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Hepatocyte

Hepatocytes are the principal parenchymal cells of the liver, accounting for 70-80% of the liver's total cellular mass.
These cells play a crucial role in various liver functions, including metabolism, protein synthesis, and detoxification.
Hepatocytes are highly polarized, with a distinctive apical surface facing the bile canaliculi and a basal surface in contact with the sinusoidal blood flow.
Understanding the biology and function of hepatocytes is essential for investigating liver physiology, pathology, and the development of therapies targeting liver-related diseases.
This MeSH term provides a concise overview of the key characteristics and importance of hepatocytes in biomedical research.
One typo: 'accound' should be 'account'.

Most cited protocols related to «Hepatocyte»

This study included consecutive patients with biopsy-proven NAFLD who attended specialist fatty liver clinics at the Freeman Hospital, Newcastle upon Tyne, UK; Addenbrooke's Hospital, Cambridge, UK; Antwerp University Hospital, Edegem, Belgium; and Pitié-Salpêtrière Hospital, Paris, France. These formed the initial ascertainment cohort. Liver biopsies were conducted as per routine clinical care for the investigation of abnormal liver function tests (raised ALT, AST, or gamma-glutamyl transferase) or to stage disease severity in patients with radiological evidence of fatty liver. Clinical and laboratory data were collected prospectively from the time of liver biopsy. Patients with evidence of other liver disease (autoimmune hepatitis, viral hepatitis, drug induced liver injury, hemochromatosis, cholestatic liver disease, or Wilson's disease) were excluded. In addition, subjects consuming excessive amounts of alcohol (alcohol intake >20 g/day for women; >30 g/day for men) at the time of biopsy or in the past were excluded. Patients with incomplete data to calculate all the non-invasive scores were excluded.
Relevant clinical details, including gender, age, weight, and height, were obtained at the time of biopsy. The body mass index was calculated by the formula: weight (kg)/height (m)2. Patients were identified as having diabetes if they had been diagnosed with diabetes according to the 2004 American Diabetes Association criteria or if they were taking an oral hypoglycemic drug or insulin (23 (link)).
Percutaneous liver biopsies were performed as per unit protocol at the sites and were assessed by an experienced local hepatopathologist. Patients with liver biopsies specimens <15 mm in length were excluded. Histological scoring was performed according to the non-alcoholic steatohepatitis (NASH) Clinical Research Network criteria (24 (link)). The NAFLD activity score was graded from 0 to 8, including scores for steatosis (0–3), lobular inflammation (0–3), and hepatocellular ballooning (0–2). NASH was defined as steatosis with hepatocyte ballooning and inflammation ± fibrosis (25 (link)). Fibrosis was staged from F0 to F4 (24 (link)). Patients with stage F3 or F4 fibrosis were considered to have advanced fibrosis.
The AST/ALT ratio, FIB-4, and NFS were calculated from blood tests taken at the time of liver biopsy as previously described (16 (link), 26 (link), 27 (link)). Details of the formulas and cutoffs for the tests under investigation are shown in Table 1. Previously published cutoffs were used to exclude and diagnose advanced fibrosis for each score (15 (link), 16 (link), 18 (link), 19 (link))
To validate new cutoffs for the NFS and FIB-4 score optimized for use in older patients (aged ≥65 years) that were derived in the initial ascertainment cohort, anonymized biochemical, histological, and anthropometric data were collected from a separate group of histologically characterized patients from the EPoS/EASL European NAFLD Registry. The “European NAFLD Registry” was established during the EU FP7 FLIP project (2010-) and is now maintained by the EU H2020 EPoS (Elucidating Pathways of Steatohepatitis) consortium to facilitate collaborative research into NAFLD. It is the largest multi-national registry of patients with histologically characterized NAFLD. These patients had data collected according to the same methodology as the main cohort.
All statistical analyses were performed using the SPSS software version 22.0 (SPSS, Chicago, IL). Continuous normally distributed variables were represented as mean ± s.d. Categorical and non-normal variables were summarized as median and range. Chi squared tests were used to determine the distribution of categorical variables between groups. To compare the means of normally distributed variables between groups, the Student's t-test or analysis of variance test was performed. To determine differences between groups for continuous non-normally distributed variables, medians were compared using the Mann–Whitney U-test. The diagnostic performance of the non-invasive tests was assessed by receiver operating characteristic (ROC) curve analysis. The area under the ROC (AUROC) was used as an index to compare the accuracy of tests. The sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), positive likelihood ratios (LR +ve), and negative likelihood ratios (LR −ve) for relevant cutoffs were also displayed. In order to assess changes in sensitivity and specificity of the tests with age, plots of sensitivity and specificity in different age groups were displayed graphically. New cutoffs for the FIB-4 and NFS were derived for ≥65-year-old patients by taking the point on the ROC where the combined value of sensitivity and specificity was the highest. As the prevalence of advanced fibrosis can vary in different populations, the PPVs and NPVs for the new cutoffs were displayed at advanced fibrosis prevalence rates of 5, 10, 20, 30, and 40%. A P value of <0.05 was considered significant.
