32 results about "Cells hepatic stellate" patented technology

The present invention relates to the discovery of an epigenetic relay pathway that controls hepatic stellate cell activation and the wound-healing response in fibrogenesis, including fibrogenesis of the injured liver. Methods of inhibiting fibrogenesis, including liver fibrogenesis and secondary disease states and conditions thereof, and in treating liver damage, including cirrhosis of the liver (which may be caused by viruses or chemicals, including alcohol), are aspects of the present invention. The methods utilize certain nucleoside compounds and / or antibodies which are optionally conjugated. Pharmaceutical compositions represent additional aspects of the invention.

Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

The invention provides a new use of a macrocyclic polyphenol compound separated from a penthorum chinense pursh extract in pharmacy. The macrocyclic polyphenol compound comprises a compound 1, a compound 2, a compound 3 and a compound 4, wherein the structural formulas of the compounds are as shown in the specification; the compounds have the following pharmacological activities that (1) the alpha-amylase activity is significantly inhibited, and the compounds have certain hypoglycemic effects, and (2) TGF (transforming growth factor)-beta1-induced hepatic stellate cell proliferation is significantly inhibited, and the compounds have anti-liver-fibrosis effects by pharmacology and efficacy experiments. The invention provides a novel medicament for preventing and treating diabetes mellitus, and an anti-liver fibrosis medicament. The medicament is abundant in raw material source, small in side effect, and beneficial to environmental protection, and has a relatively great clinical application value.

The invention relates to the technical field of medicine, in particular to the use of 13-methylamino-18-thiomatrine compound (I) and its salts in the preparation of anti-fibrosis drugs. The present invention proves from cytological tests that 13-methylamino-18-thiomatrine can inhibit proliferation and activation of extracellular matrix producing cells hepatic stellate cells, and inhibit fibrotic liver epithelial cell-mesenchymal transition. In addition, it also has inhibitory effects on various other extracellular matrix-producing cells that lead to organ or tissue fibrosis. Animal experiments have proved that 13-methylamino-18-thiomatrine has a very significant anti-hepatic fibrosis effect. The results show that 13-methylamino-18-thiomatrine has definite anti-hepatic fibrosis or fibrosis of other tissues and organs, and can be used to prepare medicines for preventing and treating liver fibrosis or fibrosis of other tissues and organs.

The present invention relates to the discovery of an epigenetic relay pathway that controls hepatic stellate cell activation and the wound-healing response in fibrogenesis, including fibrogenesis of the injured liver. Methods of inhibiting fibrogenesis, including liver fibrogenesis and secondary disease states and conditions thereof, and in treating liver damage, including cirrhosis of the liver (which may be caused by viruses or chemicals, including alcohol), are aspects of the present invention. The methods utilize certain nucleoside compounds and / or antibodies which are optionally conjugated. Pharmaceutical compositions represent additional aspects of the invention.

The invention relates to a high-throughput screening system constructed by taking I type collagen alpha1 gene COL1A1 promoter activity as a target spot on the basis of the characteristic that I type collagen alpha1 is highly expressed in a hepatic fibrosis process. By constructing an I type collagen alpha1 gene COL1A1 promoter fragment and pGL4.17 expression vector recombinant plasmid, transfecting a human hepatic satellite cell line (LX2) and screening by taking COL1A1 promoter activity detected by virtue of luciferase expression strength of a carrier pGL4.17 as index to obtain a stable monoclonal cell strain LX2-COL, and screening compounds S1-S7 by applying the cell strain LX2-COL to obtain a compound S7 with an obvious inhibiting effect on the COL1A1 promoter activity. mRNA real-time PCR and Western blotting analysis respectively show that the compound S7 can obviously reduce expression of the I type collagen alpha1 in transcription and protein levels and is hopeful to become a candidate anti-hepatic fibrosis drug; and the mRNA real-time PCR and Western blotting analysis also respectively show that the constructed system can be applied to anti-hepatic fibrosis drug high-throughput screening.

