109 results about "Steatohepatitis" patented technology

The present invention relates to methods of treating metabolic dysfunction-associated steatohepatitis (MASH) in a human subject, comprising administering to the subject a therapeutically effective amount of indeglitazar or a pharmaceutically acceptable salt thereof.

The invention discloses a Parabacteroides goldsteinii bacterium and application of a metabolite of the Parabacteroides goldsteinii bacterium in treatment of metabolism-related steatohepatitis and fibrosis related to the metabolism-related steatohepatitis. According to the application disclosed by the invention, firstly, through biological analysis, the fact that Parabacteroides goldsteinii and a metabolite 7-Sulfocholic acid of Parabacteroides goldsteinii are closely related to the progress of MASH related fibrosis is determined; furthermore, functional intervention is implemented in a CDAHFD model, the MASH and the related fibrosis process of the MASH can be remarkably inhibited by supplementing Parabacteroides goldsteinii or 7-Sulfocholic acid, the MASH and the related fibrosis process of the MASH can be relieved, liver fatty degeneration, inflammatory infiltration and collagen deposition can be relieved, and further conversion and application feasibility can be achieved.

The invention provides a nano-phase penthorum chinense pursh extract, which is prepared by the following steps: soaking a penthorum chinense pursh medicinal material, decocting, filtering, collecting filtrate, carrying out layering centrifugation to remove precipitate, dialyzing supernate by adopting a dialysis bag with the molecular weight cutoff of 3.5 kDa, and freeze-drying dialysate to obtain the nano-phase penthorum chinense pursh extract. The invention further provides a preparation method and application of the nanometer phase-state penthorum chinense pursh extract. The invention provides an extraction method capable of accurately separating 50-200nm phase-state active components in a nanometer phase-state penthorum chinense pursh extract traditional Chinese medicine. Organic solvents are prevented from being used, and the safety of extracted products is improved; the purity of the target component is improved; the structural integrity of a natural nanometer phase state is kept; the obtained nanometer phase-state extract has the effects of remarkably improving metabolic dysfunction related steatohepatitis and resisting coagulation, is high in separation efficiency, can be completed in 2-3 days, and can be applied on a large scale; the equipment is simple and low in cost.

The application discloses a tripterine self-assembled nanoparticle microsphere, a preparation method and application thereof, and belongs to the technical field of biological medicines. The tripterine self-assembled nanoparticle microsphere takes tripterine self-assembled nanoparticles as a drug core, is formed by cross-linking of a sodium alginate-pectin composite carrier through calcium ions, can significantly improve drug solubility, realizes stable protection and intestinal targeting rapid release in the gastrointestinal tract, and effectively reduces drug systemic exposure and side effect risks. The preparation process is mild and simple, the obtained preparation has high targeting and safety. Pharmacodynamic results show that the microsphere can obviously improve liver steatosis, inflammation and fibrosis related to metabolic-related fatty liver hepatitis, and has better curative effect than conventional preparations. The application provides a novel oral delivery system for preventing and treating metabolic-related fatty liver hepatitis, and has good industrial and clinical transformation prospects.

Despite the high prevalence and serious clinical implications of metabolic associated steatohepatitis (MASH) in patients with type 2 diabetes (T2D), MASH is usually overlooked in clinical practice, due to the lack of accurate biomarkers. The inventors evaluated the ability of plasma large extracellular vesicles (lEVs) to serve as noninvasive biomarkers for the diagnosis of MASH, in particular in T2D patients. Proteomic analysis identified Transferrinreceptor on lEVs (TFRC-lEVs) as associated with MASH. The inventors thus measured TFRC- lEVs on plasma samples from patients included in the derivation cohort. The proportion of patients with TFRC-lEVs concentration > 61 ng / mL was significantly higher in patients with MASH than in those with steatosis. TFRC-lEVs > 61 ng / mL remained associated with MASH after adjustment on either usual laboratory variables, or on the NASH-Test or on the Fibroscan FAST-score. When combining TFRC-lEVs with available methods the population suspected of having MASH was 32% and 29%, versus 22% and 16% for NASH-test or FAST score alone, without decreasing specificity. In conclusion, TFRC-lEVs, a marker of hepatocyte ballooning, is a promising biomarker for MASH. It could be used for patients' screening to enlarge recruitment of patients with MASH in clinical trials.

