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Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota.

ABSTRACT: Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing 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. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.

SUBMITTER: Dong Y

PROVIDER: S-EPMC8283677 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota

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>

2021-06-21 | MTBLS2406 | MetaboLights

Effect of nanosecond pulsed electric field (nsPEF) on gene expression in TM3 Leydig cells

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.

2021-10-20 | GSE155355 | GEO

Gene expression induced by Nanosecond pulsed electric fields

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

2006-02-01 | GSE4106 | GEO

Nanosecond pulsed electric field induced proliferation and differentiation of osteoblasts and myoblasts.

Project description:Low-intensity electric fields can induce changes in cell differentiation and cytoskeletal stresses that facilitate manipulation of osteoblasts and mesenchymal stem cells; however, the application times (tens of minutes) are of the order of physiological mechanisms, which can complicate treatment consistency. Intense nanosecond pulsed electric fields (nsPEFs) can overcome these challenges by inducing similar stresses on shorter timescales while additionally inducing plasma membrane nanoporation, ion transport and intracellular structure manipulation. This paper shows that treating myoblasts and osteoblasts with five 300 ns PEFs with intensities from 1.5 to 25 kV cm-1 increased proliferation and differentiation. While nsPEFs above 5 kV cm-1 decreased myoblast population growth, 10 and 20 kV cm-1 trains increased myoblast population by approximately fivefold 48 h after exposure when all cell densities were set to the same level after exposure. Three trials of the PEF-treated osteoblasts showed that PEF trains between 2.5 and 10 kV cm-1 induced the greatest population growth compared to the control 48 h after treatment. Trains of nsPEFs between 1.5 and 5 kV cm-1 induced the most nodule formation in osteoblasts, indicating bone formation. These results demonstrate the potential utility for nsPEFs to rapidly modulate stem cells for proliferation and differentiation and motivate future experiments to optimize PEF parameters for in vivo applications.

| S-EPMC6597781 | biostudies-literature

Cellular Processes Involved in Jurkat Cells Exposed to Nanosecond Pulsed Electric Field.

Project description:Recently, nanosecond pulsed electric field (nsPEF) has been considered as a new tool for tumor therapy, but its molecular mechanism of function remains to be fully elucidated. Here, we explored the cellular processes of Jurkat cells exposed to nanosecond pulsed electric field. Differentially expressed genes (DEGs) were acquired from the GEO2R, followed by analysis with a series of bioinformatics tools. Subsequently, 3D protein models of hub genes were modeled by Modeller 9.21 and Rosetta 3.9. Then, a 100 ns molecular dynamics simulation for each hub protein was performed with GROMACS 2018.2. Finally, three kinds of nsPEF voltages (0.01, 0.05, and 0.5 mV/mm) were used to simulate the molecular dynamics of hub proteins for 100 ns. A total of 1769 DEGs and eight hub genes were obtained. Molecular dynamic analysis, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the Rg, demonstrated that the 3D structure of hub proteins was built, and the structural characteristics of hub proteins under different nsPEFs were acquired. In conclusion, we explored the effect of nsPEF on Jurkat cell signaling pathway from the perspective of molecular informatics, which will be helpful in understanding the complex effects of nsPEF on acute T-cell leukemia Jurkat cells.

| S-EPMC6929111 | biostudies-literature

Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.

Project description:Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

| S-EPMC7024567 | biostudies-literature

Safety and Efficacy of Nanosecond Pulsed Electric Field Treatment of Sebaceous Gland Hyperplasia.

Project description:BackgroundNanosecond pulsed electric field (nsPEF) technology involves delivery of ultrashort pulses of electrical energy and is a nonthermal, drug-free technology that has demonstrated favorable effects on cellular structures of the dermis and epidermis.ObjectiveDetermine the tolerability and effectiveness of nsPEF treatment of sebaceous gland hyperplasia (SGH).MethodsThis study was a prospective, randomized, open-label, multisite, nonsignificant risk trial in which each subject served as their own control. After injection of local anesthetic, high-intensity, ultrashort pulses of electrical energy were used to treat 72 subjects resulting in a total of 222 treated lesions. Subjects returned for 3 to 4 follow-up evaluations with photographs.ResultsAt the final study visit, 99.6% of treated SGH lesions were rated clear or mostly clear and 79.3% of the subjects were satisfied or mostly satisfied with the outcome. At 60 days after nsPEF treatment, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild post-treatment hyperpigmentation. At the last observation for all lesions, 32% of the 222 lesions were noted as having slight volume loss.ConclusionNanosecond pulsed electric field procedure is well tolerated and is very effective in the removal of SGHs.Trial registrationClinicalTrials.gov NCT03612570.

| S-EPMC7266004 | biostudies-literature

Molecular dynamics simulation of the nanosecond pulsed electric field effect on kinesin nanomotor.

