3D cell cultures contain hepatic cells and are infected by a pathogen. Such cell cultures are prepared by, for example, inoculating a single-cell suspension containing hepatic cells expanded in a 2D culture in an agitation-based culture system. Next, the resulting cell culture is agitated at a given agitation rate. Then, the resulting 3D cell culture containing cell aggregates is incubated with a pathogen.

The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Provided are compositions related to HSD17B13 variants, including nucleic acid molecules and polypeptides related to variants of HSD17B13, and cells comprising those nucleic acid molecules and polypeptides. Also provided are methods related to HSD17B3 variants. Such methods include methods for detecting the presence of the HSD17B13 rs72613567 variant in a biological sample comprising genomic DNA, for detecting the presence or levels of any one of variant HSD17B13 Transcripts C, D, E, F, G, and H, and particularly D, in a biological sample comprising mRNA or cDNA, or for detecting the presence or levels of any one of variant HSD17B13 protein Isoforms C, D, E, F, G, or H, and particularly D, in a biological sample comprising protein. Also provided are methods for determining a subject's susceptibility to developing a liver disease or of diagnosing a subject with liver disease.

The invention provides a medium additive, medium composition and a culture method and the like, capable of efficiently culturing cells or tissues in a well dispersed state, and further, permitting cell image analysis of the cells or tissues. The medium additive or medium composition contains agar, which preferably is a low molecular weight agar having a weight average molecular weight of 10,000-60,000. Using same, cells or tissues can be cultured in a well-dispersed state in a medium, and a proliferation promoting effect for the cells or tissues can also be obtained. In addition, the cells can be cultured in any of a floating state and a precipitated state by adjusting the concentration of the aforementioned agar.

The present invention derives from the unexpected finding that ADRA2a antagonists decrease fibrosis in non-alcoholic fatty liver disease (NAFLD). Thus, by antagonising ADRA2a, many of the unwanted consequences or symptoms of NAFLD, may be reduced, such as impaired cognitive activity and fibrosis progression. The present invention utilises these findings to identify and provide ADRA2a antagonists that may be used in the treatment of fibrosis in NAFLD.

The present invention provides a method for producing hepatic stem/progenitor cells from mammal hepatocytes, comprising bringing a TGF-receptor inhibitor, and optionally a GSK3 inhibitor and/or a ROCK inhibitor into contact with the hepatocytes in vitro.

A method for determining at least one parameter of interest of a material comprises directing, using a radio frequency (RF) applicator, one or more RF energy pulses into a region of interest, the region of interest comprising a material having a parameter of interest and at least one reference, the material and the reference separated by at least one boundary; detecting, using an acoustic receiver, at least one multi-polar acoustic signal generated in the region of interest in response to the RF energy pulses; processing the at least one multi-polar acoustic signal to determine an electric field strength at the boundary; calculating a voltage standing wave ratio (VSWR) of the one or more RF energy pulses; and determining the at least one parameter of interest of the material based at least on the determined electric field strength and the VSWR.

The present disclosure relates to methods for evaluating the interaction of a candidate compound on 3D hepatocyte spheroid in an invitro culture, including evaluating the metabolism of a candidate compound, for use in various biochemical and molecular biology studies. The methods are performed in labware that combine 3D spheroid culture with micro-patterned design that allows for multiple to several hundreds of spheroids to be treated under the same conditions and to produce sufficient materials (e.g., parent drug, drug metabolites, DNA, RNA, and proteins from cells) and higher detection signal intensity for ADME/Tox (absorption, distribution, metabolism, excretion and toxicity) studies. The methods allow for, among other uses, the investigation and generation of accurate invitro intrinsic clearance data and thus more accurate prediction of in vivo clearance, particularly with low clearance compounds.

Provided is a component analysis device, which comprises an analysis unit for measuring a component fed to the plurality of containers and analyzing the component thus measured, wherein the plurality of containers are at least a first container and a second container, wherein the first container retains a first solution containing a substance that releases adhesion between multiple cells forming the liver cell tissue, and the second container retains a buffer solution, and wherein the analysis unit measures an amount of the component discharged from the liver cell tissue in the first container into the first solution and an amount of the component discharged from the liver cell tissue in the second container into the buffer solution in the second container, and analyzes an amount of the component to be discharged via a bile duct in the liver cell tissue.

Cell culture compositions containing LFM-A13 or a structurally related compound can enhance global hepatic function. For example, LFM-A13 is shown to enhance levels of a broad variety of drug metabolism enzymes, including CYP enzymes, and other hepatic enzymes. LFM-A13 is also shown to promote differentiation of stem cells into hepatocytes. LFM-A13 and structurally related compounds can be used in cell culture to enhance global drug metabolism of liver cells for enhanced in vitro study the effects of drug metabolism on other candidate drug compounds.