39 results about "Hepatic parenchymal cell" patented technology

The invention discloses a pharmaceutical composition containing a hiHeps-derived exosome, an application of the pharmaceutical composition or the hiHeps-derived exosome in preparation of a medicine for treating liver diseases, and an application of the pharmaceutical composition or the hiHeps-derived exosome in preparation of a medicine for reducing inflammation. The pharmaceutical composition comprises an exosome, a liposome and a nucleic acid drug, wherein the exosome is derived from hiHeps. The pharmaceutical composition can realize better nucleic acid delivery, has lower immunotoxicity and better biocompatibility compared with single cationic liposome delivery, and can efficiently realize expression and functions in in-vitro cell lines, primary hepatocytes and in-vivo mice. Compared with other exosomes, the pharmaceutical composition constructed by the hiHeps exosome also has higher liver targeting property and parenchymal hepatic cell targeting property.

The invention belongs to the technical field of medicines, and particularly relates to application of isosalicin in preparation of liver injury medicines. The invention provides the application of the isosalicin in the aspect of preparing the liver injury medicine for the first time. The isosalicin is isosalicin (the molecular formula is C13H18O7; the compound has a molecular weight of 286.28, hereinafter referred to as IS), and the medicine IS does not show toxicity in an investigated concentration range (6.25-100 [mu] M), can significantly improve the cell survival rate of acetaminophen induced damaged parenchymal hepatic cells AML-12 at the investigated concentration of 6.25-25 [mu] M, has a significant liver protection effect, and has a good application prospect in preparation of medicines for preventing and treating liver injury.

The application discloses a preparation method and application of large-size human liver organoids, and belongs to the technical field of cell culture. In the application, 2D culture mature human primary liver parenchymal cells with different cell amounts are resuspended by using a hepatocyte maturation medium HIM, and are added into a U-shaped bottom 96-hole plate for low-oxygen static culture. After the cells are aggregated, the cells are cultured in normal oxygen and are shaken, so that large-size human liver organoids with different cell contents are prepared. The method does not need biological materials, and can induce human primary liver parenchymal cells to self-assemble and construct functional liver organoids with high uniformity in scale through specific culture conditions. The method solves the problems of large batch difference, high heterogeneity and dedifferentiation in the prior art, and can be widely applied to drug hepatotoxicity testing, in-vitro modeling of liver diseases and development of a bioartificial liver system.

The invention discloses an application of anethomycin in preparation of a medicine for treating hereditary hemochromatosis. The anethomycin has the effect of promoting liver hepcidin expression, so that the liver iron level is reduced, and the anethomycin is used for treating hereditary hemosis. The research on the action mechanism of the anethomycin shows that the anethomycin promotes parenchymal hepatic cells to secrete hepcidin by up-regulating the expression of a key regulatory factor BMP6 of hepcidin expressed by hepatic sinus endothelial cells, so that the treatment application of hereditary hemochromia is realized, and the anethomycin has good commercial application prospects and scientific research values.

The invention particularly discloses a medicine for treating hereditary liver diseases and application thereof, and relates to the technical field of gene therapy. The invention provides a lipid nanoparticle containing alanine glyoxylate aminotransferase mRNA (messenger Ribonucleic Acid). The lipid nanoparticle comprises an mRNA solution and a lipid mixed solution, the concentration ratio of the mRNA solution to the lipid mixed solution is 1: (20-120). According to the lipid nanoparticles provided by the invention, the problem that the parenchymal hepatic cell AGT enzyme of a patient with primary type 1 hyperoxaluria is deficient is solved, the AGT mRNA delivery efficiency is further improved, and the urine oxalate reduction effect of a protein replacement therapy is improved. The invention provides a theoretical basis and an experimental basis for developing a new treatment strategy, and has good clinical transformation and clinical application prospects.

