161 results about "Hepatic stellate cell" patented technology

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 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 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.

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 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.

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 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.

The invention relates to the technical field of chromatography, in particular to a preparation method and application of primary hepatic stellate cell membrane biological chromatography for screening anti-hepatic fibrosis active ingredients. The method has the advantages that the primary hepatic stellate cell membrane is used for packing the chromatographic column; the characteristic that primary hepatic stellate cells are closer to in-vivo cells is utilized, the advantage that more real drug response can be provided can be provided, and the method is applied to screening and identification of active ingredients of anti-hepatic fibrosis traditional Chinese medicines. The chromatographic column disclosed by the invention integrates the advantages of primary hepatic stellate cells and a comprehensive two-dimensional cell membrane chromatographic analysis system. Establishment of a comprehensive two-dimensional primary hepatic stellate cell membrane chromatography-reversed phase chromatography system is realized for the first time, and the method can be applied to screening of anti-hepatic fibrosis active components.

The present invention relates to a three-dimensional hepatocyte tissue comprising a cell structure containing at least hepatocytes and a hydrogel, in which the cell structure does not contain hepatic stellate cells, and the cell structure is embedded in the hydrogel.

The present application relates to the technical field of biological medicine, in particular to application of small molecule compound NX-1607 in preparation of products for treating liver fibrosis. The present application finds that NX-1607 has high-efficiency anti-liver fibrosis effect, and shows significant anti-fibrosis effect in multiple mouse models of liver fibrosis, and has wide adaptability. The present application also finds that NX-1607 can up-regulate expression of a key inhibitory factor SMAD7 of a TGF-beta signal pathway, reduce activation of hepatic stellate cells, thereby effectively relieving liver fibrosis, and this mechanism is different from existing anti-liver fibrosis drugs, thereby providing new technical support for liver fibrosis treatment. And NX-1607 does not find obvious toxic side effects in an effective dose range (3-8 mg / kg / d), and has good safety. It can be seen that NX-1607 is a safe and effective anti-liver fibrosis drug, and can improve the problems of limited current curative effect and large side effects.

The application provides a kind of double (2,3-dihydroxy benzamide) compound and its preparation method and application, belong to medical technology field.The application obtains a series of double (2,3-dihydroxy benzamide) compound with novel structure and good inhibiting effect on cholestatic liver disease and liver fibrosis by structural modification of sporangium chelae, the compound can significantly inhibit the expression of hepatic stellate cell COL1A1 mRNA in vitro, has strong anti-liver fibrosis effect;In vivo, it can significantly alleviate the liver injury related biochemical indicators of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) induced cholestatic liver disease mouse model, inhibit the expression of liver fibrosis related genes, reduce the content of liver collagen fiber, inhibit liver inflammation and bile duct response, and can be used for treating cholestatic liver disease and liver fibrosis.

The present disclosure relates to a TSG-6 fragment and a pharmaceutical composition for preventing or treating liver disease including the TSG-6 fragment as an active ingredient. The TSG-6 fragment according to the present disclosure inhibited the cleavage of CD44 by MMP-14 in human hepatic stellate cells, thereby inhibiting the expression of genes related to hepatic stellate cell activation and fibrosis. In addition, the TSG-6 fragment alleviated liver damage and inflammation in an alcohol-related liver disease mouse model and inhibited fatty liver and liver fibrosis. Therefore, the TSG-6 fragment according to the present disclosure may be used as various therapeutic agents for liver diseases accompanied by liver damage and liver fibrosis.

The invention discloses rhizoma acori graminei polysaccharide as well as a preparation method and application thereof. According to the method disclosed by the invention, the acorus tatarinowii polysaccharide is obtained from the root tuber of the acorus tatarinowii Schott by adopting the methods of water extraction, alcohol precipitation and column separation and purification. Cell experiment results show that the rhizoma acori graminei polysaccharide can significantly inhibit activation of TGF-beta induced hepatic stellate cells (LX-2), and carbon tetrachloride (CCl4) induced hepatic fibrosis mouse model experiments show that the rhizoma acori graminei polysaccharide can significantly reduce CCl4 induced collagen deposition and expression of liver tissue alpha-smooth muscle actin (alpha-SMA), and can significantly inhibit TGF-beta induced hepatic stellate cells (LX-2) activation. The content of asparaginic acid aminotransferase (AST), alanine aminotransferase (ALT) and the like in serum of a hepatic fibrosis model mouse is reduced, and the compound can be used for preparing candidate carbohydrate drugs or liver protection health care products for treating and / or treating hepatic fibrosis.

