161 results about "Steatohepatitis" patented technology

The present invention relates to the use of a pharmaceutical composition in the form of extended-release tablets containing Pirfenidone for treating NAFLD / NASH and advanced liver fibrosis by decreased serum cholesterol and triglycerides as well as reducing the content of hepatic fat accumulation, both in the form of macrosteatosis and microsteatosis. Additionally, its use as an agonist for PPARgamma (peroxisome proliferation receptor activated gamma), PPARalpha (peroxisome proliferation receptor activated alpha), LXR and CPT1, key molecules in the metabolism of fatty degradation and inflammation of the liver. In addition, another use is the induction of decreased expression of NFKB master gene, transcriptional inducer of hepatic inflammatory process factor. All of these events results in the reversal of NAFLD / NASH and advanced liver fibrosis.

The present invention relates to a composition for inducing liver disease in a mammal and a mammal with a liver disease induced using the same. The animal model of the present invention has been found to be an excellent animal model in which fatty liver, hepatic fibrosis, and insulin resistance are evenly induced, and which successfully reproduces the progression of a series of severe liver diseases, from hepatitis and excessive fibrogenesis in liver tissue through tissue hardening (cirrhosis) to liver cancer, and reflects the characteristics of each stage with high reliability. Accordingly, the present invention may be useful as a means for developing a therapeutic agent for chronic liver disease as well as studying the molecular and circulatory mechanisms of each stage of liver disease.

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 disclosure provides methods and uses of CCL5 variants for modulating GPR75 signaling in a cell or subject, treating a GPR75-related disease or disorder in a subject, treating obesity, hypertension, metabolic syndrome, metabolic dysfunction-associated steatohepatitis, and / or diabetes in a subject, and inducing weight loss and / or preventing weight gain in a subject, wherein the CCL5 variant comprises a variant N-terminal portion and a C-terminal portion with at least 70% identity to the corresponding portion of wild type CCL5.

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 invention belongs to the field of biomedical technology and provides an application of betulinone and its analogs in the prevention and treatment of fatty liver disease and adjuvant lipid-lowering. The present invention also provides a composition for treating fatty liver disease or adjuvant lipid-lowering, which comprises an effective dose of betulinone and its analogs. The betulinone and its analogs provided by the present invention have the effects of reducing blood triglyceride and liver triglyceride in vivo, reversing liver steatosis, and can improve liver fibrosis and inflammatory symptoms of mice with fatty hepatitis, and have good safety and no toxic side effects, and can be used for preparing preventive and therapeutic drugs for fatty liver disease, fatty hepatitis and related diseases.

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 discloses an application of a benzofuro [3, 2-c] quinolinone compound in prevention and treatment of metabolic dysfunction related steatohepatitis. For example, a compound P82, namely 3, 8-dihydroxybenzofuro [3, 2-c] quinoline-6 (5H)-ketone, which is prepared through synthesis and purification of an intermediate, can obviously improve liver fatty degeneration, inflammatory infiltration and fibrosis in an HFHC-induced metabolic dysfunction-related steatohepatitis model, so that the progress of metabolic dysfunction-related steatohepatitis is effectively delayed; meanwhile, liver cell lipid accumulation induced by oleic acid and palmitic acid can be improved, so that the compound is expected to be developed into a new medicine for preventing and treating metabolic dysfunction related steatohepatitis.

The disclosure provides methods for identifying metabolic disfunction-associated steatotic liver disease (MASLD) in a subject. The disclosure also provides methods for identifying metabolic disfunction-associated steatohepatitis (MASH) and fibrosis in a subject.

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.