The present application relates to a kind of FAPi, FAPi intermediate, FAPi modified HSP47siRNA loaded lipid nanoparticles and its application, belong to the field of biological medicine.The inventor constructs a kind of HSP47siRNA loaded lipid nanoparticles (FAPi-LNP / siHSP47) of Fibroblast activation protein inhibitor (FAPi) modification in view of the problems of high morbidity of existing technology liver fibrosis, so far no medicine, and ordinary LNP mainly target delivery to liver parenchymal cell after intravenous injection, and cannot enter the activated hepatic stellate cell (HSC) that plays a key role in the development of liver fibrosis.The expression of HSP47 can be effectively knocked down by the mediation of the high expression of Fibroblast activation protein on the surface of activated HSC, and the content of liver fibrosis marker protein a-SMA can be reduced.Compared with LNP without FAPi modification, FAPi-LNP / siHSP47 actively targets activated HSC after entering liver tissue, enters cell under the mediation of FAP, significantly knocks down the expression of HSP47, reduces collagen deposition, and significantly improves liver fibrosis.

The invention relates to dual-targeting bionic hydrotalcite inorganic nanoparticles as well as a preparation method and application thereof. The preparation method comprises the following steps: obtaining a fresh erythrocyte membrane; obtaining an aged erythrocyte membrane; adding a fresh erythrocyte membrane and an aged erythrocyte membrane into the hydrotalcite inorganic nano-particles according to a certain proportion, mixing and stirring, and centrifuging to obtain the bionic hydrotalcite inorganic nano-particles. The dual-targeting bionic hydrotalcite inorganic nano-particles have the beneficial effects that the dual-targeting bionic hydrotalcite inorganic nano-particles have dual-targeting capability of being delivered to parenchymal hepatic cells and hepatic macrophages in a balanced manner, and oxidative stress and inflammatory response can be relieved at the same time.

The invention discloses a preparation method and application of a hepatic parenchymal cell targeting gene delivery system, and relates to construction and preparation of a hepatic parenchymal cell targeting lipid material GalNAc-PEG2000-DSPE modified MKK4-siRNA (siMKK4) loaded lipid nanoparticle gene delivery system GalNAc-LNP-siMKK4, and the hepatic parenchymal cell targeting gene delivery system can be used for active targeting gene therapy of hepatic failure. The parenchymal hepatic cell targeted gene delivery system selects siMKK4 as a liver regeneration promoting gene therapy drug, has the advantages of clear target spot and capability of accurately silencing a target gene, and can protect siMKK4 from being degraded by extracellular nuclease as a gene delivery carrier, so that the targeted gene delivery system has a good application prospect. N-acetylgalactosamine (GalNAc) is selected as a target head, so that therapeutic genes can be precisely targeted and delivered to parenchymal hepatic cells, the risk of tumorigenesis of other parts of an organism can be reduced while liver regeneration is promoted, and a new thought and a new method are provided for liver regeneration treatment of hepatic failure patients.

The invention discloses a ruminant parenchymal hepatic cell subtype analysis system, which belongs to the technical field of bioinformatics and animal genetics, and comprises a data processing module, which is used for executing cell typing, cell cycle analysis, quasi-time sequence analysis and function enrichment analysis based on single cell sequencing data, and integrating the multi-dimensional analysis results based on a weighted decision rule to carry out cross validation and identification on the subtype of the parenchymal hepatic cells. The method provided by the invention overcomes the defect that in the prior art, human and mouse cells are directly used for marking ruminants to cause inaccurate subtypes of the parenchymal hepatic cells, and provides a reliable tool for accurate identification of subtypes of the parenchymal hepatic cells of the ruminants by establishing a set of special analysis system.

The invention belongs to the technical field of medicines, and particularly relates to application of vanillyl-beta-D-glucopyranoside in preparation of a medicine for treating liver injury. The invention provides the application of vanillyl-beta-D-glucopyranoside in the aspect of preparing the liver injury medicine for the first time. The vanillyl-beta-D-glucopyranoside is Vanillyl-beta-D-glucopyranoside (the molecular formula of the vanillyl-beta-D-glucopyranoside is C14H20O8, the molecular formula of the vanillyl-beta-D-glucopyranoside is C14H20O8 According to the present invention, the drug A has the molecular weight of 316.3, hereinafter referred to as VA, and the drug VA does not show toxicity in the investigated concentration range (6.25-100 [mu] M), can significantly improve the cell survival rate of acetaminophen induced damaged parenchymal hepatic cells AML-12 at the investigated concentration of 6.25-25 [mu] M, has significant liver protection effect, and has good application prospects in the preparation of the drugs for prevention and treatment of liver injury.

