249 results about "Hepatic stellate cell" patented technology

This invention relates to inhibition of αv integrins, especially αvβ3 and αvβ6 integrins, by specific antagonists, preferably non-peptidic antagonists, related compounds and compounds with comparable specificity, that downregulate fibrogenesis by inhibiting cell migration and production of pro-fibrogenic molecules (e.g., collagens, TIMP-1) and cytokines (e.g., CTGF) by activated hepatic stellate cells/myofibroblasts, activated epithelia and endothelia. These antagonists alone or in combination with other agents can effectively prevent, mitigate or even reverse development of advanced fibrosis, such as fibrosis/cirrhosis of the liver and fibrosis of other organs, such as lungs, kidneys, intestine, pancreas, skin and arteries.

The present invention provides methods for treating or preventing portal hypertension comprising administering to a patient in need of such treatment or prevention at least one Rev-erb modulating agent (REMA) in an amount effective to treat or prevent said portal hypertension. The REMA can be SR6452 or a related compound, such as SR9009 or SR9011. The amount of the REMA administered can comprises a quantity sufficient to modulate Rev-erbα expression, activity, and/or subcellular location and/or to inhibit or reverse hepatic stellate cell (HSC) activation and contractility.

The present invention is based on the finding that the artificial induction of hepatic stellate cell (HSC) apoptosis in vivo can promote the resolution of liver fibrosis. Thus, the present invention provides methods for treating liver disease in a subject involving administration of an inducer of apoptosis which is capable of selectively inducing hepatic stellate cell apoptosis in the liver of the subject or of an agent which is capable of giving rise to such an inducer in the subject. In addition, the invention provides methods for treating liver fibrosis in a subject comprising the selective delivery of an inducer of apoptosis specifically to the hepatic stellate cells of the subject or of an agent which is capable of giving rise to an inducer of hepatic stellate cell apoptosis.

The present invention discloses an application of tetrandrine 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 tetrandrine.

The invention relates to an oxymatrine hepatic targeting nano drug delivery system and a preparation method thereof. The oxymatrine hepatic targeting nano drug delivery system is prepared by the following steps of: with polyethylene glycol-polycaprolactone block polymer as a carrier, preparing polymer nanoparticles by adopting a film dispersion method, a reverse evaporation method or an organic solvent injection method, encapsulating oxymatrine into the polymer nanoparticles, then modifying a new glycoprotein or cyclic octapeptide ligand to be taken as a ligand on the surfaces of the nanoparticles, and constructing an anti-hepatic fibrosis nano targeting drug delivery system for hepatic stellate cells (HSCs). The nano drug delivery system has the advantages that particle size is 50-260nm, encapsulation efficiency is 18-42%, drug loading capacity is 2-12% and the surface of the nano drug delivery system is rich in new glycoprotein M6PHSA (mannose-6-phosphate human serum albumin) or cyclic octapeptide RGD (arg gly asp). The oxymatrine hepatic targeting nano drug delivery system provided by the invention can increase opportunities that nanoparticles enter the liver through blood circulation, is beneficial to targeting distribution of drugs at focus parts of the liver and is beneficial to absorption of drug-carrying nanoparticles at lesion parts of the liver and ingestion of HSCs, so that hepatic fibrosis treatment is enhanced.

The invention relates to a screening method for a medicine for targeting NS5ATP9 (HCV NS5A-transactivated protein 9) prevention or treatment of tissue fibrosis and tissue sclerosis, and the medicine obtained by screening using the method. NS5ATP9 significantly regulates the expression of extracellular matrix collagen and non-collagen glycoprotein and affects the occurrence and development of tissue fibrosis by regulating a TGFbeta1/Smad3 signaling pathway; and the NS5ATP9 promotes the apoptosis of hepatic stellate cells, inhibits the proliferation of the hepatic stellate cells and regulates extracellular matrix deposition by regulating the phosphorylation level and the intracellular translocation condition of a Smad3 protein. TDF/TAF can effectively regulate the expression of NS5ATP9 gene,and is verified in CCl4-induced mouse liver fibrosis model, and the TDF/TAF achieves significant effects in the prevention or treatment of CCl4-induced liver fibrosis in mice.

A method of inhibiting graft rejection includes isolating Hepatic Stellate Cells from a mammal liver, activating the isolated Hepatic Stellate Cells, and administering a combination of Hepatic Stellate cells and a graft to a mammal.

The invention relates to application of compounds and salt thereof, and particularly relates to application of matrine compounds and salt thereof in preparation of anti-hepatic fibrosis and anti-liver cancer medicaments. The compounds have the advantages of remarkably inhibiting the proliferation of hepatoma cell lines Hep-G2, Hun-7, MHCC-97L, SMMC-7721 and Hep-3B and proliferation activities of fibroblast BJ, human hepatic stellate cells LX-2 and hepatic stellate cells HSC-T6, and can be used for preparing medicaments for treating hepatic fibrosis and liver cancer.

