scholarly journals Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies

2017 ◽  
Vol 37 (9) ◽  
Keyword(s):  
Mammalian Cells ◽  
In Vivo Studies

Enhanced xenobiotic transporter expression in normal teleost hepatocytes: response to environmental and chemotherapeutic toxins

2001 ◽  
Vol 204 (2) ◽  
pp. 217-227
Author(s):  
J.A. Albertus ◽  
R.O. Laine
Keyword(s):  
Mammalian Cells ◽  
Cellular Localization ◽  
Fundulus Heteroclitus ◽  
Environmental Pollutants ◽  
Human Tumor ◽  
Aquatic Organisms ◽  
In Vivo Studies ◽  
Multixenobiotic Resistance

Many aquatic organisms are resistant to environmental pollutants, probably because their inherent multi-drug-resistant protein extrusion pump (pgp) can be co-opted to handle man-made pollutants. This mechanism of multixenobiotic resistance is similar to the mechanism of multidrug resistance exhibited in chemotherapy-resistant human tumor cells. In the present study, a variety of techniques were used to characterize this toxin defense system in killifish (Fundulus heteroclitus) hepatocytes. The cellular localization and activity of the putative drug efflux system were evaluated. In addition, in vitro and in vivo studies were used to examine the range of expression of this putative drug transporter in the presence of environmental and chemotherapeutic toxins. The broad range of pgp expression generally observed in transformed mammalian cells was found in normal cells of our teleost model. Our findings suggest that the expression of the pgp gene in the killifish could be an excellent indicator of toxin levels or stressors in the environment.

In vitro and in vivo studies of antimutagenic properties of bioginseng in mammalian cells

1991 ◽  
Vol 111 (5) ◽  
pp. 658-661 ◽  
Author(s):  
N. V. Umnova ◽  
T. L. Michurina ◽  
N. I. Smirnova ◽  
I. V. Aleksandrova ◽  
G. G. Poroshenko
Keyword(s):  
Mammalian Cells ◽  
In Vivo Studies

scholarly journals WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases.

1997 ◽  
Vol 17 (8) ◽  
pp. 4877-4882 ◽  
Author(s):  
V V Ogryzko ◽  
P Wong ◽  
B H Howard
Keyword(s):  
Mammalian Cells ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
S Phase ◽  
In Vivo Studies ◽  
Nuclear Antigen ◽  
Phase Progression

The p21(WAF1/CIP1/sdi1) gene product (WAF1) inhibits DNA replication in vitro (J. Chen, P. Jackson, M. Kirschner, and A. Dutta, Nature 374:386-388, 1995; S. Waga, G. Hannon, D. Beach, and B. Stillman, Nature 369:574-578, 1994), but in vivo studies on the antiproliferative activity of WAF1 have not resolved G1-phase arrest from potential inhibition of S-phase progression. Here, we demonstrate that elevated WAF1 expression can retard replicative DNA synthesis in vivo. The WAF1-mediated inhibitory effect could be antagonized by cyclin A, cyclin E, or the simian virus 40 small-t antigen with no decrease in the levels of WAF1 protein in transfected cells. Proliferating-cell nuclear antigen (PCNA) overexpression was neither necessary nor sufficient to antagonize WAF1 action. Expression of the N-terminal domain of WAF1, responsible for cyclin-dependent kinase (CDK) interaction, had the same effect as full-length WAF1, while the PCNA binding C terminus exhibited modest activity. We conclude that S-phase progression in mammalian cells is dependent on continuing cyclin and CDK activity and that WAF1 affects S phase primarily through cyclin- and CDK-dependent pathways.

scholarly journals Advances in NAD-Lowering Agents for Cancer Treatment

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1665
Author(s):  
Moustafa S. Ghanem ◽  
Fiammetta Monacelli ◽  
Alessio Nencioni
Keyword(s):  
Mammalian Cells ◽  
In Vivo Studies ◽  
Clinical Activity ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Production Route ◽  
Cellular Events ◽  
Cancer Cell Survival ◽  
Key Enzyme

Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor, but it also acts as a substrate for NAD-consuming enzymes, regulating cellular events such as DNA repair and gene expression. Since such processes are fundamental to support cancer cell survival and proliferation, sustained NAD production is a hallmark of many types of neoplasms. Depleting intratumor NAD levels, mainly through interference with the NAD-biosynthetic machinery, has emerged as a promising anti-cancer strategy. NAD can be generated from tryptophan or nicotinic acid. In addition, the “salvage pathway” of NAD production, which uses nicotinamide, a byproduct of NAD degradation, as a substrate, is also widely active in mammalian cells and appears to be highly exploited by a subset of human cancers. In fact, research has mainly focused on inhibiting the key enzyme of the latter NAD production route, nicotinamide phosphoribosyltransferase (NAMPT), leading to the identification of numerous inhibitors, including FK866 and CHS-828. Unfortunately, the clinical activity of these agents proved limited, suggesting that the approaches for targeting NAD production in tumors need to be refined. In this contribution, we highlight the recent advancements in this field, including an overview of the NAD-lowering compounds that have been reported so far and the related in vitro and in vivo studies. We also describe the key NAD-producing pathways and their regulation in cancer cells. Finally, we summarize the approaches that have been explored to optimize the therapeutic response to NAMPT inhibitors in cancer.

scholarly journals Temporal analysis of mRNA expression profiles in Orientia infected C3HeB/FeJ mouse

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chien-Chung Chao ◽  
Ruoting Yang ◽  
Zhiwen Zhang ◽  
Tatyana Belinskaya ◽  
Chye-Teik Chan ◽  
...  
Keyword(s):  
Post Infection ◽  
Mammalian Cells ◽  
Time Course ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
In Vivo Studies ◽  
Coagulation Cascade ◽  
Global Changes

Abstract Background Scrub typhus causes up to 35% mortality if left untreated. One billion people living in the endemic regions are at risk. In spite of its heavy disease burden in some of the most populated areas in the world, there is no vaccine available. Although the disease can be effectively treated by proper antibiotics, timely and accurate diagnosis remains a challenge. Orientia tsutsugamushi infects a variety of mammalian cells in vitro and replicates in the cytoplasm of the infected cells. Microarray analysis has been used extensively to study host-pathogen interactions in in vitro models to understand pathogenesis. However there is a lack of in vivo studies. Results In this study, C3HeB/FeJ (C3H) mice were infected by O. tsutsugamushi via the intraperitoneal route and monitored gene expression at 10 different time points post infection. We observed two distinct types of expression profiles in the genes that we analyzed. There are two valleys (4–18 h and 2–4 days) with low number of differentially expressed genes (DEG) with three peaks with high number of DEG at 2 h, 1-day and 7-day post infection. Further analysis revealed that pathways like complement and coagulation cascade, and blood clotting cascade pathways showed significant global changes throughout entire time course. Real time quantitative Polymerase Chain Reaction (RT-qPCR) confirmed the change of expression for genes involved in complement and coagulation cascade. These results suggested dynamic regulation of the complement and coagulation cascades throughout most of the time post infection while some other specific pathways, such as fatty acid metabolism and tryptophan metabolism, are turned on or off at certain times post infection. Conclusions The findings highlight the complex interconnection among all different biological pathways. It is conceivable that specific pathways such as cell growth control and cell development in the host are affected by Orientia in the initial phase of infection for Orientia to grow intracellularly. Once Orientia is replicating successfully inside the host as infection progresses, the infection could activate pathways involved in cellular immune responses to defend for host cell survival and try to eliminate the pathogen.

