smoking exposure
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The female reproductive system represents a sensitive target of the harmful effects of cigarette smoke, with folliculogenesis as one of the ovarian processes most affected by this exposure. The aim of this study was to analyze the impact of tobacco smoking on expression of oxidative stress-related genes in cumulus cells (CCs) from smoking and non-smoking women undergoing IVF techniques. Real time PCR technology was used to analyze the gene expression profile of 88 oxidative stress genes enclosed in a 96-well plate array. Statistical significance was assessed by one-way ANOVA. The biological functions and networks/pathways of modulated genes were evidenced by ingenuity pathway analysis software. Promoter methylation analysis was performed by pyrosequencing. Our results showed a down-regulation of 24 genes and an up-regulation of 2 genes (IL6 and SOD2, respectively) involved in defense against oxidative damage, cell cycle regulation, as well as inflammation in CCs from smoking women. IL-6 lower promoter methylation was found in CCs of the smokers group. In conclusion, the disclosed overall downregulation suggests an oxidant-antioxidant imbalance in CCs triggered by cigarette smoking exposure. This evidence adds a piece to the puzzle of the molecular basis of female reproduction and could help underlay the importance of antioxidant treatments for smoking women undergoing IVF protocols.

Objective: The purpose of this study was to compare the effects of different levels of nicotine and tobacco extract exposure on Streptococcus mutans biofilm formation and the inhibitory effect of the polyphenol epigallocatechin-3 gallate (EGCG) found in green tea. This study addressed the results of biofilm assays with EGCG and varying relative concentrations of nicotine and tobacco extract consistent with primary, secondary and tertiary levels of smoking exposure. Primary smoking exposure to nicotine has been demonstrated to significantly increase biofilm formation, while EGCG has been demonstrated to reduce S. mutans biofilm formation.Methods:S. mutans was treated with varying levels of nicotine or cigarette smoke condensate (CSC) concentrations (0–32 mg/ml and 0–2 mg/ml, respectively) in Tryptic Soy broth supplemented with 1% sucrose for different lengths of time simulating primary, secondary and tertiary smoking exposure with and without 0.25 mg/ml EGCG. The amount of total growth and biofilm formed was determined using a spectrophotometric crystal violet dye staining assay.Results: For both nicotine and CSC, primary exposure displayed overall significantly less growth compared to secondary exposure. For nicotine, secondary exposure demonstrated significantly greater growth than tertiary exposure levels. Overall, significantly greater total bacterial growth and biofilm formation in the presence of nicotine and CSC was observed in the absence of EGCG than in the presence of EGCG. However, biofilm growth was not significantly different among different concentrations of CSC.Conclusion: The results of this study help illustrate that nicotine-induced S. mutans biofilm formation is reduced by the presence of EGCG. This provides further evidence of the potential beneficial properties of polyphenols.

Short root anomaly (SRA) is a dental anomaly with short dental roots and its pathogenesis is poorly understood. This study investigated the association between maternal smoking during pregnancy and SRA in offspring. A survey was conducted on 558 children aged 8–16 years from two public schools in Ulaanbaatar, Mongolia. SRA was diagnosed using cases with a root-crown ratio of maxillary central incisors of ≤1.0. A questionnaire survey was conducted to assess maternal lifestyle habits. Multiple logistic regression was used to analyse the association between maternal smoking during pregnancy and SRA in offspring after adjusting for possible confounders. The prevalence of SRA in these children was 14.2%. Children whose mothers smoked from pregnancy to date were found to be 4.95 times (95% confidence interval [CI]: 1.65–14.79) more likely to have SRA than those whose mothers never smoked, after adjusting for possible confounders. Additionally, children whose mothers had been exposed to passive smoking during pregnancy were found to be 1.86 times (95% CI: 1.02–3.40) more likely to have SRA than those whose mothers had not been exposed to passive smoke. Our population-based study suggests that maternal and passive smoking exposure during pregnancy can affect tooth root formation in children.

