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Cell Biology and Toxicology

Helen Devine, Rickie Patani
The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies...
December 3, 2016: Cell Biology and Toxicology
Dharmendra Kumar, Taruna Anand, Wilfried A Kues
The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations...
November 29, 2016: Cell Biology and Toxicology
Kai Kaarniranta, Paulina Tokarz, Ali Koskela, Jussi Paterno, Janusz Blasiak
Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells...
November 29, 2016: Cell Biology and Toxicology
Tao Liu, Wei-Hong Liu, Jin-Sheng Zhao, Fan-Zheng Meng, Heng Wang
In the present study, we determined the protective role of lutein against Aβ 25-35 peptide-induced oxidative stress and apoptosis in bEND.3 cells. Cell viability was determined through MTT assay. Reactive oxygen species, lipid peroxides, and antioxidant enzyme activities were evaluated to analyze the oxidative stress status. NF-κB and Nrf-2 downstream target protein expressions were determined through western blot. Apoptosis was analyzed through caspase activities and subG1 accumulation. The results showed that Aβ 25-35 significantly increased (p < 0...
November 22, 2016: Cell Biology and Toxicology
Wenwen Gu, Nian Dong, Peng Wang, Changgen Shi, Jun Yang, Jian Wang
The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER(+)) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER(+) breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium...
November 11, 2016: Cell Biology and Toxicology
Nneka E Mbah, Jean H Overmeyer, William A Maltese
Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes...
November 7, 2016: Cell Biology and Toxicology
Preeyaporn Plaimee Phiboonchaiyanan, Kesarin Busaranon, Chuanpit Ninsontia, Pithi Chanvorachote
Exposure to compounds with cancer-potentiating effects can contribute to the progression of cancer. Herein we have discovered for the first time that benzophenone-3 (BP-3), a chemical used as sunscreen in various cosmetic products, enhances the ability of lung cancer cells to undergo metastasis. The exposure of the lung cancer cells to BP-3 at non-toxic concentrations significantly increased the number of anoikis resistant cells in a dose-dependent manner. Also, BP-3 increased the growth rate as well as the number of colonies accessed by anchorage-independent growth assay...
October 28, 2016: Cell Biology and Toxicology
Xiaodan Luo, Lihua Xu, Yangqiu Li, Huo Tan
Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival...
October 21, 2016: Cell Biology and Toxicology
Michael P Chu, Jitra Kriangkum, Christopher P Venner, Irwindeep Sandhu, Joanne Hewitt, Andrew R Belch, Linda M Pilarski
Cancer heterogeneity is a significant factor in response to treatment and escape leading to relapse. Within an individual cancer, especially blood cancers, there exists multiple subclones as well as distinct clonal expansions unrelated to the clinically detected, dominant clone. Over time, multiple subclones and clones undergo emergence, expansion, and extinction. Although sometimes this intra-clonal and inter-clonal heterogeneity can be detected and/or quantified in tests that measure aggregate populations of cells, frequently, such heterogeneity can only be detected using single cell analysis to determine its frequency and to detect minor clones that may subsequently emerge to become drug resistant and dominant...
October 19, 2016: Cell Biology and Toxicology
Cristiane C Denardin, Leo A M Martins, Mariana M Parisi, Moema Queiroz Vieira, Silvia R Terra, Florencia M Barbé-Tuana, Radovan Borojevic, Márcia Vizzotto, Tatiana Emanuelli, Fátima Costa Rodrigues Guma
Activated hepatic stellate cells (HSC) are the major source of collagen I in liver fibrosis. Eugenia uniflora L. is a tree species that is widely distributed in South America. E. uniflora L. fruit-popularly known as pitanga-has been shown to exert beneficial properties. Autophagy contributes to the maintenance of cellular homeostasis and survival under stress situation, but it has also been suggested to be an alternative cell death pathway. Mitochondria play a pivotal role on signaling cell death. Mitophagy of damaged mitochondria is an important cell defense mechanism against organelle-mediated cell death signaling...
October 15, 2016: Cell Biology and Toxicology
Madhav Bhatia
No abstract text is available yet for this article.
October 6, 2016: Cell Biology and Toxicology
Carmen Fierbinteanu-Braticevici, Crina Sinescu, Alexandru Moldoveanu, Ana Petrisor, Sorina Diaconu, Dragos Cretoiu, Bogdan Braticevici
Nonalcoholic fatty liver disease (NAFLD) is very prevalent and now considered the most common cause of chronic liver disease. Staging the severity of liver damage is very important because the prognosis of NAFLD is highly variable. The long-term prognosis of patients with NAFLD remains incompletely elucidated. Even though the annual fibrosis progression rate is significantly higher in patients with nonalcoholic hepatitis (NASH), both types of NAFLD (nonalcoholic fatty liver and nonalcoholic steatohepatitis) can lead to fibrosis...