The present disclosure relates to the field of nucleic acid drugs, and specifically discloses a compound represented by formula (I), a preparation method thereof, and uses thereof. The targeting ligand and RNAi drug prepared by using the compound provided by the present disclosure can highly effectively target hepatocytes, and effectively inhibit the expression of target genes in hepatocytes, and can be used for treating and / or preventing liver-derived diseases, and has the advantages of high in vivo activity, stable and lasting drug effect, excellent safety, and low toxicity.

The present invention relates to a material for local drug delivery and use thereof. Specifically provided is a nanoparticle composition. The nanoparticle composition comprises a cationic lipid, a PEG lipid, and a structural lipid, wherein the lipid component of the PEG lipid is 1.0-5.5 mol%, or a range between any two of the described values. The nanoparticle composition of the present invention is delivered only at the site of administration.

The invention discloses a construction method of a three-dimensional liver micro-tissue model and hepatotoxicity assessment application of the three-dimensional liver micro-tissue model, and belongs to the technical field of environmental science and engineering. The 3D liver micro-tissue model constructed by the invention consists of three cell lines, namely HepaRG (parenchymal hepatic cells), THP-1 (kupffer cells) and hTERT-HSC (hepatic stellate cells), so that a real liver environment can be better simulated, and the defects of a traditional model are overcome; particularly, the occurrence of hepatic fibrosis relates to complex interaction among a plurality of cell lines, however, most of the previous models for evaluating the potential of hepatic fibrosis by chemical substances are lack of consideration of interaction among multiple types of cells no matter whether hepatic parenchymal cell lines or hepatic stellate cell lines are used, and the 3D hepatic micro-tissue model takes the factor into account, so that the potential of hepatic fibrosis cannot be evaluated. Key hepatic fibrosis events caused by hepatic fibrosis substances can be copied, and a more suitable test platform is provided for evaluating the potential of chemical substance hepatic fibrosis.

The invention provides an improved method for separating liver parenchymal cells from non-parenchymal cells of a mouse with a non-alcoholic fatty liver disease induced by a high fat diet. According to the method, the NAFLD mouse model is successfully constructed by feeding a high-fat feed containing 60% of fat for 12-16 weeks. An improved two-step collagenase perfusion technology is adopted, a low-concentration enzyme solution is combined, and digestion time is accurately controlled, so that cell damage is effectively reduced. The efficient separation and purification of parenchymal hepatic cells and non-parenchymal cells are realized through a Percoll solution with a specific proportion by utilizing a density gradient centrifugation method. Flow cytometry and molecular biological technical verification show that the separated cells are high in survival rate and excellent in purity. The method provides a high-quality primary cell material for research on NAFLD pathogenesis and drug target discovery, and has important application value.

This invention belongs to the field of biomedical technology and discloses the use of catalpol and mesenchymal stem cells in the preparation of drugs for treating liver fibrosis, wherein the concentration of catalpol is 50–200 μM and the concentration of exosomes is 20–50 μg / mL. Simultaneously, this invention constructs a spatially resolved liver fibrosis chip model based on GelMA hydrogel, integrating Kupffer-like cells, hepatic stellate cells, hepatic parenchymal cells, and endothelial cells through a layered sequential seeding strategy, achieving high-precision biomimicry of the liver fibrosis microenvironment. In vitro chip and in vivo animal experiments confirmed that this combined approach can significantly inhibit the expression of collagen synthesis-related genes, improve liver function indicators, and effectively reduce collagen deposition; its anti-fibrotic efficacy is significantly better than the simple superposition of the effects of single components, exhibiting a clear synergistic effect. This invention provides a novel synergistic drug strategy and a highly biomimetic in vitro evaluation platform for the treatment of liver fibrosis.