The invention discloses application of serum MSTN (myostatin) as a marker in preparation of a metabolism-related steatohepatitis diagnosis product, and belongs to the technical field of biomedical detection. The biomarker for noninvasive diagnosis of the metabolism-related steatohepatitis is serum myosostatin MSTN, and the biomarker can be used as a detection target for preparing a noninvasive diagnosis product of the metabolism-related steatohepatitis. As an independent biomarker, the MSTN is higher in diagnosis efficiency in AST normal patients; the MSTN and the ALT or the AST are jointly applied, so that the specificity and the positive predictive value (PPV) of single use of the ALT or the AST can be improved, the misdiagnosis rate of the ALT or the AST can be reduced, non-MASH patients can be more accurately excluded, and unnecessary, invasive or expensive subsequent examinations are reduced.

The invention belongs to the field of pharmaceutical preparations. The invention relates to lipid nanoparticles modified by probiotic coupled galactose and coated with diammonium glycyrrhizinate, L-arginine and copper tannic acid nano enzyme as well as a preparation method and application of the lipid nanoparticles. The lipid nanoparticles prepared by coupling and wrapping the diammonium glycyrrhizinate, the L-arginine and the copper tannic acid nano-enzyme with the probiotics have good biocompatibility, the preparation method is simple, the particle size distribution of the nanoparticles is uniform, the half-life period of a medicine circulating in a body can be prolonged, the inherent beneficial functions of the probiotics are cooperated, and the bioavailability of the medicine is improved. The potential application value is realized in the fields of treating the metabolic dysfunction related steatohepatitis and the like.

Provided is a polynucleotide including a nucleotide sequence encoding a vestigial like 4 protein and a cis-regulatory element that controls hepatocyte-specific expression of the sequence encoding a vestigial like 4 protein. Also provided is a viral vector including the polynucleotide, and a cell or organism transfected by the polynucleotide. Also provided is a method of treating steatohepatitis, obesity, hyperglycemia, diabetes, insulin resistance, liver inflammation, or decreasing white adipose tissue in the subject. Also provided is a method of screening a treatment for fatty liver disease or prevention of cirrhosis, comprising feeding a diet high in fat, fructose, and / or cholesterol to a transgenic animal having an hepatocyte-specific vestigial like protein gene disruption, administering the treatment to the transgenic animal, and detecting a difference in liver morphology or liver function between the transgenic animal and a control animal.

The present disclosure is directed to a method of monitoring treatment of metabolic dysfunction-associated steatohepatitis (MASH) in a patient by initiating a treatment by administering Compound 1: (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof to the patient, determining percentage increase in the level of SHBG from baseline, and continuing administration of Compound 1 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof to the patient if the percentage increase in the level of SHBG is at least 50% from baseline.

The invention belongs to the field of medicine, and relates to a Keap1 degradation agent and a preparation method and application thereof, the Keap1 degradation agent is a compound shown in the formula I or pharmaceutically acceptable salt, optical isomer, stereoisomer or metabolite of the compound, and further, the invention further discloses application of the compound and a pharmaceutical composition of the compound in preparation of a medicine serving as the Keap1 degradation agent, and application of the Keap1 degradation agent in preparation of the medicine serving as the Keap1 degradation agent in preparation of the medicine serving as the Keap1 degradation agent in preparation of the medicine serving as the Keap1 degradation agent. The compound can be used for treating metabolic diseases, cardiovascular diseases, rheumatoid arthritis or steatohepatitis.

The invention is concerned with a Desulfovibrio species, preferably Desulfovibrio piger or relative thereof for use in preventing and / or treating hepatic steatosis, particularly metabolic dysfunction-associated steatotic liver disease (MASLD) and / or metabolic dysfunction-associated steatohepatitis (MASH). Said Desulfovibrio species may be combined with at least one Eubacterium species or Anaerobutyricum species, preferably Anaerobutyricum soehngenii or relative thereof.

The invention discloses an adeno-associated virus overexpressing GPR110 and application of the adeno-associated virus in preparation of a medicine for treating metabolism-related steatohepatitis. The adeno-associated virus comprises a GPR110 gene sequence encoded and operably connected to a liver specific promoter TBG, an in-vivo experiment is carried out in a constructed MASH mouse model, and the result shows that the expression of the GPR110 gene in the liver tissue of the MASH mouse model is reduced, so that the GPR110 gene can be used as a biomarker and a therapeutic target of MASH, and the application of the GPR110 gene in the MASH mouse model is proven. According to the present invention, the MASH-related symptoms can be significantly improved through the AAV adeno-associated virus targeting liver specific overexpression GPR110, wherein the MASH-related symptoms comprise liver triglyceride content reducing, liver injury relieving, liver inflammation improving and liver fibrosis improving; the AAV-mediated GPR110 overexpression can effectively improve the MASH pathological process, and new intervention drugs and means can be provided for MASH treatment.