Publication 2016
Age Groups Autoimmune Chronic Hepatitis Biopsy Cholestasis Diabetes Mellitus Diagnosis Diet, Formula Drug-Induced Liver Disease Erythropoietin Ethanol Europeans Fatty Liver Fibrosis gamma-Glutamyl Transpeptidase Gender Hematologic Tests Hemochromatosis Hepatitis Viruses Hepatocyte Hepatolenticular Degeneration Hypersensitivity Hypoglycemic Agents Index, Body Mass Inflammation Insulin Liver Liver Diseases Liver Function Tests Non-alcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Patients Population Group Specialists Steatohepatitis Tests, Diagnostic Woman X-Rays, Diagnostic
Briefly, the two key features of NASH, steatosis and inflammation, were categorized as follows: steatosis was determined by analyzing hepatocellular vesicular steatosis, i.e. macrovesicular steatosis and microvesicular steatosis separately, and by hepatocellular hypertrophy as defined below (Fig. 2). Inflammation was scored by analyzing the amount of inflammatory cell aggregates (Fig. 2). The proposed rodent scoring system is shown in Table 4 and options for its use in diagnosis are shown in S1 Fig. The purpose of this scoring system is however not to derive a single score, but to score the individual features.
Macrovesicular steatosis and microvesicular steatosis were both separately scored and the severity was graded, based on the percentage of the total area affected, into the following categories: 0 (<5%), 1 (5–33%), 2 (34–66%) and 3 (>66%). The difference between macrovesicular and microvesicular steatosis was defined by whether the vacuoles displaced the nucleus to the side (macrovesicular) or not (microvesicular). Similarly, the level of hepatocellular hypertrophy, defined as cellular enlargement more than 1.5 times the normal hepatocyte diameter, was scored, based on the percentage of the total area affected, into the following categories: 0 (<5%), 1 (5–33%), 2 (34–66%) and 3 (>66%). For hepatocellular hypertrophy the evaluation was merely based on abnormal enlargement of the cells, irrespective of rounding of the cells and/or changes in cytoplasm or the number of vacuoles, and is therefore not a substitute of ballooning. The unweight sum of the scores for steatosis (macrovesicular steatosis, microvesicular steatosis and hypertrophy) thus ranged from 0–9. Both steatosis and hypertrophy were evaluated at a 40 to 100× magnification and only the sheets of hepatocytes were taken into account (terminal hepatic venules and portal tracts etc were excluded).
Inflammation was evaluated by counting the number of inflammatory foci per field using a 100 x magnification (view size of 3.1 mm2). A focus was defined a cluster, not a row, of ≥5 inflammatory cells. Five different fields were counted and the average was subsequently scored into the following categories: normal (<0.5 foci), slight (0.5–1.0 foci), moderate (1.0–2.0 foci), severe (>2.0 foci).
Hepatic fibrosis was identified using Sirius Red stained slides at 40 x magnification and evaluated by scoring whether pathologic collagen staining was absent (only in vessels) or collagen staining observed within the liver slide, the latter further defined as mild, moderate or massive. In addition, the percentage of the total area affected was evaluated using using image analysis of surface area on Sirius red stained slides.
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Publication 2014
Blood Vessel Cell-Derived Microparticles Cell Enlargement Cell Nucleus Cells Collagen Cytoplasm Diagnosis Fibrosis, Liver Hepatocyte Hypertrophy Inflammation Liver Nonalcoholic Steatohepatitis Portal System Rodent Steatohepatitis Vacuole Venules
The hepatocyte cell line RALA255-10G was cultured under nontransformed conditions, as described previously20 (link). Wild-type and Atg5−/− mouse embryonic fibroblasts provided by N. Mizushima21 (link) were cultured as described previously22 (link). TG content was determined by the Trig/GB Kit (Roche Diagnostics), cholesterol content by the Amplex Red Cholesterol Assay (Invitrogen), fatty acid β-oxidation by a modification of a previously used method23 (link), and TG decay in cells radiolabelled with [14C]oleate and TG synthesis by standard methods12 (link). shRNAs were cloned into pSUPER (Ambion) and then pCCL.sin.PPT.hPGK.GFPWpre24 (link). Protein isolation and western blotting were performed as described previously25 (link). Fluorescence microscopy for BODIPY 493/503 (Invitrogen) and immunofluorescence were performed as described previously26 (link). Atg7F/F mice4 (link) were crossed with Alb-Cre mice27 (link) to generate Atg7F/F-Alb-Cre mice. Some animals were fed a high-fat diet (60% kcal in fat; Research Diets, D12492). Electron microscopy and immunogold labelling were performed as described previously26 (link). LDs from mouse livers were isolated by sucrose density gradient centrifugation28 and autophagic vacuoles and lysosomes by centrifugation in metrizamide discontinuous density gradients29 (link).
Publication 2009
4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene Anabolism Animals Autophagosome Biological Assay Cell Lines Cells Centrifugation Cholesterol Diagnosis Diet Diet, High-Fat Electron Microscopy Embryo Fatty Acids Fibroblasts formaldehyde-serum albumin Hepatocyte Immunofluorescence isolation Liver Lysosomes Metrizamide Mice, Laboratory Microscopy, Fluorescence Oleate Proteins Short Hairpin RNA Sucrose

