238 results about "Hepatic stellate cell" patented technology

The invention belongs to the technical field of biological medicines, and particularly relates to an umbilical cord mesenchymal stem cell preparation and application thereof to treatment of hepatic diseases. The umbilical cord mesenchymal stem cell preparation comprises umbilical cord mesenchymal stem cells from the third generation to the sixth generation, a GPR55 peptide conjugate and pharmaceutically acceptable auxiliary materials. And the amino acid sequence of the GPR55 peptide conjugate is selected from CKKNSPTLC, CKKNTPTQC or CKKNSPTGC. The umbilical cord mesenchymal stem cell preparation can obviously reduce alpha-SMA and COL-I secreted by hepatic stellate cells and inhibit activation of the hepatic stellate cells, and the fact that the umbilical cord mesenchymal stem cell preparation has anti-hepatic fibrosis activity is further verified in a CCl4 induced hepatic fibrosis model.

The invention relates to the field of biomedical application of inorganic materials, in particular to application of lanthanum carbonate in preparation of drugs for resisting liver cirrhosis and inhibiting liver inflammations, the drugs comprise lanthanum carbonate and pharmaceutically acceptable auxiliary materials, the drugs are ground and then mixed with food to prepare a drug mixture, and the drug mixture is prepared into the drug for resisting liver cirrhosis and inhibiting liver inflammations. The mass ratio of the lanthanum carbonate in the medicine mixture is 1-10%, and the mechanism of the lanthanum carbonate for treating the liver cirrhosis is as follows: interference or blocking of activation and proliferation of hepatic stellate cells, inhibition of extracellular matrix generation and promotion of extracellular matrix degradation. According to the invention, a rat liver cirrhosis model is constructed through chemical induction, and the effects of reversing liver cirrhosis and inhibiting liver inflammation are found when a rat is treated by taking lanthanum carbonate orally, so that a new candidate drug is provided for clinical treatment of liver cirrhosis.

The invention provides application of an aromatic sulfonamide compound in preparation of a medicine for preventing and treating liver injury. The aromatic sulfonamide compound BC2059 provided by the invention can be used for inhibiting transcription and protein synthesis of related genes of Fibronectin and CollagenI in hepatic stellate cells, and plays a role in treating liver injury mice induced by bile duct ligation and carbon tetrachloride. The invention provides a potential drug molecule with a new action mechanism for treating liver injury.

The invention belongs to the technical field of traditional Chinese medicine biology, and particularly relates to application of a phenolic compound in preparation of a medicine for preventing or treating hepatic fibrosis. A pair of phenolic diastereoisomers (+)-fresh bamboo juice phenol C and (-)-fresh bamboo juice phenol C are separated from fresh bamboo juice, and an anti-hepatic fibrosis activity screening test shows that (+)-fresh bamboo juice phenol C has a remarkable inhibition effect on human hepatic stellate cells LX-2, has clinical application potential in anti-hepatic fibrosis treatment, and has broad application prospects. The method can be used for preparing medicines for preventing or treating hepatic fibrosis, and a new basis is provided for pharmacological research of fresh bamboo juice.

The invention discloses an efficient targeting anti-hepatic fibrosis nano drug delivery system and a preparation method thereof. According to the system, a pentacyclic triterpenoid compound lupeol extracted from cichorium glandulosum is taken as an active ingredient, and the hyaluronic acid modified ZIF-8 loaded lupeol nano drug delivery system (HA / Lupeol ZIF-8) is constructed aiming at the problems of poor water solubility, low stability, weak targeting property and the like of the pentacyclic triterpenoid compound lupeol. The system is synthesized by a room-temperature solution method, hydrophobic lupeol is efficiently entrapped by using a porous structure of ZIF-8, and active targeting of a CD44 receptor on the surface of the hepatic stellate cell is realized by surface modification of hyaluronic acid. The particle size of the nano drug delivery system is 50-200nm, the encapsulation efficiency is 97.4%, and the drug loading capacity is 23.8%. In a fibrotic acidic microenvironment, the ZIF-8 carrier can responsively degrade and release a drug, and effectively penetrates through a collagen deposition barrier, so that precise drug delivery is realized. According to the invention, a new strategy is provided for anti-hepatic fibrosis treatment by combining degradation of ZIF-8 in a hepatic fibrosis acidic microenvironment and active targeting bifunctional characteristics of hyaluronic acid for the first time.