Disclosed is use of a polypeptide in the preparation of drugs, foods, or health care products for treating obesity and comorbidities thereof, which belongs to the technical field of biological medicines. The polypeptide is a human GPR15L polypeptide or a mouse GPR15L polypeptide and a polypeptide conjugate thereof. The treatment of obesity includes: reducing fat accumulation, promoting fat thermogenesis and catabolism, increasing energy consumption, and reducing body weight. The obesity comorbidities include: chronic inflammation, fatty liver, steatohepatitis, metabolic diseases, cardiovascular and cerebrovascular diseases, osteoarticular diseases, Alzheimer's disease, depression, tumors, and skin diseases. A novel mechanism of action reduces blood glucose and body weight, thereby effectively treating obesity and comorbidities 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 invention discloses a GATA4 gene-based MAFLD animal model construction method and application in prevention and treatment drugs, and belongs to the field of mouse model construction, and the GATA4 gene-based MAFLD MASH animal model construction method comprises the following steps: S1, hybridizing a GATA flox transgenic hybrid mouse and a Vil1-Cre transgenic mouse to obtain an F1 generation, and hybridizing the GATA flox transgenic hybrid mouse and a Vil1-Cre transgenic mouse with the genotype of GATA4 flox / +, Vil1-Cre transgenic mouse in the F1 generation to obtain a GATA4 flox / +, Vil1-Cre transgenic mouse to obtain a GATA4 flox / +, Vil1-Cre transgenic mouse; the method comprises the following steps: S1, carrying out selfing on transgenic mice with GATA4 flox / flox and Vil1-Cre to obtain F2-generation mice, and S2, sequentially giving GATA4 intestinal specific knockout mice with genotypes of GATA4 flox / flox and Vil1-Cre in the F2-generation mice with high-fat and high-cholesterol feed (HFD), and inducing to obtain an intestinal GATA4 specific knockout metabolism-related steatohepatitis (MASH) and hepatic fibrosis mouse model. The invention provides a model construction method of MASH and hepatic fibrosis animals in which the intestinal GATA4 gene is specifically knocked out, and application of the intestinal GATA4 serving as a target to preparation of drugs for preventing and treating related diseases such as liver injury and liver diseases caused by the MASH, and the intestinal GATA4 has an important clinical prospect.

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 invention provides a fusion protein for treating metabolic diseases, and a preparation method and use thereof. The fusion protein has a general formula of R1-L-R2 or R2-L-R1, wherein R1 is FGF21 protein, an FGF21 protein analog, or a similar peptide with the biological function of FGF21 protein; R2 is GIP, mutant GIP or a similar peptide with the biological function of GIP; and L is a linker peptide. The fusion protein of the present invention is used as a therapeutic agent or a pharmaceutical composition in the treatment of diseases associated with hyperglycemia and hyperlipidemia, including diabetes, obesity, steatohepatitis or cardiovascular diseases,

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.

The invention discloses an efficient detection method for hepatic balloon-like variant cells based on deep learning. The method comprises the following steps: establishing a hepatic pathological image data set containing abnormal information; an abnormal information auxiliary coding structure and a high-efficiency mixed layer attention module are taken as a core, a hepatic balloon-like cell detection network is constructed, and multi-stage training and testing are carried out. The detection network mainly comprises a backbone network, a local area guidance coding network, a feature fusion network, a global guidance coding network and a header network, wherein the local area guidance coding network and the global guidance coding network are mainly used for strengthening the liver cell multi-scale abnormal information coding capability of the backbone network and the feature fusion network in a training stage. According to the method, all balloon-like variable cells in the full-view slice image of the liver can be timely and effectively recognized, quantitative diagnosis and treatment of diseases such as metabolism-related steatohepatitis are facilitated, and the method has important clinical application value.

The invention relates to the technical field of biological medicines, in particular to application of cinnamyl glycine in preparation of products for predicting or preventing and treating metabolism-related fatty liver diseases. The present invention is based on the prevention and / or treatment of metabolism-related fatty liver diseases and related conditions thereof on the basis of cinnamoylglycine. Experimental results show that the cinnamyl glycine can effectively predict the risk of metabolism-related fatty liver diseases and high-risk metabolism-related fatty hepatitis of community population; cinnamoylglycine intervention can effectively reduce the weight, the triglyceride level and the cholesterol level of mice induced by high-fat and high-cholesterol diet, and improve liver lipid deposition, inflammatory cell infiltration and liver cell ballooning. Cinnamoylglycine can improve metabolism-related fatty liver diseases by inhibiting FDPS expression and activity. The invention provides a new effective intervention thought and means for metabolism-related fatty liver diseases and related diseases thereof.

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.