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Journal of Clinical and Experimental... Sep 2016Giant-cell hepatitis (GCH) is characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the...
Giant-cell hepatitis (GCH) is characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the liver. Although it is commonly described in neonates, it rarely occurs in adults. Here we report a case of GCH because of herbal medicine intake.
PubMed: 27746622
DOI: 10.1016/j.jceh.2016.02.007 -
Journal of Biomedical Materials... Apr 2016Whole organ engineering and cell-based regenerative medicine approaches are being investigated as potential therapeutic options for end-stage liver failure. However, a...
Whole organ engineering and cell-based regenerative medicine approaches are being investigated as potential therapeutic options for end-stage liver failure. However, a major challenge of these strategies is the loss of hepatic specific function after hepatocytes are removed from their native microenvironment. The objective of the present study was to determine if solubilized liver extracellular matrix (ECM), when used as a media supplement, can better maintain hepatocyte phenotype compared to type I collagen alone or solubilized ECM harvested from a non-liver tissue source. Liver extracellular matrix (LECM) from four different species was isolated via liver tissue decellularization, solubilized, and then used as a media supplement for primary rat hepatocytes (PRH). The four species of LECM investigated were human, porcine, canine and rat. Cell morphology, albumin secretion, and ammonia metabolism were used to assess maintenance of hepatocyte phenotype. Biochemical and mechanical characterization of each LECM were also conducted. Results showed that PRH's supplemented with canine and porcine LECM maintained their phenotype to a greater extent compared to all other groups. PRH's supplemented with canine and porcine LECM showed increased bile production, increased albumin production, and the formation of multinucleate cells. The findings of the present study suggest that solubilized liver ECM can support in-vitro hepatocyte culture and should be considered for therapeutic and diagnostic techniques that utilize hepatocytes.
Topics: Animals; Cell Culture Techniques; Cells, Cultured; Collagen Type I; Culture Media; Dogs; Extracellular Matrix; Hepatocytes; Humans; Hydrogels; Liver; Rats; Rats, Sprague-Dawley; Rheology; Solubility; Swine
PubMed: 26704367
DOI: 10.1002/jbm.a.35636 -
Cell Cycle (Georgetown, Tex.) 2021Multipolar mitosis was observed in cancer cells under mechanical stress or drug treatment. However, a comprehensive understanding of its basic properties and...
Multipolar mitosis was observed in cancer cells under mechanical stress or drug treatment. However, a comprehensive understanding of its basic properties and significance to cancer cell biology is lacking. In the present study, live-cell imaging was employed to investigate the division and nucleation patterns in four different cell lines. Multi-daughter divisions were observed in the three cancer cell lines HepG2, HeLa and A549, but not in the transformed non-cancer cell line RPE1. Multi-daughter mother cells displayed multi-nucleation, enlarged cell area, and prolonged division time. Under acidic pH or treatment with the anti-cancer drug 5-fluorouracil (5-FU) or the phytochemical compound wogonin, multi-daughter mitoses were increased to different extents in all three cancer cell lines, reaching as high as 16% of all mitoses. While less than 0.4% of the bi-daughter mitosis were followed by cell fusion events under the various treatment conditions, 50% or more of the multi-daughter mitoses were followed by fusion events at neutral, acidic or alkaline pH. These findings revealed a "Daughter Number Variation" (DNV) process in the cancer cells, with multi-daughter divisions in Stage 1 and cell fusions leading to the formation of cells containing up to five nuclei in Stage 2. The Stage 2-fusions were inhibited by 5-FU in A549 and HeLa, and by wogonin in A549, HeLa and HepG2. The parallel relationship between DNV frequency and malignancy among the different cell lines suggests that the inclusion of anti-fusion agents exemplified by wogonin and 5-FU could be beneficial in combinatory cancer chemotherapies.
Topics: A549 Cells; Antimetabolites, Antineoplastic; Cell Division; Cell Fusion; Cell Line, Transformed; Flavanones; Fluorouracil; Genetic Variation; HeLa Cells; Hep G2 Cells; Humans; Neoplasms
PubMed: 33596747
DOI: 10.1080/15384101.2021.1883363 -
Avian Diseases Dec 2014A broiler breeder flock was subcutaneously vaccinated at the hatchery with a live avian orthoreovirus (ARV) vaccine against viral arthritis. Chicks began to die at 3...
A broiler breeder flock was subcutaneously vaccinated at the hatchery with a live avian orthoreovirus (ARV) vaccine against viral arthritis. Chicks began to die at 3 days of age and postmortem examination revealed massive subcutaneous hemorrhages and edema on the dorsal aspect of the neck at the site of vaccination, a severe necrotic hepatitis, and pulmonary edema. Microscopically, the main lesion was a multifocal vacuolar degeneration and necrosis of randomly distributed small groups of hepatocytes with presence of apoptotic and multinucleated syncytial cells. Necrotic foci were also found in the lungs as well as a hemorrhagic, granulomatous, and heterophilic cellulitis and myositis of the neck and a generalized depletion and lymphocytolysis of lymphoid organs. At 8 days of age, birds also began to show hock swelling histologically characterized by a fibrinoleucocytic inflammation of the articulation and tendon sheaths, with hyperplasia of the synovial membrane, and lymphoplasmocytic infiltration. PCR and viral culture of livers were positive for ARV. Partial sequencing of the S1 gene from the virus isolate showed 99.2% to 99.8% homology with three vaccinal strains (ARV S1133, 1733, and 2408). Viral particles compatible with reovirus virions were observed at transmission electron microscopy. Investigation at the hatchery revealed that chicks were inadvertently administered an S1133 reovirus vaccine labeled for water administration in 10- to 17-week-old chickens. This human error is most likely the reason for this unusually severe viremic reovirus infection that affected this flock at such an early age.
