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World Journal of Hepatology Apr 2021Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically... (Review)
Review
Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically associated with autoimmune hemolytic anemia in the absence of any other systemic or organ-specific autoimmune comorbidity. The etiology is unknown; concomitant viral infections (as potential trigger factors) have been identified in a few patients. The pathogenesis reportedly relies upon immune-mediated/ autoimmune mechanisms. This condition should be considered in any infant developing Coombs-positive anemia; indeed, anemia usually precedes the development of hepatitis. The clinical course is usually aggressive without the appropriate immunosuppressive therapy, which may include steroids, conventional immunosuppressors (, azathioprine and cyclophosphamide as first-line treatments), intravenous immunoglobulin, and biologics (rituximab). Improvements in medical management (including the availability of rituximab) have significantly reduced the mortality of this condition in the last decade.
PubMed: 33959224
DOI: 10.4254/wjh.v13.i4.411 -
In Vivo (Athens, Greece) 2009Muscle injury induces strong changes in muscle cells and extracellular matrix. Muscle regeneration after injury has similarities to muscle development during... (Review)
Review
Muscle injury induces strong changes in muscle cells and extracellular matrix. Muscle regeneration after injury has similarities to muscle development during embryogenesis and seems to follow the same procedure. The initial phase of muscle repair is characterized by inflammation and degeneration of the damaged tissue. Almost simultaneously, previous quiescent myogenic cells, called satellite cells, are activated, proliferate, differentiate and fuse to form multinucleated myofibers. Other non-muscle stem cells may also take part in this process. Secreted factors, such as hepatocyte growth factor (HGF), fibroblast growth factors (FGFs), transforming growth factor-betas (TGF-betas), insulin-like growth factors (IGFs), tumour necrosis factor alpha (TNFalpha) and others, are released during muscle repair and guide muscle regeneration, however, their exact functions and effects on muscle remodeling remain unknown. Intensive research is currently addressing the regenerative mechanisms which are involved in acute muscle injuries and chronic muscle diseases.
Topics: Animals; Cell Differentiation; Cytokines; Extracellular Matrix; Humans; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Stem Cells; Wound Healing
PubMed: 19779115
DOI: No ID Found -
International Journal of Molecular... Mar 2020The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed... (Review)
Review
The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed that bone marrow-derived stem cells (BMSCs) could adopt the specific properties of a different organ by cell fusion, thereby restoring organ function. Cell fusion first results in the production of bi- or multinucleated hybrid cells, which either remain as heterokaryons or undergo ploidy reduction/heterokaryon-to-synkaryon transition (HST), thereby giving rise to mononucleated daughter cells. This process is characterized by a merging of the chromosomes from the previously discrete nuclei and their subsequent random segregation into daughter cells. Due to extra centrosomes concomitant with multipolar spindles, the ploidy reduction/HST could also be associated with chromosome missegregation and, hence, induction of aneuploidy, genomic instability, and even putative chromothripsis. However, while the majority of such hybrids die or become senescent, aneuploidy and genomic instability appear to be tolerated in hepatocytes, possibly for stress-related adaption processes. Likewise, cell fusion-induced aneuploidy and genomic instability could also lead to a malignant conversion of hybrid cells. This can occur during tissue regeneration mediated by BMSC fusion in chronically inflamed tissue, which is a cell fusion-friendly environment, but is also enriched for mutagenic reactive oxygen and nitrogen species.
Topics: Aneuploidy; Animals; Cell Fusion; Chromosomal Instability; Humans; Hybrid Cells; Polyploidy; Regeneration
PubMed: 32155721
DOI: 10.3390/ijms21051811 -
Toxicon : Official Journal of the... Oct 2020Some species of the genus Brachiaria are cultivated worldwide in tropical and subtropical climate regions as the main feed for ruminants. Several studies report...