The invention discloses construction of human liver organoid and fatty liver organoid models. The construction method of the human liver organoid comprises the following steps: culturing human liver stellate cells, human liver parenchymal cells and human liver non-parenchymal cells not containing the human liver stellate cells according to a liver cell in-vivo proportion to obtain the 3D human liver organoid microsphere model. The construction method of the fatty liver organoid model comprises the step of culturing the constructed human liver organoid in a fatty liver induction culture medium to obtain the fatty liver organoid model. According to the construction method of the liver organ, firstly, multiple primary liver cells are subjected to mixed culture, particularly, independently-added human hepatic stellate cells are used, no auxiliary materials such as scaffolds are used, the cells are self-assembled to form a scaffold-free microsphere-induced disease model, and the disease organ model can be used for screening and developing clinical drugs.

The invention relates to a composite nanoparticle VZTM-Gal and a preparation method thereof.According to the VZTM-Gal, efficient loading of a VDAC1 inhibitor VBIT-4 is achieved on the basis of a ZIF-8 nano system, then tannic acid is introduced to be coordinated with exogenous Mg < 2 + > and Zn < 2 + > on the surface of ZIF-8, a metal-polyphenol layer on the surface of ZIF-8 is constructed, and the composite nanoparticle is rapidly disintegrated and released in a lysosome environment; the surface-coupled GalNAc ligand can significantly enhance the specific recognition and uptake of the drug to parenchymal hepatic cells; the preparation process is mild in conditions and simple and convenient in steps, and the obtained nanoparticles are uniform in particle size; the invention further relates to application of the VZTM-Gal in treatment of cadmium-induced acute liver injury and non-alcoholic steatohepatitis induced by combined choline deficiency L-amino acid limited high fat diet exposure, experiments prove that VBIT-4 released by the VZTM-Gal can inhibit VDAC1 oligomerization and inhibit mitochondrial excessive autophagy, tannic acid can remove active oxygen, and the VZTM-Gal can be used for treating cadmium-induced acute liver injury and non-alcoholic steatohepatitis induced by choline deficiency L-amino acid limited high fat diet exposure. Mg < 2 + > synergistically reduces calcium overload caused by cadmium, recovers mitochondrial morphology and functions, and improves liver functions.

The invention discloses an application of polypeptide in prevention and treatment of plateau hepatic lipid accumulation. The amino acid sequence of the polypeptide is shown as SEQ ID NO.1. The polypeptide effectively blocks abnormal lipid deposition in parenchymal liver cells and macrophages in the plateau low-oxygen environment by competitively inhibiting the function of endogenous CIRP. Animal and cell experiments show that the polypeptide can significantly improve liver fatty degeneration caused by plateau exposure, thereby providing a brand new targeted therapy strategy and drug candidate for prevention and treatment of plateau-related non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC).

The application belongs to the technical field of medicine, and particularly relates to application of isosalicine in preparation of liver injury drugs. 13 H 18 O7; molecular weight is 286.28, hereinafter referred to as IS), the drug IS does not show toxicity in the investigated concentration range (6.25-100 muM), can significantly improve the cell survival rate of liver parenchymal cells AML-12 induced by acetaminophen, has a significant liver protection effect, and has a good application prospect in preparation of drugs for preventing and treating liver injury.

The invention provides an antioxidant nano-enzyme for liver-related diseases as well as a preparation method and application of the antioxidant nano-enzyme, and belongs to the technical field of nano-enzymes. The invention provides an antioxidant nano-enzyme. The antioxidant nano-enzyme comprises a Prussian blue nano-enzyme and / or a copper monatomic nano-enzyme. Compared with the prior art, the prussian blue nano-enzyme or the copper monatomic nano-enzyme is prepared by a simpler method and has multiple enzyme activities. The anti-oxidation nano-enzyme aims at parenchymal hepatic cells to achieve the effects of removing ROS (reactive oxygen species) in damaged hepatic cells, relieving oxidative stress damage of damaged liver parts and reducing the level of pro-inflammatory macrophages, so that inflammation-induced hepatic cell necrosis is prevented, and accurate and efficient treatment of the anti-oxidation nano-enzyme including hepatic transplantation injury and hepatic ischemia reperfusion is realized.

