Flavor Toolbox Assessment
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Affymetrix GeneChip Scanner 3000 7G
ORGANISM(S): Homo sapiens
SUBMITTER: Belcastro Vincenzo
PROVIDER: E-MTAB-5317 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The toxicity and potential associated molecular mechanism of a reference cigarette, 3R4F and THS2.2 a candidate modified risk tobacco products ((p)MRTP) were investigated with human bronchial epithelial cells using high-throughput screening and whole transcriptomics analysis.
2016-01-05 | E-MTAB-3738 | biostudies-arrayexpress
Project description:The toxicity and potential associated molecular mechanism of a reference cigarette, 3R4F and a prototypic modified risk tobacco products ((p)MRTP) were investigated with human bronchial epithelial cells using high-throughput screening and whole transcriptomics analysis.
2015-11-02 | E-MTAB-3734 | biostudies-arrayexpress
Project description:The development of reduced-risk products is aimed at providing adult smokers, who are unable to quit, with alternatives to cigarettes that present less risk of harm and smoking-related disease. The use of flavors in the development of these reduced-risk products fulfils an important role in product acceptance. While most flavors are also used by the food industry and are considered safe when ingested, their impact when inhaled is still debated. To overcome this research gap, we developed a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays and gene expression analysis. As a case study, a list of 28 flavors, commonly used in e-liquid formulation, were selected and dissolved individually or as a mixture in a Base Solution composed of propylene glycol, vegetable glycol, and 0.6% nicotine. Various dilutions of these mixtures were assessed in normal human bronchial epithelial cells. Using a real-time impedance-based assay, a Tox-Score corresponding to the ratio of the Base Solution EC50 over flavored solution EC50 was determined for each tested e-liquid. We complemented the e-liquid evaluation by computing a Phenotypic-Score that recapitulates the exposure effects measured using a battery of high-content screening endpoints. Using a systems toxicology approach, we also identified and quantified perturbed molecular pathways impacted specifically by the Base Solution or by the 28-flavor mixture. To conclude, employing a three-pillar based approaches to investigate the effects of flavored solutions in vitro, we were in a position to identify individual flavors that appeared to have the potential to contribute greatly to the overall mixture effect (citronellol and alpha-pinene). Finally, by assessing modified mixtures we showed that, although cytotoxic effect where found when assessed individually, alpha-pinene was not contributing to the overall mixture cytotoxicity. Most of the cytotoxic effect appeared to mainly derive by the presence of citronellol and remaining flavors were still contributing due to synergistic effects.
2019-11-01 | E-MTAB-7748 | biostudies-arrayexpress
Project description:Inferring in humans biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine and cannot be easily studied in humans. Thus, biomedical research has continuously relied on animal models for studying the impact of these compounds and attempted to M-^StranslateM-^T the results to humans. In this context, the Systems Biology Verification for Industrial Methodology for Process Verification in Research (SBV IMPROVER) initiative had run a Species Translation Challenge for the scientific community to explore and understand the limit of translatability from rodent to human using systems biology. Therefore, a multi-layer omics dataset was generated that comprised of phosphoproteomics, transcriptomics and cytokine data derived from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in parallel to more than 50 different stimuli under identical conditions. The present manuscript describes in detail the experimental settings, the generation, processing and quality control analysis of the multi-layer omics dataset. The datasets are accessible in public repositories could be leveraged for further translation studies.
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Project description:The interaction of lung epithelial and lung mesenchymal cells (fibroblasts) was investigated in a novel co-culture model of human pulmonary fibrosis. Remarkably, co-culturing both cell types induced cell-type-specific responses, including fibroblast-to-myofibroblast differentiation and epithelial-to-mesenchymal transition (EMT), which were fully dependent on direct epithelial / fibroblast contact. Primary normal human lung fibroblasts (NHLF) and normal human bronchiolar epithelial cells (NHBE) were fluorescently labelled prior to seeding, then grown either as mono or co-cultures and collected in triplicates for mRNA-seq at the start (T=0h) and after 3h and 18h. Each harvested cell culture was FACS sorted into individual NHLF and NHBE cell populations, which were then then lysed and sequenced.
2022-10-03 | E-MTAB-11832 | biostudies-arrayexpress
Project description:RhoBTB2 is a novel Rho GTPase that undergoes loss, underexpression and mutation in breast and lung cancer. We have shown that we can mimic loss of RhoBTB2 through siRNA treatment of primary cells. We propose to perform comparative microarray analysis of primary lung cells to establish the identification of the gene targets of RhoBTb2 regulation. Experiment Overall Design: Primary lung cells (NHBE) transfected with siRNA oligonucleotides against cyclophilin or Lamin A/C (controls) were compared to cells transfected with siRNA oligonucleotides against RhoBTB2. We used two siRNA oligonucleotides against RhoBTB2 (1 and 2) to determine any non-specific effects. Cells expressed the siRNA oligonucleotides for 72 hours before total RNA extraction. 10 samples have been analysed.