A Review of the Genotoxicity of Triallate

2003 ◽  
Vol 22 (3) ◽  
pp. 233-251 ◽  
Author(s):  
Charles E. Healy ◽  
Larry D. Kier ◽  
Fabrice Broeckaert ◽  
Mark A. Martens
Keyword(s):  
Dna Synthesis ◽  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
In Vivo Studies ◽  
Weight Of Evidence ◽  
Unscheduled Dna Synthesis ◽  
Vitro Assay

Triallate is a selective herbicidal chemical used for control of wild oats in wheat. It has an extensive genotoxicity database that includes a variety of in vitro and in vivo studies. The chemical has produced mixed results in in vitro assay systems. It was genotoxic in bacterial mutation Ames assays, predominantly in Salmonella typhimurium strains TA100 and TA1535 in the presence of S9. Weaker responses have been observed in TA100 and TA1535 in the absence of S9. Mixed results have been observed in strain TA98, whereas no genotoxicity has been observed in strains TA1537 and TA1538. The presence and absence of S9 and its source seem to play a role in the bacterial response to the chemical. There have also been conflicting results in other test systems using other bacterial genera, yeast, and mammalian cells. Chromosome effects assays (sister-chromatid exchange and cytogenetics assays) have produced mixed results with S9 but no genotoxicity without S9. Triallate has not produced any genotoxicity in in vitro DNA damage or unscheduled DNA synthesis assays using EUE cells, human lymphocytes, and rat and mouse hepatocytes. In a series of in vivo genotoxicity assays (cytogenetics, micronucleus, dominant lethal, and unscheduled DNA synthesis), there has been no indication of any adverse genotoxic effect. Metabolism data indicate that the probable explanation for the differences observed between the in vitro studies with S9 and without S9 and between the in vitro and the in vivo studies is the production of a mutagenic intermediate in vitro at high doses of triallate is expected to be at most only transiently present in in vivo studies. The weight of evidence strongly suggests that triallate is not likely to exert mutagenic activity in vivo due to toxicokinetics and metabolic processes leading to detoxification.

scholarly journals In vitro circadian rhythms: imaging and electrophysiology

2011 ◽  
Vol 49 ◽  
pp. 103-117 ◽  
Author(s):  
Christian Beaulé ◽  
Daniel Granados-Fuentes ◽  
Luciano Marpegan ◽  
Erik D Herzog
Keyword(s):  
Mammalian Cells ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Genetic Determinants ◽  
Experimental Conditions ◽  
Cell Synchronization ◽  
Circadian Oscillators ◽  
Circadian Pacemakers

In vitro assays have localized circadian pacemakers to individual cells, revealed genetic determinants of rhythm generation, identified molecular players in cell–cell synchronization and determined physiological events regulated by circadian clocks. Although they allow strict control of experimental conditions and reduce the number of variables compared with in vivo studies, they also lack many of the conditions in which cellular circadian oscillators normally function. The present review highlights methods to study circadian timing in cultured mammalian cells and how they have shaped the hypothesis that all cells are capable of circadian rhythmicity.

scholarly journals Disruption of Microtubule Organization and Centrosome Function by Expression of Tobacco Mosaic Virus Movement Protein

2006 ◽  
Vol 80 (12) ◽  
pp. 5807-5821 ◽  
Author(s):  
Jacqueline Ferralli ◽  
Jamie Ashby ◽  
Monika Fasler ◽  
Vitaly Boyko ◽  
Manfred Heinlein
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Cell Biology ◽  
Mammalian Cells ◽  
Movement Protein ◽  
Infected Plant ◽  
In Vivo Studies ◽  
Microtubule Organization

