38 results about "Hepatocyte apoptosis" patented technology

The invention relates to a preparation method of a hepatocyte apoptosis animal disease model by coinduction of D-galactosamine and lipopolysaccharide, in particular to a simple inducer formula and a simple operation process which can generate a hepatocyte apoptosis rate above 80% and reproduce a stable and reliable hepatocyte apoptosis animal model. The invention also relates to the application of the hepatocyte apoptosis animal model to the research on the pathogenesis of hepatitis and evaluation of novel anti-hepatitis medicaments.

The disclosure provides for a method for treating a fatty liver disease or disorder in a subject in need thereof, comprising selecting a subject having or suspected of having a fatty liver disease or disorder, wherein the subject is non diabetic, pre-diabetic, mildly diabetic; has normal or substantially normal biliary tract function; or has non or early stage hepatocyte apoptosis; and administering a therapeutically effective amount of a pharmaceutical composition comprising EPAs.

The invention relates to polypeptide and application thereof, in particular to polypeptide capable of promoting hepatocyte proliferation and / or inhibiting hepatocyte apoptosis and application thereof.Amino acid sequence of the polypeptide is selected from at least one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. The polypeptide has activity equivalent to orbetter than that of HIP / PAP and has the advantages of being small in molecular weight, easy in synthesis and low in immunogenicity, thereby having wide application prospect.

An application of human s DR5 protein in preparing the medicines for treating the viral hepatitis B, especially the acute severe viral hepatitis B, by protecting liver cells and preventing the wither of liver cells is disclosed.

The invention belongs to the field of molecular biology, relating to the applications of Grp75 in the preparation of drugs for the treatment of oxidative damages of liver cells and liver fibrosis by using gene transfection techniques. According to the invention, based on that Grp75 is an important chaperone in cytoplasm and mitochondria, wherein the 1-23 loci of the N-terminal thereof is a mitochondrial transmembrane signal, can help a protein to be correctly folded, assist the transport of the protein, and has the characteristics such as removal of ROS and antiapoptosis, experiments of cytoprotective effects of Grp75 on H2O2-induced oxidative stress in cells, and protective effects on CCL4-induced hepatic fibrosis as a pathological basis in animal models are carried out. When an injury occurred in the liver cells, the GRP75 gene is transfected in the cells, and the expressions of Grp75 protein are upregulated respectively at a cells level and a whole level; and results show that the effect of the treatment of liver fibrosis can be achieved through the effects of anti-oxidative damage and inhibition of hepatocyte apoptosis of the Grp75 protein. The Grp75 gene of the present invention can be used for preparing drugs for the treatment of liver fibrosis.

The invention discloses an evaluation model for early prediction of non-alcoholic steatohepatitis (NASH) and a calculation formula. According to the model, large-sample-size hepatic puncture pathological diagnosis is used as a grouping basis, an M30 fragment of a hepatocyte apoptosis marker keratin 18 is introduced, a new algorithm and a calculation formula are obtained by adding age, gender, height, waistline, hemoglobin, glutamic-pyruvic transaminase and gamma-glutamyl transpeptidase for simulation, the negative prediction value of the formula applied to early-stage NASH reaches 0.902, and the area under an ROC curve reaches 0.826.

The invention discloses an application of a targeted complement inhibitor in preparation of drugs for improving brain death donor livers. The application of the targeted complement inhibitor in preparation of the drugs for improving the brain death donor livers is characterized in that a complement receptor 2 (CR2) is utilized to connect a membrane binding regulatory factor Crry; with targeted binding of the CR2 to complement activation and local injury, the membrane-binding regulatory factor utilized to regulate different stages of complement cascade, and a mouse brain death model established, the changes of the liver functions between a CR2-Cryy treatment group and a control group are compared; results indicate that the targeted complement inhibitor CR2-Crry is effective in improving donor liver injury after brain death and can reduce liver inflammatory response, oxidative stress damage and hepatocyte apoptosis. The role of this complement inhibitor in improving donor liver functionafter brain death is further confirmed by complement knockout mice.

The invention discloses an application of methane injection in preparation of medicaments for treating ischemia-reperfusion injury, which comprises a preparation method of the methane injection. Animal experiments are performed on the methane injection, and the results prove that the methane injection can be used for obviously reducing the level of alanine transaminase, reducing liver injury and reducing hepatocyte apoptosis against a rat model with liver ischemia-reperfusion injury, so that the methane injection can be used for treating the liver ischemia-reperfusion injury. Thus, the methane injection disclosed by the invention can be used for preparing the medicaments for treating the ischemia-reperfusion injury.