The invention relates to a multi-mode targeted probe for early hepatic fibrosis diagnosis and a preparation method thereof. The multi-mode targeted probe for the early hepatic fibrosis diagnosis is characterized by comprising a vector, and the vector is connected with a fluorescence group and a magnetic resonance imaging group and can be connected with a targeted compound group, which can be combined with a receptor on the surface of a hepatic stellate cell in hepatic fibrosis / cirrhosis, through a bridging group. The preparation method comprises the steps of: connecting the targeted compound group, which can be combined with the receptor on the surface of the hepatic stellate cell in the hepatic fibrosis / cirrhosis, with the bridging group, and sequentially connecting the targeted compoundgroup, the fluorescence group and the magnetic resonance imaging group on the vector. The targeted probe has higher sensitivity when being used for diagnosing and evaluating the fibrosis diagnosis.

An application of artesunate in preparing the medicines for preventing and treating the hepatic fibrosis and preventing heptocirrhosis and liver cancer is disclosed.

The invention provides a composition containing an SUMO inhibitor, and belongs to the technical field of medicines. The composition is prepared from an FXR (farnesoid X receptor) agonist and the SUMOinhibitor. According to the composition, in the high-activation state of hepatic stellate cells, the FXR (farnesoid X receptor) agonist does not have the effect of inhibiting the activation of the hepatic stellate cells; after the FXR (farnesoid X receptor) agonist and the SUMO inhibitor are compounded, the activation of the hepatic stellate cells can also be inhibited in the high-activation stateof the hepatic stellate cells; and the hepatic stellate cells of an individual with fibrosis symptoms are in an activated state, using the FXR (farnesoid X receptor) agonist alone cannot generate a good anti-fibrosis effect. The composition of the FXR (farnesoid X receptor) agonist and the SUMO inhibitor has the advantages that the activation of the hepatic stellate cells can be obviously inhibitd, deposition of collagenous fibers can be reduced, and therefore a remarkable anti-fibrosis effect can be achieved.

The present invention immunizes mouse with HAb18G / CD147 extra-cellular region protein to prepare specific hybrid tumor cell strain HAb18Gedomab1, obtain monoclonal antibody HAb18Gedomab1, which can combine specifically to HAb18G / CD147 expressed effectively in human liver fibrosis tissue and liver stellate cell and possesses functions of promoting MMPs secretion and degrades extra-cellular matrix. The antibody may be used in preparing medicine for reversing liver fibrosis and other matrix deposition related diseases. The present invention clones the light and heavy chain variable area genes successively. Several forms of small molecular gene engineering antibody are constituted and expressed based on the genes and gene engineering method, and the polypeptide coded based on the genes is cross-linked with several effect factors, so as to prepare medicine for reversing liver fibrosis and other matrix deposition related diseases.

The invention belongs to the field of medicine chemistry, and particularly relates to a 2-amino-7-substituted benzothiazole compound as well as a preparation method and application thereof. The 2-amino-7-substituted benzothiazole compound can be used for remarkably inhibiting synthesis of activated rat liver star-shaped cell collagen I type and extracellular matrix and regulating the expression of relevant synthetic gene and enzyme, has an obvious inhibition effect on generation of mouse liver fibrosis model cell periplasm, and can be used as a medicine for resisting hepatitis and liver fibrosis. The preparation method of the 2-amino-7-substituted benzothiazole compound adopts raw materials which are wide in source, and is short in reaction steps, simple and convenient in after-treatment and relatively high in yield.

The invention discloses applications of a DLK1 gene as a target spot for curing hepatic fibrosis-renal tubular ectasia syndrome; namely the DLK1 gene is used as the target spot for designing a relevant medicine to reduce DLK1 expression and inhibit hepatic stellate cell activation so as to reduce the hepatic fibrosis-renal tubular ectasia syndrome. The invention also discloses applications of siRNA, bone marrow mesenchymal stem cells and cell factors FGF2 to preparing the medicine for curing the hepatic fibrosis-renal tubular ectasia syndrome.

