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Nicotine, a key constituent of tobacco/electronic cigarettes causes cardiovascular injury and mortality. Nicotine is known to induce oxidative stress and mitochondrial dysfunction in cardiomyocytes leading to cell death. However, the underlying mechanisms remain unclear. Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) is a member of metal-dependent protein phosphatase (PPM) family and is known to dephosphorylate several AGC family kinases and thereby regulate a diverse set of cellular functions including cell growth, survival, and death. Our lab has previously demonstrated that PHLPP1 removal reduced cardiomyocyte death and cardiac dysfunction following injury. Here, we present a novel finding that nicotine exposure significantly increased PHLPP1 protein expression in the adolescent rodent heart. Building upon our in vivo finding, we determined the mechanism of PHLPP1 expression in cardiomyocytes. Nicotine significantly increased PHLPP1 protein expression without altering PHLPP2 in cardiomyocytes. In cardiomyocytes, nicotine significantly increased NADPH oxidase 4 (NOX4), which coincided with increased reactive oxygen species (ROS) and increased cardiomyocyte apoptosis which were dependent on PHLPP1 expression. PHLPP1 expression was both necessary and sufficient for nicotine induced mitochondrial dysfunction. Mechanistically, nicotine activated extracellular signal-regulated protein kinases (ERK1/2) and subsequent eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) to increase PHLPP1 protein expression. Inhibition of protein synthesis with cycloheximide (CHX) and 4EGI-1 abolished nicotine induced PHLPP1 protein expression. Moreover, inhibition of ERK1/2 activity by U0126 significantly blocked nicotine induced PHLPP1 expression. Overall, this study reveals a novel mechanism by which nicotine regulates PHLPP1 expression through ERK-4E-BP1 signaling axis to drive cardiomyocyte injury. [Display omitted] • Nicotine increases PHLPP1 expression in cardiomyocytes leading to increased ROS, mitochondrial dysfunction, and death. • Overexpression of PHLPP1 alone increased ROS and mitochondrial dysfunction in cardiomyocytes. • Removal of PHLPP1 protected cardiomyocytes from nicotine induced oxidative stress, mitochondrial dysfunction, and damage. • Nicotine increased PHLPP1 through ERK/4E-BP1 signaling axis. [ABSTRACT FROM AUTHOR]

Emerging data from clinical studies have shown pro-inflammatory effects associated with e-cigarette use. Fractional exhaled nitric oxide (FeNO) is a biomarker of pulmonary type 2 (T2) inflammation. The effect of chronic e-cigarette use on FeNO is unclear. The aim of this study was to compare FeNO levels in COPD ex-smokers who use e-cigarettes (COPDE + e-cig) to COPDE ex-smokers (COPDE) and COPD current smokers (COPDS). FeNO levels were significantly higher in COPDE + e-cig (median 16.2 ppb) and COPDE (median 18.0 ppb) compared to COPDS (median 7.6 ppb) (p = 0.0003 and p < 0.0001 respectively). There was no difference in FeNO levels between COPDE + e-cig compared to COPDE (p > 0.9). The importance of our results is that electronic cigarette use does not alter the interpretation of FeNO results, and so does not interfere with the use of FeNO as a practical biomarker of T2 inflammation, unlike current cigarette smoking in COPD. Whilst the effect of electronic cigarette use on FeNO levels is not the same as cigarette smoke, this cannot be taken as evidence that electronic cigarettes are harmless. These differential pulmonary effects can be attributed to differences in the chemical composition of the two products. • E-cigarette use does not alter the interpretation of FeNO results in COPD. • E-cigarette does not interfere with the use of FeNO as a biomarker of T2 inflammation. • This cannot be taken as evidence that e-cigarettes are harmless. [ABSTRACT FROM AUTHOR]

Smoking cigarettes during pregnancy is associated with adverse effects on infants including low birth weight, defective lung development, and skeletal abnormalities. Pregnant women are increasingly turning to vaping [use of electronic (e)-cigarettes] as a perceived safer alternative to cigarettes. However, nicotine disrupts fetal development, suggesting that like cigarette smoking, nicotine vaping may be detrimental to the fetus. To test the impact of maternal vaping on fetal lung and skeletal development in mice, pregnant dams were exposed to e-cigarette vapor throughout gestation. At embryonic day (E)18.5, vape exposed litter sizes were reduced, and some embryos exhibited growth restriction compared to air exposed controls. Fetal lungs were collected for histology and whole transcriptome sequencing. Maternally nicotine vaped embryos exhibited histological and transcriptional changes consistent with impaired distal lung development. Embryonic lung gene expression changes mimicked transcriptional changes observed in adult mouse lungs exposed to cigarette smoke, suggesting that the developmental defects may be due to direct nicotine exposure. Fetal skeletons were analyzed for craniofacial and long bone lengths. Nicotine directly binds and inhibits the Kcnj2 potassium channel which is important for bone development. The length of the maxilla, palatal shelves, humerus, and femur were reduced in vaped embryos, which was further exacerbated by loss of one copy of the Kcnj2 gene. Nicotine vapor exposed Kcnj2 KO/+ embryos also had significantly lower birth weights than unexposed animals of either genotype. Kcnj2 mutants had severely defective lungs with and without vape exposure, suggesting that potassium channels may be broadly involved in mediating the detrimental developmental effects of nicotine vaping. These data indicate that intrauterine nicotine exposure disrupts fetal lung and skeletal development likely through inhibition of Kcnj2. Nicotine vaping disrupts lung airway development, lung gene expression, craniofacial and long bone development, and increases sensitivity of skeletal consequences to variations in Kcnj2 function. [Display omitted] • Maternal e-cigarette use disrupts lung development. • Maternal nicotine vaping decreases expression of lung development genes. • Fetal exposure to nicotine vaping increases expression of cigarette smoking associated genes. • Embryonic exposure to e-cigarettes decreases the size of craniofacial and long bones. • Loss of one copy of Kcnj2 sensitizes embryos to the skeletal consequences of nicotine vaping. [ABSTRACT FROM AUTHOR]