The invention relates to an application of caffeic acid in preparation of drugs for treating hepatic microcirculation disturbance and hepatic injury. Through a series of observation of caffeic acid on hepatic ischemia reperfusion rats, caffeic acid is found to improve the hepatic surface blood flow quantity by the action routes: AMPK[alpha] phosphorylation and PKC[delta] membrane translocation are inhibited, NADPH subunit P41 and P47 membrane translocation is inhibited and NADPH-derived peroxides are inhibited; the activity of a hepatic ischemia reperfusion rat mitochondria respiratory chain is improved, and peroxide production caused by mitochondria injury is reduced, so as to increase the production of ATP; hepatocyte apoptosis caused by ischemia reperfusion is inhibited; and hepatic cell internal cytoskeleton injury caused by ischemia reperfusion is attenuated. The new application in preparation of the drugs for treating hepatic microcirculation disturbance and hepatic injury is provided.

The invention discloses polypeptide GPR5 and application thereof to promoting of hepatocyte proliferation and inhibiting of hepatocyte apoptosis. The invention discloses polypeptide and application thereof to promoting of hepatocyte proliferation and / or inhibiting of hepatocyte apoptosis. According to the polypeptide capable of promoting hepatocyte proliferation and / or inhibiting hepatocyte apoptosis, compared with an amino acid sequence shown in SEQ ID NO:1, the amino acid sequence of the polypeptide has 3 / 5 or above sequence consistency, the polypeptide length is 5 amino acids, the polypeptide has the advantages of being small in molecular weight, easy to synthesize, low in immunogenicity and the like, and therefore the polypeptide has broad application prospects in treatment of hepatopathy.

The invention relates to the field of biological medicines. A hepatocyte growth factor (HGF) activating factor is plasma protein secreted by hepatocyte, and an activated HGFA is 33Kd polypeptide, is just distributed in the damaged tissues and organs, can activate the monomer HGF secreted by a liver nonparenchyma cell into the HGF at the damaged local part and plays roles of cell protection and tissue repair at the local parts of the damaged tissues and organs. The acute and chronic liver function failure has the main pathological characteristics of large-area hepatocyte apoptosis and necrosisand hepatocyte reproducing function inhibition. The clinical manifestation is dangerous, and the mortality of a patient is as high as 70-90 percent because of lacking an effective curing approach. Theinvention provides a recombinant anthropogenic HGF activating factor which has a nucleotide sequence and a coded amino acid sequence shown as SEQ ID NO:3 and can be used for an application of preparing a medicine for treating acute or subacute severe hepatitis hepatocyte necrosis.

The present invention discloses a polypeptide and uses thereof for promoting liver cell proliferation and / or inhibiting hepatocyte apoptosis. An amino acid sequence of the polypeptide capable of promoting hepatocyte proliferation and / or inhibiting hepatocyte apoptosis has a sequence identity of 3 / 4 or more compared with an amino acid sequence shown in SEQ ID NO:1, length of the polypeptide is 4 amino acids, and the polypeptide has advantages of small molecular weight, easy synthesis, low immunogenicity, etc., and thus has broad application prospects in treatment of liver diseases.

The invention provides application of rhIL-1Ra in preparing medicaments for treating acute liver failure. Compared with a control group, the rhIL-1Ra can obviously inhibit the activity of alanine aminotransferase and aspartate aminotransferase in serum, the death of liver cells is reduced, and the proliferation of the liver cells is promoted, so that the rhIL-1Ra has obvious therapeutic effects ofprotecting liver injury and promoting liver regeneration. In addition, the rhIL-1Ra inhibits apoptosis mediated by caspase-3, caspase-8 and caspase-9 activation in liver tissue by decreasing mitochondrial cytochrome c release. In summary, the rhIL-1Ra provides a strategy for the preparation of candidate drugs capable of reducing hepatocyte apoptosis for the treatment of APAP-induced acute liver failure and liver injury.

The invention relates to a method for maturation and amplification of hepatocyte-like cells. The method comprises the following steps: S1, culturing stem cells in vitro by using an induction liquid toinduce mesenchymal stem cells to differentiate into hepatocyte-like cells; S2, injecting the hepatocyte-like cells into the liver vector of an FAH gene-deficient rat through the spleen in a fixed-point manner; S3, stimulating FAH gene-deficient rat liver vector autologous hepatocyte apoptosis, and promoting maturation and proliferation of the hepatocyte-like cells; and S4, separating and purifying to obtain human primary hepatocyte. Human mesenchymal stem cells are induced in vitro to form the hepatocyte-like cells, the hepatocyte-like cells are injected into the liver of the FAH gene-deficient rat in the fixed-point manner through the spleen, and the internal environment of the liver of the FAH gene-deficient rat is utilized to efficiently differentiate the hepatocyte-like cells into mature human hepatocytes and realize rapid amplification of the hepatocytes. Therefore, the defects of immaturity, small scale, high cost and the like of the hepatocytes obtained by a hepatocyte in-vitroregeneration method are overcome.

