scholarly journals The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 965
Author(s):  
Mohammad Abdullah-Al-Shoeb ◽  
Kenta Sasaki ◽  
Saori Kikutani ◽  
Nanami Namba ◽  
Keiichi Ueno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Culture ◽  
Liver Injury ◽  
Protective Effect ◽  
Acute Liver Injury ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cell Culture Model ◽  
Culture Model ◽  
Apap Hepatotoxicity

An overdose of acetaminophen (APAP), the most common cause of acute liver injury, induces oxidative stress that subsequently causes mitochondrial impairment and hepatic necroptosis. N-acetyl-L-cysteine (NAC), the only recognized drug against APAP hepatotoxicity, is less effective the later it is administered. This study evaluated the protective effect of mitochondria-specific Mito-TEMPO (Mito-T) on APAP-induced acute liver injury in C57BL/6J male mice, and a three dimensional (3D)-cell culture model containing the human hepatoblastoma cell line HepG2. The administration of Mito-T (20 mg/kg, i.p.) 1 h after APAP (400 mg/kg, i.p.) injection markedly attenuated the APAP-induced elevated serum transaminase activity and hepatic necrosis. However, Mito-T treatment did not affect key factors in the development of APAP liver injury including the activation of c-jun N-terminal kinases (JNK), and expression of the transcription factor C/EBP homologous protein (CHOP) in the liver. However, Mito-T significantly reduced the APAP-induced increase in the hepatic oxidative stress marker, nitrotyrosine, and DNA fragmentation. Mito-T markedly attenuated cytotoxicity induced by APAP in the HepG2 3D-cell culture model. Moreover, liver regeneration after APAP hepatotoxicity was not affected by Mito-T, demonstrated by no changes in proliferating cell nuclear antigen formation. Therefore, Mito-T was hepatoprotective at the late-stage of APAP overdose in mice.

scholarly journals Cytotoxicity Profile of Endodontic Sealers Provided by 3D Cell Culture Experimental Model

2016 ◽  
Vol 27 (6) ◽  
pp. 652-656 ◽  
Author(s):  
Emmanuel João Nogueira Leal Silva ◽  
Nancy Kudsi de Carvalho ◽  
Carina Taboada Ronconi ◽  
Gustavo De-Deus ◽  
Mario Luis Zuolo ◽  
...  
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Type I ◽  
Cell Culture Model ◽  
Cytotoxic Effects ◽  
Culture Model ◽  
Ah Plus ◽  
Endodontic Sealers ◽  
Dimensional Cell

Abstract The aim of the present study was to evaluate the cytotoxic effects of five endodontic sealers (AH Plus, Endomethasone N, EndoSequence BC, MTA Fillapex and Pulp Canal Sealer EWT) using a three-dimensional (3D) cell culture model. A conventional bi-dimensional (2D) cell culture model was used as reference technique for comparison. Balb/c 3T3 fibroblasts were cultured in conventional bi-dimensional cell culture and in rat-tail collagen type I three-dimensional cell culture models. Then, both cell cultures were incubated with elutes of freshly mixed endodontic sealers for 24 h. Cell viability was measured by the methyl-thiazol-diphenyltetrazolium assay (MTT). Data were statistically analyzed using ANOVA and the Tukey test at a significance level of p<0.05. All tested sealers exhibited cytotoxic effects; however, cytotoxic effect was culture model- and sealer-dependent. Sealers showed higher cytotoxicity in 2D than in 3D cell culture model (p<0.05). In both conditions, EndoSequence BC showed the lowest cytotoxicity (p<0.05). MTA Fillapex was much more cytotoxic than the other tested endodontic sealers (p<0.05), with the exception of AH Plus in the 2D cell culture model (p>0.05). Endomethasone N and Pulp Canal Sealer EWT showed lower cytotoxic effects than AH Plus in 2D cell culture model (p<0.05); however no statistical differences was observed among these sealers in 3D cell culture model. It may be concluded that cytotoxicity was higher in 2D cell culture compared to 3D cell culture. EndoSequence BC sealer exhibited the highest cytocompatibility and MTA Fillapex the lowest cytocompatibility.

scholarly journals Recapitulating Amyloid ß and Tau Pathology in Human Neural Cell Culture Models—Clinical Implications