Implications. Nicotine exposure during adolescence mediates sexually dimorphic patterns of learning and memory, with wild-type female adolescent mice being more susceptible to the effects of sub-threshold nicotine exposure than adolescent male mice. Hypersensitivity of the CHRNA2 gene encoding for the α 2 subunit of nicotinic acetylcholine receptors in female adolescent mice resulted in learning that is equal to wild-type animals at baseline, but no enhancement of learning and memory when exposed to nicotine. These results illustrate how nicotine exposure during adolescence leads to differential neurobehavioral and neurodevelopmental effects in males and females. [Display omitted] Adolescence is characterized by a critical period of maturation and growth, during which regions of the brain are vulnerable to long-lasting cognitive disturbances. Adolescent exposure to nicotine can lead to deleterious neurological and psychological outcomes. Moreover, the nicotinic acetylcholine receptor (nAChR) has been shown to play a functionally distinct role in the development of the adolescent brain. CHRNA2 encodes for the α 2 subunit of nicotinic acetylcholine receptors associated with CA1 oriens lacunosum moleculare GABAergic interneurons and is associated with learning and memory. Previously, we found that adolescent male hypersensitive CHRNA 2 L9′S/L9′ mice had impairments in learning and memory during a pre-exposure-dependent contextual fear conditioning task that could be rescued by low-dose nicotine exposure. In this study, we assessed learning and memory in female adolescent hypersensitive CHRNA 2 L9′S/L9′ mice exposed to saline or a subthreshold dose of nicotine using a hippocampus-dependent task of pre-exposure-dependent contextual fear conditioning. We found that nicotine-treated wild-type female mice had significantly greater improvements in learning and memory than both saline-treated wild-type mice and nicotine-treated CHRNA 2 L9′S/L9′ female mice. Thus, hyperexcitability of CHRNA 2 in female adolescent mice ablated the nicotine-mediated potentiation of learning and memory seen in wild-types. Our results indicate that nicotine exposure during adolescence mediates sexually dimorphic patterns of learning and memory, with wild-type female adolescents being more susceptible to the effects of sub-threshold nicotine exposure. To understand the mechanism underlying sexually dimorphic behavior between hyperexcitable CHRNA 2 mice, it is critical that further research be conducted. [ABSTRACT FROM AUTHOR]

Constituents of cigarette smoke are known to be carcinogens. Additionally, there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Nicotine, the primary constituent of tobacco, plays a role in cancer progression. In our previous study, it was found that nicotine enhances the proliferation of a human normal fetal hepatic (WRL68) cell due to the activation of p53 mutation at Ser249 (p53-RS)/STAT1/CCND1 signaling pathway. Here, we further elucidated the mechanism of regulating this pathway. Firstly, dose-dependent increase of SETDB1 protein level in WRL68 cells upon exposure to nicotine (1.25, 2.5, and 5 μM), significantly enhanced cellular proliferation. In addition, the upregulation of SETDB1 protein was necessary for the nuclear translocation of p53-RS to establish a ternary complex with STAT1 and SETDB1, which facilitated p53-RS di-methylation at K370 (p53-RS/K370me2). After that, the activation of CCND1/PI3K/AKT pathway was initiated when STAT1 stability was enhanced by p53-RS/K370me2, ultimately resulting in cell proliferation. Altogether, the study revealed that the increase in SETDB1 expression could potentially have a significant impact on the activation of CCND1/PI3K/AKT pathway through p53-RS/K370me2, leading to the proliferation of WRL68 cells induced by nicotine, which could contribute to hepatocellular carcinoma for smokers. Besides, the results of this study provided a foundation for the development of anticancer therapies for cancers associated with tobacco use. [Display omitted] • SETDB1 in WRL68 cells treated with nicotine is increased. • Translocation of p53-RS to form complex with STAT1 and SETDB1 to di-methylate p53-RS. • CCND1/PI3K/AKT axis is activated when STAT1 stability is enhanced by p53-RS/K370me2. [ABSTRACT FROM AUTHOR]

This study identifies brands of nicotine pouches used in 2021, just before the surge in popularity of Zyn use. We conducted a national, cross-sectional online survey of a general U.S. population (November to December 2021; N = 6131; age 13–40) via Qualtrics panels. Descriptive analyses and chi-squared tests (alpha = 0.05) were performed to assess ever and past-30-day use of nicotine pouch brands across adolescents (13−20), young adults (21–24), and adults (25–40), and to assess frequency of popular brands used among peers. The top brands ever used were Zyn (overall: 30.9%; adolescents: 31.9%; young adults: 33.2%; adults: 28.3%) and Lyft (overall: 28.8%; adolescents: 28.4%; young adults: 32.9%; adults: 26.3%), with no differences in ever-use by age group (p's > 0.095). The top brands used in the past-30-days were Zyn (overall: 26.4%; adolescents: 24.5%; young adults: 24.3%; adults: 30.0%) and Rush (overall: 24.2%; adolescents: 21.0%; young adults: 22.7%; adults: 28.6%). Adults (vs. adolescents, young adults) were more likely to report past-30-day use of Lyft (p = 0.004). Participants indicated Zyn (18.5%) and Lyft (18.2%) to be the most popular brands among peers. Even in 2021, Zyn was the most popular brand of nicotine pouches. Findings will help regulate and reduce impact of marketing of Zyn. [ABSTRACT FROM AUTHOR]

Widespread misperceptions about nicotine may have unintended effects on public health. We examined associations between existing messages about nicotine or tobacco and beliefs about nicotine and reduced nicotine cigarettes (RNC). 2962 U.S. 18–45-year-olds were randomized in a May 2022 web-based survey to view one of 26 text-based messages about tobacco or nicotine from three sources: ongoing research (n = 8), messages authorized by FDA for VLN cigarettes (n = 6), and FDA's "From Plant to Product to Puff" campaign (n = 12); six messages from FDA's campaign did not reference nicotine and were treated as the reference source. Analyses examined associations between messages, grouped by source and individually, with beliefs about nicotine and RNC addictiveness and harms. Relative to FDA messages that did not reference nicotine, all message sources were associated with greater odds of a correct belief about nicotine (Odds Ratios [ORs] = 1.40–1.87, p 's < 0.01); VLN messages were associated with greater correct beliefs about RNC addictiveness (b = 0.23, p <.05). No campaign produced greater correct beliefs about RNC harms. At the individual level, only five messages were associated with a correct belief about nicotine (ORs = 2.12–2.56, p -values <.01), and one with correct beliefs about RNC harms (b = 1.09, p <.05), vs. the reference message. Few existing messages improved understanding of the risks of nicotine separately from the risks of combustible products. Communication research is needed to promote greater public understanding of nicotine while minimizing unintended effects on nicotine and tobacco use. • 2962 U.S. adults viewed one of 26 text-based messages about tobacco or nicotine. • Nicotine message source groups were associated with correct beliefs about nicotine. • VLN messages were associated with more correct beliefs about RNC addictiveness. • Few individual messages were associated with correct nicotine or RNC beliefs. • Findings highlight the difficulty in correcting misperceptions about nicotine. [ABSTRACT FROM AUTHOR]