September 28, 2016: Cell Biology and Toxicology
Krishna Kumar Ganta, Anirban Mandal, Binay Chaubey
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and an active constituent of the highly active antiretroviral therapy regime. It has significantly contributed in control and management of human immunodeficiency virus propagation. However, EFV administration has also led to severe adverse effects, several reports highlighted the role of EFV in mitochondrial dysfunction and toxicity but the molecular mechanism has been poorly understood. In present study, human hepatoma cells Huh 7.5 were treated with clinically relevant concentrations of EFV and parameters like cytotoxicity, mitochondrial transmembrane potential, mitochondrial morphology, cytochrome c release, mitochondria-mediated apoptosis, mtDNA and mtRNA levels and EFV distribution into mitochondrial compartment were evaluated to understand sequence of events leading to cell death in EFV-treated cells...
September 17, 2016: Cell Biology and Toxicology
Xiaochen Zhang, Hongqiang Yin, Zhigui Li, Tao Zhang, Zhuo Yang
Autophagy is a cellular pathway involved in degradation of damaged organelles and proteins in order to keep cellular homeostasis. It plays vital role in podocytes. Titanium dioxide nanoparticles (nano-TiO2) are known to induce autophagy in cells, but little has been reported about the mechanism of this process in podocytes and the role of autophagy in podocyte death. In the present study, we examined how nano-TiO2 induced authophagy. Besides that, whether autophagy could protect podocytes from the damage induced by nano-TiO2 and its mechanism was also investigated...
December 2016: Cell Biology and Toxicology
Lianmin Bao, Hua Diao, Nian Dong, Xiaoqiong Su, Bingbin Wang, Qiongya Mo, Heguo Yu, Xiangdong Wang, Chengshui Chen
The reversibility of non-genotoxic phenotypic changes has been explored in order to develop novel preventive and therapeutic approaches for cancer. Quisinostat (JNJ-26481585), a novel second-generation histone deacetylase inhibitor (HDACi), has efficient therapeutic actions on non-small cell lung cancer (NSCLC) cell. The present study aims at investigating underlying molecular mechanisms involved in the therapeutic activity of quisinostat on NSCLC cells. We found that quisinostat significantly inhibited A549 cell proliferation in dose- and time-dependent manners...
December 2016: Cell Biology and Toxicology
Maurish Bukhari, Hayley Burm, Damien S K Samways
Ionic "vital dyes" are commonly used to assess cell viability based on the idea that their permeation is contingent on a loss of membrane integrity. However, the possibility that dye entry is conducted into live cells by endogenous membrane transporters must be recognized and controlled for. Several cation-selective plasma membrane-localized ion channels, including the adenosine 5'-triphosphate (ATP)-gated P2X receptors, have been reported to conduct entry of the DNA-binding fluorescence dye, YO-PRO-1, into live cells...
October 2016: Cell Biology and Toxicology
Xiangdong Wang
No abstract text is available yet for this article.
October 2016: Cell Biology and Toxicology
Thamizhiniyan Venkatesan, Young-Woong Choi, Sung-Phil Mun, Young-Kyoon Kim
In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP)...
October 2016: Cell Biology and Toxicology
Georgios Divolis, Panagiota Mavroeidi, Olga Mavrofrydi, Panagiota Papazafiri
Calcium signaling participates in the regulation of numberless cellular functions including cell cycle progression and cellular migration, important processes for cancer expansion. Cancer cell growth, migration, and invasion are typically supported by PI3K/Akt activation, while a hypoxic environment is critical in cancer development. Accordingly, in the present study, we aimed at investigating whether perturbations in calcium homeostasis induce alterations of HIF-1α and activate Akt levels in epithelial A549 and A431 cells...
October 2016: Cell Biology and Toxicology
Lianmin Bao, Yong Zhang, Jian Wang, Haiyun Wang, Nian Dong, Xiaoqiong Su, Menglin Xu, Xiangdong Wang
Lung cancer is one of the most common malignancies worldwide. The present study aimed to investigate specific genotypes of different subtypes or stages of lung cancer through gene expression variations of chromosome 2 genes, trying to identify predictors for diagnosis or prognosis of lung cancer. About 537 patients with lung adenocarcinoma (ADC), 140 patients with lung squamous carcinoma (SQC), 9 patients with lung large cell carcinoma (LCC), 56 patients with small cell lung cancer (SCLC), and 590 patients without cancer were analyzed in present study...
October 2016: Cell Biology and Toxicology
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