The application belongs to the technical field of biological medicine and molecular biology, and particularly relates to a CAR-macrophage with enhanced efferocytosis targeting apoptotic cells and a preparation method and application thereof. The CAR provided by the application comprises a signal peptide segment, a ligand recognition domain, a tag gene, a hinge region, a transmembrane region and an intracellular signal domain, can recognize lipid or protein signals exposed on the surface of apoptotic cells in an inflammatory microenvironment, and realizes targeted phagocytosis and aggregation in an inflammatory area. DKP type unsaturated ionizable lipids have protonation characteristics in an acidic microenvironment, which helps mRNA encapsulation and endosome escape. Lipid nanoparticles contain CAR mRNA and can respond to broken surface ligands. Under inflammatory conditions, the ligands fall off to expose DOPS, thereby improving the endocytosis capacity of macrophages. The CAR-macrophage and the nanoparticles can be used to prepare drugs for treating diseases such as metabolic-associated fatty liver disease and atherosclerosis, realize multiple synergies, have high specificity and safety, and have good industrialization prospects.

The invention relates to application of guaiacol or a derivative thereof in preparation of a medicine for preventing or treating metabolic syndrome, and belongs to the technical field of medicines. The guaiacol and the derivative thereof provided by the invention have the advantages that by regulating a fat metabolism pathway, the insulin resistance condition is obviously improved, the inflammatory response and oxidative stress injury are relieved, and the prevention and treatment on the metabolism-related fatty liver disease (MASLD), hyperlipidemia, hypercholesteremia, obesity and diabetes mellitus are realized through the synergistic effect of multiple dimensions.

The present invention relates to RNAi constructs for reducing expression of the CNR1 gene. Methods of using such RNAi constructs to reduce visceral adiposity and treat or prevent obesity and obesity-related conditions, such as type 2 diabetes, fatty liver disease, steatohepatitis, and cardiovascular disease, are also described.

The application relates to application of guaiacol or a derivative thereof in preparation of a medicine for preventing or treating metabolic syndrome, and belongs to the technical field of medicines. The guaiacol and the derivative thereof provided by the application can significantly improve insulin resistance conditions by regulating a fat metabolism channel, and can simultaneously reduce inflammatory reaction and oxidative stress damage, and can realize prevention and treatment of metabolic associated steatohepatitis (MASLD), hyperlipidemia, hypercholesterolemia, obesity and diabetes through synergistic action in multiple dimensions.

Described herein are small interfering RNA (siRNA) molecules and their use in methods and pharmaceutical compositions for inhibiting the expression of EF-hand domain-containing protein 1. Also, described herein are the use of said siRNA molecules in the treatment of metabolic liver disease, metabolic dysfunction-associated steatotic liver disease, or steatohepatitis, and reduces Ca2+-induced mitochondrial fission.

The present invention relates to GLP-1 / GIP / GCG triple receptor agonists and their use in the treatment or prevention of type 2 diabetes (T2DM), hyperlipidemia / dyslipidemia, metabolic syndrome, metabolic dysfunction-related fatty liver disease (MASLD), metabolic dysfunction-related steatohepatitis (MASH), neurodegenerative disorders, fibrosis, cardiovascular risk and / or obesity.

The present application relates to a kind of PLOD2 gene and / or protein as biomarker in the application of preparation auxiliary MASH detection kit.It is also provided that the reagent for detecting the expression amount of PLOD2 in sample is applied to the preparation of auxiliary detection MASH detection kit.The present application finds that the content of PLOD2 in the plasma exosome of patient with metabolic dysfunction-related steatohepatitis is up-regulated, suggesting that the plasma or serum exosome rich in PLOD2 can be used as a new non-invasive biomarker, which can be used for early diagnosis and early treatment of auxiliary MASH patient, and for the progress research and drug research of MASH.