Adding fruit tree branches to the compost pile in appropriate proportions is one of the methods used to address the challenge of tobacco waste recycling. However, the effects of different proportions of fruit tree branches on nicotine concentration and microbial diversity during tobacco waste composting have not been reported. In this study, a composting system with tobacco waste, cow dung, and fruit tree branches was established in a laboratory fermenter to assess the impact of adding 10%, 20%, and 30% fruit tree branches on quantity changes. In addition, the relationships between nicotine degradation, compost properties, enzyme activities, and microbial diversities were determined using biochemical assay methods and high-throughput sequencing. The results showed that adding appropriate proportions of fruit branch segments affected changes in physical and chemical properties during composting and promoted tobacco waste compost maturity. Aerobic composting effectively degraded nicotine in tobacco waste. Increased proportions of fruit branch segments led to elevations in nicotine degradation rates and enzyme activities related to lignocellulose degradation. The addition of fruit branches influenced the relative abundance and species of dominant bacteria and fungi at the phylum and genus levels. However, it did not significantly affect the relative abundance of the main bacterial genera involved in nicotine degradation. Nevertheless, it reduced the sensitivity of enzyme activity to nicotine content within heaps, increasing reliance on total nitrogen changes. The results of this study provide a theoretical basis for the utilization of tobacco waste in composting systems and indicate that fruit tree branches can enhance nicotine degradation efficiency during tobacco waste composting. [Display omitted] • Addition of fruit branch segments enhanced tobacco waste compost maturity. • Fruit branch segments led to increased nicotine gradation rates. • Fruit branch segments strengthened lignocellulose degradation enzyme activities. • Fruit branch segments affected the diversity of microorganisms in the heap. • Fruit branch segments reduced enzyme activity sensitivity to nicotine content. [ABSTRACT FROM AUTHOR]

Neonicotinoids form a class of insecticides that are chemically related to nicotine and are widely used in crop protection. They have adverse effects on the neuronal nicotinic acetylcholine receptors (nAChRs). One of the neonicotinoids approved for control of the invasive pest Drosophila suzukii is acetamiprid. Despite concerns regarding its genotoxicity and data indicating the presence of small amounts of this substance in fruits intended for consumption, effects of its low doses on nerve cells are yet to be investigated. To determine whether the neurotoxic effects are species-specific and vary depending on the insecticide present in diet, multigenerational cultures of Drosophila melanogaster and D. suzukii were prepared, in this study, in media supplemented with different concentrations (below the LC50) of acetamiprid and nicotine. Acetamiprid, analogous to nicotine, caused damage to the DNA of neuroblasts in both species, at sublethal concentrations, along with a decrease in mobility, which remained at a similar level over subsequent generations. D. suzukii was found to be more sensitive to nicotine and acetamiprid, due to which the genotoxic effects were stronger even at lower doses of toxins. The results collectively indicated that even low concentrations of acetamiprid affect the stem cells of developing fly brain, and that long-term response to the tested insecticides is species-specific. • Neurotoxic effects of neonicotinoids were studied for species-specificity in flies. • D. melanogaster and D. suzukii were cultured in presence of acetamiprid and nicotine. • Sub-lethal levels of acetamiprid damaged neuroblast DNA in both species. • Motion abilities decreased and persisted over subsequent generations. • D. suzukii was more sensitive to the toxins and was susceptible to even lower doses. [ABSTRACT FROM AUTHOR]

E-cigarette flavors can create sensations of sweetness and coolness while masking the aversiveness of nicotine. Recently, non-tobacco nicotine (NTN) products were introduced to the market, but little is known about flavors in NTN e-cigarette use. We examined associations between flavors (i.e., sweet, mint/menthol) and susceptibility to and use of NTN e-cigarettes. 1239 US young adults (18–25 years) completed an anonymous, online survey in Fall 2021. The analytic sample included 520 participants who had used e-cigarettes and heard of NTN. Multinomial logistic regression models analyzed associations of flavored e-cigarette use (sweet and mint/menthol) with NTN e-cigarette use status (i.e., current [past-month] use, past [ever but not current] use, susceptible to use, and non-susceptible to use [reference]). Overall, 46.2% of participants reported current NTN use, 14.8% reported past use, 16.7% were susceptible to use, and 22.3% reported no susceptibility. Participants reported dual-use of sweet and mint/menthol NTN e-cigarette flavors (56.5%), sweet flavors use (24.8%), and mint/menthol flavor use (1.7%). Ever dual use of sweet and mint/menthol flavors was associated with current (OR = 9.64, 95%CI: 3.21–28.98) and past NTN e-cigarette use (8.30, [2.10–32.80]). Ever sweet flavor use was associated with current NTN use (3.80, 95%CI: 1.44–10.03) and susceptibility to future use (4.25, [1.53–11.81]). Similar findings were observed for mint/menthol flavors (current: 5.03, [1.41–17.99]; susceptible: 5.65, [1.64–19.51]). The use of sweet and mint/menthol flavors was significantly associated with NTN e-cigarette use among US young adults, highlighting the need for ongoing surveillance of flavored NTN e-cigarettes and appropriate regulations to discourage use. • Sweet flavor use was related to current use and susceptibility to NTN e-cigarettes. • Mint/menthol flavor use was related to current use and susceptibility to NTN e-cigarettes. • Dual sweet and mint/menthol flavor use was related to current and past NTN e-cigarette use. • Regulating sweet and mint/menthol flavors may help to reduce NTN product use. [ABSTRACT FROM AUTHOR]

The U.S. Food and Drug Administration is considering a policy to reduce nicotine in cigarettes to non-addictive levels. Although current evidence supports the public-health benefits of a reduced-nicotine policy, almost half of people who smoke (∼ 40%) do not support the policy. This study estimates the factors most strongly associated with support or opposition toward the policy, including tobacco use status, perceived effects of a reduced nicotine policy, trust in the FDA, and psychological distress. The study aims to inform messaging campaigns and policy makers. Data were collected in 2021 with nationally representative samples of U.S. adults (n = 1763). After receiving information about the reduced nicotine policy, participants indicated their beliefs and support for or opposition to the policy, along with other individual difference characteristics. Univariate population parameters and multinomial logistic regression coefficients were estimated. In adjusted models, people who formerly or never smoked were less likely to oppose the policy compared to those who currently smoke; people with higher psychological distress and those who believe the policy will promote switching to e-cigarettes were more likely to oppose the policy. In addition, people were more likely to support the policy if they believed it would make quitting easier or that the FDA is trustworthy. Educational campaigns about reduced nicotine policy should expect higher impact by targeting prevalent perceptions and those more strongly associated with policy sentiment. In anticipation of the policy rollout, there may be a critical window to shape public opinion. • A policy to reduce nicotine in cigarettes is under consideration in the US. • Several (mis)perceptions are associated with (lack of) support for the policy. • Educational campaigns should target these beliefs prior to policy rollout. • Tobacco-use behavior remains the strongest predictor of policy support. [ABSTRACT FROM AUTHOR]

