment on the HepG2 cells cultured in the step 1 by adopting PA with different concentrations; detecting the survival condition of the HepG2 cells treated by the PA; 3, observing the morphological change of the cells, and observing the morphological change of the HepG2 cells treated by the PA; 4, measuring ATP in the cells, and detecting the ATP content in the HepG2 cells after PA treatment; 5, measuring the ROS level of cell active oxygen, and detecting the ROS level in the HepG2 cell after PA treatment; and 6, carrying out molecular specific gene combination verification, carrying out cell total RNA extraction and real-time fluorescent quantitative PCR, extracting the total RNA of the HepG2 cell after PA treatment, and carrying out RT-PCR detection to complete the construction of the hepatic lipid toxicity injury cell model.

The invention relates to the field of biological medicine, in particular to application of paeoniflorin in preparation of a medicine for repairing pancreatic beta cell injury. The paeoniflorin has the effect of repairing the pancreatic beta cell injury, specifically, the paeoniflorin can repair the healing ability and migration ability of pancreatic beta cells under glycolipid toxicity (glycotoxicity and / or lipotoxicity), reduce oxidative stress caused by the pancreatic beta cell injury caused by the glycolipid toxicity, and repair the pancreatic beta cell injury by activating an HGF / c-Met pathway.

The invention provides siRNA of a targeted FASN gene, a compound and application of the siRNA and the compound, and belongs to the technical field of gene therapy drugs. A sense strand and an antisense strand of the siRNA of the targeted FASN gene have sequences as shown in SEQ ID No.1 and SEQ ID No.2; the sequences are as shown in SEQ ID No.3 and SEQ ID No.4, or the sequences are as shown in SEQ ID No.3 and SEQ ID No.4; the sequences are shown as EQ ID No.5 and SEQ ID No.6, or the sequences are shown as EQ ID No.5 and SEQ ID No.6; the siRNA can inhibit expression of FASN genes and reduce protein abundance of FASN in the liver, so that deposition of liver fat is reduced, lipid toxicity and inflammatory response are reduced, and accurate treatment of MAFLD is achieved. The siRNA provided by the invention is chemically modified, so that the stability of the siRNA is improved.

The invention discloses application of attapulgite in recovery of lysosome acidity and autophagy flux, and belongs to the field of nano biotechnology medicine. The invention finds that attapulgite can recover lysosome acidity decrease caused by lipotoxicity, chloroquine, lysosome inhibitors and the like and recover blocked autophagy flux. The invention finds that ATT can effectively regulate cytotoxicity of chloroquine and recover lysosome acidity decrease and blocked autophagy flow caused by chloroquine or lipotoxicity. Besides, ATT shows a remarkable treatment effect on lysosomal dysfunction related diseases such as NAFLD, lysosomal acidity and autophagy flow in a high-fat feeding induced NAFLD model can be recovered, lipid accumulation and liver biochemical indexes can be effectively reduced, and the tolerance of glucose can be improved. In addition, the activity of lysosome hydrolase can be increased, and degradation of mutant huntingtin is accelerated.

The invention discloses curcumin additive feed capable of relieving zebra fish liver lipid toxicity induced by iron overload and a preparation method of the curcumin additive feed. The feed comprises the following raw materials: casein, dextrin, corn starch, fish meal, gelatin, soybean oil, lysine, vitamin C phospholipids, monocalcium phosphate, choline chloride, sodium alginate, composite vitamins, iron-free mixed minerals, dimethyl beta-propiothetin, microcrystalline cellulose, ferrous sulfate heptahydrate and curcumin. The invention relates to a feed formula, in particular to a method for adding curcumin serving as a lipid-lowering agent into an iron overload feed so as to relieve liver lipid toxicity caused by the iron overload feed and maintain liver health. The feed disclosed by the invention not only has comprehensive and rich nutritional ingredients, can effectively promote fish growth and improve liver health, but also can regulate and control fish body lipid metabolism and remarkably reduce lipid deposition, so that the economic benefit and sustainability of aquaculture are improved.

This invention relates to the application of secretin in the preparation of drugs for treating steatohepatitis associated with metabolic dysfunction, belonging to the field of biomedical technology. This invention provides the application of secretin in the preparation of drugs for treating steatohepatitis associated with metabolic dysfunction. Cell model, gene knockout, in vivo complementation, and exogenous protein intervention experiments were conducted, revealing that secretin has significant in vitro and in vivo protective effects against steatohepatitis associated with metabolic dysfunction. In vitro, secretin can significantly improve oleic acid-induced lipid accumulation in hepatocytes, inhibit abnormal accumulation of lipid droplets in hepatocytes, reduce the expression of inflammatory factors in hepatocytes, alleviate hepatocyte inflammatory damage caused by lipotoxicity, and enter hepatocytes through endocytosis. It can alleviate high-fat diet-induced hepatic steatosis and inflammatory infiltration in MASH mice, and reduce the degree of liver fibrosis.