US Neurology ◽  
2015 ◽  
Vol 11 (02) ◽  
pp. 102 ◽  
Author(s):  
Se Hoon Choi ◽  
Young Hye Kim ◽  
Carla D’Avanzo ◽  
Jenna Aronson ◽  
Rudolph E Tanzi ◽  
...  
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
Amyloid Β ◽  
3D Cell Culture ◽  
Neural Cell ◽  
Cell Culture Model ◽  
Pathogenic Mechanisms ◽  
Culture Model ◽  
Culture Models ◽  
Human Neural Cell

The “amyloid β hypothesis” of Alzheimer’s disease (AD) has been the reigning hypothesis explaining pathogenic mechanisms of AD over the last two decades. However, this hypothesis has not been fully validated in animal models, and several major unresolved factors remain. We recently developed a human neural cell culture model of AD based on a three-dimensional (3D) cell culture system. This unique, cellular model recapitulates major events of the AD pathogenic cascade, including β-amyloid plaques and neurofibrillary tangles. Our 3D human neural cell culture model system provides a premise for a new generation of cellular AD models that can serve as a novel platform for studying pathogenic mechanisms and for high-throughput drug screening in a human brain-like environment.

scholarly journals Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5320
Author(s):  
Emma Polonio-Alcalá ◽  
Marc Rabionet ◽  
Santiago Ruiz-Martínez ◽  
Sònia Palomeras ◽  
Rut Porta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cell Culture ◽  
Cancer Stem Cells ◽  
Lung Adenocarcinoma ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cell Culture Model ◽  
Culture Model ◽  
Lung Cancer Stem Cells

The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.

S1792 Effects of Ethanol and Acetaldehyde on Epithelial Integrity in a Three Dimensional (3D) Epithelial Cell Culture Model

2010 ◽  
Vol 138 (5) ◽  
pp. S-275
Author(s):  
Elhaseen Elamin ◽  
Daisy Jonkers ◽  
Freddy Troost ◽  
Kati Juuti-Uusitalo ◽  
Sven C. van IJzendoorn ◽  
...  
Keyword(s):  
Cell Culture ◽  
Epithelial Cell ◽  
Three Dimensional ◽  
Cell Culture Model ◽  
Epithelial Cell Culture ◽  
Epithelial Integrity ◽  
Culture Model

scholarly journals Effects of Ethanol and Acetaldehyde on Tight Junction Integrity: In Vitro Study in a Three Dimensional Intestinal Epithelial Cell Culture Model

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35008 ◽  
Author(s):  
Elhaseen Elamin ◽  
Daisy Jonkers ◽  
Kati Juuti-Uusitalo ◽  
Sven van IJzendoorn ◽  
Freddy Troost ◽  
...  
Keyword(s):  
Cell Culture ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Three Dimensional ◽  
In Vitro Study ◽  
Intestinal Epithelial ◽  
Cell Culture Model ◽  
Epithelial Cell Culture ◽  
Culture Model

PNU-74654 enhanced the antiproliferative activity of gemcitabine via targeting Wnt/β-catenin Pathway in Pancreatic cancer

2021 ◽  
Author(s):  
Sajjad Sharifi ◽  
Farzad Rahmani ◽  
Abolfazl Nosrati-Tirkani ◽  
Shima Mehrabadi ◽  
Hamid Fiuji ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Culture ◽  
Wnt Pathway ◽  
3D Cell Culture ◽  
Current Therapy ◽  
Beta Catenin ◽  
Cell Culture Model ◽  
Novel Therapy ◽  
3 Dimensional ◽  
Culture Model

Abstract Background : The Wnt/beta-catenin pathway is dysregulated in pancreatic cancer and is reported to be associated with poor prognosis, indicating the need for identification of novel agents to improve the efficacy of current therapy or have better activity. Therefore in the present study we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3 dimensional cell culture model of pancreatic cancer. Methods: The MTT assay was applied to determine the viability of PC cancerous cells (PCC), while the cytotoxicity of this agent was evaluated in 3D cell culture model (spheroid). The effects of PNU-74654 was investigated in established cell migration/invasion assays. Result: The expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122±0.4 umol/L, and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells through perturbation of E-cadherin. Conclusion: In aggregate our findings demonstrated the profound antitumor properties of PNU-74654 in pancreatic cancer, supporting further studies to evaluate the therapeutic impact of this novel therapy to target Wnt pathway in the treatment of pancreatic cancer.

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