This study utilized a socioecological approach to prospectively identify intrapersonal, familial, and environmental factors associated with single nicotine product use (NPU) and multiple NPU among U.S. youth. Participants were 10,029 youths (ages 12–17 years) who had completed the Population Assessment of Tobacco Health study's Wave 1 (2013–2014) and Wave 4 (2016–2018) assessments and data on past 30-day nicotine product use. Multinomial logistic regression was fit for the 3-level outcome (no use, single NPU, multiple NPU) to estimate adjusted associations between the predictors and the outcome. The current study found that intrapersonal (sex, age, race/ethnicity, internalizing symptoms, sensation seeking, harm perceptions, lifetime history of using two or more tobacco products), familial (parental discussion about not using tobacco and living with someone who uses tobacco products) and environmental factors (exposure to tobacco advertising) commonly associated with tobacco use differentiated between individuals who later reported past 30-day NPU (either multiple or single NPU) from those who did not report past 30-day NPU. One familial factor only differentiated between lifetime users who were single NPUs from those who reported no NPU: non-combustible tobacco product use allowed anywhere in the home. Intrapersonal factors differentiated multiple NPU from single NPU: older age, being male, lifetime history of using nicotine product and less harm perceptions. This study identified factors that may be studied to prevent any NPU, along with factors that may be studied to promote harm reduction by preventing escalation of single NPU to problematic patterns of multiple NPU. • We examined factors associated with single and multiple nicotine product use (NPU). • Intrapersonal, familial, and environmental factors were associated with any NPU. • Some factors differentiated multiple vs. single NPU. • Harm reduction may be tested to target differentiators of multiple and single NPU. [ABSTRACT FROM AUTHOR]

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin , lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A , a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts. [Display omitted] • Nicotine intake increased the abundance of symbiotic gut bacterium BsNLG8, leading to a stronger bacteriostatic effect. • Nicotine stimulated the differential expression of immune genes, with Defensin A exhibiting a significant response. • Silencing of Defensin A in N. lugens reduced survival, enhanced nicotine sensitivity and decreased the abundance of BsNLG8. • Reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine-induced stress was unveiled. [ABSTRACT FROM AUTHOR]

Exposure to nicotine by cigarette smoking have shown strongly defectives on the physiological function of ovaries, which in turn leads to disorders of fertility in women. However, the potential molecular mechanisms remain to be elucidated. In this study, we notably found that nicotine was likely to specifically raise the expression of histone deacetylase 3 (HDAC3) to promote the apoptosis and autophagy of granulosa cells (GCs) and block follicular maturation. Moreover, prostaglandin E2 (PGE2) inhibited the apoptosis of GCs and facilitated follicular maturation, and nicotine appeared to inhibit PGE2 secretion by freezing the expression of cyclooxygenase 1 (COX1), which was the rate-limiting and essential enzyme for PGE2 synthesis. Epigenetically, the nicotine was observed to diminish the histone H3 lysine 9 acetylation (H3K9ac) level and compact the chromatin accessibility in −1776/-1499 bp region of COX1 by evoking the expression of HDAC3 , with the deactivated Cas9- HDAC3 /sgRNA system. Mechanistically, the COX1 protein was found to pick up and degrade the autophagy related protein beclin 1 (BECN1) to control the autophagy of GCs. These results provided a potential new molecular therapy to recover the damage of female fertility induced by nicotine from cigarette smoking. • Nicotine exposure promotes the apoptosis and autophagy of granulosa cells, and arrests follicular maturation. • Nicotine exposure diminishes the H3K9ac level in −1776/-1499 bp region of COX1 by evoking the expression of HDAC3. • The COX1 protein picks up and degrades the autophagy related protein BECN1 to control the autophagy of granulosa cells. [ABSTRACT FROM AUTHOR]

Smoking is linked with numerous adverse health effects. Nicotine staining on fingers or teeth is thought to suggest active or heavy smoking. The significance of nicotine staining within gastroenterology remains unclear. We set out to establish the predictive value of nicotine staining for adenomas and advanced adenomas. This was a cross-section study of patients who underwent colonoscopy at the Oklahoma City Veterans Affairs Medical Center from November 2019 to November 2020. Pre-procedure patient survey ascertained current smoking status. Endoscopist performed a nicotine staining survey upon completion of the respective colonoscopy. Chart review allowed determination of patient demographics, comorbidities, and colonoscopy findings. Patients without smoking history were assigned to a control cohort. We applied one-way analysis of variance when comparing the mean of continuous variables and the Chi-square test when comparing categorical variables. Lastly, we used stepwise logistic regression to estimate adjusted odds ratio. A p -value <0.05 was considered statistically significant. Compared to those without smoking history or evidence of nicotine staining, patients with positive nicotine staining were older (P = 0.03), leaner (P < 0.0001), and more likely to have chronic obstructive pulmonary disease (P < 0.0001) or history of alcohol abuse (P < 0.0001). Furthermore, presence of nicotine staining independently predicted increased likelihood of multiple adenomas (OR 1.5, 95% CI [1.2–1.9]) and advanced adenomas (OR 1.6, 95% CI [1.2–2.2]). This marks the first investigation of nicotine staining within gastroenterology. We have demonstrated that the presence of nicotine staining independently predicts numerous adenomas and advanced adenomas. [ABSTRACT FROM AUTHOR]

