Project description:We use a human whole genome microarray to analyze the effects of nanosecond pulsed electric fields on Jurkat cells with the focus on early response genes to DNA damage. Keywords: nanosecond pulsed electric fields, jurkat cells, DNA damage
Project description:The aim of our study was to analyze cell response to nanosecond pulsed electric field (nsPEF) at the gene expression level. TM3 Leydig cells were used as a model. Transcriptomics analysis was carried out immediately after exposure (0 h) and 4 or 24 h after treatment.
Project description:In this project we aimed at deciphering modulation in genes expression induced by external pulsed electric fields applied in reversible electroporation-based treatments. Thanks to their local application and transient effects, physical stimuli appear as attractive tools to remodel extracellular matrix, which was the point of interest in our to be published study. We assessed the potential of pulsed electric field technology, classically applied to drug delivery, to induce collagen remodeling at the tissue scale. A sophisticated in vitro tissue-engineered human dermal substitute, a tissue model rich in endogeneous extracellular matrix such as collagens, was used to demonstrate the effects of microsecond and millisecond pulsed electric fields applied respectively in electrochemotherapy (ECT) treatment and gene electrotransfer (GET) strategy. Our analyses, focused on matrisome genes and extracellular matrix remodeling, underpin that pulsed electric fields, a technology already approved for clinical use combined with anti-cancer agents, are particularly promising to provide local and effective treatment of abnormal extracellular matrix. Part of this dataset was used to describe how pulsed electric field on its own (with no addition of external drugs) induce extracellular matrix (ECM) remodeling at human dermal scale, by focusing at genes related to matrisome subset. In this manuscript to be published, electrochemotherapy (ECT) parameters were named SP for "short pulses" and gene electrotransfer (GET) parameters were named LP for "long pulses". W demonstrated that these both types of electric parameters inducing reversible electroporation of the cells whitin the dermal tissue substitute induced 1) a rapid modulation (4h after electrostimulation) of mRNA’s genes composing the matrisome, particularly a down-regulation of pro-collagens and ECM maturation’s enzymes such as transglutaminase TG2 and LOX-like; 2) a transient decrease in pro-collagens production and hydroxyproline tissue content within a week after electrostimulation; 3) a long-lasting ROS-dependent over-activation of MMPs for at least 48h and 4) a down-regulation at both mRNA and protein level of pro-fibrotic TGF-β.
Project description:Catheter ablation is an effective treatment to prevent recurrence of Atrial fibrillation (AF) and can be used to maintain sinus rhythm and improve symptoms of AF, but to some extent it can cause a range of adverse effects associated with catheter ablation. Pulsed electric field is a newer treatment modality to replace catheter ablation for atrial fibrillation due to its fewer side effects. Different from radiofrequency ablation, which destroys diseased myocardial tissue by thermal energy, pulsed electric field ablation achieves the purpose of atrial fibrillation ablation by inducing damage to diseased myocardial cells through irreversible electroporation. However, some experimental parameters and mechanism of pulsed electric fields remain unclear.
Project description:The scarcity of effective treatment options for high grade brain tumours has led to a wide ranging search for alternative means of therapy for these difficult to treat tumours. Electrical field therapy is one such area that has been considered. The OptuneTM system is an FDA approved novel anti-mitotic device that delivers continuous alternating electric fields to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM) (tumor treating fields - TTFields). Alternative electric fields delivery systems are also being investigated for the treatment of various cancers.To further explore alternative potential mechanisms of electric fields as a whole, we ran Optune, DBS electric fields treated and control untreated KNS42, U87 and GIN-31 (primary) cell lines on Clariom S Human Assays to produce genome-wide expression data.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:<p>Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that based on high-intensity electric voltage to achieve tumor-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys, and other organs with rich blood supply. When we were looking at the safety and feasibility of applying nsPEF on porcine livers, we found that the indicators of liver function after ablation fluctuated. To further study the influence of this technique in the treatment of liver, we collected serum and fecal specimens of the pigs pre-treatment and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analyzing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS) based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. </p>
Project description:In the last few years, pulsed electric fields have emerged as promising clinical tools for tumor treatments. This study highlights the distinct impact of a specific pulsed electric field protocol named PEF-5 (0.3 MV/m, 40 µs, 5 pulses) on astrocytes (NHA), medulloblastoma (D283) and gli-oblastoma (U87 NS) cancer stem-like cells. We pursued this goal performing ultrastructural analyses corroborated by molecular/omics approaches to understand the vulnerability or re-sistance mechanisms triggered by PEF-5 exposure in the different cell types. Electron microscopic analyses showed that, independently of exposed cells, the main targets of PEF-5 were the cell membrane and the cytoskeleton, presenting indiscriminate filopodia disappearance on the cell surface accompanied by a rapid cell swelling. Nevertheless, cells activated different responses stemming from intracellular organelles. NHA triggered a protective mechanism to recover from the damaged membranes and eliminated the detrimental ROS to maintain cell vital functions. Conversely, PEF-5 induced a different action on mitochondria of cancer stem-like cells, more prominent on D283 compared to U87 NS cells, in correlation with a higher basal level of CD133 protein in D283 cells. In this case, a complete mitochondrial dysfunction was demonstrated, inhibiting the recovery of D283 vital processes, while a mild perturbation was observed in mito-chondria of U87 NS cells, not sufficient to impair their cell functions. Altogether, these results suggest the possibility to use PEF-based technology as a novel strategy to target selectively mi-tochondria of CSCs, preserving healthy cells. Ultrastructural analysis, supported by transcriptomic characterization in microsecond pulsed electric field exposed normal brain and brain tumor cells