The invention belongs to the technical filed of medicine, and discloses a compound in sabia parviflora and a preparation method and an application thereof. The compound is 2-methyl-2-hydroxymethyl-5,6-dihydroxy-7-(3-methyl-3-hydroxy-1-butenyl)-1H-indene-1-ketone-3-O-glucoside. The preparation method of the compound is simple, and obtain the pure compound through separation. The experiment shows that the compound can obviously reduce the hepatocyte triacylglycerol content and caspase3 activity due to aliphatic acid, increases the MDA content, reduces hepatocyte apoptosis rate, and can be usedfor preventing non-alcoholic fatty liver damage. The invention provides the application of the compound in preparation of medicines for treating non-alcoholic fatty liver damage.

The invention belongs to the field of medicine research and development, and particularly relates to novel application of algin in treatment of hepatolenticular degeneration. An oral administration in-vivo animal experiment research proves that the algin can be used for complexing copper ions in an animal body, enhancing the expression of animal liver cell copper cyanin, increasing the content of serum copper cyanin, reducing the content of urine copper and liver copper and reducing the activity of serum alanine aminotransferase and aspartate aminotransferase; the hepatic fibrosis and hepatic cell apoptosis can be resisted, so that the effects of removing copper and protecting liver are achieved in the treatment of hepatolenticular degeneration. The treatment effect is good, and market application and popularization are facilitated.

The present disclosure provides a method of preventing and / or treating hepatocellular apoptosis and liver damage in a liver disease, particularly NASH, by targeting the AMPK / caspase-6 axis to inhibit caspase-6 activity and / or activate AMPK activity. Also disclosed is the pharmaceutical composition for preventing and / or treating a liver disease comprising one or more caspase-6 inhibitor and / or AMPK activator of the present disclosure. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

The disclosure provides for a method for treating a fatty liver disease or disorder in a subject in need thereof, comprising selecting a subject having or suspected of having a fatty liver disease or disorder, wherein the subject is non diabetic, pre-diabetic, mildly diabetic; has normal or substantially normal biliary tract function; or has non or early stage hepatocyte apoptosis; and administering a therapeutically effective amount of a pharmaceutical composition comprising EPAs.

The invention relates to the field of biomedicine, and provides a Kupffer cell activity inhibitor. The activity inhibitor is a recombinant human IL-1 receptor antagonist (rhIL-1Ra). Experiments find that the rhIL-1Ra significantly inhibits the activity of large Kupffer cells with high expression of IL-1RI, and inhibits the ultrastructure and phagocytic activity of Kupffer cells, thereby inhibitingthe activity of the Kupffer cells, significantly reducing hepatocyte apoptosis and promoting liver cell proliferation. According to the above conclusions, the recombinant human IL-1 receptor antagonist (rhIL-1Ra) reduces the hepatocyte apoptosis and promotes hepatocyte regeneration by inhibiting the activity of the Kupffer cells, and provides a strategy for preparing a drug for treating acute liver failure and liver injury.

The invention relates to the technical field of medicine synthesis, and provides a cholic acid derivative as well as a preparation method and application thereof. The cholic acid derivative provided by the invention has a remarkable effect of inhibiting hepatocyte apoptosis, can effectively inhibit hepatocyte damage induced by glycochenodeoxycholic acid, and the inhibition rate of part of the derivative is superior to that of a positive control tauroursodeoxycholic acid; the cholic acid derivative provided by the invention provides a reference for research and development of liver protection drugs, and has a wide application prospect in preparation of the liver protection drugs.

The invention discloses application of chicken-derived small molecule peptide in preparation of a product for preventing and improving liver injury and secondary symptoms thereof and the product, and relates to the field of food and medicine health. The small molecule peptide is a chicken-derived natural free active peptide, the small molecule peptide is specifically dipeptide Cyclo (L-Phe-L-Phe), the small molecule peptide shows strong antioxidant ability in cells, the oxidative stress state of the liver can be improved through the effects of increasing the activity of antioxidant enzyme GPx, reducing the level of oxidative stress product malonaldehyde MDA and the like, and the liver protection effect is achieved. The CPP has the advantages of low toxicity, wide medication window and high safety, and can be applied to functional foods, health foods, pharmaceuticals, compositions and other products for preventing or improving liver injury and related secondary symptoms thereof.