Nicotine exposure from smoking constitutes a significant global public health concern. Furthermore, smoking represents a pivotal risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of nicotine on HNSCC remains relatively underexplored. Our aim was to unravel the molecular mechanisms that underlie the effect of nicotine on the metastatic cascade of HNSCC. In this study, we discovered a significant association between smoking and HNSCC metastasis and prognosis. Nicotine significantly enhanced HNSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Analysis of TCGA-HNSCC and FDEENT-HNSCC cohorts revealed reduced miR-375–3p levels in HNSCC tumor tissues, particularly among current smokers. Additionally, miR-375–3p level was strongly correlated with both lymph node metastasis and tumor stage. By downregulating miR-375–3p, nicotine promotes HNSCC cell metastasis in vitro and hematogenous metastatic capacity in vivo. Utilizing transcriptomic sequencing, molecular docking, dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH), we demonstrated that miR-375–3p specifically binds to 3′ untranslated region (3'UTR) of NTRK2 mRNA. Thus, this study uncovers a novel nicotine-induced mechanism involving miR-375–3p-mediated NTRK2 targeting, which promotes HNSCC metastasis. These findings have implications for improving the prognosis of patients with HNSCC, especially in smokers. • Nicotine enhances HNSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). • Nicotine facilitates metastasis of HNSCC cells by suppressing miR-375–3p. • Nicotine-regulated miR-375–3p mediates HNSCC metastasis by targeting NTRK2 mRNA's 3′UTR. [ABSTRACT FROM AUTHOR]

Cytoglobin (Cygb) has been identified as the major nitric oxide (NO) metabolizing protein in vascular smooth muscle cells (VSMCs) and is crucial for the regulation of vascular tone. In the presence of its requisite cytochrome B5a (B5)/B5 reductase-isoform-3 (B5R) reducing system, Cygb controls NO metabolism through the oxygen-dependent process of NO dioxygenation. Tobacco cigarette smoking (TCS) induces vascular dysfunction; however, the role of Cygb in the pathophysiology of TCS-induced cardiovascular disease has not been previously investigated. While TCS impairs NO biosynthesis, its effect on NO metabolism remains unclear. Therefore, we performed studies in aortic VSMCs with tobacco smoke extract (TSE) exposure to investigate the effects of cigarette smoke constituents on the rates of NO decay, with focus on the alterations that occur in the process of Cygb-mediated NO metabolism. TSE greatly enhanced the rates of NO metabolism by VSMCs. An initial increase in superoxide-mediated NO degradation was seen at 4 h of exposure. This was followed by much larger progressive increases at 24 and 48 h, accompanied by parallel increases in the expression of Cygb and B5/B5R. siRNA-mediated Cygb knockdown greatly decreased these TSE-induced elevations in NO decay rates. Therefore, upregulation of the levels of Cygb and its reducing system accounted for the large increase in NO metabolism rate seen after 24 h of TSE exposure. Thus, increased Cygb-mediated NO degradation would contribute to TCS-induced vascular dysfunction and partial inhibition of Cygb expression or its NO dioxygenase function could be a promising therapeutic target to prevent secondary cardiovascular disease. • Cytoglobin controls nitric oxide (NO) metabolism through NO dioxygenation. • Tobacco smoking exposure induces loss of vascular NO; however, the cause was unknown. • Vascular smooth muscle cell exposure first triggered increased superoxide generation. • This was followed by induction of cytoglobin and the B5/B5R reducing system. • Together, this greatly increased the rate of NO decay in vascular smooth muscle cells. [ABSTRACT FROM AUTHOR]

Heated tobacco products (HTPs) are an emerging class of tobacco goods that claim to have lower health risks than those of smoking combustible tobacco products. In this study, we exposed human lung epithelial cell lines to extracts prepared from HTP aerosols and combustible cigarette smoke to compare cytotoxicity. We focused on the effects of aldehydes present in the aerosols of HTPs at levels close to those in combustible cigarette smoke. Significant toxicity was confirmed for the HTP extract, albeit to a lesser extent than that with the combustible cigarette extract. When redox balance was evaluated by the oxidative loss of low-molecular-weight thiols in the cells, we found that total glutathione (GSH) contents and low-molecular-weight thiol levels were significantly decreased after exposure to the aerosol extract of HTPs. These results indicated that GSH is rapidly consumed during the detoxification of xenobiotics, such as aldehydes from tobacco extracts. Accordingly, exposure to the aerosol extract of HTPs resulted in the enhanced carbonylation of many proteins. In a simple comparison, the results for HTPs were significantly different from those obtained with combustible cigarette smoke, suggesting reduced toxicity of HTPs. However, we found significant and harmful effects after exposing lung epithelial cells to the aerosol extract of HTPs. Thus, a further comprehensive study is needed to clarify the lung damage induced via the long-term inhalation of aerosols from HTPs. [Display omitted] • Aerosol extract of heated tobacco product (HTP) is cytotoxic to lung epithelial cell. • Total GSH contents were drastically decreased by exposure to aerosol extract of HTPs. • Exposure to aerosol extract of HTPs causes protein carbonylation in human lung cells. [ABSTRACT FROM AUTHOR]

Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately after nicotine cessation and was significantly higher than that of mice continued on nicotine. Mice switched to vehicle consumed more food than nicotine-continued mice during the first week of cessation, while oxygen consumption was comparable. Elevated expression of orexigenic agouti-related peptide was observed in the hypothalamic appetite center. Pair-feeding experiment revealed that the accelerated weight gain after nicotine withdrawal is explained by enhanced energy intake. As a showcase of an efficacy of pharmacologic intervention, exendin-4 was administered and showed a potent suppression of energy intake and weight gain in mice withdrawn from nicotine. Our current model provides a unique platform for the investigation of the changes of energy regulation after smoking cessation. • Smoking cessation is accompanied by increased body weight. • A mouse model of weight gain after nicotine withdrawal is established. • Food intake and orexigenic peptide expression are enhanced immediately after nicotine withdrawal. • Dependence of body weight gain on increased food intake is shown by pair-feeding experiment. • Exendin-4, a glucagon-like peptide-1 analog, proves to be an effective therapy. [ABSTRACT FROM AUTHOR]

Chronic use of nicotine is known to dysregulate metabolic signaling through altering circulating levels of feeding-related hormones, contributing to the onset of disorders like type 2 diabetes. However, little is known about the acute effects of nicotine on hormonal signaling. We previously identified an acute increase in food intake following acute nicotine, and we sought to determine whether this behavior was due to a change in hormone levels. We first identified that acute nicotine injection produces an increase in feeding behavior in dependent rats, but not nondependent rats. We confirmed that chronic nicotine use increases circulating levels of insulin, leptin, and ghrelin, and these correlate with rats' body weight and food intake. Acute nicotine injection in dependent animals decreased circulating GLP-1 and glucagon levels, and administration of glucagon prior to acute nicotine injection prevented the acute increase in feeding behavior. Thus, acute nicotine injection increases feeding behavior in dependent rats by decreasing glucagon signaling. • Acute nicotine injection in nicotine-dependent rats produces increased feeding. • Chronic nicotine exposure dysregulates circulating feeding hormones. • Acute nicotine injection decreases circulating glucagon and active GLP-1. • Peripheral glucagon administration prevents acute nicotine-induced feeding behavior. [ABSTRACT FROM AUTHOR]