The present invention provides a cell-culturing model and a method for screening compounds which can be applied in treating or preventing hepatic cirrhosis. The cell culturing model comprises a population of hepatocytes and hepatic stellate cells (HSCs) derived from co-culturing, and at least one population of the cells comprises a nucleotide sequence fragment of a reporter gene and a cell specific regulatory sequence. The cell-culturing model of the present invention can be applied in high throughput screening for effective compounds of medication, and also in understanding the functional mechanism of the effective compounds.

The invention relates to the technical field of medical bioengineering, and provided with a specificity surface molecule marker CD63 of a hepatic stem cell. The invention further provided with application of the specificity surface molecule marker CD63 of the hepatic stem cell. A method that the molecule marker is used for quickly separating, culturing and amplifying the hepatic stem cell from a liver specifically comprises the steps that the specificity surface molecule marker CD63 of the hepatic stem cell is used to quickly separate the hepatic stem cell from prepared liver cell suspension through a flow cytometer. The hepatic stem cell of the CD63+ has the characters of self-renewing and bilateral differentiation out of a body, and has therapeutical effects on a damaged mouse liver. According to the specificity surface molecule marker CD63 of the hepatic stem cell and the application of the specificity surface molecule marker CD63 of the hepatic stem cell, the hepatic stem cell obtained by separation can be served as a seed cell for liver drug screening, systematization projection liver and hepatic disease cell therapy, and provides an ideal cell model for liver development and the cell biological property research of the hepatic stem cell.

The present invention relates generally to the treatment and prevention of diseases characterized by excess cell proliferation and/or activation. In particular, the present invention provides compositions and methods to suppress the activation and/or proliferation of various cells. In some preferred embodiments, the present invention provides compositions and methods to suppress the activation and/or proliferation of mesenchymally derived cells (including, but not limited to hepatic stellate cells), as well as cells with abnormal growth characteristics. In some particularly preferred embodiments, the present invention provides compositions and methods to inhibit or eliminate fibrosis. In alternative preferred embodiments, the present invention provides compositions and methods to induce fibrosis. In still further embodiments, the present invention provides methods and compositions to treat and/or prevent cancer.

Pro-apoptotic agents such as ligands and agonists of agonistic TRAIL receptors can induce or increase apoptosis of cells that cause fibrosis and underlying diseases such as liver, pancreatic, lung and skin diseases characterized by fibrosis, cirrhosis, or complications thereof. The compositions and methods can be used to selectively remove activated hepatic stellate cells (HSCs), the originators of liver fibrosis and cirrhosis, and activated pancreatic stellate cells (PSCs), the originators of pancreas fibrosis and pancreatitis, and can be effective to reduce or prevent further chronic fibrosis by simultaneously reducing multiple fibrosis-associated molecules secreted or induced by such activated stellate cells. The compositions are typically effective to target agonistic TRAIL receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5 that are selectively expressed in activated HSCs and PSCs in physiological conditions. Ligands and agonists that can be used to target agonistic TRAIL receptors include, but are not limited to, TRAIL-R1/DR4 and/or TRAIL-R2/DR5 agonists.

Pro-apoptotic agents such as ligands and agonists of agonistic TRAIL receptors can induce or increase apoptosis of cells that cause fibrosis and underlying diseases such as liver, pancreatic, lung and skin diseases characterized by fibrosis, cirrhosis, or complications thereof. The compositions and methods can be used to selectively remove activated hepatic stellate cells (HSCs), the originators of liver fibrosis and cirrhosis, and activated pancreatic stellate cells (PSCs), the originators of pancreas fibrosis and pancreatitis, and can be effective to reduce or prevent further chronic fibrosis by simultaneously reducing multiple fibrosis-associated molecules secreted or induced by such activated stellate cells. The compositions are typically effective to target agonistic TRAIL receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5 that are selectively expressed in activated HSCs and PSCs in physiological conditions. Ligands and agonists that can be used to target agonistic TRAIL receptors include, but are not limited to, TRAIL-R1/DR4 and/or TRAIL-R2/DR5 agonists.

The invention provides an application of O-GlcNAc glycosylation modification in preventing and treating hepatic fibrosis. In the invention, excessive activation and proliferation of hepatic stellate cells as well as the expression of alpha-smooth muscle actin and I-type collagen and the formation of fibrous septum can be inhibited by enhancing O-GlcNAc glycosylation modification, and the O-GlcNAc glycosylation modification has a good application prospect in preventing and/or treating hepatic fibrosis.