Some species of the genus Brachiaria are cultivated worldwide in tropical and subtropical climate regions as the main feed for ruminants. Several studies report photosensitization by Brachiaria decumbens, Brachiaria brizantha, and Brachiaria humidicola, but the poisoning by Brachiaria ruziziensis have been reported only twice. Cutaneous and hepatic lesions may be caused by the steroidal saponins present in the leaves or by the mycotoxin sporidesmin produced by the saprophyte fungus Pithomyces chartarum. The present report describes the clinical and pathological changes observed in an outbreak of hepatogenic photosensitization in sheep kept in B. ruziziensis pastures. In addition, the present study will provide a better understanding of the etiology of this photosensitization through the evaluation of the saponin protodioscin and the spore count of P. chartarum. Santa Inês and Lacaune mixed-breed sheep showed signs of photosensitization after feeding B. ruziziensis. Clinical signs included jaundice, apathy, dehydration, and photosensitization characterized by facial edema and cutaneous scars, especially in the ears. Pathological examination of the liver revealed diffuse infiltrates of foamy cells, rare multinucleated cells, and mild enlargement of hepatocytes (megalocytosis). The skin showed acute epidermal and dermal necrosis with occlusive thrombi. B. ruziziensis showed low levels of protodioscin (0.020 ± 0.024% in mature leaves and 0.065 ± 0.084% in sprouts) but high P. chartarum spore counts (mean of 479,844 ± 443,951 spores/g plant). Thus, sheep grazing B. ruziziensis pastures must be closely monitored because of the risk of photosensitization.
Topics: Animals; Brachiaria; Diosgenin; Liver; Photosensitivity Disorders; Plant Poisoning; Saponins; Sheep; Sheep Diseases; Skin
PubMed: 32598988
DOI: 10.1016/j.toxicon.2020.06.022 -
Autophagy Mar 2023Although it is admitted that secondary infection can complicate viral diseases, the consequences of viral infection on cell susceptibility to other infections remain...
Although it is admitted that secondary infection can complicate viral diseases, the consequences of viral infection on cell susceptibility to other infections remain underexplored at the cellular level. We though to examine whether the sustained macroautophagy/autophagy associated with measles virus (MeV) infection could help cells oppose invasion by Typhimurium, a bacterium sensitive to autophagic restriction. We report here the unexpected finding that markedly replicated in MeV-infected cultures due to selective growth within multinucleated cells. Hyper-replicating localized outside of LAMP1-positive compartments to an extent that equaled that of the predominantly cytosolic mutant . Bacteria were subjected to effective ubiquitination but failed to be targeted by LC3 despite an ongoing productive autophagy. Such a phenotype could not be further aggravated upon silencing of the selective autophagy regulator TBK1 or core autophagy factors ATG5 or ATG7. MeV infection also conditioned primary human epithelial cells for augmented replication. The analysis of selective autophagy receptors able to target revealed that a lowered expression level of SQSTM1/p62 and TAX1BP1/T6BP autophagy receptors prevented effective anti- autophagy in MeV-induced syncytia. Conversely, as SQSTM1/p62 is promoting the cytosolic growth of , MeV infection led to reduced replication. The results indicate that the rarefaction of dedicated autophagy receptors associated with MeV infection differentially affects the outcome of bacterial coinfection depending on the nature of the functional relationship between bacteria and such receptors. Thus, virus-imposed reconfiguration of the autophagy machinery can be instrumental in determining the fate of bacterial coinfection. ACTB/β-ACTIN: actin beta; ATG: autophagy related; BAFA1: bafilomycin A; CFU: colony-forming units; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; FIP: fusion inhibitory peptide; GFP: green fluorescent protein; LAMP1: lysosomal associated membrane protein 1; LIR: MAP1LC3/LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MOI: multiplicity of infection; OPTN: optineurin; PHH: primary human hepatocyte; SCV: Salmonella-containing vacuoles; SQSTM1/p62: sequestosome 1; . Typhimurium: serovar Typhimurium; TAX1BP1/T6BP: Tax1 binding protein 1; TBK1: TANK binding kinase 1.
Topics: Humans; Autophagy; Sequestosome-1 Protein; Coinfection; Measles virus; Salmonella typhimurium; Carrier Proteins
PubMed: 35900944
DOI: 10.1080/15548627.2022.2107309 -
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 -
Scientific Reports Jun 2021Previous reports have demonstrated that Reversine can reverse differentiation of lineage-committed cells to mesenchymal stem cells and suppress tumors growth. However,...
Previous reports have demonstrated that Reversine can reverse differentiation of lineage-committed cells to mesenchymal stem cells and suppress tumors growth. However, the molecular mechanisms of antitumor activity and promoting cellular dedifferentiation for reversine have not yet been clearly elucidated. In the present study, it was demonstrated that reversine of 5 μM could induce multinucleated cells through cytokinesis failure rather than just arrested in G2 or M phase. Moreover, reversine reversed the differentiation of sheep fibroblasts into MSC-like style, and notably increased the expression of pluripotent marker genes Oct4 and MSCs-related surface antigens. The fibroblasts treated with reversine could transdifferentiate into all three germ layers cells in vitro. Most importantly, the induced β-like cells and hepatocytes had similar metabolic functions with normal cells in vivo. In addition, reversine promoted fibroblasts autophagy, ROS accumulation, mitochondrial dysfunction and cell apoptosis via the mitochondria mediated intrinsic pathway. The results of high-throughput RNA sequencing showed that most differentially expressed genes (DEGs) involved in Mismatch repair, Nucleotide excision repair and Base excision repair were significantly up-regulated in reversine treated fibroblasts, which means that high concentration of reversine will cause DNA damage and activate the DNA repair mechanism. In summary, reversine can increase the plasticity of sheep fibroblasts and suppress cell growth via the mitochondria mediated intrinsic pathway.