Project description:Kinesin is a biological molecular nanomotor which converts chemical energy into mechanical work. To fulfill various nanotechnological tasks in engineered environments, the function of biological molecular motors can be altered by artificial chemical modifications. The drawback of this approach is the necessity of designing and creating a new motor construct for every new task. We propose that intense nanosecond-scale pulsed electric field could modify the function of nanomotors. To explore this hypothesis, we performed molecular dynamics simulation of a kinesin motor domain docked on a subunit of its microtubule track - a single tubulin heterodimer. In the simulation, we exposed the kinesin motor domain to intense (100 MV/m) electric field up to 30 ns. We found that both the magnitude and angle of the kinesin dipole moment are affected. Furthermore, we found that the electric field affects contact surface area between kinesin and tubulin, the structure and dynamics of the functionally important kinesin segments, including microtubule binding motifs as well as nucleotide hydrolysis site which power the nanomotor. These findings indicate that external intense nanosecond-scale electric field could alter kinesin behavior. Our results contribute to developing novel electromagnetic methods for modulating the function of biomolecular matter at the nanoscale.

| S-EPMC6928163 | biostudies-literature

Nanosecond pulsed electric field ablates rabbit VX2 liver tumors in a non-thermal manner.

Project description:BackgroundLiver tumor remains an important cause of cancer-related death. Nanosecond pulsed electric fields (nsPEFs) are advantageous in the treatment of melanoma and pancreatic cancer, but their therapeutic application on liver tumors need to be further studied.MethodsHep3B cells were treated with nsPEFs. The biological behaviors of cells were detected by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine, and transmission electron microscopy (TEM) assays. In vivo, rabbit VX2 liver tumor models were ablated by ultrasound-guided nsPEFs and radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) was used to evaluate the ablation effect. HE staining and Masson staining were used to evaluate the tissue morphology after ablation. Immunohistochemistry was performed to determine the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin at different time points after ablation.ResultsThe cell viability of Hep3B cells was continuously lower than that of the control group within 3 days after pulse treatment. The proliferation of Hep3B cells was significantly affected by nsPEFs. TEM showed that Hep3B cells underwent significant morphological changes after pulse treatment. In vivo, CEUS imaging showed that nsPEFs could completely ablate model rabbit VX2 liver tumors. After nsPEFs ablation, the area of tumor fibrosis and the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin were decreased. However, after RFA, rabbit VX2 liver tumor tissue showed complete necrosis, but the expression of PCNA and α-smooth muscle actin did not decrease compared to the tumor group.ConclusionsnsPEFs can induce Hep3B cells apoptosis and ablate rabbit VX2 liver tumors in a non-thermal manner versus RFA. The ultrasound contrast agent can monitor immediate effect of nsPEF ablation. This study provides a basis for the clinical study of nsPEFs ablation of liver cancer.

| S-EPMC10016630 | biostudies-literature

Electrosensitization assists cell ablation by nanosecond pulsed electric field in 3D cultures.

Project description:Previous studies reported a delayed increase of sensitivity to electroporation (termed "electrosensitization") in mammalian cells that had been subjected to electroporation. Electrosensitization facilitated membrane permeabilization and reduced survival in cell suspensions when the electric pulse treatments were split in fractions. The present study was aimed to visualize the effect of sensitization and establish its utility for cell ablation. We used KLN 205 squamous carcinoma cells embedded in an agarose gel and cell spheroids in Matrigel. A local ablation was created by a train of 200 to 600 of 300-ns pulses (50 Hz, 300-600 V) delivered by a two-needle probe with 1-mm inter-electrode distance. In order to facilitate ablation by engaging electrosensitization, the train was split in two identical fractions applied with a 2- to 480-s interval. At 400-600 V (2.9-4.3 kV/cm), the split-dose treatments increased the ablation volume and cell death up to 2-3-fold compared to single-train treatments. Under the conditions tested, the maximum enhancement of ablation was achieved when two fractions were separated by 100 s. The results suggest that engaging electrosensitization may assist in vivo cancer ablation by reducing the voltage or number of pulses required, or by enabling larger inter-electrode distances without losing the ablation efficiency.

| S-EPMC4796786 | biostudies-other

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