ABSTRACT The movement protein (MP) of Tobacco mosaic virus mediates the cell-to-cell transport of viral RNA through plasmodesmata, cytoplasmic cell wall channels for direct cell-to-cell communication between adjacent cells. Previous in vivo studies demonstrated that the RNA transport function of the protein correlates with its association with microtubules, although the exact role of microtubules in the movement process remains unknown. Since the binding of MP to microtubules is conserved in transfected mammalian cells, we took advantage of available mammalian cell biology reagents and tools to further address the interaction in flat-growing and transparent COS-7 cells. We demonstrate that neither actin, nor endoplasmic reticulum (ER), nor dynein motor complexes are involved in the apparent alignment of MP with microtubules. Together with results of in vitro coprecipitation experiments, these findings indicate that MP binds microtubules directly. Unlike microtubules associated with neuronal MAP2c, MP-associated microtubules are resistant to disruption by microtubule-disrupting agents or cold, suggesting that MP is a specialized microtubule binding protein that forms unusually stable complexes with microtubules. MP-associated microtubules accumulate ER membranes, which is consistent with a proposed role for MP in the recruitment of membranes in infected plant cells and may suggest that microtubules are involved in this process. The ability of MP to interfere with centrosomal γ-tubulin is independent of microtubule association with MP, does not involve the removal of other tested centrosomal markers, and correlates with inhibition of centrosomal microtubule nucleation activity. These observations suggest that the function of MP in viral movement may involve interaction with the microtubule-nucleating machinery.

scholarly journals Doxycycline inducible overexpression systems: how to induce your gene of interest without inducing misinterpretations

2021 ◽  
Vol 32 (17) ◽  
pp. 1517-1522
Author(s):  
Jolan De Boeck ◽  
Catherine Verfaillie
Keyword(s):  
Cell Proliferation ◽  
Side Effects ◽  
Genomic Instability ◽  
Mammalian Cells ◽  
In Vivo Studies ◽  
The Past ◽  
Wet Lab ◽  
Overexpression System

The doxycycline inducible overexpression system is a highly flexible and widely used tool for both in vitro and in vivo studies. However, during the past decade, a handful of reports have explicitly called for caution when using this system. The raised concerns are based on the notion that doxycycline can impair mitochondrial function of mammalian cells and can alter properties such as cell proliferation. As such, experimental outcomes can be confounded with the side effects of doxycycline and valid interpretation can be seriously threatened. Today, no consensus seems to exist about how these problems should be prevented. Moreover, some of the strategies that have been used to cope with these difficulties can actually introduce additional problems that are related to genomic instability and genetic modification of the cells. Here, we elaborate on the above statements and clarify them by some basic examples taken from our personal wet-lab experience. As such, we provide a nuanced overview of the doxycycline inducible overexpression system, some of its limitations and how to deal with them.

scholarly journals In vitro and in vivo studies into the biological activities of 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione and its copper(ii) and silver(i) complexes

2012 ◽  
Vol 1 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Malachy McCann ◽  
André L. S. Santos ◽  
Bianca A. da Silva ◽  
Maria Teresa V. Romanos ◽  
Alexandre S. Pyrrho ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Galleria Mellonella ◽  
Biological Activities ◽  
In Vivo Studies ◽  
Hep G2 ◽  
Swiss Mice ◽  
Highly Active ◽  
Insect Cell Lines

Abstract 1,10-Phenanthroline (phen, 5), 1,10-phenanthroline-5,6-dione (phendione, 6), [Cu(phendione)3](ClO4)2·4H2O (12) and [Ag(phendione)2]ClO4 (13) are highly active, in vitro, against a range of normal and cancerous mammalian cells, fungal and insect cell lines, with the metal complexes offering a clear enhancement in activity. Cytoselectivity was not observed between the tumorigenic and non-tumorigenic mammalian lines. In in vivo tests, using Galleria mellonella and Swiss mice, all four compounds were well tolerated in comparison to the clinical agent, cisplatin. In addition, blood samples taken from the Swiss mice showed that the levels of the hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), remained unaffected. Immunocompromised nude mice showed a much lower tolerance to 13 and, subsequently, when these mice were implanted with Hep-G2 (hepatic) and HCT-8 (colon) human-derived tumors, there was no influence on tumor growth.

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