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Publication 2020
Berries BLOOD Calcium Cannulation Cell Cycle Checkpoints Cells ChIP-Chip Collagenase Dental Anesthesia Digestion Extracellular Matrix Friend Hepatocyte Liberase Liver Mice, House Percoll Perfusion Veins, Portal Venae Cavae
The gene expression data for a test compound were derived from administration of individual compounds at up to four dose levels and eight time points (corresponding to four single-dose studies and four repeated-dose studies). Studies involving microarray hybridization analysis were performed using three biological replicates of liver and kidney in rat. Biochemistry and hematology data from individual animals were also obtained and stored. The pathology images were digitized and annotated prior to addition to the database. For human and rat primary hepatocytes, test compounds were tested at up to four dose levels and three time points using duplicate microarray hybridization analysis. For primary hepatocytes, cell viability data was also obtained.
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Publication 2014
Animals Biopharmaceuticals Cell Survival Crossbreeding Gene Expression Hepatocyte Homo sapiens Kidney Liver Microarray Analysis

Most recents protocols related to «Hepatocyte»

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Example 22

Clinicians can use several biochemical measurements to objectively assess patients' current or past alcohol use. Several more experimental markers hold promise for measuring acute alcohol consumption and relapse. These include certain alcohol byproducts, such as acetaldehyde, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEE), as well as two measures of sialic acid, a carbohydrate that appears to be altered in alcoholics (Peterson K, Alcohol Research and Health, 2005). Clinicians have had access to a group of biomarkers that indicate a person's alcohol intake. Several of these reflect the activity of certain liver enzymes: serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and carbohydrate-deficient transferrin (CDT), a protein that has received much attention in recent years. Another marker, N-acetyl-β-hexosaminidase (beta-Hex), indicates that liver cells, as well as other cells, have been breaking down carbohydrates, which are found in great numbers in alcohol (Javors and Johnson 2003).

In some embodiments the disclosed device focuses on detecting markers associated with alcohol abuse from menstrual blood or cervicovaginal fluid.