Topics: Animals; Chickens; Female; Injections, Subcutaneous; Male; Medication Errors; Orthoreovirus, Avian; Reoviridae Infections; Viral Vaccines
PubMed: 25619015
DOI: 10.1637/10860-050914-Case.1 -
BMC Biotechnology Nov 2017The myxomycetes derive their common name (slime molds) from the multinucleate trophic stage (plasmodium) in the life cycle, which typically produces a noticeable amount...
BACKGROUND
The myxomycetes derive their common name (slime molds) from the multinucleate trophic stage (plasmodium) in the life cycle, which typically produces a noticeable amount of slimy materials, some of which is normally left behind as a "slime track" as the plasmodium migrates over the surface of a particular substrate. The study reported herein apparently represents the first attempt to investigate the chemical composition and biological activities of slime tracks and the exopolysaccharides (EPS) which cover the surface of the plasmodia of Physarum polycephalum and Physarella oblonga.
RESULTS
Chemical analyses indicated that the slime tracks and samples of the EPS consist largely of carbohydrates, proteins and various sulphate groups. Galactose, glucose and rhamnose are the monomers of the cabohydrates present. The slime tracks of both species and the EPS of Phy. oblonga contained rhamnose, but the EPS of Ph. polycephalum had glucose as the major monomer. In term of biological activities, the slime tracks displayed no antimicrobial activity, low anticancer activity and only moderate antioxidant activity. However, EPSs from both species showed remarkable antimicrobial activities, especially toward Candida albicans (zone of inhibition ≥20 mm). Minimum inhibitory concentrations of this fungus were found to be 2560 μg/mL and 1280 μg/mL for EPS from Phy. oblonga and Ph. polycephalum, respectively. These EPS samples also showed moderate antioxidant activities. However, they both displayed cytotoxicity towards MCF-7 and HepG2 cancer cells. Notably, EPS isolated from the plasmodium of Phy. oblonga inhibited the cell growth of MCF-7 and HepG2 at the half inhibitory concentration (IC50) of 1.22 and 1.11 mg/mL, respectively.
CONCLUSIONS
EPS from Ph. polycephalum plasmodium could be a potential source of antifungal compounds, and EPS from Phy. oblonga could be a potential source of anticancer compounds.
Topics: Antioxidants; Biological Products; Candida albicans; Cell Proliferation; Hep G2 Cells; Humans; MCF-7 Cells; Microbial Sensitivity Tests; Mycetozoa; Physarum polycephalum; Polysaccharides; Staphylococcus aureus
PubMed: 29121887
DOI: 10.1186/s12896-017-0398-6 -
Scientific Reports Nov 2020Tilapia lake virus (TiLV) causes high mortality and high economic losses in tilapines. We describe an experimental challenge study focusing on early post challenge...
Tilapia lake virus (TiLV) causes high mortality and high economic losses in tilapines. We describe an experimental challenge study focusing on early post challenge innate immune responses. Nile tilapia (Oreochromis niloticus) were infected with 10 TCID/mL TiLV intraperitoneally, followed by virus quantification, histopathology and gene expression analysis in target (brain/liver) and lymphoid (spleen/headkidney) organs at 3, 7, 12, 17, and 34 days post challenge (dpc). Onset of mortality was from 21 dpc, and cumulative mortality was 38.5% by 34 dpc. Liver and kidney histopathology developed over the period 3-17 dpc, characterized by anisocytosis, anisokaryocytosis, and formation of multinucleated hepatocytes. Viral loads were highest at early time (3 dpc) in liver, spleen and kidney, declining towards 34 dpc. In brain, viral titer peaked 17 dpc. Innate sensors, TLRs 3/7 were inversely correlated with virus titer in brain and headkidney, and IFN-ß and Mx showed a similar pattern. All organs showed increased mRNA IgM expression over the course of infection. Overall, high virus titers downplay innate responses, and an increase is seen when viral titers decline. In silico modeling found that TiLV segments 4, 5 and 10 carry nucleolar localization signals. Anti-viral effects of TiLV facilitate production of virus at early stage of infection.
Topics: Animals; Antibodies, Viral; Brain; Cichlids; Fish Diseases; Gene Expression Regulation; Hepatocytes; Host-Pathogen Interactions; Immunity, Innate; Immunoglobulin M; Interferon-beta; Kidney; Liver; Negative-Sense RNA Viruses; Spleen; Survival Analysis; Time Factors; Toll-Like Receptor 3; Toll-Like Receptor 7
PubMed: 33230226
DOI: 10.1038/s41598-020-73781-y -
BMB Reports Jul 2017We previously reported that p53 plays a role as a key regulator in the tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then...
