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Register a new userCold-atmospheric plasma induces tumor cell death in preclinical in vivo and in vitro models of human cholangiocarcinoma
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Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the biliary tree with few efficient treatments. In the present study, we aimed at deciphering the molecular mechanisms underlying the antitumor effects of CAP towards CCA both in an in vivo and in vitro context. In vivo, using subcutaneous xenografts into immunocompromised mice, CAP treatment of CCA induced DNA lesions and tumor cell apoptosis, as evaluated by 8-oxoguanine and cleaved caspase-3 immunohistochemistry, respectively. Analysis of the tumor microenvironment showed changes in markers related to macrophage polarization. In vitro, incubation of CCA cells with CAP-treated culture media (i.e. plasma-activated media, PAM) led to a dose response decrease in cell survival. At molecular level, CAP treatment induced double-strand DNA breaks, followed by an increased phosphorylation and activation of the cell cycle master regulators CHK1 and p53, leading to cell cycle arrest and cell death by apoptosis. In conclusion, CAP is a novel therapeutic option to consider for CCA in the future.
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Human placenta is a complex and heterogeneous organ interfacing between the mother and the fetus that supports fetal development. Alterations to placental structural components are associated with various pregnancy complications. To reveal the heterogeneity among various placenta cell types in normal and diseased placentas, as well as elucidate molecular interactions within a population of placental cells, a new genomics technology called single cell RNA-Seq (or scRNA-seq) has been employed in the last couple of years. Here we review the principles of scRNA-seq technology, and summarize the recent human placenta studies at scRNA-seq level across gestational ages as well as in pregnancy complications such as preterm birth and preeclampsia. We list the computational analysis platforms and resources available for the public use. Lastly, we discuss the future areas of interest for placenta single cell studies, as well as the data analytics needed to accomplish them.
Cold atmospheric plasma (CAP) was shown to affect cells not only directly, but also indirectly by means of plasma pre-treated solution. This study investigated a new application of CAP generated in deionized (DI) water for the cancer therapy. In our experiments, the CAP solution was generated in DI water using helium as carrier gas. We report on the effects of this plasma solution in breast (MDA-MD-231) and gastric (NCI-N87) cancer cells. The results revealed that apoptosis efficiency was dependent on the plasma exposure time and on the levels of reactive oxygen and nitrogen species (ROS and RNS). The plasma solution that resulted from 30-minute treatment of DI water had the most significant effect in the rate of apoptosis.
Hydrogen peroxide (H2O2) is an important signaling molecule in cancer cells. However, the significant secretion of H2O2 by cancer cells have been rarely observed. Cold atmospheric plasma (CAP) is a near room temperature ionized gas composed of neutral particles, charged particles, reactive species, and electrons. Here, we first demonstrated that breast cancer cells and pancreatic adenocarcinoma cells generated micromolar level H2O2 during just 1 min of direct CAP treatment on these cells. The cell-based H2O2 generation is affected by the medium volume, the cell confluence, as well as the discharge voltage. The application of cold atmospheric plasma (CAP) in the cancer treatment has been intensively investigated over the past decade. Several cellular responses to the CAP treatment have been observed including the consumption of the CAP-originated reactive species, the rise of intracellular reactive oxygen species, the damage on DNA and mitochondria, as well as the activation of apoptotic events. This is a new previously unknown cellular response to CAP, which provides a new prospective to understand the interaction between CAP and cells.
The maintenance of the proliferative cell niche is critical to epithelial tissue morphology and function. In this paper we investigate how current modelling methods can result in the erroneous loss of proliferative cells from the proliferative cell niche. Using an established model of the inter-follicular epidermis we find there is a limit to the proliferative cell densities that can be maintained in the basal layer (the niche) if we do not include additional mechanisms to stop the loss of proliferative cells from the niche. We suggest a new methodology that enables maintenance of a desired homeostatic population of proliferative cells in the niche: a rotational force is applied to the two daughter cells during the mitotic phase of division to enforce a particular division direction. We demonstrate that this new methodology achieves this goal. This methodology reflects the regulation of the orientation of cell division.
Here, we investigated the influence of physicochemical characteristics of chondroitin sulfate (CS) on its in vitro absorption and anti-inflammatory activity. We used eight different synthetic and natural CS samples with a range of molecular weights (7-35 kDa) and sulfation patterns. Our studies indicate that the absorption of CS is moderately correlated to percentage of chondroitin-6-sulfate while the anti-inflammatory activity may be weakly related to the molecular weight and the amount of total sulfation in the samples. Our in vitro studies could provide helpful screening tools for quick and effective evaluation of CS samples as a preliminary step towards in vivo studies.
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