The present invention provides compositions and methods for selectively inhibiting the proliferation of stellate cells, which are important for the development of liver fibrosis upon liver injury. The invention describes conditioned media from immortalized hepatocytes as containing a death factor that induces apoptosis of activated liver stellate cells. This pro-apoptotic activity is shown to be associated with an 80 kDa protein, which is associated with a fetuin peptide sequence and an albumin peptide sequence.

The invention provides a traditional Chinese medicine composition for treatment of liver lenticular degeneration hepatic fibrosis. The traditional Chinese medicine composition is prepared from the following raw materials of radix rehmanniae preparata, fructus schisandrae, radix morindae officinalis, radix salviae miltiorrhizae, curcuma zedoary, rhizoma curcumae longae, radix et rhizoma rhei, herbalysimachiae and rhizoma coptidis. The invention further provides application of the traditional Chinese medicine composition to the treatment of liver lenticular degeneration hepatic fibrosis. According to the traditional Chinese medicine composition for the treatment of liver lenticular degeneration hepatic fibrosis, the action of tonifying the kidney and resolving the turbidity, and activatingthe blood and removing the stasis is achieved, the action of a Chinese herbal compound is performed in multiple links and at multiple levels for pathogenesis (copper metabolic block)-kidney deficiency, a key link (liver sternzellen activation and proliferation)-phlegm stagnation, the end (hepatic fibrosis)-accumulation and the like, and the characteristic of treating both the symptoms and root causes is achieved; theories of 'homogeny of the liver and kidney' and 'marrow losing and liver producing' of the traditional Chinese medicine are applied for the first time, and WD hepatic fibrosis is diagnosed and treated from the 'kidney'; and mutual confirmation is achieved from clinical and experimental aspects, the traditional Chinese medicine composition has the remarkable therapeutic effect on WD hepatic fibrosis, the purpose of treating both the symptoms and root causes is achieved, and good application prospects are achieved.

The invention in general relates to human hepatic 3D co-culture models, more in particular 3D spheroid co-cultures of human hepatocyte-like cells and hepatic stellate cells. Furthermore, the invention provides a method for obtaining such co-cultures, as well as the use of said co-cultures in the identification of pro-fibrotic and / or anti-fibrotic compounds.

The invention relates to novel application of massoia lactone and 5-hydroxy-2-caproleic acid. An animal model test proves that for a CCL4 induced mouse hepatic fibrosis and liver cirrhosis model, after massoia lactone or 5-hydroxy-2-caproleic acid is used for intervention, the abnormal liver function can be remarkably improved, the serum aspartate amino transferase, glutamic-pyruvic transaminase and the total bilirubin level are lowered, the content of hepatic tissue hydroxyproline is decreased, hepatic stellate cell activation is inhibited, the type I collagen expression is reduced, and liver tissue collagen deposition is restrained; for a HepG-2 nude-mouse transplanted tumor model, after massoia lactone or 5-hydroxy-2-caproleic acid is used for intervention, increase of the weight and size of transplantation tumors can be remarkably inhibited. Accordingly, the two compounds can be used for preparing liver fibrosis, liver cirrhosis and liver cancer resistance drugs.

Although it is known that adiponectin, which is adipose-specific protein, has effects of suppressing the proliferation and migration of vascular smooth muscle, an effect against arteriosclerosis, an effect of inhibiting the activation of monocytes and macrophages and an anti-inflammatory effect, its action on hepatic stellate cells has never been known hitherto. The present invention has elucidated that adiponectin inhibits the actions of TGFB and PDGF on hepatic stellate cells and thereby exerts effects of suppressing hepatic fibrosis and promoting the proliferation of normal hepatocytes.

The invention belongs to the technical field of medicines, and discloses an application of an andrographolide derivative in the preparation of medicaments for preventing and treating various fibrosis.The invention relates to an application of 14-deoxy-11, 12-dehydrogenation-7, 8-ene-andrographolide and a 15-subunit substituted derivative. Experiments prove that the compound obviously inhibits themigration and activation of hepatic stellate cells; significantly inhibits TGF-beta1 induced mesenchymal transformation of human alveolar type II epithelial cells A549; significantly inhibits TGFbeta1 induced HK-2 mesenchymal transformation of human renal cortical proximal tubular epithelial cells; inhibits the migration of HCFB in primary human cardiac fibroblasts induced by angiotensin II (AngII). In a model of common bile duct ligation in mice, a model of pulmonary fibrosis induced by silica in mice and a model of unilateral ureteral ligation in mice, the compound shows good anti-fibrosisactivity in vivo. The compound is used as an active ingredient for preparing the anti-fibrosis medicament, has high efficiency and low toxicity, and has a good prospect of developing various anti-fibrosis medicaments.