The invention discloses a method for simultaneously extracting multiple types of cells from the same liver tissue, which is characterized by comprising the following steps: preparing a single-cell suspension; extracting parenchymal hepatic cells; extracting bile duct epithelial cells; extracting hepatic stellate cells; wherein the extraction step of the parenchymal hepatic cells, the bile duct epithelial cells and the hepatic stellate cells is carried out step by step according to the sequence. According to the technical scheme, efficient extraction of liver tissue cells and culture of functional organoid are achieved, various defects in the prior art are overcome, meanwhile, the technical scheme has a wide application range and is suitable for various liver tissues, and important technical support is provided for research and treatment of liver diseases.

A polypeptide complex, a protein, a nucleic acid, a composition and uses thereof. A cell specific high expression and long retention (ePR) strategy is employed to overexpress specific mRNA in hepatic stellate cells into therapeutic proteins and to promote long-term anchoring of the therapeutic proteins in a fibrotic matrix microenvironment. The first-generation and second-generation retinol derivatives containing carboxyl are determined, can partially replace cholesterol in lipoid nanoparticles (LNP), and are enriched in a fibrosis area through intravenous injection, so that the expression of mRNA in a fibrosis liver is improved by about 10 times. Furthermore, therapeutic mRNA has been engineered by coupling the gene sequence of the collagen binding domain (CBD) to the C-terminus of the therapeutic protein. In screening, it is found that the peptide sequence of placental growth factor (PLGF) shows the strongest collagen affinity, the liver residence time of overexpressed therapeutic protein can be prolonged, and systemic side effects are reduced to the minimum.

The invention discloses preparation and application of a mesoporous polydopamine drug delivery system with multiple antioxidant functions, and belongs to the technical field of medicines.The drug delivery system is characterized in that plant exosomes with antioxidant and anti-inflammatory performance wrap mesoporous polydopamine to serve as a carrier, and the carrier with antioxidant and anti-inflammatory functions is loaded through an adsorption equilibrium method. A nano drug delivery system of a drug having an anti-inflammatory effect; the constructed nano drug delivery system has multiple antioxidant properties, and can regulate the phenotype of macrophages, increase the release of anti-inflammatory factors and promote the apoptosis of hepatic stellate cells.

The application relates to the field of biological nanotechnology, and provides a multimodal diagnosis and treatment integrated AIE carbon nitride composite nano system and a preparation method thereof. The composite nano system takes selenium-doped carbon nitride nanosheets as a core carrier, realizes active targeting of hepatic stellate cells through VA-PEG2000 modification, simultaneously loads a first AIE photosensitizer and a second AIE photosensitizer with near-infrared two-region emission, and forms a double-photosensitizer composite system. The composite nano system has the dual imaging modalities of near-infrared two-region fluorescence imaging and photoacoustic imaging under the excitation of 660nm and / or 808nm laser, simultaneously generates reactive oxygen through a photodynamic effect to play a treatment function. The application further co-loads an anti-fibrosis drug in the nano system, realizes photodynamic-chemical combined treatment under the guidance of imaging, and solves the technical problems of single imaging modality and insufficient functional integration of an existing liver fibrosis nano diagnosis and treatment system, so that multimodal precise positioning and synergistic enhanced treatment integration of liver fibrosis lesions can be realized.

The invention provides application of bruceine D in preparation of a medicine for treating hepatic fibrosis, belongs to the technical field of biological medicines, and proves that the bruceine D has an effect of inhibiting hepatic stellate cell activation by utilizing a human hepatic stellate cell line LX2 induced by TGF-beta1 and a human primary hepatic stellate cell activation model. A CCl4-induced hepatic fibrosis mouse model is utilized to prove that the bruceine D can obviously inhibit the expression of stellate cell activation markers in vivo. Therefore, in vitro and in vivo, the bruceine D can prevent activation of the stellate cells, so that hepatic fibrosis is inhibited; the compound can be applied to preparation of medicines for treating hepatic fibrosis, and has a good application prospect.

The application discloses application of a CCL15 neutralizing antibody in preparation of a medicine for inhibiting growth of liver cancer, and comprises the following steps: S1, constructing a mouse liver cancer PDX model and performing passage; S2, randomly dividing the immunodeficient mouse after passage into a control group and an experimental group, and performing dosing treatment on the control group and the experimental group every three days; S3, PDX model tumor tissue evaluation, stripping tumor tissues after 11 times of dosing of the control group and the experimental group, and respectively observing and recording the volume and weight of the tumor tissues of the control group and the experimental group; the method for inhibiting growth of liver cancer provided by the application, CCL15 acts on the stellate cells to activate the stellate cells and make the expression spectrum of the stellate cells change significantly, the CCL15 neutralizing antibody has an anti-tumor effect in the liver cancer PDX model through injection, and tumor-derived CCL15 can indirectly promote growth of liver cancer cells by activating the hepatic stellate cells.