The invention discloses a pharmaceutical composition for treating Alpers-Huttenlocher syndrome, particularly drugs of the pharmaceutical composition and application of the drugs and pharmaceutical composition. The pharmaceutical composition for treating Alpers-Huttenlocher syndrome comprises sodium valproate and an anti-hepatic injury drug, wherein the anti-hepatic injury drug is selected from at least one of cyclosporin A, L-carnitine and N-acetylcysteine. The pharmaceutical composition can be used for treating Alpers-Huttenlocher syndrome, has favorable treatment effect, and is capable of obviously inhibit hepatocyte apoptosis, obviously relieving acute hepatic failure when the sodium valproate is used for treating patients with Alpers-Huttenlocher syndrome, and lowering the mortality of the patients.

Disclosed is a use of trimethazine in the preparation of drugs for preventing and treating liver diseases. Trimethazine is capable of inhibiting activation of resting T-cells to activated lymphocytes, reducing release of cytokines, and reducing hepatocyte injury caused by immune system; inhibiting fatty acid metabolism in hepatocytes, and optimizing the energy process in hepatocytes; and maintaining normal function of mitochondrial permeability transition pores, and reducing hepatocyte apoptosis. Trimethazine has the efficacy of maintaining the liver functions, and reducing transminase (comprising glutamic pyruvic transaminase, glutamic oxalacetic transaminase, etc.).

The invention discloses an application of a targeted complement inhibitor in preparation of drugs for improving brain death donor livers. The application of the targeted complement inhibitor in preparation of the drugs for improving the brain death donor livers is characterized in that a complement receptor 2 (CR2) is utilized to connect a membrane binding regulatory factor Crry; with targeted binding of the CR2 to complement activation and local injury, the membrane-binding regulatory factor utilized to regulate different stages of complement cascade, and a mouse brain death model established, the changes of the liver functions between a CR2-Cryy treatment group and a control group are compared; results indicate that the targeted complement inhibitor CR2-Crry is effective in improving donor liver injury after brain death and can reduce liver inflammatory response, oxidative stress damage and hepatocyte apoptosis. The role of this complement inhibitor in improving donor liver functionafter brain death is further confirmed by complement knockout mice.

The invention discloses an application of methane injection in preparation of medicaments for treating ischemia-reperfusion injury, which comprises a preparation method of the methane injection. Animal experiments are performed on the methane injection, and the results prove that the methane injection can be used for obviously reducing the level of alanine transaminase, reducing liver injury and reducing hepatocyte apoptosis against a rat model with liver ischemia-reperfusion injury, so that the methane injection can be used for treating the liver ischemia-reperfusion injury. Thus, the methane injection disclosed by the invention can be used for preparing the medicaments for treating the ischemia-reperfusion injury.

The present application relates to a preparation method of a curcuma oil clathrate that can be used for preventing or treating acute liver failure, the obtained curcuma oil clathrate and a pharmaceutical composition containing the same. The curcuma oil inclusion compound and pharmaceutical composition of the present application have obvious therapeutic effects on acute liver failure such as reducing mortality, reducing transaminase, inhibiting liver cell apoptosis and necrosis, and inhibiting immune inflammation damage.

This invention discloses an isolated peptide containing an amino acid sequence of SEQ ID No.1. The isolated peptide is capable of providing the effects in suppressing hepatocyte apoptosis, attenuating hepatic triglyceride accumulation, suppressing the expression of inflammatory cytokines, inhibiting expression of pro-apoptotic proteins, enhancing expression of survival factor and inhibiting the expression of biomarker of hepatic fibrosis. Therefore, this invention discloses the peptide as the effective ingredient in a composition for treating or preventing liver related diseases.

The invention discloses a method for constructing a rat model of non-diabetes-based severe non-alcoholic chronic steatohepatitis. Rats are given a single injection of diethylnitrosamine in two weeks after birth, and fed with high-fat and high-cholesterol cholate feeds for 8-12 consecutive weeks from four weeks after birth to construct the rat model of severe non-alcoholic chronic steatohepatitis accompanied with moderate chronic hepatic fibrosis. The model has the characteristic of severe non-alcoholic chronic steatohepatitis (NASH) accompanied with moderate chronic hepatic fibrosis; induced animals have severe fatty changes, severe inflammatory lesions and ballooning degeneration of aggravating hepatocyte apoptosis in hepatic tissue; and the rat model generates a basic pathological process of the severe NASH, especially a pathologic change accompanied with significant hepatic fibrosis.