Detection of Cytomorphological Changes in Oral Mucosa among Alcoholics and Cigarette Smokers.
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ABSTRACT:
SUBMITTER: Abdelaziz MS
PROVIDER: S-EPMC3215449 | biostudies-other | 2011 Sep
REPOSITORIES: biostudies-other
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Project description:This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed.
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Project description:Alterations in the oral microbiota composition may influence mental health. However, linkages between compositional changes in the oral microbiota and their role in mental health among cigarette smokers remain largely unknown. In this study, we used shotgun metagenomics data for the oral microbiome of 105 participants. The data showed Bacteroidota, Fusobacteriota, Firmicutes, Proteobacteria, and Actinobacteria to be the most abundant phyla; Streptococcus, Haemophilus D, and Veillonella are the most abundant genera. Then, we clustered our subjects into avoidance and activation groups based on the behavioral activation for depression scale (BADS). Interestingly, the avoidance group exhibited a higher oral microbiome richness and diversity (alpha diversity). Differential abundance testing between BADS avoidance and activation groups showed the phyla Bacteroidota (effect size 0.5047, q = 0.0037), Campylobacterota (effect size 0.4012, q = 0.0276), Firmicutes A (effect size 0.3646, q = 0.0128), Firmicutes I (effect size 0.3581, q = 0.0268), and Fusobacteriota (effect size 0.6055, q = 0.0018) to be significantly increased in the avoidance group, but Verrucomicrobiota (effect size-0.6544, q = 0.0401), was found to be significantly decreased in the avoidance risk group. Network analysis of the 50 genera displaying the highest variation between both groups identified Campylobacter B, Centipeda, and Veillonella as hub nodes in the avoidance group. In contrast, Haemophilus and Streptococcus were identified as hub nodes in the activation group. Next, we investigated functional profiles of the oral microbiota based on BADS avoidance and activation groups and found Lysine degradations pathway was significantly enriched between both groups (ANCOM-BC, q = 0.0692). Altogether, we provide evidence for the presence of depression-related changes in the oral microbiota of smokers and possible functional contribution. The identified differences provide new information to enrich our understanding of oral microbiota-brain axis interplay and their potential impact on mental health.
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Project description:Sildenafil citrate, a widely-used oral therapy for erectile dysfunction, is a cytochrome P3A4 (CYP3A4) enzyme substrate. Studies have reported that this substrate has an inhibitory effect on CYP3A4 enzymes in long-term cigarette and cannabis smokers, which predominantly mediate the hepatic elimination of sildenafil. Cigarette and/or cannabis smoking could therefore alter the exposure of sildenafil. The aim of this study was to examine the effect of smoking cigarettes and/or cannabis on the pharmacokinetics, pharmacodynamics, safety and tolerability of sildenafil. Thirty-six healthy human subjects were equally divided into three groups: non-smokers, cigarette smokers and cannabis smokers. Each group was administered a single dose of sildenafil (50 mg tablets). The primary outcome measures included the maximum concentration of sildenafil in plasma (Cmax), the elimination half-life (t1/2) and the area under the plasma concentration time curve from zero to time (AUC0-t). The pharmacodynamics were assessed by the International Index of Erectile Function (IIEF-5). The exposure of sildenafil (AUC0-t) showed a statistically significant increase in cigarette smokers (1156 ± 542 ng·h/mL) of 61% (p < 0.05) while in cannabis smokers (967 ± 262 ng·h/mL), a non-significant increase in AUC0-t of 35% (p > 0.05) was observed relative to non-smokers (717 ± 311 ng·h/mL). Moreover, the Cmax of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability.
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Project description:BackgroundElectronic cigarettes (e-cigs) vaping, cigarette smoke, and waterpipe tobacco smoking are associated with various cardiopulmonary diseases. microRNAs are present in higher concentration in exosomes that play an important role in various physiological and pathological functions. We hypothesized that the non-coding RNAs transcript may serve as susceptibility to disease biomarkers by smoking and vaping.MethodsPlasma exosomes/EVs from cigarette smokers, waterpipe smokers and dual smokers (cigarette and waterpipe) were characterized for their size, morphology and TEM, Nanosight and immunoblot analysis. Exosomal RNA was used for small RNA library preparation and the library was quantified using the High Sensitivity DNA Analysis on the Agilent 2100 Bioanalyzer system and sequenced using the Illumina NextSeq 500 and were converted to fastq format for mapping genes.ResultsEnrichment of various non-coding RNAs that include microRNAs, tRNAs, piRNAs, snoRNAs, snRNAs, Mt-tRNAs, and other biotypes are shown in exosomes. A comprehensive differential expression analysis of miRNAs, tRNAs and piRNAs showed significant changes across different pairwise comparisons. The seven microRNAs that were common and differentially expressed of when all the smoking and vaping groups were compared with non-smokers (NS) are hsa-let-7a-5p, hsa-miR-21-5p, hsa-miR-29b-3p, hsa-let-7f-5p, hsa-miR-143-3p, hsa-miR-30a-5p and hsa-let-7i-5p. The e-cig vs. NS group has differentially expressed 5 microRNAs (hsa-miR-224-5p, hsa-miR-193b-3p, hsa-miR-30e-5p, hsa-miR-423-3p, hsa-miR-365a-3p, and hsa-miR-365b-3p), which are not expressed in other three groups. Gene set enrichment analysis of microRNAs showed significant changes in the top six enriched functions that consisted of biological pathway, biological process, molecular function, cellular component, site of expression and transcription factor in all the groups. Further, the pairwise comparison of tRNAs and piRNA in all these groups revealed significant changes in their expressions.ConclusionsPlasma exosomes of cigarette smokers, waterpipe smokers, e-cig users and dual smokers have common differential expression of microRNAs which may serve to distinguish smoking and vaping subjects from NS. Among them has-let-7a-5p has high sensitivity and specificity to distinguish NS with the rest of the users, using ROC curve analysis. These findings will pave the way for the utilizing the potential of exosomes/miRNAs as a novel theranostic agents in lung injury and disease caused by tobacco smoking and vaping.