We previously reported that p53 plays a role as a key regulator in the tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then prevents uncoupled DNA replication and nuclear division without cytokinesis. In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was reduced, but p27/Kip1 was increased, after actin damage-induced cytokinesis blockade. The role of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2. After actin damage, ectopic expression of Skp2 resulted in DNA synthesis and accumulation of multinucleated cells, and ultimately, induction of apoptosis. These results suggest that Skp2 repression is important for sustaining tetraploid G1 arrest after cytokinesis blockade and is required to prevent uncoupled DNA replication and nuclear division without cytokinesis. [BMB Reports 2017; 50(7): 379-383].
Topics: Actins; Cyclin-Dependent Kinase Inhibitor p27; Cytokinesis; G1 Phase Cell Cycle Checkpoints; HCT116 Cells; Hep G2 Cells; Humans; S-Phase Kinase-Associated Proteins; Tetraploidy; Tumor Cells, Cultured
PubMed: 28648144
DOI: 10.5483/bmbrep.2017.50.7.063 -
European Journal of Clinical... Jan 2019
Topics: Animals; Cell Nucleus; Hepatocytes; Rats; Rifabutin
PubMed: 30368739
DOI: 10.1007/s10096-018-3411-7 -
Food Science and Biotechnology Jun 2022Sub-chronic toxicity studies using rats have been conducted for (Maxim.) Hemsley (CW) and Royle ex Wight (CA). CW water extract didn't show any adverse effects whereas...
Sub-chronic toxicity studies using rats have been conducted for (Maxim.) Hemsley (CW) and Royle ex Wight (CA). CW water extract didn't show any adverse effects whereas administering CW powder decreased body weights in complication with decreased food consumptions. In the case of CA water extract, triglyceride and absolute/relative liver weights were elevated and vacuolation was observed in liver. Treated CA powder in male rats increased alanine aminotransferase and aspartate aminotransferase and induced single cell necrosis and multinucleated hepatocyte in liver. As for female rats, increased absolute/relative weights and hypertrophy/vacuolation in adrenal glands and vacuolation in ovaries were observed when administered CA powder. In conclusion, no observed adverse effect level (NOAEL) of CW water extract was over 5000 mg/kg/day, while NOAEL of CW powder was 700 mg/kg/day for female and 150 mg/kg/day for male. In case of CA, NOAEL of water extract was 1500 mg/kg/day for male and 2000 mg/kg/day for female, while NOAEL of powder was 150 mg/kg/day for both gender. To the best of our knowledge, this is the first sub-chronic toxicity study on the adverse effects, target organs and its dose levels of (Maxim.) Hemsley and Royle ex Wight following GLP protocols.
PubMed: 35646417
DOI: 10.1007/s10068-022-01072-5 -
Parasitology Research Jun 2019We describe the type species of a novel genus of microsporidian parasite, Pseudokabatana alburnus n. gen. n. sp., infecting the liver of topmouth culter, Culter alburnus... (Review)
Review
We describe the type species of a novel genus of microsporidian parasite, Pseudokabatana alburnus n. gen. n. sp., infecting the liver of topmouth culter, Culter alburnus Basilewsky, 1855, from Lake Poyang off Xingzi county, Jiangxi Province, China. The parasite elicits formation of spherical xenomas of up to 1.2 mm in diameter containing all observed life stages from early merogonal plasmodia to mature spores contained within the cytoplasm of host hepatocytes. Merogonal plasmodia existed in direct contact with the host cytoplasm and contained up to 20 visible nuclei. Plasmotomy of the multinucleate plasmodium led to formation of uninucleate cells in which the nucleus underwent further division to form bi-nucleate presporonts, sporonts (defined by cells with a thickened endospore) and eventually sporoblasts (containing pre-cursors of the spore extrusion apparatus). Mature spores were pyriform and monokaryotic, measuring 2.3 ± 0.19 μm long and 1.3 ± 0.10 μm wide. Spores possessed a bipartite polaroplast and 5-6 coils of a polar filament, in a single rank. The obtained partial SSU rRNA gene sequence, 1383 bp in length, did not match any of microsporidia available in GenBank. SSU rDNA-based phylogenetic analysis indicated a new taxon branching with Kabatana rondoni, a parasite infecting the skeletal muscle of Gymnorhamphichthys rondoni from the Amazon River. Due to different host and tissue tropism, the novel taxon did not fit the diagnostic criteria for the genus Kabatana. Further, based on SSU rDNA-inferred phylogenetic analyses, different ultrastructural features of developmental stages, and ecological considerations, a new genus Pseudokabatana and type species Pseudokabatana alburnus n. sp. was erected for the parasite in topmouth culter.
Topics: Animals; China; Cyprinidae; DNA, Ribosomal; Fish Diseases; Liver; Microsporidia; Microsporidiosis; Phylogeny
PubMed: 30976967
DOI: 10.1007/s00436-019-06303-z