The invention discloses an application of senkyunolide I in preparation of a medicine for treating hepatic fibrosis, which can obviously inhibit HSC (hepatic stellate cell) activation in vitro and evaluate the treatment effect of senkyunolide I on hepatic fibrosis in vivo by adopting a C57BL / 6 mouse hepatic fibrosis model induced by CCl4. The expression levels of liver alpha-smooth muscle actin, type I collagen and matrix metalloproteinase tissue inhibition factor 1 of individuals needing anti-hepatic fibrosis are obviously reduced in vivo and in vitro, and the hepatic fibrosis progress can be effectively intervened. Therefore, according to the application of the senkyunolide I in the hepatic fibrosis, the provided compound senkyunolide I has huge potential for inhibiting the hepatic fibrosis, an effective traditional Chinese medicine monomer component medicine is provided for treating the hepatic fibrosis, the new clinical adaptation application of the senkyunolide I is expanded, and the application prospect is good.

The invention relates to a system for monitoring mRNA m6A methylation in hepatic stellate cells based on a hybridization chain reaction and a detection method, and belongs to the technical field of analysis and detection. In order to solve the problem of poor sensitivity and detection precision in the prior art, the invention provides a system for monitoring mRNA m6A methylation in hepatic stellate cells based on hybridization chain reaction and a detection method, the method comprises the following steps: contacting a target mRNA m6A methylation sample to be detected with a group of probes comprising a probe a and a probe b; the probe b is connected to an anti-rabbit IgG antibody to form a probe b attached with the anti-rabbit IgG antibody; combining with a rabbit monoclonal anti-m6A antibody; the rabbit monoclonal anti-m6A antibody can be combined with a target mRNA m6A methylated sample to be detected; a hairpin probe H1 monomer and a hairpin probe H2 monomer are subjected to a hybridization chain reaction to form a polymer, and imaging detection is carried out. The method has the advantages of high detection sensitivity, high detection selectivity and strong intuition.

Long awaited is a human liver-like three-dimensional construct that makes it possible to carry out evaluation of human-specific toxicity and the like accurately and in a simple manner. The present invention provides a human liver-like three-dimensional construct comprising a heterospheroid, in which human hepatic cells and other human-derived cells which are not human hepatic cells are aggregated. This human liver-like three-dimensional construct is characterized in that the other human-derived cells are at least one selected from human hepatic stellate cells and the like, and the other human-derived cell to the human hepatic cell count ratio is at least 0.01 but less than 1.

The application discloses a kind of benzofused heterocyclic ring amine pyrazolopyrimidine ketone derivatives, preparation method and application, belong to the technical field of pharmaceutical chemistry, the compound of the application has the structure shown in formula (I) or its pharmaceutically acceptable salt.The preparation method is with amino pyrazole as starting material, cyclization, chlorination, selective hydrolysis is prepared pyrazolopyrimidine ketone nucleus, again, the target compound is obtained by nucleophilic substitution reaction with benzofused heterocyclic ring substituted cyclic amine side chain of nucleus, simple operation, suitable for industrial production.The in vitro activity evaluation result shows that compound can significantly inhibit TGF-β1 induced hepatic stellate cell activation, effectively down-regulate the expression of fibronectin and collagen type I;Animal in vivo pharmacodynamics experiment further confirms that representative compound can dose-dependently reduce the degree of CCl4 induced mouse liver fibrosis, reduce collagen deposition, improve liver tissue pathological damage after oral administration (I).

The invention discloses application of a p97 / VCP inhibitor in preparation of a pharmaceutical preparation for treating hepatic fibrosis, and belongs to the field of biological medicine. The p97 / VCP inhibitor CB5081 disclosed by the invention shows an anti-fibrosis function by promoting the aging of hepatic stellate cells. When CB-5083 is used for treating fibrosis mice, activation of hepatic stellate cells is inhibited, and hepatic fibrosis is relieved. In addition, in-vivo experiments show that CB-5083 promotes HSC aging and reduces YAP expression. The invention emphasizes that the medicine taking p97 / VCP as a target spot has the effect of relieving hepatic fibrosis.