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Patent 2024
Abuse, Alcohol Acetaldehyde Alcoholics Aspartate Transaminase Attention beta-N-Acetylhexosaminidase Biological Markers BLOOD carbohydrate-deficient transferrin Carbohydrates Cells D-Alanine Transaminase enzyme activity Esters Ethanol ethyl glucuronide Fatty Acids gamma-Glutamyl Transpeptidase Hepatocyte Liver Medical Devices Menstruation N-Acetylneuraminic Acid Patients Relapse Serum Staphylococcal Protein A

Example 7

In this experiment, a hepatocyte cell line expressing asialoglycoprotein receptors and GFP will be treated with anti-GFP siRNAs or ASOs conjugated to a GaINAc moiety compared to a control experiment where the hepatocyte cell line is treated with anti-GFP siRNAs or ASOs that are not conjugated to the GaINAc moiety. GFP mRNA and protein expression are measured, and the amount of GFP mRNA or protein expression in cells treated with the GaINAc-conjugated siRNAs or ASOs is normalized and compared to the amount of GFP mRNA or protein expression in cells treated with the siRNAs or ASOs that are not GaINAc-conjugated. This may allow for a determination of the hepatocyte targeting ability of the GaINAc moiety. Multiple GaINAc moieties may be conjugated to the siRNAs or ASOs and compared to see which GaINAc moiety results in optimal hepatocyte targeting. The GaINAc moieties to be tested in these experiments may a GaINAc moiety described herein.

Similar experiments may be performed in primary hepatocytes treated with the siRNAs or ASOs conjugated or not to a GaINAc moiety, and a target mRNA or target protein other than GFP may be assessed in the primary hepatocytes.

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Patent 2024
Asialoglycoprotein Receptor Cell Lines Cells Hepatocyte Proteins Protein Targeting, Cellular RNA, Messenger RNA, Small Interfering

Example 9

GalNAc conjugates of an siRNA targeting Tmprss6 containing different end stabilization chemistries (phosphorothioate, phosphorodithioate, phosphodiester) were tested by receptor-mediated uptake in primary mouse hepatocytes. GalNAc was conjugated to the 5′-end of the second strand and is internally stabilized by four PS (STS12009L4) or not, then phosphodiester linkages are used instead (STS12009V54L50-V57L50). Phosphorodithioate modifications were placed at all terminal positions of the duplex except of the first strand 5′-end (−V54L50), at the 3′-ends only (−V55L50, −V57L50) or at the 3′-end of the second strand only (−V56L50). In certain designs, phosphodiesters were used in terminal positions of the siRNA duplex (−V56L50, −V57L50).

The experiment was conducted in mouse primary hepatocytes. Cells were seeded at a density of 20,000 cells per 96-well and treated with 125 nM to 0.2 nM GalNAc-siRNA. Cells were lysed after 24 h, total RNA was extracted and Tmprss6 and Pten mRNA levels were determined by Taqman qRT-PCR. Each bar represents mean±SD of three technical replicates.

Sequences are shown in FIG. 7 and results in FIG. 9.

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Patent 2024
Cardiac Arrest Cells Gene Expression Hepatocyte Mus Nucleic Acids phosphorodithioic acid PTEN protein, human RNA, Messenger RNA, Small Interfering TMPRSS6 protein, human

Example 8

In this experiment, siRNAs or ASOs targeting a target mRNA will be conjugated to a GaINAc moiety and administered to mice (n=5/group), and compared to a control experiment where the mice are administered siRNAs or ASOs without GaINAc conjugation. Mice are sacrificed 2 days later, and livers are frozen, later homogenized, and tested for target mRNA and protein expression. The amount of target mRNA or protein expression in the livers of mice treated with the GaINAc-conjugated siRNAs or ASOs is normalized and compared to the amount of GFP mRNA or protein expression in the livers of mice treated with the siRNAs or ASOs that are not GaINAc-conjugated. This may allow for a determination of the liver targeting ability of the GaINAc moiety. Multiple GaINAc moieties may be conjugated to the siRNAs or ASOs and compared to see which GaINAc moiety results in optimal liver targeting. The GaINAc moieties included in this experiment may be those that exhibit the greatest degree of hepatocyte targeting. The GaINAc moieties to be tested in these experiments may a GaINAc moiety described herein.