Cigarette smoking is one of the most impactful behavior-related risk factors for multiple cancers including hepatocellular carcinoma (HCC). Nicotine, as the principal component of tobacco, is not only responsible for smoking addiction but also a carcinogen; nevertheless, the underlying mechanisms remain unclear. Here we report that nicotine enhances HCC cancer stemness and malignant progression by upregulating the expression of GC-rich binding factor 2 (GCF2), a gene that was revealed to be upregulated in HCC and whose upregulation predicts poor prognosis, and subsequently activating the Wnt/ꞵ-catenin/SOX2 signaling pathway. We found that nicotine significantly increased GCF2 expression and that silencing of GCF2 reduced nicotine-induced cancer stemness and progression. Mechanistically, nicotine could stabilize the protein level of GCF2, and then GCF2 could robustly activate its downstream Wnt/β-catenin signaling pathway. Taken together, our results thus suggest that GCF2 is a potential target for a therapeutic strategy against nicotine-promoted HCC. • GCF2 is required for nicotine-induced stemness and progression in HCC. • Nicotine can stabilize the GCF2 protein. • GCF2 is unregulated in HCC and is associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

The alkaloid, nicotine, produced by tobacco and other Solanaceae as an anti-herbivore defence chemical is one of the most toxic natural insecticides in nature. However, some insects, such as the whitefly species, Trialeurodes vaporariorum and Bemisia tabaci show strong tolerance to this allelochemical and can utilise tobacco as a host. Here, we used biological, molecular and functional approaches to investigate the role of cytochrome P450 enzymes in nicotine tolerance in T. vaporariorum and B. tabaci. Insecticide bioassays revealed that feeding on tobacco resulted in strong induced tolerance to nicotine in both species. Transcriptome profiling of both species reared on tobacco and bean hosts revealed profound differences in the transcriptional response these host plants. Interrogation of the expression of P450 genes in the host-adapted lines revealed that P450 genes belonging to the CYP6DP subfamily are strongly upregulated in lines reared on tobacco. Functional characterisation of these P450s revealed that CYP6DP1 and CYP6DP2 of T. vaporariorum and CYP6DP3 of B. tabaci confer resistance to nicotine in vivo. These three genes, in addition to the B. tabaci P450 CYP6DP5 , were also found to confer resistance to the neonicotinoid imidacloprid. Our data provide new insight into the molecular basis of nicotine resistance in insects and illustrates how divergence in the evolution of P450 genes in this subfamily in whiteflies may have impacted the extent to which different species can tolerate a potent natural insecticide. [Display omitted] • B. tabaci and T. vaporariorum are able to colonise the challenging host plant tobacco. • A strong tolerance to nicotine was induced on whitefly lines reared on tobacco. • Transcriptomic analysis revealed over-expression of the P450 CYP6DPx clade. • These P450s conferred resistance to synthetic compounds when expressed in D. melanogaster. [ABSTRACT FROM AUTHOR]

Exposure to nickel, an environmental respiratory toxicant, is associated with lung diseases including asthma, pulmonary fibrosis, bronchitis and cancers. Our previous studies have shown that a majority of the nickel-induced transcriptional changes are persistent and do not reverse even after the termination of exposure. This suggested transcriptional memory, wherein the cell 'remembers' past nickel exposure. Transcriptional memory, due to which the cells respond more robustly to a previously encountered stimulus has been identified in a number of organisms. Therefore, transcriptional memory has been described as an adaptive mechanism. However, transcriptional memory caused by environmental toxicant exposures has not been well investigated. Moreover, how the transcriptional memory caused by an environmental toxicant might influence the outcome of exposure to a second toxicant has not been explored. In this study, we investigated whether nickel-induced transcriptional memory influences the outcome of the cell's response to a second respiratory toxicant, nicotine. Nicotine, an addictive compound in tobacco, is associated with the development of chronic lung diseases including chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Our results show that nicotine exposure upregulated a subset of genes only in the cells previously exposed to nickel. Furthermore, our analyses indicate robust activation of interferon (IFN) signaling in these cells. IFN signaling is a driver of inflammation, which is associated with many chronic lung diseases. Therefore, our results suggest that nicotine exposure of lung cells that retain the transcriptional memory of previous nickel exposure could result in increased susceptibility to developing chronic inflammatory lung diseases. • This study investigates the consequences of nickel-induced transcriptional memory. • Nicotine upregulated a unique set of genes only in the cells previously exposed to nickel. • Nicotine activated IFN signaling in the cells that retain the memory of previous nickel exposure. [ABSTRACT FROM AUTHOR]

A method of preparing heated tobacco product aerosol condensate (HTPAC) was developed to expedite HTP toxicity evaluation, and the effectiveness was assessed. To prepare HTPAC, HTP aerosol was generated and collected using a Cambridge filter (particulate phase) and Dulbecco's phosphate buffered saline (DPBS; gaseous phase). The aerosol collected on the Cambridge filter was extracted using methanol, which was thereafter removed by nitrogen purging. The HTP aerosol residue was mixed with DPBS loaded with the collected HTP vapor, ultimately yielding HTPAC. Nicotine and formaldehyde, key harmful compounds in HTP aerosol, were detected in HTPAC (901 ± 224 and 22.2 ± 3.90 µg stick–1, respectively, comparable to those in HTP aerosol (990–1350 (nicotine) and 2.33–21.9 µg stick–1 (formaldehyde)). Propylene glycol and vegetable glycerin, which influence the amount of HTP aerosol, were detected at similar levels in HTPAC and HTP aerosol (propylene glycol = 616 ± 57.1 (HTPAC) and 320–630 µg stick–1 (aerosol) and vegetable glycerin = 2418 ± 224 (HTPAC) and 1667–4000 µg stick–1 (aerosol)). Known components of HTP aerosol (hydroxyacetone, acetic acid, triacetin, and 2-furanmethanol) were also detected in HTPAC. Consequently, HTPAC offers an effective method for concentrating harmful compounds found in HTP aerosols. This, in turn, facilitates comprehensive toxicity assessments, paving the way for guidelines ensuring the safe utilization of HTP. [Display omitted] • Novel HTPAC preparation method was developed to expedite HTP toxicity evaluation. • HTPAC allows easy storage and transportation of large sample quantities. • Nicotine and formaldehyde concentrations in HTPAC and HTP aerosol were comparable. • HTPAC could contribute to establishing guidelines for the safe use of HTPs. [ABSTRACT FROM AUTHOR]