This invention discloses a method for preparing a co-loaded dual-gene targeted delivery system and its application, involving the construction and preparation of a dual-gene (pHNF4α, pFOXA3) delivery system. This delivery system can target myofibroblasts (MFs) and activated hepatic stellate cells (aHSCs) and can be used for gene therapy of liver fibrosis. This invention synthesizes the targeting carrier material PEI. 25K -PEG 2K -pPB, through electrostatic adsorption, combines with pHNF4α and pFOXA3 to form a co-loaded dual-gene targeted delivery system, F4α / A3@PP-pPB. This delivery system, through the targeting group pPB, binds to MFs (metacellular matrix cells) that lead to excessive accumulation of extracellular matrix in fibrotic livers and to PDGFR (polydimethylformamide) highly expressed on the surface of aHSCs. On the one hand, it inhibits the activation of aHSCs; on the other hand, it transdifferentiates MFs into hepatocyte-like cells (iHep). These two modes, while combating liver fibrosis, can also achieve a certain degree of liver function reconstruction through transdifferentiated iHep cells, providing new ideas and methods for the effective treatment of liver fibrosis.

The invention belongs to the technical field of biological medicines, and particularly relates to application of MIM2 and derivatives thereof in preparation of products for treating tissue fibrosis. It is found that the compound MIM2 can effectively inhibit expression and synthesis of various cancers (extracellular matrix proteins such as collagen and laminin in cells). In-vitro experiments show that after MIM2 treatment, collagen and laminin expression of the cancer cells, skin fibroblasts, hepatic stellate cells and embryonic lung cells is remarkably reduced. Animal experiments further prove that the MIM2 can effectively inhibit collagen deposition in tumor tissues of tumor-bearing mice, can slow down the fibrosis process of liver fibrosis and pulmonary fibrosis mouse models, and can reduce the level of plasma hyaluronic acid at the same time. The results show that the MIM2 has the effects of inhibiting extracellular matrix deposition and delaying tissue fibrosis, and is expected to be developed into small molecular drugs for treating cancer-related fibrosis and other fibrosis diseases.

The present invention discloses the application of Zanthoxylum bungeanum exosomes in the preparation of a drug for preventing and / or treating hepatic diseases, and specifically relates to the field of biomedical technologies. The application of Zanthoxylum bungeanum exosomes in the preparation of a drug for preventing and / or treating hepatic diseases is based on the principle of inhibiting the proliferation, migration and fibrosis indicators of hepatic stellate cells. For the alcohol-induced chemical injury liver fibrosis model in mice, intervention with Zanthoxylum bungeanum exosomes can significantly improve the pathological changes of liver tissue, inhibit collagen deposition, reduce the number of lipid droplets in liver tissue, and decrease the activities of serum AST and ALT, with significantly better effects than the non-drug-administered model group. The present invention provides a drug containing Zanthoxylum bungeanum exosomes or related biological materials. Compared with traditional therapeutic drugs, this drug has the advantages of being easy to separate, easy to detect, rich in sources, high in safety, good in stability, and can also be used as a drug delivery system to load targeted drugs, etc., thereby improving the treatment efficiency of liver fibrosis diseases.

The invention belongs to the technical field of medical biology, and particularly relates to application of a detection reagent in a vascular targeted drug screening kit and a screening method. The detection reagent comprises a first detection reagent for detecting Rho GTP enzyme in experimental samples and a second detection reagent for detecting Rho kinase 2 in the experimental samples, the experimental samples comprise a first experimental sample and a second experimental sample, the first experimental sample comprises vascular endothelial cells highly expressed by Rho kinase 2, and the second experimental sample comprises vascular endothelial cells highly expressed by Rho kinase 2. The second experimental sample comprises hepatic stellate cells with high expression of Rho kinase 2; the blood vessel targeting drug is an anti-hepatic fibrosis drug taking a blood vessel as a target spot. The ROCK2 capable of targeting vascular endothelial cells and hepatic stellate cells at the same time can be effectively screened out, the anti-hepatic fibrosis medicine with the blood vessel as the target spot is further screened out, and a new thought is provided for screening of the anti-hepatic fibrosis medicine.

The present invention discloses a pharmaceutical composition for treating non-alcoholic steatohepatitis, liver fibrosis and / or liver cirrhosis, which is prepared from the following raw materials in the following weight ratios: 15-50 parts of Astragalus membranaceus, 5-25 parts of turtle shell, 5-25 parts of Angelica sinensis, 10-30 parts of safflower, 10-30 parts of peach kernel, and 1-10 parts of liquorice. The pharmaceutical composition of the present invention for treating non-alcoholic steatohepatitis can reduce serum transaminase, and significantly reduce lipid deposition, liver tissue inflammation and collagen fiber deposition; the composition of the present invention for treating liver fibrosis can significantly reduce liver tissue pathological inflammation and collagen fiber deposition, as well as the numerical values of related indexes such as serum liver function ALT and AST, and at the same time significantly down-regulate the numerical values of related indexes such as serum PⅢP, PCⅣ, HA and LN, significantly inhibit the activation of hepatic stellate cells (HSCs), the central link of liver fibrosis, significantly reduce the activation of NLRP3 inflammasome in liver tissue, reduce HSC autophagy and activation, and has a good therapeutic effect on both liver fibrosis and liver cirrhosis.

