Project description:BxPC3 pancreatic cancer cell lines were treated with Gold Nanoparticles and RNA was isolated from untreated and treated cells, RNA was sequences by NGS method and data reported
Project description:Gold nanoparticle (AuâNP) oligonucleotide complexes hold considerable promise as an approach for manipulating intracellular gene regulation. We show that the uptake and intracellular fate of AuâNP oligonucleotide complexes is associated with endocytosis and signal transduction. A transcriptomeâwide functional analysis of gene expression implicated multiple signaling pathways specific for AuâNP oligonucleotide complexes. In primary immune cells, the complexes trigger the expression of proâinflammatory nonâchemotactic cytokines rather than the many IFNâstimulated genes critical for induction of the immune response to a microbial challenge. Concordant with these changes, exposure to AuâNP oligonucleotide complexes is also accompanied by marked activation of immune cells. This distinct gene expression profile is not replicated in the lineageârestricted 293T cell line. These findings provide insight into the functional significance of the recruitment of AuâNP oligonucleotide complexes to endocytic structures and highlight the need to study the systems effects of nanomaterials in a biologically relevant model. We investigated the effect of AuâNP antisense EGFP oligonucleotide complexes on the transcriptome by expression profiling of 293T cells under four conditions and PBMCs under six conditions plus HIV infection with the Affymetrix U133 Plus 2.0 microarray. To control for experimental variability, three of the six PBMC conditions (24â and 48âhours after AuâNP oligonucleotide complex treatment, and the negative control) were assayed independently a second time (biological replicates) so that 13 microarrays were hybridized in total. A different batch of AuâNP oligonucleotide complexes was used in the generation of the four 293T and three replicate PBMC samples, and the microarrays for these samples were processed separately.
Project description:Nanometric revolution is underway, promising technical innovations in a wide range of applications, leading to a potential boost in environmental discharges. Nanoparticle propensity to be transferred throughout trophic chains and to generate toxicity was mainly assessed in primary consumers while a lack of knowledge for higher trophic levels persists. This study focused on a predatory fish, the European eel Anguilla anguilla exposed to gold nanoparticles (AuNP, 10 nm, PEG-coated) for 21 days at three concentration levels in food: 0 (NP0), 1 (NP1) and 10 (NP10) mg Au.kg-1 . Transfer was assessed by gold quantification in eel tissues and transcriptomic responses in the liver and brain were revealed by a high-throughput RNA-sequencing approach. Eels fed at NP10 presented an erratic feeding behaviour while gold quantification only indicated transfer to intestine and kidney of NP1 exposed eels. RNA-Sequencing was performed in NP0 and NP1 eels. A total of 258 genes and 156 genes were significantly differentially transcribed in response to AuNP trophic exposure in the liver and brain, respectively. Enrichment analysis highlighted modifications in the immune system-related processes in the liver. In addition, results pointed out a shared response of both organs regarding 13 genes, most of them being involved in immune functions. This finding may shed light into the mode of action and toxicity of AuNP in fish.
Project description:Aberrant regulation of angiogenesis involves in the growth and metastasis of tumors, but angiogenesis inhibitors fail to improve overall survival of pancreatic cancer patients in previous phase III clinical trials. A comprehensive knowledge of the mechanism of angiogenesis inhibitors against pancreatic cancer is helpful for clinical purpose and for the selection of patients who might benefit from the inhibitors. In this work, multi-omics analyses (transcriptomics, proteomics and phosphoproteomics profiling) were carried to delineate the mechanism of anlotinib, a novel angiogenesis inhibitor, against pancreatic cancer cells.
Project description:In this study, we attempted to compare among the stress of Y2O3 nanoparticle and YCl3 to yeast cells. Yttrium oxide (Y2O3) nanoparticle is used in widespread applications. It has been reported that Y2O3 nanoparticle showed toxic activities. However, we assumed that the most important toxic factor of nanoparticles was metal ion release. We tried to prove the toxicity of yttrium nanoparticles comes from yttrium ion. Therefore, we used YCl3 as a positive control for evaluation of effects of yttrium ion.
Project description:Gold nanorods mediated photothermal therapy represents a promising technique for cancer treatment, utilizing GNRs in conjunction with near-infrared laser irradiation to convert energy into heat. In the present study, we employed PTT to induce apoptosis in pancreatic cancer cells and investigated its underlying mechanisms through quantitative proteomics analysis.
Project description:Gold nanoparticles (Au NPs) are uniquely suited for various biomedical applications due to the combination of their optical properties with their easily functionalized surfaces. The Au NP surface can be tailored to improve biocompatibility while also attaching targeting ligands or drugs. However, information on how these tailored surface chemistries may affect cell gene expression is scarce. Using two model human cells line, human dermal fibroblasts and prostate cancer cells, microarray experiments measured gene expression over 27,000 human genes. Each of the cell lines was exposed to four related types of surface-modified Au NPs at two different concentrations, and the microarray data was analyzed by weighted gene correlation network analysis and gene functional annotation. Au NPs were shown to affect genes associated with a variety of cellular functions, and surface charge and chemistry were linked with the types of parthways changed and the degree of which those changes occured. Nanoparticle induced gene expression in PC3 and HDF cells was measured after 24 hour exposure to nanoparticles of four different surface coating types. RNA from three separate culture samples were used for each nanoparticle-cell combinations, along with three control samples not exposed to nanoparticles at all.
Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Transcriptomic and proteomic analyses revealed the mechanism of this direct cytotoxicity.
Project description:An antivirulence approach targets bacterial virulence rather than cell viability in the antibiotic approach that can readily lead to drug resistance. Opportunistic human pathogen Pseudomonas aeruginosa produces a variety of virulence factors, and biofilm cells of this bacterium are much more resistant to antibiotics than planktonic cells. To identify novel inorganic antivirulence compounds, the dual screenings of thirty-six metal ions were performed to identify that zinc ions and ZnO nanoparticle inhibited the pyocyanin production and biofilm formation in P. aeruginosa without affecting the growth of planktonic cells. Moreover, zinc ion and ZnO nanoparticle markedly reduced the production of 2-heptyl-3-hydroxy-4(1H)-quinolone and siderophore pyochelin, while increased the production of another sideropore pyoverdine and swarming motility. Further, zinc ion and ZnO nanoparticle clearly suppressed hemolytic activity in P. aeruginosa. Transcriptome analyses showed that ZnO nanoparticle induced zinc cation efflux pump czc operon, porin genes (oprD and opdT), and Pseudomonas type III repressor A ptrA, while repressed pyocyanin-related phz operon, which partially explains the phenotypic changes. Overall, ZnO nanoparticle is a potential candidate for use in an antivirulence approach against persistent P. aeruginosa infection. P. aeruginosa Genechip Genome Array (Affymetrix, P/N 900339) was used in order to study the cells after the addition of ZnO nanoparticles. DNA microarray analysis with one biological replicate was performed with an Affymetrix system. P. aeruginosa was inoculated in 25 ml of LB medium in 250 ml shaker flasks with overnight cultures (1 : 100 dilution). Cells were cultured for 5 h with shaking at 250 rpm with and without ZnO nanoparticles (1 mM). Before sample collection, RNase inhibitor (RNAlater, Ambion, TX, USA) was added, and the cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 s before centrifugation at 16,000 g for 2 min. The cell pellets were immediately frozen with dry ice and stored at –80°C. Total RNA was isolated using a Qiagen RNeasy mini Kit (Valencia, CA, USA).