352 results about "Hepatica" patented technology

Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

The present invention relates to an in vitro diagnostic method for malaria in an individual comprising placing a tissue or a biological fluid taken from an individual in contact with a molecule or polypeptide composition, wherein said molecule or polypeptide composition comprises one or more peptide sequences bearing all or part of one or more T epitopes of the proteins resulting from the infectious activity of P. falciparum, under conditions allowing an in vitro immunological reaction to occur between said composition and the antibodies that may be present in the tissue or biological fluid, and in vitro detection of the antigen-antibody complexes formed. The invention further relates to a polypeptide comprising at least one T epitope from a liver-stage specific protein produced by P. falciparum and a vaccine composition directed against malaria comprising a molecule having one or more peptide sequences bearing all or part of one or more T epitopes resulting from the infectious activity of P. falciparum in the hepatic cells.

The invention relates to methods that allow for the efficient differentiation to form pancreatic endoderm cells from pluripotent stem cells such as human embryonic stem cells and definitive endoderm cells. The invention is directly applicable to the ultimate generation of pancreatic beta cells that could be used as part of a therapy to treat or even cure diabetes. Additionally, the present invention may be used to generate liver endoderm cells from human embryonic stem cells and definite endoderm cells as well. This invention relates to a method for generating definitive endoderm and pancreatic endoderm cells from stem cells, preferably human embryonic stem cells using defined media in the absence of feeder cells. A simply two step procedure to provide pancreatic endoderm cells from embryonic stem cells represents further embodiments of the present invention.

The invention provides a cultivation method of Cyp gene knocked-out rats, and a preparation method of liver microsome of the rats. The Cyp gene knock-out herein includes Cyp single gene knock-out and Cyp multiple gene knock-out. In the method, firstly a Cyp gene knocked-out rat is constructed by means of a CRISPR / Cas system, which includes selection of a knocked-out target site, in-vitro synthesis and transcription of sg RNA and Cas9m RNA, preparation of a pseudopregnant female rat, in-vitro micro-injection and transplanting of a single-cell embryo, and cultivation of the rat, and finally, a homozygote Cyp gene knocked-out rat can be cultured. Furthermore, the liver of the Cyp gene knocked-out rat is extracted and is subjected to homogenization and differential centrifugation to prepare the liver microsome of the rat in Cyp gene deletion. The invention also provides an application of the Cyp gene knocked-out rats and the liver microsome thereof in study on drug metabolism.

A method is provided for screening a subject for hepatocellular carcinoma by determining the level of glypican-3 (GPC3) in a body fluid sample from the subject. A further method is provided for diagnosing hepatocellular carcinoma by detecting GPC3 in a liver tissue sample. Also provided are antibodies which bind specifically to GPC3.

The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin.

A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein. The method includes the steps of providing a culture of hepatocytes comprising a transport protein, the culture having at least one bile canaliculus; exposing a candidate compound to the culture; and determining an amount of candidate compound in the at least one bile canaliculus, the amount of candidate compound in the at least one bile canaliculus indicating the susceptibility of the candidate compound to biliary excretion by the transport protein. In some embodiments determining the amount of candidate compound in the bile canaliculus comprises inhibiting expression of the transport protein, measuring the amount of candidate compound in the bile canaliculus and comparing amounts of compound in the canalicules with and without inhibition of the transport protein. A difference in the amount of candidate compound in the canaliculus indicates susceptibility of the candidate compound to biliary excretion by the transport protein. In one embodiment, expression of the transport protein is inhibited through introduction of a RNA having a sequence corresponding to a coding strand of the gene encoding the transport protein into the hepatocyte. Optionally, the culture of hepatocytes is a long-term culture in a sandwich configuration. The method is particularly applicable to the screening of multiple candidate compounds in a single effort.

One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. Although embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. The present invention provides for a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. In one embodiment, mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiate and proliferate into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17 and AFP, and could further differentiate into hepatocyte-like cells that demonstrate hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.