2008-10-25 | E-GEOD-8837 | biostudies-arrayexpress
Project description:The interaction of lung epithelial and lung mesenchymal cells was investigated in a novel co-culture model of human pulmonary fibrosis. Remarkably, co-culturing both cell types induced cell-type-specific responses, including fibroblast-to-myofibroblast differentiation and epithelial-to-mesenchymal transition (EMT), which were fully dependent on direct epithelial / fibroblast contact. We used single-cell RNA sequencing (scRNA-seq) to evaluate the transcriptional fate of the normal human lung fibroblasts (NHLF) and normal human bronchiolar epithelial cells (NHBE) during the course of co-cultivation, and compare the single cell profiles with their counterpart isolated from patients with idiopathic pulmonary fibrosis (IPF). NHLF and normal NHBE cells were grown as co-cultures, cell suspensions were collected at the time points t = 0h, 3h and 18h and analyzed by single-cell RNA-seq on a Chromium Platform. Eight samples were sequenced, resulting in a total of xx single cell transcription profiles.
2022-10-03 | E-MTAB-11847 | biostudies-arrayexpress
Project description:Propylene glycol (PG) is a common carrier in e-vapor formulations and its properties have been extensively studied. In this 13-week subchronic nose-only inhalation study, Sprague Dawley rats were exposed to filtered air (sham control group), propylene glycol/water (PG/W; 90:10) or a propylene glycol/vegetable glycerin/water (PG/VG/W; 50:40:10) reference. The reference containing vegetable glycerin group was added at the high dose to observe any changes that might be associated with a carrier more in line with e-vapor products. The objectives of this study were to increase the PG exposure above the concentrations tested by Suber et al. and use a systems toxicology analysis of lung tissue to further our understanding of molecular events after PG exposures (Suber et al. 1989). Macroscopic examinations at necropsy as well as terminal organ weights revealed no observations that were associated with exposure to PG/W or reference. Food consumption and body weights were unaffected by PG/W or reference when compared to the sham. No exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or BALF cytology and clinical chemistry. Although clinical observations of dried red material around the nose in the high dose PG/W group were reported, histopathology of the nasal cavity showed no nasal hemorrhaging. There were non-adverse PG/W and reference related findings of minimal mucus cell hyperplasia noted in nasal cavity section II. These findings were considered non-adverse as they were also found to a lesser extent in the filtered air controls. No other exposure-related findings were noted in the primary or recovery necropsies. A systems toxicology analysis on lung tissue showed no statistically-significant differentially expressed transcripts or proteins compared to the sham group. The endpoints measured from the PG/W high dose group did not differ significantly from those in the more common carrier PG/VG/W. Accordingly, the highest PG exposure (5 mg/L, 6 hrs/day) was regarded as the no observed adverse effect concentration (NOAEC), corresponding to a PG delivered dose of 1,152 mg/kg/day in rats.
2021-09-07 | E-MTAB-10006 | biostudies-arrayexpress
Project description:This experiment captures the baseline expression of two cell lines (A549, BEAS-2B) selected for Project 3, Open Targets 020 (http://opentargets.org). These cell lines are both possible models for lung disease. In addition, the baseline expression of bronchial epithelial primary cells (NHBE cells) from 3 donors has also been measured. <br> This RNA-seq experiment is being carried out as part of the Open Targets project to identify a gene expression signature of common immortalized cell lines/models. This signature will be used in combination with data from ChIP-seq experiments from the same cell lines against primary cells and tissues. The overall aim of the Open Targets Cell Line Epigenome project is to establish a systematic approach for the determination of human biological and disease relevance through the generation of transcriptomic and epigenomic data in cell lines of interest. Comparison of cell line mRNA expression and epigenome data with existing and newly generated reference data from human tissue and cell types will identify assay systems that will provide greater confidence in translating target biology and compound pharmacology to patients.
2017-07-04 | E-MTAB-4729 | biostudies-arrayexpress
Project description:The main constituents of electronic cigarette liquids are nicotine, propylene glycol (PG), and vegetable glycerin (VG), together with distilled water and flavors. To assess the toxicity of PG/VG mixtures with and without nicotine as basic components of liquids used in e-cigarettes, a 90-day rat inhalation study according to the Organization for Economic Co-operation and Development test guideline 413 was conducted. Sprague-Dawley (SD) rats were nose-only exposed, 6?h/day, 5 days/week to filtered air, or nebulized vehicle (saline), or three concentrations of PG/VG (0.174 mg PG/l + 0.210 mg VG/l; 0.520 mg PG/l + 0.630 mg VG/l; 1.520 mg PG/l + 1.890 mg VG/l) � with (test item) and without (reference item) 23 �g nicotine/L. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared to vehicle exposure, the tested PG/VG aerosols showed only very limited biological effects with no signs of toxicity, both for the standard toxicological endpoints (e.g., histopathology, clinical chemistry) and the systems toxicological analyses (transcriptomics, proteomics, and lipidomics). The addition of nicotine to the PG/VG aerosols (23 �g/l) resulted in effects in line with nicotine effects in previous studies. These included up-regulation of xenobiotic enzymes (Cyp1a1 and Fmo3) in the lung and metabolic effects, e.g., reduction in serum lipid concentrations and changes in the expression of metabolic enzymes in the liver. Signs of a generalized stress response to nicotine exposure such as decreased thymus weights were observed; and likely, a subset of the observed metabolic alterations was interlinked with this generalized stress response. Under the conditions of this 90-day SD rat inhalation study, no toxicologically relevant effects of PG/VG aerosols (up to 1.520 mg PG/l + 1.890 mg VG/l) were observed, and the no observed adverse effect level (NOAEL) for PG/VG/nicotine was determined to be 438/544/6.7 mg/kg/day. Further the study demonstrated how complementary systems toxicology analyses can reveal, also in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.
2017-11-03 | E-MTAB-5544 | biostudies-arrayexpress