Topics: Animals; Apoptosis; Autophagy; Cell Cycle; Cell Differentiation; DNA; DNA Damage; DNA Repair; Fibroblasts; Mesenchymal Stem Cells; Mitochondria; Morpholines; Purines; Sequence Analysis, RNA; Sheep
PubMed: 34117304
DOI: 10.1038/s41598-021-91468-w -
Developmental Dynamics : An Official... Jun 2021Axolotls have remarkable organ-level regeneration capability. They can regenerate their limbs, tail, brain, gills, and heart. The liver had been considered to be a...
BACKGROUND
Axolotls have remarkable organ-level regeneration capability. They can regenerate their limbs, tail, brain, gills, and heart. The liver had been considered to be a regenerative organ in these highly regeneration-competent animals. Therefore, no research had been performed on liver regeneration in urodele amphibians. In the present study, we focused on axolotl liver regeneration and found a unique regeneration mechanism compared with other vertebrates.
RESULTS
Partial hepatectomy (PH) was performed to assess axolotl liver regeneration. Regeneration was assessed using block-face imaging (CoMBi), histology, cell proliferation, weight gain, and Albumin (Alb) + area. Axolotl liver histology was compared with other vertebrates. Axolotl liver consists of Glisson's capsule, sinusoids, and hepatic cord with no apparent lobule structures. Hepatocytes were mononucleated or multinucleated. PH increased the multinucleated hepatocytes and the Alb + area, but there was no apparent liver shape recovery even 40 days after PH. Gene expression pattern suggests that no epimorphic regeneration takes place. We also found that the increase in the number of proliferating hepatocytes was regulated by ERK-signaling.
CONCLUSION
Our findings suggest that axolotls, which have epimorphic regeneration ability, regenerate their liver via unique mechanisms, compensatory congestion.
Topics: Ambystoma mexicanum; Animals; Cell Proliferation; Hepatectomy; Liver; Liver Regeneration; MAP Kinase Signaling System; Weight Gain
PubMed: 33064366
DOI: 10.1002/dvdy.262 -
International Journal of Clinical... Jan 2014Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and...
BACKGROUND
Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic modality against congenital toxoplasmosis or to eliminate the persistent chronic infection.
HYPOTHESIS
Diclazuril to be safe in pregnancy and effective against gastrointestinal toxoplasmosis.
METHODS
CD1 programmed pregnant mice were divided into groups and administered a diet containing diclazuril, or sham control. Treatments were initiated on Day 5 of pregnancy and continued until Day 16 when dams were euthanatized. On Day 8 of pregnancy dams were infected intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from Type II strain. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of the experiments.
RESULTS
Infected dams developed moderate to severe related complications in tachyzoites dose dependent manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril effectively protected dams from ascities and anemia (p < 0.05). Infected dams showed splenomegaly, with massive infiltration of epithelioid cells compared with the protective effect of diclazuril in treated animals. Infected dams exhibited severe hepatitis (score 0 to 4 scale = 3.5 ± 0.01) with influx of inflammatory and plasma cells, dysplastic hepatocytes, multinucleated giant cell transformation and hepatic cells necrosis. Diclazuril treatment significantly protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent manner (respectively infected-treated versus infected controls, p < 0.001, p < 0.01 and p < 0.05). Colonic tissues were significantly shortened in length, with infiltration of lymphocytes, and macrophages and microabscess formations in the cryptic structures, with significant improvement in diclazuril treated animals. Additionally, the number of fetuses, fetal length and fetal weight were preserved in diclazuril treated dams.
CONCLUSIONS
This is the first report describing of diclazuril safety in pregnancy as well as efficacy against mild to moderate hepato-gastrointestinal syndrome in dams and fetal toxoplasmosis (Special issue, "Treatment of Liver Diseases").
PubMed: 24851194
DOI: 10.4236/ijcm.2014.53017 -
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