Magnetic and superparamagnetic iron oxide nanoparticles are emerging as promising candidates for various applications in biology and medicine, and especially in oncology. These applications, however, require that a specific set of physical, chemical, and biological properties be combined in a given sample of nanoparticles for them to act as intended. Some of these properties are fundamental: They strictly determine the nanoparticles' behavior both in vitro and in vivo. These properties are the charge, the solution stability and zeta potential, and the coating of the nanoparticles. A certain combination of these properties may satisfy a researcher in an in vitro study, but other properties should also be considered when in vivo applications are planned. For in vivo experiments, additional determinants of the quality of nanoparticles are their size, shape, modifications with targeting moieties, and degradation/excretion pathways. All these properties are in the focus of the present review.
XPDT does not end with killing of cancer cells. Its effects and safety are to be tracked down to excretion.
Pathway activity assessment-based approaches are becoming highly influential in various fields of biology and medicine. However, these approaches mostly rely on analysis of mRNA expression, and total mRNA from a given locus is measured in the majority of cases. Notably, a significant portion of protein-coding genes produces more than one transcript. This biological fact is responsible for significant noise when changes in total mRNA transcription of a single gene are analyzed. The NFE2L2/AP-1 pathway is an attractive target for biomedical applications. To date, there is a lack of data regarding the agreement in expression of even classical target genes of this pathway. In the present paper we analyzed whether transcript variants of GPX2, NQO1 and SQSTM1 were characterized by individual features of expression when HeLa cells were exposed to pro-oxidative stimulation with hydrogen peroxide. We found that all the transcripts (10 in total) appeared to be significantly individually regulated under the conditions tested. We conclude that individual transcripts, rather than total mRNA, are best markers of pathway activation. We also discuss here some biological roles of individual transcript regulation.
Background: Berberine has multitudinous anti-cancer stem cells effects making it a highly promising candidate substance for the next-generation cancer therapy. However, berberine modes of action predispose it to significant side-effects that probably limit its clinical testing and application. Materials and Methods: HeLa cells were treated with two concentrations of berberine (30 and 100 µM) for 24 hours to assess the functioning of the NFE2L2/AP-1, NFκB and HIF1A pathways using 22 RNAs expression qPCR-based analysis. Results: Berberine effects appeared to be highly dose-dependent, with the lower concentration being capable of suppressing the NFκB functioning and the higher concentration causing severe signaling side-effects seen in the HIF1A pathway and the NFE2L2 sub-pathways, and especially and more importantly in the AP-1 sub-pathway. Conclusion: The results of the study suggest that berberine has clinically valuable anti-NFκB effects however jeopardized by its side effects on the HIF1A and especially NFE2L2/AP-1 pathways, its therapeutic window phenomenon and its cancer type-specificity. These, however, may be ameliorated using the cocktail approach, provided there is enough data on signaling effects of berberine.
The ever-increasing biomedical application of magnetic nanoparticles (MNPs) implies increasing demand in their scalable and high-throughput production, with finely tuned and well-controlled characteristics. One of the options to meet the demand is microbial production by nanoparticles-synthesizing bacteria. This approach has several benefits over the standard chemical synthesis methods, including improved homogeneity of synthesis, cost-effectiveness, safety and eco-friendliness. There are, however, specific challenges emanating from the nature of the approach that are to be accounted and resolved in each manufacturing instance. Most of the challenges can be resolved by proper selection of the producing organism and optimizing cell culture and nanoparticles extraction conditions. Other issues require development of proper continuous production equipment, medium usage optimization and precursor ions recycling. This mini-review focuses on the related topics in microbial synthesis of MNPs: producing organisms, culturing methods, nanoparticles characteristics tuning, nanoparticles yield and synthesis timeframe considerations, nanoparticles isolation as well as on the respective challenges and possible solutions.
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