The invention relates to a material for local drug delivery and an application thereof. The invention specifically provides a nano-particle composition. The nano-particle composition comprises cationic lipid, PEG (polyethylene glycol) lipid and structural lipid, wherein the content of the lipid component of the PEG lipid is 1.0-5.5 mol%, or a range between any two of the above values. The nanoparticle compositions of the invention are delivered only at the site of administration.

The invention discloses preparation of a liver-targeted fucoxanthin nano delivery system based on probiotic vesicles and application of the liver-targeted fucoxanthin nano delivery system in improvement of bioavailability, and belongs to the field of biological medicine. Pure mycoderm fragments are obtained by combining a differential centrifugation-tangential flow filtration system, the pure mycoderm fragments are treated by an ultrasonic-assisted technology to form complete membrane nano-vesicles, galactosamine with sialic acid glycoprotein receptor targeting ability is modified to distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000-carboxyl through an amide reaction, and the sialic acid glycoprotein receptor targeting galactosamine nano-vesicles are prepared. The hepatic parenchymal cell sialoglycoprotein receptor targeting ligand is obtained. And co-incubating the hepatocyte sialoglycoprotein receptor targeted nano-vesicle with the nano-vesicle to obtain the hepatocyte sialoglycoprotein receptor targeted nano-vesicle. The hydrophobic food functional factors or drugs are encapsulated in the nano-vesicles, so that the water solubility, oxidation resistance, environmental stability and gastrointestinal digestive system stability of the hydrophobic food functional factors or drugs can be improved, and the bioavailability of blood and liver of oral administration of the hydrophobic food functional factors or drugs can be improved.

The invention discloses a multi-organ regulation and control combined nano preparation and application thereof, and belongs to the technical field of medicines. The combined nano preparation consists of a nano preparation A and a nano preparation B, the nano preparation A is a parenchymal hepatic cell regulation and control nano delivery system and is prepared from phospholipid, cholesterol, PEGylated phospholipid, DSPE-PEG-Glactase and a THR-beta agonist; and the nano preparation B is an adipose cell regulation and control nano delivery system and is prepared from phospholipid, cholesterol, PEGylated phospholipid, DSPE-PEG-CKGGRAKDC and a PPAR gamma agonist. According to the invention, malignant crosstalk formed by liver-adipose tissue axes is utilized for the first time, and a strategy for treating fatty hepatitis and hepatic fibrosis related to metabolic dysfunction by cooperatively regulating lipid metabolism balance between two organs of liver and fat by using two types of liposomes is innovatively provided; the invention provides a new strategy and way for treating metabolic liver diseases.

Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

The invention relates to the technical field of drug carriers, in particular to a preparation method and application of self-assembled glycyrrhizic acid supported paeoniflorin nano-micelles. The preparation method adopts a membrane separation method and comprises the steps of solution preparation, membrane formation, hydration, particle size homogenization and purification. The prepared glycyrrhizic acid loaded paeoniflorin nano-micelle can be used for preparing medicines for treating liver cancer. According to the invention, the nano-micelle with the particle size in the range of 100-150nm can be stably prepared. The micelles can be efficiently taken by liver cells and are enriched in parenchymal liver cells in a targeted manner. Meanwhile, the targeted enrichment of the liver can reduce the kidney distribution of the medicine, so that the occurrence rate of pseudoaldosterone is reduced, and the renal toxicity of the medicine is reduced. According to the present invention, the cytotoxicity of the drug on normal liver cells is not increased while the inhibition effect on the liver cancer cell HepG2 can be significantly increased so as to provide the new strategy and the new treatment scheme for reducing the treatment dose, reducing the side effect or overcoming the drug resistance in the clinical application.