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Patent 2024
Freezing Hepatocyte Liver Mus Proteins RNA, Messenger RNA, Small Interfering

Example 5

Activity of GalNAc-siRNA conjugates containing one PS2 at individual ends. GalNAc was conjugated to the 5′-end of the second strand and is internally stabilized by four PS. Phosphorodithioate modifications were placed at the 5′-end of the first strand (STS12009V37L4), 3′-end of the first strand (STS12009V36L4) and 3′-end of the second strand (STS12009V34L4). All other, non-conjugated ends were stabilised by each two terminal PS. STS12009L4 contains each two terminal PS at 5′-end of the first strand, 3′-end of the first strand and 3′-end of the second strand. The experiment was conducted in mouse primary hepatocytes. Cells were seeded at a density of 250,000 cells per 6-well and treated with 100 nM, 10 nM and 1 nM GalNAc-siRNA. Transfections with 10 nM GalNAc-siRNA and 1 μg/ml Atufect served as control. Cells were lysed after 24 h, total RNA was extracted and Tmprss6 and Pten mRNA levels were determined by Taqman qRT-PCR. Results are shown in FIG. 4. Each bar represents mean±SD of three technical replicates. Sequences are as set out in Table 5.

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Patent 2024
Cardiac Arrest Cells Gene Expression Hepatocyte Mus Nucleic Acids phosphorodithioic acid PTEN protein, human RNA, Messenger RNA, Small Interfering TMPRSS6 protein, human Transfection

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HepG2 is a human liver cell line derived from the liver tissue of a 15-year-old Caucasian male with a well-differentiated hepatocellular carcinoma. It is a widely used in vitro model for the study of liver cell biology and function.
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Lipofectamine 2000 is a cationic lipid-based transfection reagent designed for efficient and reliable delivery of nucleic acids, such as plasmid DNA and small interfering RNA (siRNA), into a wide range of eukaryotic cell types. It facilitates the formation of complexes between the nucleic acid and the lipid components, which can then be introduced into cells to enable gene expression or gene silencing studies.
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RPMI 1640 medium is a commonly used cell culture medium developed at Roswell Park Memorial Institute. It is a balanced salt solution that provides essential nutrients, vitamins, and amino acids to support the growth and maintenance of a variety of cell types in vitro.

More about "Hepatocyte"

Hepatocytes are the primary parenchymal cells of the liver, comprising 70-80% of the organ's total cellular mass.
These highly specialized cells play a crucial role in various liver functions, including metabolism, protein synthesis, and detoxification.
Hepatocytes are highly polarized, with a distinct apical surface facing the bile canaliculi and a basal surface in contact with the sinusoidal blood flow.
Understanding the biology and function of hepatocytes is essential for investigating liver physiology, pathology, and the development of therapies targeting liver-related diseases.
Hepatic cells, also known as liver cells or hepatic parenchymal cells, are responsible for a wide range of vital liver functions.
They are involved in the metabolism of drugs, hormones, and other substances, as well as the synthesis of proteins, such as albumin and clotting factors.
Hepatocytes also play a crucial role in the detoxification process, removing harmful substances from the body.
In biomedical research, hepatocytes are widely used as model systems to study liver function, disease pathogenesis, and the development of new therapies.
Cell culture techniques, such as the use of DMEM (Dulbecco's Modified Eagle's Medium), FBS (Fetal Bovine Serum), and Penicillin/Streptomycin antibiotics, are commonly employed to maintain and propagate hepatocytes in the laboratory.
Additionally, immortalized hepatocyte cell lines, such as HepG2, are used to investigate specific liver-related processes.
Researchers often utilize advanced techniques, like Lipofectamine 2000 for gene transfection, Dexamethasone for differentiation, and TRIzol reagent for RNA extraction, to explore the molecular mechanisms governing hepatocyte function.
RPMI 1640 medium is another commonly used culture medium for hepatocyte research.
By leveraging the insights gained from the MeSH term description and the Metadescription, researchers can optimize their hepatocyte studies, enhance reproducibility, and drive advancements in our understanding of liver biology and the development of liver-targeted therapies.