Abstract Background: Endogenous and exogenous processes are active in leukemia initiation. Single-base substitution (SBS) data permits aggregation into mutational signatures [MS] with potential for clinical application. Acetaldehyde and Benzo [a] pyrene (BaP) are tobacco mutagens that "drive" signature SBS4 [Catalog of Somatic Mutations in Cancer (COSMIC) https://cancer.sanger.ac.uk/signatures/sbs/] in lung cancer characterized by C>A transversion. This specific MS is associated with favorable response to immune-checkpoint therapy (ICT). Previous epidemiologic data correlate smoking with cancer including leukemia. Tobacco mutagens are ubiquitously distributed in organs once inhaled. However, how mutagenicity develops in hemopoietic stem cell/progenitor is unknown. In this study, our primary objective was to investigate the incidence of MS among patients (pt) diagnosed with Acute Myelogenous Leukemia (AML) with smoking exposure. Methods: After IRB approval, we performed retrospective analysis using the BCM AML database. Data from 58 AML pt was available. For all analysis, current and past smoking were aggregated into "positive exposure". SBSs (C>A, C>G, C>T, T>C, T>G, G>C, G>A, GT and AG) in smokers and never smoker were annotated from ELN 2017 predefined subgroups [i.e. CEBPA, NPM1, P53, ASLX1, RUNX1 and FLT3ITD] and all additional mutations in individual pt. We used descriptive statistics to detect differential clinical predictors for smoking induced MS. Chi-square was used to determine association between SBSs and smoking history. Stepwise logistic regression allowed identification of independent MS that correlated with smoking. Results: Median age for 58 AML pt was 65.5 years [y] (range, 22-89) and 58.3% were male. Smokers were 26/58 (44.8%). Whites, African Americans, Hispanics and Asians comprised 35/60 (58.3%), 7/60 (7.1%), 16/60 (26.6%) and 2/60 (2.3%), respectively. 112 myeloid mutations [91 SBSs, 16 duplications, 16 deletions, and 3 insertions] were recorded. 32/58 (55.1%) had positive smoking exposure. Previous reports suggest that C>A [COSMIC=SBS4], G>C [COSMIC= SBS2 and SBS13] and T>C [COSMIC=SBS5] retain strong smoking association with cancer. However, in addition to C>A [HR=0.10 (0.01-0.6), p=0.02], our logistic model identified G>A, HR=0.12 (0.02-0.4), p=0.002, as predictors of exposure. C>A+G>A MS was observed in 19/25 (76%) of AML pt with smoking exposure, OR=6.56 (1.8-23.9), p=0.002. By ELN-2017 defined subgroups, P53, ASXL1, RUNX1, FLT3 and NPM1 mut were detected in 11/58 (18.9%), 5/58 (8.6%), 4/58 (6.8%), 13/58 (22.4%) and 5/58 (8.6%). RAS was seen in 12/58 (20.6%), IDH 12/58 (20.6%), DNMT3A 10/58 (17.2%) and TET2 7/58 (12%). Interestingly, among smokers exhibiting or not C>A+G>A SBP substitution, P53 was identified in 3/3 (100%) v 0/3 (0%), p=0.05 and RAS in 75% v 25%, p=0.08. Conclusions: Our data suggest that C>A and G>A SBS substitutions are frequently observed in AML pt with smoking exposure. Hemopoietic stem cell/progenitors exposed to smoking products may initiate similar SBSs substitutions as those observed in tobacco induced solid tumors. Previously, lung cancer studies demonstrated that TP53 and KRAS mutations tumors exhibited high rate of C>A transversion associated with tumor-infiltrating lymphocytes (TIL) and high program-death 1 ligand (PD-L1) expression. Further similar studies are needed in adult diagnosed with P53 AML. Figure 1 Figure 1. Disclosures Mims: IDEC: Current holder of individual stocks in a privately-held company; Biogen: Current holder of individual stocks in a privately-held company; Incyte: Research Funding; Pfizer: Research Funding; AVEO: Research Funding; Celgene: Research Funding.

Most studies on the association of in utero exposure to cigarette smoking and childhood overweight or obesity (OWO) were based on maternal self-reported smoking data and few were based on objective biomarkers. In this study, we evaluated the associations between self-reported and biomarkers of in utero exposure to cigarette smoking with risk of childhood OWO. We analyzed data from 2351 mother-child pairs in the Boston Birth Cohort, a US low-income minority cohort that enrolled children at birth and followed prospectively up to age 18 years. In utero smoking exposure was measured by maternal self-report and by maternal and cord plasma cotinine and hydroxycotinine metabolites. We assessed the individual and joint associations of each smoking exposure measure and maternal OWO with childhood OWO using multinomial logistic regressions. We used nested logistic regressions to investigate the childhood OWO prediction performance when adding maternal and cord plasma biomarkers as input covariates on top of self-reported data. Our results demonstrated that in utero cigarette smoking exposure defined by self-report and by maternal or cord metabolites were consistently associated with increased risk of long-term child OWO. Adding maternal and cord plasma biomarker information to self-reported data improved the prediction accuracy of long-term child OWO risk.