The application relates to a method for establishing a MASH and a related liver cancer model by using a liver stellate cell-specific Lonp1 knockout mouse. flox / flox Mice are crossed with Lrat-2A Cre Mice to obtain mice with specific Lonp1 gene deletion in liver stellate cells. The mice do not have obvious liver abnormalities at 2 weeks old, liver fibrosis and lipid accumulation appear at 6 weeks old, cirrhosis and inflammation foci formation appear at 6 months old, and liver cancer gradually appears at 10 months old. More importantly, the mice can form a large number of large liver cancer nodules within 16 weeks under the induction of GAN diet. In addition, when melanoma cells are injected into the spleen to establish a splenic liver metastasis model, the liver stellate cell Lonp1 deletion mice show a significantly increased number of metastatic tumors. The model can effectively simulate the pathological process of MASH progressing to liver cancer, and provides a reliable tool for related mechanism research and drug development.

This invention discloses a sophoridine tricyclic derivative or its pharmaceutical salt, with the following general structural formula: R1 is selected from hydrogen, C1-C20 straight-chain alkyl, and C1-C20 branched alkyl. In vitro experiments have verified that the sophoridine tricyclic derivative can inhibit TGF-β-induced activation of hepatic stellate cells, improve CCl4- and bile duct ligation-induced liver injury and liver fibrosis in mice, inhibit TGF-β / Smads signaling pathway activation, and also inhibit diethylnitrosamine-induced primary liver cancer in mice. Therefore, this invention provides new evidence for the treatment, alleviation, or improvement of liver fibrosis or primary liver cancer using sophoridine tricyclic derivatives.

The present disclosure provides lipid nanoparticles that are beneficially effective in the targeting of hepatic stellate cells with enhanced specificity. The lipid nanoparticles include five lipid components, including a permanently charged cationic lipid that is a quaternary ammonium lipid. The disclosure also provides pharmaceutical compositions and methods including the provided lipid nanoparticles.

The invention discloses an application of hsa-miR-17-3p in the prevention and / or treatment of hepatic fibrosis. Through clinical sample sequencing, it is found for the first time that expression of hsa-miR-17-3p (SEQ ID NO.1) in hepatitis B related hepatic fibrosis tissue is remarkably reduced. Furthermore, a dual luciferase reporter gene experiment proves that the hsa-miR-17-3p can be directly combined with a 3'untranslated region of the TGFBR1 in a targeting manner to inhibit mRNA and protein expression of the TGFBR1, so that activation of hepatic stellate cells is effectively inhibited, and secretion of I-type and III-type collagen is remarkably reduced. The discovery not only reveals a new mechanism of hepatic fibrosis, but also provides a theoretical basis and candidate molecules for developing novel targeted therapeutic drugs based on miRNA, and has important clinical application value and wide prospects in the aspects of early intervention, treatment and diagnosis of hepatic fibrosis.

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 present disclosure provides lipid nanoparticles that are beneficially effective in the targeting of hepatic stellate cells with enhanced specificity. The lipid nanoparticles include five lipid components, including a permanently charged cationic lipid that is a quaternary ammonium lipid. The disclosure also provides pharmaceutical compositions and methods including the provided lipid nanoparticles.

The present invention relates to lipid nanoparticles capable of delivering a target substance to hepatic stellate cells. The lipid nanoparticles are for delivering a target substance to hepatic stellate cells and comprise a pH-sensitive cationic lipid including a hydrophilic portion and two hydrophobic portions, wherein an acid dissociation constant pKa of a lipid membrane constituting the lipid nanoparticles is greater than or equal to 6.7 and less than 8.2.

The invention discloses a chondroitin sulfate modified dihydromyricetin solid lipid nanoparticle, and belongs to the field of pharmaceutics. The nanoparticle is composed of a solid lipid component, dihydromyricetin encapsulated in the solid lipid component and a chondroitin sulfate targeting ligand modified on the surface. According to the invention, the chondroitin sulfate is specifically combined with the high-expression CD44 receptor on the surface of the hepatic stellate cell, so that the active targeting delivery of the drug to the hepatic fibrosis focus is realized. The nanoparticles have the characteristics of uniform particle size, high encapsulation efficiency and good slow release effect, can significantly improve the enrichment concentration of dihydromyricetin in the liver, enhance the anti-hepatic fibrosis curative effect and reduce the systemic side effects, and have good application prospects in preparation of hepatic fibrosis targeted therapy drugs.