A method of monitoring steatotic liver disease and / or steatohepatitis in a subject comprises assessing mitochondrial bioenergetics reserve in hepatocytes from the subject, and determining that the steatotic liver disease and / or steatohepatitis status of the subject by comparing mitochondrial bioenergetics reserve to a. reference. A method of monitoring treatment of steatotic liver disease and / or steatohepatitis in a subject comprises administering a neurotensin inhibitor to the subject, and determining that the steatotic liver disease and / or steatohepatitis sta tus of the subject by comparing mitochondrial bioenergetics reserve to a reference. A method of prophylactic or therapeutic treatment of steatotic liver disease and / or steatohepatitis comprises identifying a. subject at risk of or having steatotic liver disease and / or steatohepatitis, and administering a neurotensin inhibitor. In some embodiments, the subject is identified as being at risk of or having steatotic liver disease and / or steatohepatitis by comparing mitochondrial bioenergetics reserve in hepatocytes from the subject to a reference.

The invention relates to compounds of formula (I), wherein R1 is selected from the group consisting of H, C1-3-alkyl, C1-3-haloalkyl, -CH2-CO-NH2, -CH2-CO-NHCH3 and -CH2-CO-N(CH3)2 R2 is selected from the group consisting of H, halogen, (C1-3)-alkyl and halo-(C1-3)-alkyl, R3 is selected from the group consisting of C1-3-alkyl, five- or six-membered heterocyclic ring with 1 to 3 heteroatoms selected from N, O, S or SO2 and a five- or six-membered carbocyclic ring, wherein R3 is substituted by one or two substituents R8 which are each independently selected from the group consisting of H, C1-3-alkyl, -CO-O-(C1-4-alkyl), halogen, CN, OH, O-C1-3-methyl and -CO-(C1-3-alkyl), wherein each V, U, Q and T are independently from each other selected from C or N, wherein R4 is selected from the group consisting of H, halogen, -methyl, -O-C1-3-haloalkyl and -C1-3-haloalkyl, wherein R5 is selected from H, halogen, methyl, -O-C1-3-haloalkyl and -C1-3-haloalkyl, wherein R6 is selected from H, halogen, methyl, -O-C1-3-haloalkyl and -C1-3-haloalkyl, wherein R7 is selected from H, halogen, methyl, -O-C1-3-haloalkyl and -C1-3-haloalkyl, and pharmaceutical acceptable salts thereof, for the treatment of diseases such as systemic lupus erythematosus, systemic sclerosis (SSc), interferonopathies, metabolic dysfunction associated Steatohepatitis (MASH), interstitial lung disease (ILD), decompensated liver cirrhosis and idiopathic pulmonary fibrosis (IPF).

The invention discloses an application of NMT2 and an inhibitor alkannic acid thereof in treatment of metabolic dysfunction related steatohepatitis, and belongs to the technical field of medicines and disease treatment. The invention provides application of NMT2 as a target spot in preparation or screening of drugs for treating metabolic dysfunction related steatohepatitis. The invention further provides application of the reagent for specifically inhibiting the NMT2 in preparation of the medicine for treating the metabolic dysfunction related steatohepatitis. The reagent for specifically inhibiting the NMT2 comprises alkannic acid. Experiments prove that NMT2 gene knock-down can significantly relieve the progress of MASH in mice; the alkannic acid obtained through screening is an efficient specific inhibitor of NMT2, the protection effect of the alkannic acid depends on an NMT2 target spot, and the accuracy and the treatment potential of the alkannic acid serving as the inhibitor are proved. In conclusion, the invention provides a new target and a specific inhibitor for prevention and treatment of MASH, and has important clinical application value.

The present invention relates to extracellular vesicles having FGF21 linked to the surface thereof, and use thereof. The extracellular vesicles according to one embodiment can alleviate steatosis, reduce inflammation and fibrosis, and alleviate a decrease in bone density, which is a side effect occurring when FGF21 is used alone, and thus can be effectively used for preventing and treating liver diseases including metabolic abnormality-related steatohepatitis.

The invention belongs to the technical field of medical risk assessment, and provides a fibrosis metabolism related steatohepatitis risk assessment system. Comprising a data acquisition module configured to determine candidate prediction indexes; the primary screening module is configured to perform single-factor logistic regression analysis on the candidate prediction indexes to determine key prediction indexes of fibrosis metabolism related steatohepatitis; the secondary screening module is configured to screen out four independent predictive factors from key predictive indexes of fibrosis metabolism related steatohepatitis through stepwise multiple regression analysis; and the model training module is configured to train the constructed multi-factor logistic regression model based on the screened four independent predictive factors. According to the method, four indexes of aspartate transaminase, alanine transaminase, triglyceride and high-density lipoprotein cholesterol are integrated, a fibrosis MASH evaluation and prediction model for obese people is constructed, and the evaluation performance is better.