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Project description:Smoking-related biomarkers for lung cancer and other diseases are needed to enhance early detection strategies and to provide a science base for tobacco product regulation. An untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS) totaling 957 assays was used in a novel experimental design where 105 current smokers smoked two cigarettes 1?h apart. Blood was collected immediately before and after each cigarette allowing for within-subject replication. Dynamic changes of the metabolomic profiles from smokers' four blood samples were observed and biomarkers affected by cigarette smoking were identified. Thirty-one metabolites were definitively shown to be affected by acute effect of cigarette smoking, uniquely including menthol-glucuronide, the reduction of glutamate, oleamide, and 13 glycerophospholipids. This first time identification of a menthol metabolite in smokers' blood serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers, and also provides new opportunities in studying menthol-containing tobacco products in humans. Gender and race differences also were observed. Network analysis revealed 12 molecules involved in cancer, notably inhibition of cAMP. These novel tobacco-related biomarkers provide new insights to the effects of smoking which may be important in carcinogenesis but not previously linked with tobacco-related diseases. © 2016 Wiley Periodicals, Inc.
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| S-ECPF-GEOD-16149 | biostudies-other
Project description:A few studies have assessed the short-term effects of low-dose nicotine e-cigarettes, while data about nicotine-free e-cigarettes (NF e-cigarettes) are scanty. Concerns have been expressed about the use of NF e-cigarettes, because of the high concentrations of propylene glycol and other compounds in the e-cigarette vapor.This laboratory-based study was aimed to compare the effects of ad libitum use of a NF e-cigarette or and a traditional cigarette for 5 min in healthy adult smokers (n = 10) and non-smokers (n = 10). The main outcome measures were pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide (FeCO) in exhaled breath.The traditional cigarette induced statistically significant increases in FeCO in both smokers and non-smokers, while no significant changes were observed in FeNO. In non-smokers, the traditional cigarette induced a significant decrease from baseline in FEF75 (81 % ± 35 % vs 70.2 % ± 28.2 %, P = 0.013), while in smokers significant decreases were observed in FEF25 (101.3 % ± 16.4 % vs 93.5 % ± 31.7 %, P = 0.037), FEV1 (102.2 % ± 9.5 % vs 98.3 % ± 10 %, P = 0.037) and PEF (109.5 % ± 14.6 % vs 99.2 % ± 17.5 %, P = 0.009). In contrast, the only statistically significant effects induced by the NF e-cigarette in smokers were reductions in FEV1 (102.2 % ± 9.5 % vs 99.5 ± 7.6 %, P = 0.041) and FEF25 (103.4 % ± 16.4 % vs 94.2 % ± 16.2 %, P =? .014).The present study demonstrated that the specific brand of NF e-cigarette utilized did not induce any majoracute effects. In contrast, several studies have shown that both traditional cigarettes and nicotine-containing e-cigarettes have acute effects on lung function. Our study expands on previous observations on the effects of NF e-cigarettes, but also for the first time describes the changes induced by smoking one traditional cigarette in a group of never smokers.The short-term use of the specific brand of NF e-cigarette assessed in this study had no immediate adverse effects on non-smokers and only small effects on FEV1 and FEF25 in smokers. The long-term health effects of NF e-cigarette use are unknown but worthy of further investigations.Clinicaltrials.gov: NCT02102191.
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Project description:BackgroundSmokers may react to cigarette excise tax increases by engaging in price-minimization strategies (i.e., finding ways to reduce the cost of cigarette smoking) rather than by quitting or reducing their cigarette use, thereby reducing the public health benefits of such tax increases.PurposeTo evaluate the state and national prevalence of five common cigarette price-minimization strategies and the size of price reductions obtained from these strategies.MethodsUsing data from the 2009-2010 National Adult Tobacco Survey, the prevalence of five common price-minimization strategies by type of strategy and by smoker's cigarette consumption level were estimated. The price reductions associated with these price-minimization strategies also were evaluated. Analyses took place in November 2012.ResultsApproximately 55.4% of U.S. adult smokers used at least one of five price-minimization strategies in the previous year, with an average reduction of $1.27 per pack (22.0%). Results varied widely by state.ConclusionsCigarette price-minimization strategies are practiced widely among current smokers, and resulting price reductions are relatively large. Policies that decrease opportunities to effectively apply cigarette price-minimization strategies would increase the public health gains of cigarette excise tax increases.
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