Project description:Cigarette smoke is a major risk factor for the development and progression of chronic obstructive pulmonary disease. Tobacco smoking is also the main cause of lung cancer and the main preventable cause of other lung and heart disease. Strategies to eliminate cigarette smoking have led to the emergence of new tobacco-related products as alternatives for cigarette smoking or tools for smoking cessation. Electronic cigarettes (E-cigarettes) have been introduced to the market in recent years as an alternative to smoking conventional cigarettes. E-cigarettes are nicotine delivery devices by heating and converting to aerosol a liquid mixture composed of propylene glycol, vegetable glycerine, flavouring chemicals, and nicotine. Despite the lack of appropriate studies, e-cigarettes are nowadays widely used and advertised as safe cigarette replacements and the number of users is rapidly growing. Unlike cigarette smoke, where the determinant effects are well studied and documented, very limited amount of research has been done on the health effects and public health of e-cigarettes. The study aims to investigate the effects of e-cigarette vapour extract on gene expression in different primary isolated mouse lung cells [pulmonary arterial smooth muscle cells (PASMC) and alveolar epithelial type two cells (AECII)]. The cells will be exposed to e-cigarette vapour extract (ECVE).
Project description:Extrinsic stressors must have a role in driving clonal hematopoiesis since only a fraction of individuals with clonal hematopoiesis of indeterminate potential (CHIP) develop hematologic malignancy. Smoking behavior is associated with CHIP, but the effects of cigarette smoke on hematopoietic stem cells (HSCs) are unknown. The exploding use of electronic (E)-cigarettes has led to significant concern on their health effects. In this project, we aimed to determine the impact of cigarette smoke on the frequency and numbers of HSCs and inflammatory gene expression changes in bone marrow hematopoietic cells using wildtype mice. We also determined if cigarette smoke drives clonal expansion in mosaic mice containing both wildtype and Jak2V617F mutant cells. We also performed gene expression profiling on the wildtype fraction of bone marrow hematopoietic cells from mosaic mice exposed to cigarette smoke or air to determine if the presence of mutant cells alters the signature of wildtype cells.
Project description:The emerging concern about chemicals in electronic cigarettes, even those without nicotine, de-mands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects.
Project description:As part of current harm reduction strategies, candidate modified risk tobacco products (MRTP) are developed to offer adult smokers who want to continue using tobacco product an alternative to cigarettes while potentially reducing individual risk and population harm compared to smoking cigarettes. One of these candidate MRTPs is the Tobacco Heating System (THS) 2.2 which does not burn tobacco, but instead heats it, thus producing significantly reduced levels of harmful and potentially harmful constituents (HPHC) compared with combustible cigarettes (CC). A controlled, parallel group, open-label clinical study was conducted with subjects randomized to three monitored groups: (1) switching from CCs to THS2.2; (2) continuous use of non-menthol CC brand (CC arm); or (3) smoking abstinence (SA arm) for five days. Exposure response was assessed by measuring biomarkers of exposure to selected HPHCs. To complement the classical exposure response measurements, we have used the previously reported whole blood derived gene signature that can distinguish current smokers from either non-smokers or former smokers with high specificity and sensitivity. We tested the small signature consisting of only 11 genes on the blood transcriptome of subjects enrolled in the clinical study and showed a reduced exposure response in subjects that either stopped smoking or switched to a candidate MRTP, the THS2.2, compared with subjects who continued smoking their regular tobacco product.
Project description:Background: Adult vapers are likely to co-use electronic cigarettes (e-cigs) and combustible cigarettes or have a prior history of smoking. Teasing out the health consequences of vaping in adults, while accounting for the confounding effects of smoking, remains a research priority. Methods: We have segregated the biological effects of vaping from smoking by constructing the whole transcriptome in leukocytes of healthy adult vapers (with and without a history of smoking) and exclusive smokers in comparison to control nonsmokers non-vapers (n = 37, 22, 23, respectively). Results: Age- and sex-adjusted limmaVoom analysis of RNA-seq data showed significant dysregulation of key genes and molecular pathways in both vapers and smokers as compared to controls. The extent of transcriptomic effects, as reflected by the number of differentially expressed genes, was more pronounced in smokers than vapers (683 vs. 92). Computational modeling, combining primary and sensitivity analyses, revealed that e-cig use, but not past smoking, is significantly associated with gene dysregulation in vapers. Comparative analysis of the gene networks and canonical pathways impacted in vapers and smokers showed strikingly similar biological outcomes in the two groups, although the number of affected genes was several-fold higher in smokers than vapers. Of significance is the preferential targeting of mitochondrial genes in both vapers and smokers, consistent with impaired functional networks, which are known to drive mitochondrial DNA-related disorders. Equally remarkable is the dysregulation of immune response genes in both vapers and smokers, modulated by upstream cytokines, including members of the interleukin and interferon family, that play a crucial role in inflammation. Conclusions: The concurrent targeting of mitochondrial- and immune response genes in vapers and smokers suggests a consequential role for vaping and smoking in inflammation. Our findings accord with the growing evidence on the central role of mitochondria as signaling organelles that govern fundamentals of immunity and inflammatory response. In view of the widespread use of e-cigs among youth and young adults, these novel findings have significant implications for tobacco regulatory science and public health.
Project description:We found that mainstream cigarette smoking (4 cigarettes/day, 5 days/week for 2 weeks using Kentucky Research Cigarettes 3R4F) resulted in >20% decrease in the percentage of normal Paneth cell population in Atg16l1 T300A mice but showed minimal effect in wildtype littermate control mice, indicating that Atg16l1 T300A polymorphism confers sensitivity to cigarette smoking-induced Paneth cell damage. We performed 16S rRNA sequencing to identify potential microbiota changes associated with Paneth cell defect in Atg16l1 T300A mice exposed to cigarette smoking. Female mice were used at 4-5 weeks of age. Cigarette smoking was performed using smoking chamber with the dosage and schedule as described above. The fecal samples from the mice were collected for 16S rRNA sequencing analysis after completing 6 weeks of smoking.
Project description:Electronic nicotine delivery system (E-Cigarette) use is prevalent among pregnant women. We examined whether E-Cigarette exposure impairs implantation. RNA microarray was performed on day 4.5 pseudopregnant mice exposed to E-Cigarettes or sham during each day of pregnancy.