Disclosed is a method for expressing hepatitis C virus in an in vivo, animal model. Viable, hepatitis C virus-infected, human hepatocytes are transplanted into a liver parenchyma of a scid / scid mouse host. The scid / scid mouse host is then maintained in a viable state, for up to five days or greater, whereby viable, morphologically intact human hepatocytes persist in the donor tissue and hepatitis C virus is replicated in the persisting human hepatocytes.

The present invention features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection. The animals of the invention are also useful in assessing toxicity of various agents, as well as the activity of agents in decreasing blood lipids.

This invention relates to method of diagnosing the presence and / or severity of a liver pathology and / or of monitoring the effectiveness of a curative treatment against a liver pathology in an individual, leading to a score, comprising the combination, of at least one blood test and of at least one data issued from a physical method of diagnosing liver fibrosis, said data being selected from the group consisting of medical imaging data and clinical measurements, said combination being performed through a mathematical function.This invention also relates to a method wherein the combination through a mathematical function, of at least one blood test and of at least one data issued from a physical method of diagnosing liver fibrosis, is performed at least twice and the at least two resulting scores are combined in an algorithm based on the diagnostic reliable intervals.

The invention relates to the field of bioengineering technology, and in particular to a method for in-vitro induction of cholangiocyte-like transformation of primary hepatocytes and for long-term culture, amplification and differentiation and an application of the method. The invention provides a hepatocyte cholangiocyte-like transformation medium determined by chemical ingredients and / or a system which is composed of a hepatocyte mature medium and is applicable to long-term stable culture, amplification and differentiation of the primary hepatocytes; the invention also provides the method for in-vitro induction of cholangiocyte-like transformation of the primary hepatocytes and for long-term culture, amplification and differentiation; and with the application of the method, the cholangiocyte-like hepatocyte conversion of the primary hepatocytes can be induced in vitro, so that the obtained hepatocytes have characteristics of biliary epithelial cells and hepatic precursor cells, and the hepatocytes are applicable to long-term stable culture and amplification. The breedable cholangiocyte-like hepatocytes and hepatocytes, which are mature in differentiation, prepared by the invention are applicable to such aspects as toxicologic and pharmacological evaluation of compounds and drugs, researches and diagnosis & treatment of hepatitis viruses, treatment by hepatocyte transplantation, preparation of bioartificial liver and the like.

The invention disclosed in this application relates to a pharmaceutical formulation prepared from the biotyped variety of the medicinal plant, Phyllanthus amarus which is useful for the treatment of Hepatitis B (both acute and chronic), Hepatitis C (both acute and chronic) and other related viral infections of the liver with antihepatotoxic and liver cell regenerating potentials and immunomodulating properties. The invention confirms, that when pars of the biotyped variety of the medicinal plant, Phyllanthus amarus are extraceted separately with a polar solvent alone, polar solvent and water in specific ratios and water alone and when such extracts are mixed together, the resultant formulation has all the essential antiviral and biological properties, while the individual polar or aqueous extracts alone does not possess one or more of these properties. The present invention also relates to a process for the preparation of the above said new pharmaceutical formulation with biological and chemical standardisation protocols.

The invention provides long noncoding RNA (ribonucleic acid) CLMAT1 related with colorectal liver metastasis and application of the long noncoding RNA CLAMT1. The long noncoding RNA CLAMT1 is positioned at a 14th chromosome chr14: 101379770-101381326, hg19; the gene sequence length is 1557bp. Compared with normal intestinal tissues, intestinal tissues with the intestinal cancer has high expression of CLAMT1 which is positively correlated with liver metastases of colorectal cancer; in addition, bad prognosis of patients also indirectly prompts that the liver metastasis probability of the patients is relatively high.

The invention relates to a detection method for simultaneously determining the metabolic products of seven CYP450 enzyme probe substrate in human liver microsomes, and belongs to the technical field of biological detection. The detection method comprises the following steps: performing incubation on specificity probe substrates of CYP450 enzyme and the human liver microsomes for different periods of reaction time to generate corresponding metabolic products, using Zaltoprofen as an interior label, adopting a high performance liquid chromatography-tandem mass spectrometry after protein precipitation pretreatment, and thus simultaneously detecting the concentrations of the metabolic products of seven probe substrates. The method disclosed by the invention is high in specificity, high in sensitivity and simple and convenient in operation, and has already successfully been applied to the research of baicalin on CYP450 enzyme inhibiting action of the human liver microsomes.