The invention discloses a preparation method of a ferritin-based magnetic resonance nanoprobe targeting hepatic stellate cells, which comprises the following steps: S1, preparing an HEPES salt solution with the working concentration of 10 mmoL / L, and adjusting the pH value to 8.3 by using a NaOH solution; s2, potassium chloroplatinite powder is dissolved in the HEPES salt solution in the S1, a ferritin solution is added, then the mixture is placed on a magnetic stirrer to be stirred for 1 h at the room temperature, and standing is conducted for 5 h. According to the preparation method of the hepatostellate cell targeting ferritin-based magnetic resonance nanoprobe, the ferritin-based magnetic resonance nanoprobe is endowed with good MRI T1 imaging ability after loading of metal manganese ions and platinum, and non-specific recognition of a ferritin receptor in a liver is shielded by modifying excessive double-active ester polyethylene glycol; then, through mediation of the specific targeting molecule RGD peptide, the nanoprobe is efficiently delivered to the fibrosis liver, the interception effect of normal liver tissue is avoided, the imaging effect is greatly enhanced, and imaging diagnosis of mouse hepatic fibrosis can be achieved.

The invention provides an application of alkaloid bicuculline in preparation of a medicine for preventing and / or treating hepatic fibrosis diseases and hepatic inflammation, and also provides an application of bicuculline in preparation of an inflammatory factor expression inhibitor and an application of bicuculline in preparation of a Toll-like receptor 4 signal channel inhibitor. 7.5 mu g / mL of bicuculline can be used for relieving the activation of hepatic stellate cells induced by TGF-beta1, remarkably reducing the expression of alpha-SMA and COL1A1, and reducing the expression of MyD88 and NF-kB as well as downstream inflammatory factors IL-6, IL-1beta and TNF-alpha in a TLR4 / MyD88 / NF-kB signal channel. By intraperitoneal injection treatment of 0.6 mg / kg of bicuculline, the liver morphology in a fibrosis model can be remarkably improved, the levels of ALT and AST in serum can be remarkably reduced, and collagen deposition and expression of alpha-SMA and COL1A1 in the liver can be remarkably reduced.

This invention discloses a method for constructing carrier-free NADH nanoparticles to restore the function of aging hepatocytes, the product, and its applications, belonging to the pharmaceutical field. The method includes preparing carrier-free nano-coordination polymer NADH-Gd using a reverse microemulsion method, followed by a two-step lipid modification process: first, DOPA modification, then DPPC, cholesterol, and DSPE-PEG. 5k NADH-PEG was synthesized by modification, with DSPE-PEG added during the modification process. 5k NADH-Gal is ultimately synthesized from NADH-Gal. NADH-Gal exhibits excellent hepatocyte targeting and can replenish NAD+ in senescent hepatocytes in the MASH environment. + The content is increased by adjusting... Aldh18a1 The expression of [a specific substance] regulates proline metabolism. Improved proline metabolism can restore mitochondrial function by promoting mitophagy and mitochondrial biosynthesis, thereby alleviating hepatocyte aging. Simultaneously, it reduces monocyte recruitment and hepatic stellate cells (HSCs), ultimately providing an effective treatment for MASH. This invention provides a novel strategy for the treatment of MASH.

The invention is applicable to the technical field of biological medicines, and provides a substituted 4-quinolinone compound as well as a preparation method and application thereof. A substituted 4-quinolinone compound with a brand new structure is developed, an in-vitro anti-hepatic fibrosis activity test shows that most of the compounds have a remarkable inhibition effect on fibronectin (FN) expression in LX-2 cells (human hepatic stellate cell lines) stimulated by TGF-beta1 at the concentration of 10 [mu] M, the inhibition rate of part of the compounds exceeds 90%, and the inhibition rate of the compound I-3 reaches 98%. The compound can inhibit activation of hepatic stellate cells and excessive deposition of extracellular matrixes and improve liver tissue damage, so that the compound has important drug value and wide clinical application prospect in the field of anti-hepatic fibrosis, and a new choice can be provided for research and development of anti-hepatic fibrosis drugs. In addition, the preparation method has the advantages of easily available raw materials, simple synthesis, high product yield and easy purification, and lays a foundation for compound structure optimization and further drug research and development.

The invention relates to the field of binding molecules comprising at least one single variable antibody domain, targeted at receptors present on myofibroblasts and / or hepatic stellate cells (HSCs). The invention also relates to a binding molecule comprising at least two single variable antibody domains, each targeting a receptor on HSCs and / or on myofibroblasts. The invention further relates to nucleic acids encoding such binding molecules, a host cell for expression of such binding molecules and to methods for preparing such binding molecules. The invention further relates to pharmaceutical compositions that comprise such binding molecule and to uses of such binding molecules and / or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.