The invention discloses a method for inducing pluripotent stem cells to differentiate into hepatic stellate cells and application of the method. The method comprises the following steps: S1, performing induced differentiation on the induced pluripotent stem cells to obtain parenchymal hepatic cells; s2, carrying out passage on the parenchymal hepatic cells in the step S1, continuously culturing the parenchymal hepatic cells for 3-7 days by using a selective enrichment culture medium for hepatic stromal cells, carrying out passage again, and continuously culturing the parenchymal hepatic cells for 3-7 days by using the selective enrichment culture medium for hepatic stromal cells to obtain hepatic stromal cells; and S3, carrying out passage on the hepatic stromal cells in the step S2, and continuously culturing the hepatic stromal cells for 3-7 days by using a hepatic stellate cell induction culture medium to obtain the hepatic stellate cells. According to the method, the efficiency and functional maturity of differentiation from the human induced pluripotent stem cells to the hepatic stellate cells are remarkably improved, and a brand-new research platform is provided for deep understanding of a development regulation mechanism, homeostasis maintenance and pathological activation of the hepatic stellate cells.

The present disclosure relates to the field of medicine, in particular to GalNAc compounds, conjugates, compositions and uses thereof. The oligonucleotide conjugates provided by the present disclosure are synthesized by the GalNAc compounds provided by the present disclosure, which can highly effectively target to hepatocytes and effectively inhibit the expression of target genes in hepatocytes, and can be used for treating and / or preventing liver-derived diseases, and have the advantages of high in vivo activity, stable and long-lasting efficacy, excellent safety and low toxicity at animal level.

The invention relates to a construction method of a centimeter-level bioartificial liver. The construction method comprises the following steps: respectively preparing a norbornene modified gelatin solution, a tetrazine modified gelatin solution and a norbornene modified RGDS solution; the method comprises the following steps: irrigating primary parenchymal hepatic cells from the liver of a mouse, performing in-vitro amplification culture by adopting a commercially available hepatic cell culture medium, collecting the cells, and resuspending by using the culture medium to obtain a primary parenchymal hepatic cell suspension; uniformly mixing the norbornene modified gelatin solution, the norbornene modified RGDS solution and the tetrazine modified gelatin solution, adding the primary parenchymal hepatic cell suspension, and continuously mixing; transferring the mixed solution into a cell culture plate, putting the cell culture plate into an incubator, and adding a cell culture medium for in-vitro culture after norbornene and tetrazine are fully reacted and solidified to form, so as to obtain the centimeter-level bioartificial liver; the obtained centimeter-level bioartificial liver is transplanted into the mesentery of the mouse, the liver function of the 90% liver cut mouse can be effectively compensated, and the survival rate of the 90% liver cut mouse is increased.

The present invention discloses a drug for treating crizotinib-induced liver toxicity by targeting the SQLE gene or protein, belonging to the field of pharmaceutical technology. The drug reverses crizotinib-induced liver toxicity by downregulating the expression of the SQLE gene or the accumulation of SQLE protein. By downregulating SQLE, the present invention can effectively reverse crizotinib-induced apoptosis of hepatocytes, revealing that the SQLE gene is a key gene for crizotinib-induced liver injury and providing a new preventive and therapeutic target for intervening in crizotinib-induced hepatotoxicity. The present invention proposes that SQLE can be degraded through the autophagy pathway, providing a new direction for currently searching for intervention strategies for drug-induced hepatotoxicity and to a certain extent solving the current situation of few clinically available intervention drugs and single mechanisms. The intervention drug reverses crizotinib-induced liver toxicity by downregulating SQLE, expanding the clinical application value of crizotinib.

The invention discloses a preparation method and application of a large-size human liver organ. Belongs to the technical field of cell culture. The method comprises the following steps: re-suspending 2D cultured mature human primary parenchymal hepatic cells with different cell quantities by using a hepatic cell maturation culture medium HIM, adding the re-suspended cells into a 96-well plate with a U-shaped bottom, carrying out low-oxygen standing culture, and carrying out normal-oxygen shaking culture after the cells are gathered, so as to prepare the large-size human liver organs with different cell contents. According to the method, biological materials are not needed, the human primary parenchymal hepatic cells are induced to be self-assembled through specific culture conditions to construct functional liver organs with highly uniform dimensions, and the problems of large batch difference, high heterogeneity and dedifferentiation in the prior art are solved; the method can be widely applied to drug hepatotoxicity testing, liver disease in-vitro modeling and bioartificial liver system development.