The cognitive effects of nicotine are linked to persistent modifications in extended neural systems that regulate cognitive and emotional processes, and these changes occur during development. Additionally, acute stress has modulatory effects on cognition that involve broad neural systems and can be influenced by prior environmental challenges. The effects of nicotine and stress may be interconnected, leading to modifications in a network of shared brain substrates. Here, we explored the interaction between nicotine and stress by evaluating the effects of acute stress exposure in spatial memory retrieval for animals pretreated with nicotine during adolescence or adulthood. Adolescent (35 days old) and adult (70 days old) male Wistar rats were treated for 21 days with one daily subcutaneous injection of nicotine 0.14 mg/ml (free base). 30 days after the last injection, rats were trained in the Barnes maze and tested 24 h later, half the rats were tested under regular conditions, and half of them were exposed to 1 h of restraining stress before the retrieval test, and brain samples were collected and c-Fos immunopositive cells were stained. Prolonged nicotine withdrawal or acute stress improved spatial memory retrieval. Acute stress in nicotine pretreated adults impaired spatial memory retrieval. Nicotine exposure during early adulthood resulted in long-lasting brain adaptations that amplified emotional responses to acute stress after prolonged drug withdrawal. [ABSTRACT FROM AUTHOR]

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo , we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microbiota by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B 1 4, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B 1 4 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages. • B. fragilis and P. bryantii produce less fermentation acids in response to nicotine. • Nicotine or high cotinine reduce protein in vesicles of B. fragilis and P. bryantii. • Low to mid cotinine exposure increased protein cargo in A. sticklandii vesicles. • Changes to B. fragilis and A. sticklandii vesicles altered inflammatory response. [ABSTRACT FROM AUTHOR]

Bacterial symbionts exhibiting co-evolutionary patterns with insect hosts play a vital role in the nutrient synthesis, metabolism, development, reproduction, and immunity of insects. The brown planthopper (BPH) has a strong ability to adapt to various environmental stresses and can develop resistance to broad-spectrum insecticides. We aimed to investigate whether gut symbionts of BPH play a major role in the detoxification of insecticides and host fitness in unfavorable environments. Nicotine-treated rice plants were exposed to BPH (early stage) and the gut microbiome of the emerging female adults were analyzed using high throughput sequencing (HTS). Nicotine administration altered the diversity and community structure of BPH symbionts with significant increases in bacterial members such as Microbacteriaceae , Comamondaceae , Enterobacteriaceae , and these changes may be associated with host survival strategies in adverse environments. Furthermore, the in-vitro study showed that four intestinal bacterial strains of BPH (Enterobacter NLB1, Bacillus cereus NL1, Ralstonia NLG26, and Delftia NLG11) could degrade nicotine when grown in a nicotine-containing medium, with the highest degradation (71%) observed in Delftia NLG11. RT-qPCR and ELISA analysis revealed an increased expression level of CYP6AY1 and P450 enzyme activities in Delftia NLG11, respectively. CYP6AY1 increased by 20% under the action of Delftia and nicotine, while P450 enzyme activity increased by 18.1%. After CYP6AY1 interference, nicotine tolerance decreased, and the mortality rate reached 76.65% on the first day and 100% on the third day. Moreover, Delftia NLG11 helped axenic BPHs to increase their survival rate when fed nicotine in the liquid-diet sac (LDS) feeding system. Compared with axenic BPHs, the survival rate improved by 25.11% on day 2% and 6.67% on day 3. These results revealed an altered gut microbiota and a cooperative relationship between Delftia NLG11 and CYP6AY1 in nicotine-treated BPH, suggesting that insects can adapt to a hostile environment by interacting with their symbionts and providing a new idea for integrated pest management strategies. • We studied the impact of gut symbiont on detoxification of insecticides and host fitness of BPH. • Nicotine administration altered the diversity and composition of BPH symbionts. • The gut bacterial strain NLG11 could increase the expression level of CYP6AY1 and affect the nicotine resistance of BPH. • Interfering with the P450 genes, the gut bacterial strain NLG11 has the independent ability to degrade nicotine. • This study suggests that insects can adapt to a hostile environment by interacting with their symbionts. [ABSTRACT FROM AUTHOR]

Nicotine contributes to the causation of atherosclerosis, which the prominent cellular components are macrophages. Long non-coding RNAs (lncRNAs) play an important role in regulating cell functions such as cell proliferation, differentiation and programmed death. However, the function and mechanism of lncRNAs in nicotine-induced macrophage pyroptosis has not been reported. We screened the deferentially expressed lncRNAs of human carotid artery plaque (GSE97210) and verified them in nicotine-induced pyroptosis of macrophages. Results showed only LINC01272 was up-regulated in a dose-dependent manner in macrophages. The immunofluorescence staining result confirmed that interfering LINC01272 inhibited nicotine-induced macrophage pyroptosis. Through bioinformatics analysis, dual luciferase reporter gene assay and qPCR, we identified miR-515 was significantly negatively correlated with the expression of LINC01272, and KLF6 is the target gene of miR-515. Furthermore, our results demonstrated that LINC01272/miR-515/KLF6 axis meditated nicotine-induced macrophage pyroptosis. In addition, in human peripheral blood mononuclear cells of smoking populations, the expression of GSDMD-N, NLRP3, LINC01272 and KLF6 was significantly increased, while the level of miR-515 was reduced. This study confirmed that nicotine increases the expression of LINC01272 to competitively bind with miR-515 in macrophages, reducing the inhibitory effect of miR-515 on its target gene KLF6, which ultimately induces macrophage pyroptosis. • LINC01272 was up-regulated in nicotine-induced pyroptosis of macrophages and related to human carotid artery plaque. • MiR-515 was significantly negatively correlated with the LINC01272 expression, and KLF6 is the target gene of miR-515. • LINC01272/miR-515/KLF6 axis meditated nicotine-induced macrophage pyroptosis. • LINC01272/miR-515/KLF6 axis has a close relationship with smoking in human peripheral blood mononuclear cells. [ABSTRACT FROM AUTHOR]

Previous studies found a positive relationship between prior violent victimization experience and substance use among adolescents based on general strain theory. However, there is limited knowledge on the link between violent victimization and vaping, which is a relatively new method of substance use. Therefore, the current study applies general strain theory to examine the relationship between violent victimization and vaping. Three types of vaping, nicotine, marijuana, and flavor only, are examined in correlation with violent victimization, utilizing data from the 2019 cohort of the Monitoring the Future study (MTF). The findings suggest that students with violent victimization experience are more likely to engage in vaping. Also, students with stronger negative emotions, weaker social bonds, and more unstructured time with peers are more likely to vape. The current study provides empirical evidence on using general strain theory to explain vaping behavior among students. Applicable policies are also discussed. [ABSTRACT FROM AUTHOR]