The invention relates to the biomedical field, and provides a process for preparing recombinant plancenta hominis globin renaturation expression and medicine application of the recombinant plancenta hominis globin to protect alcoholic liver injury. Cytoglobin (Cytogblobin, CYGB) is initially named as Hepatic Stellate cell activation-associated protein, STAP). After rhCYGB is expressed by colibacillus, renaturation and separation and purification efficiency of rhCYGB can be increased through manually adding heme renaturation and utilizing Sephacryl S-200 gel chromatography to purify. The recombinant hominis globin can effectively prevent alcoholic liver injury and can be used for preventing or curing alcoholism and alcoholic liver injury.

The invention provides an application of a lignans compound in preparation of an anti-hepatic fibrosis medicine. In-vitro, in-vivo and molecular-level tests prove that the lignans compound has strongeffect of inhibiting proliferation of hepatic stellate cells and resisting the hepatic fibrosis, and also has lower IC50 value to matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9) and transforming growth factor-beta1 (TGF-beta1). The lignans compound can be combined with the substances mentioned hereinabove and can inhibit the bioactivities of the substances, so that the lignanscompound can be used as an anti-hepatic fibrosis medicine.

The invention discloses preparation and application of traditional Chinese medicine herba centipedae active monomer component helenalin. A monomeric compound helenal is separated from the traditionalChinese medicine herba centipedae; experiments prove that the helenal can effectively inhibit herba centipedae activation and proliferation, reduce collagen deposition and reduce synthesis of inflammation-related protein, and the mechanism may be related to inhibition of PI3K / Akt channel signal conduction. A new traditional Chinese medicine monomer for effectively inhibiting hepatic stellate cellactivation is provided for treating hepatic fibrosis.

The invention discloses application of a low molecular weight basic fibroblast growth factor LMW FGF2 in preparing medicament for resisting liver fibrosis. The low molecular weight basic fibroblast growth factor LMW FGF2 provided by the invention can inhibit the expression of HSCs activation marker genes alpha smooth muscle actin (alpha-SMA) and collagen type I [col I (alpha 1)], and thereby inhibiting the activation of hepatic stellate cells and decrease liver fibrosis.

The present invention relates to the pharmaceutical composition for prevention and treatment of liver diseases containing pyrazolopyrimidine derivative as an active ingredient. According to the present invention, pyrazolopyrimidine derivative has an excellent effect on inhibiting collagen synthesis in hepatic stellate cells and acts directly on the portal vein. Particularly, it may increase the diameter and the amount of blood flow of the portal vein, and finally decrease the pressure thereof. Therefore, pyrazolopyrimidine derivative can be used advantageously for prevention and treatment of hepatic fibrosis, liver cirrhosis caused by hepatic fibrosis, portal hypertension and various complications caused by portal hypertension. In addition, pyrazolopyrimidine derivative according to the present invention can reduce dosing frequency because of its long half-life, and therefore, has an advantage to improve the drug compliance of patients suffering from chronical liver diseases.

The invention discloses an application of breviscapine in hepatic stellate cell migration inhibition drug preparation. According to the present invention, a PDGF-induced human hepatic stellate cell line (LX-2) migration screening platform is designed, and results show that PDGF-induced hepatic stellate cell (HSC) migration can be inhibited with 10<-4>-10<-7> mol / L breviscapine.