The invention discloses a medicinal liquor which has the functions of liver nourishing and kidney tonification. The medicinal liquor of the invention comprises ingredients of 30g prepared rehmannia root, 10 centipedes, 20g rhizoma atractylodis, 1 seal genital, 20g mulberry, 30g Morinda officinalis, 30g herba cistanches, 150g actinolite, 300g medlar, 200g polygonum, 200g herba epimedii, 300g fructus rosae laevigatae, 70g cornu cervi pantotrichum, 200g ginseng, 100g earthworm, 100g rhizoma curculiginis, 150g amur corktree bark, 150g rhizoma anemarrhenae, 300g semen cuscutae, 200g himalaya teasel, 300g semen psoraleae, 80g cordyceps sinensis, 15 pairs of geckos, 15 snow lotuses and 30g saffron, which are added with 25 kg grain liqueur with more than 100 proof to be soaked for above half a year. Drinking 50 to 100g of the obtained liquor for each day can result in endocrine balance in various ways, fundamental human immunity enhancement and reasonable addition of nutrition and has curative effect on rheumatoid arthritis, lumbar disc protrusion, arthritis, sciatica, vasculitis and impotence.

Mouse genes differentially expressed in comparisons of older and younger livers by gene chip analysis have been identified, as have corresponding human genes and proteins. The human molecules, or antagonists thereof, may be used for protection against faster-than-normal biological aging, or to achieve slower-than-normal biological aging. The human molecules may also be used as markers of biological aging.

The invention discloses a rapid screening method for comprehensively evaluating the in-vitro inhibitory effect of nine human liver CYP450 metabolic enzymes by utilizing 14 probe substrates and 16 probe reaction. The invention mainly relates to a method for monitoring metabolic activity variation of 9 human liver CYP450 enzymes and rapidly and comprehensively evaluating an inhibitory effect of a tested compound on the metabolic enzyme by adopting an in-vitro mixed probe incubation method and LC / MS / MS. According to the method, the exclusiveness and diversity of the probe substrate, interaction of the probe substrates, influence of different inoculation conditions (by charging organic solvent, buffer solution and BSA) in a warm inoculation system and the enzyme kinetics characteristics of 16 probe reactions under the selected inoculation condition are comprehensively considered, a brand new in-vitro system is established by integrating high-sensitive and high-selective LC-MS / MS technology, so that the inhibitory effect of the tested compounds on the nine human liver main metabolic enzymes can be more accurately and comprehensively predicted in the high-throughput screening of the novel drug development, and the predictability on the interaction of the later metabolism can be improved.

The novel gene, Rasp-1, which is up-regulated in regenerating liver, is disclosed. The novel RASP-1 protein, which is encoded by the Rasp-1 gene, is also disclosed. In addition, antibodies against the Rasp-1 gene products are also disclosed. Furthermore, the use of Rasp-1 nucleic acid sequences, Rasp-1 gene products, and antibodies against Rasp-1 gene products in the treatment and diagnosis of liver disorders is also disclosed.

Isolated polynucleotide molecules and peptides encoded by these molecules are used in the analysis of human carbamyl phosphate synthetase I phenotypes, as well as in diagnostic and therapeutic applications, relating to a human carbamyl phosphate synthetase I polymorphism. By analyzing genomic DNA or amplified genomic DNA, or amplified cDNA derived from mRNA, it is possible to type a human carbamyl phosphate synthetase I with regard to the human carbamyl phosphate synthetase I polymorphism, for example, in the context of diagnosing and treating hepatic veno-occlusive disease (HVOD) associated with bone marrow transplants.

Non-human mammalian hosts are provided, comprising functional human hepatocytes. Isolated human hepatocytes or fragments of human hepatic tissue are introduced into the xenogeneic host in conjunction with one or more agent that stimulates human hepatocyte growth factor receptor. The human hepatocytes are maintained in the host by administration of one or more agent that stimulates human hepatocyte growth factor receptor, either continuously (e.g., via an implanted catheter or intravenous apparatus) or in discrete, regular dosages of the agent (e.g., via intravenous injections or oral dosages). The human hepatocytes are able to survive and function in the host animal for a period of at least 5 months.

