Project description:Gene expression profile analysis allowed to identify a panel of genes characteristic of silica materials effect on transformation process.
Project description:Amorphous silica nanoparticles induce malignant transformation and tumorigenesis of human lung epithelial cells. We used microarrays to detail the global programme of gene expression underlying the cellular malignant transformation induced by amorphous silica nanoparticles and identified distinct classes of up-regulated and down-regulated genes during this process.
Project description:Amorphous silica nanoparticles induce malignant transformation and tumorigenesis of human lung epithelial cells. We used microarrays to detail the global programme of gene expression underlying the cellular malignant transformation induced by amorphous silica nanoparticles and identified distinct classes of up-regulated and down-regulated genes during this process. The human lung epithelial cells, Beas-2B were continuously exposed to 5 μg/mL amorphous silica nanoparticles for 40 passages, and named as BeasSiNPs-P40 (shortly as P40-5 during the further microarray detection). Meanwhile, the passage-matched control Beas-2B cells, named as Beas-P40 (shortly as NC during the further microarray detection).
Project description:Previous studies have shown that smoking induces oxidative stress and inflammation, known factors that coincide with the development and progression of silicosis. Nevertheless, the precise role of cigarette smoke exposure in silicosis and the underlying mechanisms are not clearly understood. Therefore, the objective of the present study was to determine the effect of smoking, if any, on silica-induced pulmonary response and the underlying mechanisms. Pulmonary toxicity and lung gene expression profiles were determined in male Fischer 344 rats exposed to air, crystalline silica, cigarette smoke or cigarette smoke plus crystalline silica. Silica exposure resulted in significant pulmonary toxicity which was further exacerbated by cigarette smoke exposure in the rats. Significant differences in the gene expression profiles were detected in the lungs of the rats exposed to cigarette smoke, silica or a combination of both compared with the control rats.
Project description:Biomineral forming organisms produce inorganic materials with complex, genetically encoded morphologies that are inaccessible by current synthetic chemistry. It is poorly understood which genes are involved in biomineral morphogenesis and how the encoded proteins guide this process. We addressed these questions using diatoms, which are paradigms for the self-assembly of hierarchically meso- and macroporous silica under mild reaction conditions. By isolating the intracellular organelle for silica biosynthesis, we identified a suite of new biomineralization proteins. Three of these, dAnk1-3, are specific to diatoms and contain a common protein-protein interaction domain indicating a role in coordinating assembly of the silica biomineralization machinery. Knocking out individual dank genes led to characteristic structural aberrations in silica biogenesis that point to a liquid-liquid phase separation process as underlying mechanism for pore pattern morphogenesis. Our work provides an unprecedented path for the synthesis of tailored meso- and macroporous silicas using Synthetic Biology.
Project description:From an occupational standpoint, exposure to silica can have devastating consequences. An estimated 2.3 million workers in the U.S. are exposed to dust containing crystalline silica, annually. In addition, of the 140 million people over the age of 20, employed in the U.S., 30% are obese. If and how diet-induced obesity modifies silica-induced pulmonary toxicity is unknown. Therefore, the objective of this study was to determine the effect of diet-induced obesity, if any, on silica induced pulmonary toxicity. Rats (Fischer 344, male) were fed either a regular-fat diet (RFD; 18% kcal as fat) (Envigo, Indianapolis, IN) or a high-fat diet (HFD; 60% kcal as fat) (Envigo, Indianapolis, IN) and exposed by whole-body inhalation to either air or crystalline silica (15 mg/m3, 6 hours/day, 5 days). At designated post-exposure time intervals (1, 3, 6, and 9 months), pulmonary toxicity was determined. Silica inhalation resulted in pulmonary toxicity, which progressed across all post-exposure time points, as evidenced by enhanced neutrophil infiltration, increased LDH levels, enhanced oxidant production, and increased inflammatory cytokine levels. The incidence and severity of silica-induced lung pathology was similar between the two diet groups up to 6 months post-exposure. However, by 9 months post-exposure, silica-induced pathology tended to be slightly more severe in animals fed an RFD compared to those fed an HFD. Lung gene expression profiles were then determined in the rats euthanized at the 3- and 9-month post-silica exposure time intervals by RNA sequencing to identify transcript differences between the two timepoints.
Project description:Crystallline Silica induced inflammation in lungs Intra-trachial instilliation of CS or PBS into BLT1+/+, BLT1-/-, BLT1+/+KRasLA1 and BLT1-/-KRasLA1 mice.
Project description:Exposure to crystalline silica results in serious health effects, most notably, silicosis and cancer. An understanding of the silica-induced lung toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to air or crystalline silica (15 mg/m3, 6 hours/day for 5 days). At post-exposure time intervals of 1, 3, 6, 9, 12, and 18 months, the control and silica exposed rats were euthanized, and lung toxicity and gene expression profiles determined. Histological changes indicative of lung toxicity detected in the silica exposed rats included infiltration of neutrophils, thickening of alveolar epithelium, and fibrosis. Significant increases in lactate dehydrogenase activity, number of phagocytes, and inflammatory cytokine levels were detected in the bronchoalveolar lavage (BAL) obtained from the silica exposed rats compared with the corresponding time-matched controls. Significant changes in lung gene expression profiles, corresponding to the changes in the lung toxicity parameters analyzed, were detected in the silica exposed rats. The BAL parameters of toxicity and inflammation peaked at the 12-months post-exposure time interval and declined subsequently. However, lung fibrosis continued to progress being highest at the 18-month post-exposure time interval. These results suggest that inflammation may be required for the initiation but not for the progression and/or maintenance of lung fibrosis in response to silica exposure in the rats.
Project description:We have employed whole genome microarray expression to distinguish the effect of Fumed Silica Nanoparticles on human alveolar epithelial A549 lung cells. Cells were exposed in vitro, and datasets of differentially expressed genes were identified for NPs versus control samples.