The invention discloses application of snow chrysanthemum extract and snow chrysanthemum total flavone in preparation of a drug for treating hepatic fibrosis. According to a cell experiment and an animal experiment, the snow chrysanthemum extract is given to a hepatic stellate cell line LX-2 and a CC14-induced hepatic fibrosis rat model separately, and a cell experiment result shows that the snow chrysanthemum extract can significantly reduce the DNA binding capacity of NF-kappa B, lower fibrosis markers alpha smooth muscle actin and cell matrix protein I type collagen and promote LX-2 cell apoptosis; an in-vivo result shows that compared with the model group, the snow chrysanthemum extract can decrease the content of AST and ALT of a hepatic fibrosis rat, decrease the content of hepatic collagen and reduce expression of the alpha-SMA and an ECM, and after hepatic tissue is subjected to ultrasonication to form homogenate suspension, it can be found that the DNA binding capacity of the NF-kappa B is significantly reduced; the snow chrysanthemum extract can be used for preparing the drug or functional food for treating the hepatic fibrosis by serving as an NF-kappa B signal channel inhibitor.

The invention discloses a separating method and culturing method for hepatic stellate cells of a Mongolian gerbil. The separating method includes the steps that 1, the livers of the Mongolian gerbil are moved into a combined enzyme solution to be subjected to perfused digestion, then liver capsules and Glisson pedicles are removed, the livers are smashed to be pasty, the paste is moved into a combined enzyme solution, the mixture is stirred for digestion, and a stirred digestion product is obtained; 2, a first Hank's solution is added, the mixture is filtered, liver tissues are obtained, then a second Hank's solution is added, primary centrifuging is carried out, sediment is obtained, the sediment is suspended again through a third Hank's solution, then a Nycodenz solution is added, the mixture is mixed to be even, centrifuging is carried out again, and a turbid band, namely, the separated hepatic stellate cells is obtained. The separating and culturing method includes the steps of separating and culturing. By means of the methods, the yield and the survival rate of the hepatic stellate cells can be increased, the purity of the HSCs can be guaranteed, and a foundation is laid for further researching of deposition of cell matrixes and forming of fibrosis of the hepatic stellate cells after the livers are injured.

The invention belongs to the field of biomedicine and relates to application of antibacterial peptide YD in preparing drug for treating hepatic fibrosis. The antibacterial peptide YD is antibacterialpeptide (APKGVQGPNG) separated and purified from bacillus amyloliquefaciens CBS antibacterial peptide YD1 reported in 2017, and in-vitro experiments prove that the antibacterial peptide YD has antibacterial activity and antioxidation activity. By allowing the antibacterial peptide YD to act on two cell models including a human hepatic satellite cell (LX-2) model and a lipopolysaccharide induced mice macrophage (RAW264.7) inflammation model and an in-vivo hepatic fibrosis mice model, it proves that the antibacterial peptide YD hinders occurrence and development of hepatic fibrosis by inhibitinginflammatory reaction, has effect of resisting hepatic fibrosis and is low in cytotoxicity, so that the antibacterial peptide YD can be taken as an active ingredient to prepare hepatic fibrosis resistant drug different in dosage forms by adopting pharmaceutically conventional processes and auxiliary materials, thereby having great medicinal application prospect.

The invention discloses an application of astragalosides in hepatic stellate cell migration inhibition drug preparation. According to the present invention, a PDGF-induced human hepatic stellate cell line (LX-2) migration screening platform is designed, and results show that PDGF-induced hepatic stellate cell (HSC) migration can be inhibited with 10<-4>-10<-7> mol / L astragalosides.

The invention belongs to the field of medicine chemistry, and particularly relates to a 2-amino-7-substituted benzothiazole compound as well as a preparation method and application thereof. The 2-amino-7-substituted benzothiazole compound can be used for remarkably inhibiting synthesis of activated rat liver star-shaped cell collagen I type and extracellular matrix and regulating the expression of relevant synthetic gene and enzyme, has an obvious inhibition effect on generation of mouse liver fibrosis model cell periplasm, and can be used as a medicine for resisting hepatitis and liver fibrosis. The preparation method of the 2-amino-7-substituted benzothiazole compound adopts raw materials which are wide in source, and is short in reaction steps, simple and convenient in after-treatment and relatively high in yield.