This invention belongs to the field of biomedical inorganic nanomaterials technology, and discloses a copper-doped bioglass and its application in the treatment of chronic liver injury and hepatic osteodystrophy. The bioglass is prepared by a sol-gel method, with copper as a dopant (Cu). 2+ It is doped in a form with a doping amount of 0.1-5 wt%, has a mesoporous structure, a particle size of approximately 163 nm, and can slowly release Cu in environments with pH 7.4 or 5.5. 2+ The treatment duration is 48-96 hours. This invention is the first to use the aforementioned material for the simultaneous treatment of chronic liver injury (such as metabolic-associated steatohepatitis) and its secondary hepatic osteopathy, achieving liver-targeted therapy via intravenous injection. Its mechanism of action includes: regulating glucose and lipid metabolism in the liver, enhancing mitochondrial function, and inhibiting inflammation and fibrosis; simultaneously upregulating the liver-derived factor LCAT, promoting osteogenic differentiation via the liver-bone axis, thereby synergistically improving liver injury and bone loss. This invention overcomes the limitations of separate liver and bone treatment, providing a safe and effective integrated treatment strategy.

The application discloses application of a benzofuro[3,2-c]quinolinone compound in preventing and treating metabolic dysfunction related steatohepatitis. The compound P82, i.e. 3,8-dihydroxybenzofuro[3,2-c]quinolin-6(5H)-one, is prepared through synthesis and purification of an intermediate, and can obviously improve liver steatosis, inflammatory infiltration and fibrosis in a metabolic dysfunction related steatohepatitis model induced by HFHC, thereby effectively delaying the progress of metabolic dysfunction related steatohepatitis. Meanwhile, the compound can improve lipid accumulation of liver cells induced by oleic acid and palmitic acid, and is expected to be developed into a new drug for preventing and treating metabolic dysfunction related steatohepatitis.

The present invention relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one lipid lowering agent (e.g., PPAR-alpha agonist, PPAR-delta agonist, PPAR-alpha and delta dual agonist, and / or statin). Also disclosed is use of the combination for the treatment or prevention of a FXR mediated disease or condition, such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), portal hypertension, bile acid diarrhea, NAFLD (nonalcoholic fatty liver disease), NASH (non-alcohol-induced steatohepatitis), and other chronic liver diseases. The combination of the present invention is useful for the treatment or prevention of conditions related to elevated lipid and liver enzyme levels. The present invention also relates to packs or kits including the pharmaceutical combination.

The present application relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating metabolic-related fatty hepatitis and a microbial fermentation method, The present application provides a traditional Chinese medicine composition for treating metabolic-related fatty hepatitis, which comprises the following components by weight: 10-30 parts of Rhodobryum gigantum, 5-15 parts of Smilax riparia, 5-15 parts of Sarcandra glabra, and 3-10 parts of dragon's blood; the traditional Chinese medicine composition is prepared by microbial fermentation of the above components. The present application combines Rhodobryum gigantum, Smilax riparia, Sarcandra glabra and dragon's blood to enhance the therapeutic effect of the traditional Chinese medicine composition on metabolic-related fatty hepatitis, and can significantly enhance the therapeutic effect on metabolic-related fatty hepatitis through multi-target and multi-pathway synergistic action. Furthermore, the present application uses microbial fermentation of the above components to obtain a traditional Chinese medicine composition fermentation product, which increases the content of effective components and enhances the efficacy, and has synergistic effects such as improving metabolic abnormalities, reducing adverse reactions, and improving taste.

The present application discloses the use of FGF21 / GLP-1 fusion proteins in the preparation of a medicament for preventing and / or treating at least one of type 2 diabetes, obesity, steatohepatitis, and triglyceridemia. The FGF21 / GLP-1 fusion proteins of the present application are effective in treating at least one of type 2 diabetes, obesity, steatohepatitis, and triglyceridemia, and in particular, can reduce at least one of HbA1c, blood glucose, body weight, liver fat content, ALT, AST, glutamyl transpeptidase, triglyceride, total cholesterol, low-density lipoprotein cholesterol, or increase at least one of adiponectin, insulin sensitivity, and beta-cell function in the subject.

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, ester, stereoisomer, tautomer, solvate, hydrate, or combination thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).