Abstract Background Maternal smoking exposure during pregnancy is an established risk factor for childhood asthma, but the association between maternal pre-pregnancy smoking status and asthma risk is not well understood. This study examined the association between maternal smoking status before and during pregnancy and bronchial asthma at 3 years of age. Methods The data of 75,411 mother-child pairs, excluding the missing data of exposure and outcomes from the Japan Environment and Children's Study (JECS) were used. The association between prenatal maternal smoking status and the risk of bronchial asthma at 3 years of age was determined using multivariate logistic regression analysis. Results The percentage of 3-year-old children with doctor-diagnosed bronchial asthma was 7.2%. The distribution of maternal smoking status before childbirth was as follows: Never = 60.0%, Quit before recognizing current pregnancy = 24.1%, Quit after finding out current pregnancy = 12.3%, and Still smoking = 3.6%. Maternal smoking during pregnancy was significantly associated with an increased risk of bronchial asthma at 3 years of age even after adjusting for pre- and postnatal covariates (adjusted odds ratio [aOR] 1.35, 95% confidence interval [CI] 1.16–1.57). Furthermore, mothers who quit before recognizing current pregnancy (aOR 1.10, 95% CI 1.02–1.18) or who quit after finding out about current pregnancy (aOR 1.11, 95% CI 1.01–1.23) were also significantly associated. Conclusions This study suggested that not only maternal smoking during pregnancy but also maternal smoking exposure of pre-pregnancy or early pregnancy may be associated with an increased risk of bronchial asthma in children.

AbstractLeukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.

ObjectiveThe deleterious effects of smoking on atherosclerosis were well known; however, the interaction among ageing, smoking and atherosclerosis remains unclear. This study tested the hypothesis that the association between age and vascular calcification, a critical mark of atherosclerosis, was modified by smoking.DesignCross-sectional study.SettingA nationally representative sample, the National Health and Nutrition Examination Surveys 2013–2014.ParticipantsThis study included 3140 adults aged 40–80 years with eligible data for abdominal aortic calcification (AAC). Active and passive smoking exposure was identified through self-reports and tobacco metabolites (serum cotinine and urinary 4-methylnitrosamino-3-pyridyl-1-butanol).Primary outcome measuresAAC score was determined using dual-energy X-ray absorptiometry (DXA) scans. OR was estimated using the logistic regression method to assess the association between age and the presence of severe or subclinical AAC stratified by smoking exposure. The survey-weighted Wald test was used to evaluate potential interactions.ResultsAAC was positively associated with age in the general population. After adjustment for age, sex, race/ethnicity and other cardiovascular risk factors, age was significantly associated with the odds of severe AAC (OR for each 5-year increase in age: 1.66, 95% CI 1.48 to 1.87, p<0.001). As expected, the association between age and vascular calcification was especially stronger in smokers than in never smokers (p value for interaction ≤0.014). According to spline fitting, the progression of vascular calcification was significantly increased after 45 years in smokers compared with that after 60 years in never smokers. Quitting smoking may compromise the deleteriousness of the vascellum especially in younger adults. However, the difference in age-related calcification among never smokers with or without secondhand smoke exposure was minor, regardless of the definition by self-report, serum cotinine, or urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.ConclusionsSmoking significantly accelerated the progression of age-related subclinical atherosclerosis. Early smoking cessation should be encouraged among young smokers. The effect of passive smoking exposure on arteriosclerosis should be assessed further.

Background:Although advance has been made in understanding the pathogenesis of mature T-cell neoplasms, the initiation and progression of angioimmunoblastic T cell lymphoma (AITL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remains poorly understood. A subset of AITL/PTCL-NOS patients develop concomitant hematologic neoplasms (CHN), and a biomarker to predict this risk is lacking. Methods:We generated and analyzed the mutation profiles through 537-gene targeted sequencing of the primary tumors and matched bone marrow/peripheral blood samples in 25 patients with AITL and 2 with PTCL-NOS. Results:Clonal hematopoiesis (CH)-associated genomic alterations, found in 70.4% of the AITL/PTCL-NOS patients, were shared among CH and T-cell lymphoma, as well as concomitant myeloid neoplasms or diffuse large B-cell lymphoma (DLBCL) that developed before or after AITL. Aberrant AID/APOBEC activity-associated and tobacco smoking-associated mutational signatures were respectively enriched in the early CH-associated mutations and late non-CH associated mutations during AITL/PTCL-NOS development. Moreover, analysis showed that the presence of CH harboring ≥ 2 pathogenic TET2 variants with ≥ 15% of allele burden conferred higher risk for CHN (P = 0.0006, hazard ratio = 14.01, PPV=88.9%, NPV=92.1%). Conclusion:We provided genetic evidence that AITL/PTCL-NOS, CH, CHN can frequently arise from common mutated hematopoietic precursor clones. Our data also suggests smoking exposure as a potential risk factor for AITL/PTCL-NOS progression. These findings provide insights into the cell origin and etiology of AITL and PTCL-NOS and provide a novel stratification biomarker for CHN risk in AITL patients. Funding:R01 grant (CA194547) from the National Cancer Institute to WT.