Methods of isolating and cryopreserving progenitors from human liver are disclosed which include processing human liver tissue to provide a substantially single cell suspension comprising progenitors and non-progenitors of one or more cell lineages found in human liver; subjecting the suspension to a debulking step, which reduces substantially the number of non-progenitors in the suspension, and which provides a debulked suspension enriched in progenitors exhibiting one or more markers associated with at least one of the one or more cell lineages; and selecting from said debulked suspension those cells, which themselves, their progeny, or more mature forms thereof express one or more markers associated with at least one of the one or more cell lineages. Among these markers are CD14, CD34, CD38, CD45, and ICAM. Hepatic progenitors are characterized as being 6-15μ in diameter, diploid, glycophorin A−, CD45−, AFP+++, ALB+, ICAM+, and with subpopulations varying in expression of CD14+. CD34++, CD38++, CD117+. These progenitor subpopulations have characteristics expected for cells that are particularly useful in liver cell and gene therapies and for establishing bioartificial organs.

The invention discloses an in-vitro construction method of a liver cancer organ model. Liver cancer cells, hepatic stellate cells and liver sinusoidal endothelial cells are suspended in a culture medium A in a specific proportion; on the fourth day of culture, half of culture liquid is replaced, and culture is maintained; from the seventh day, the culture medium A is replaced with a culture mediumB, and then culture is continuously conducted for seven days; amplification subculture is conducted on the fourteenth day. On the basis of complex cellularity in a tumor microenvironment, the 3D liver cancer organ in-vitro model which is uniform in size, stable in structure, capable of being used for detecting the effectiveness of anticancer drugs and capable of achieving multiplication culture is quickly constructed. The constructed liver cancer organ model is simple in method, quick to construct, high in operability and suitable for researching a liver cancer generation and development mechanism, high-throughput screening of liver cancer drugs and the like, and has industrialization significance.

This invention provides therapeutic compositions and combinations for the protection, treatment and repair of liver tissue. The invention relates to novel compositions and combinations comprising two or more compounds selected from the group consisting of S-adenosylmethionine, L-ergothioneine, and a substance selected from the group consisting of constituents of Milk thistle (Silybum marianum), silymarin and active components of silymarin, whether naturally, synthetically, or semi-synthetically derived, and to methods of preventing and treating liver disease and of repairing damaged liver tissue. The invention also provides a method of administering these compositions and combinations to humans or animals in need thereof.

Polypeptides whose expression is upregulated in liver tumor cells and cells from liver preneoplastic foci relative to expression in normal liver cells are disclosed as are polynucleotides that encode the polypeptides. In humans, the polynucleotide maps to a region of chromosome 15. The overexpression has also been confirmed in human liver, breast, colon and kidney cancer cell lines. It is believed that the polypeptides are overexpressed in tumor and preneoplastic cells in general.

Novel adult liver progenitor cells (called H2Stem Cells) have been have been characterized on the basis of a series of biological activities and markers. Methods for producing H2Stem Cells allow providing such cells in the form of adherent cells and three-dimensional cell clusters in suspension that can be differentiated into cells having strong liver-specific activities and / or that can be used for treating liver diseases or for evaluating the efficacy, the metabolism, and / or toxicity of a compound.

This invention relates to an artificial live bioreactor with nanofiber scaffold material as the culture medium for liver cells. A plasma inlet and an oxygen inlet are set at one end of the bioreactor hull, while a plasma outlet and an oxygen outlet are set at the other end. A nutrient solution inlet and an outlet are set at both ends of one side of the bioreactor hull, respectively. A culture medium composed of nanofiber scaffold and hollow fibers is set in the bioreactor hull. The nanofiber scaffold and the hollow fibers form coiled sandwich structure, with the nanofiber scaffold coiled into spiral drum and the hollow fibers encapsulated in the interlayer. The liver cell aggregates are adhered to the hollow fibers. An oxygen passage is set in the bioreactor to realize real-time oxygen supplement.