Cigarette smoking has long been recognized as a risk factor for type 2 diabetes (T2D), although the precise causal mechanisms underlying this relationship remain poorly understood. Recent evidence suggests that nicotine, the primary reinforcing component in tobacco, may play a pivotal role in connecting cigarette smoking and T2D. Extensive research conducted in both humans and animals has demonstrated that nicotine can elevate blood glucose levels, disrupt glucose homeostasis, and induce insulin resistance. The review aims to elucidate the genetic variants of nicotinic acetylcholine receptors associated with diabetes risk and provide a comprehensive overview of the available data on the mechanisms through which nicotine influences blood glucose homeostasis and the development of diabetes. Here we emphasize the central and peripheral actions of nicotine on the release of glucoregulatory hormones, as well as its effects on glucose tolerance and insulin sensitivity. Notably, the central actions of nicotine within the brain, which encompass both insulin-dependent and independent mechanisms, are highlighted as potential targets for intervention strategies in diabetes management. [ABSTRACT FROM AUTHOR]

The promise of nicotinic receptors as a therapeutic target has yet to be fully realized, despite solid data supporting their involvement in neurological and neuropsychiatric diseases. The reasons for this are likely complex and manifold, having to do with the widespread action of the cholinergic system and the biophysical mechanism of action of nicotinic receptors leading to fast desensitization and down-regulation. Conventional drug development strategies tend to focus on receptor subtype-specific action of candidate therapeutics, although the broad agonist, nicotine, is being explored in the clinic. The potential negative effects of nicotine make the search for alternate strategies warranted. Prototoxins are a promising yet little-explored avenue of nicotinic receptor drug development. Nicotinic receptors in the brain belong to a complex of proteins, including those that bind to the extracellular face of the receptor, as well as chaperones that bind the intracellular domain, etc. Lynx prototoxins have allosteric modularity effects on receptor function and number and have been implicated in complex in vivo processes such as neuroplasticity, learning, and memory. Their mechanism of action and binding specificity on sets of nAChR subtypes present intriguing possibilities for more efficacious and nuanced therapeutic targeting than nicotinic receptor subtypes alone. An allosteric drug may restrict its actions to physiologically relevant time points, which tend to be correlated with salient events which would be encoded into long-term memory storage. Rather than blanketing the brain with a steady and prolonged elevation of agonist, an allosteric nAChR compound could avoid side effects and loss of efficacy over time. This review details the potential strengths and challenges of prototoxin proteins as therapeutic targets, and some of the utility of such therapeutics based on the emerging understanding of cholinergic signaling in a growing number of complex neural processes. [ABSTRACT FROM AUTHOR]

Our recently published study of >2.4 million adults in Northern California indicated that current versus never-tobacco smoking was associated with lower risk of SARS-CoV-2 infection and less severe coronavirus disease 2019 (COVID-19). We extended this research by evaluating whether these associations were moderated by socio-demographic factors and medical comorbidities. This retrospective cohort study of 1,885,826 adults with current or never-smoking status in Kaiser Permanente Northern California from 3/5/2020 (baseline) to 12/31/2020 (pre-vaccine) included electronic health record-based socio-demographics (sex, age, race/ethnicity, neighborhood deprivation index (NDI)) and medical comorbidities (obesity, cardiovascular conditions, diabetes, renal disease, respiratory conditions). We estimated the adjusted risk of SARS-CoV-2 infection and hospitalization (≤30 days of infection) associated with smoking status using Cox proportional hazard regression models. We estimated associations within subgroups of socio-demographics and comorbidities, and tested for effect modification using interaction terms. During the study, 35,627 patients had SARS-CoV-2 infection. Current versus never-smoking status was associated with lower adjusted rates of SARS-CoV-2 infection (aHR ranging from 0.51 to 0.89) and hospitalization (aHR ranging from 0.32 to 0.70) within nearly every socio-demographic and comorbidity subgroup. Statistically significant interactions showed that the magnitude of protection for SARS-CoV-2 infection varied by sex, age, race/ethnicity, NDI, cardiovascular conditions and diabetes, and for SARS-CoV-2 hospitalization by age and renal disease. Taken together, results indicated that while some socio-demographics and comorbidities moderated the associations, the lower risk of SARS-CoV-2 infection and hospitalization associated with current versus never-smoking status persisted among patients regardless of socio-demographics or comorbidities. [ABSTRACT FROM AUTHOR]

Cigarette smoking is an independent risk factor for lung cancer. Nicotine, as an addictive substance in tobacco and e-cigarettes, is known to promote tumor progression and metastasis despite being a non-carcinogen. As a tumor suppressor gene, JWA is widely involved in the inhibition of tumor growth and metastasis and the maintenance of cellular homeostasis, including in non-small cell lung cancer (NSCLC). However, the role of JWA in nicotine-induced tumor progression remains unclear. Here, we reported for the first time that JWA was significantly downregulated in smoking-related lung cancer and associated with overall survival. Nicotine exposure reduced JWA expression in a dose-dependent manner. Gene Set Enrichment Analysis (GSEA) analysis showed the tumor stemness pathway was enriched in smoking-related lung cancer, and JWA was negatively associated with stemness molecules CD44, SOX2, and CD133. JWA also inhibited nicotine-enhanced colony formation, spheroid formation, and EDU incorporation in lung cancer cells. Mechanically, nicotine downregulated JWA expression via the CHRNA5-mediated AKT pathway. Lower JWA expression enhanced CD44 expression through inhibition of ubiquitination-mediated degradation of Specificity Protein 1 (SP1). The in vivo data indicated that JAC4 through the JWA/SP1/CD44 axis inhibited nicotine-triggered lung cancer progression and stemness. In conclusion, JWA via down-regulating CD44 inhibited nicotine-triggered lung cancer cell stemness and progression. Our study may provide new insights to develop JAC4 for the therapy of nicotine-related cancers. [Display omitted] • JWA was downregulated in current smokers with LUAD. • JWA inhibited nicotine-induced tumor stemness and progression of lung cancer. • Nicotine downregulated JWA expression via the CHRNA5-mediated AKT pathway. • JWA agonist JAC4 inhibited nicotine-induced lung cancer progression and stemness. [ABSTRACT FROM AUTHOR]

Tobacco and nicotine use are associated with disease susceptibility and progression. Health challenges associated with nicotine and smoking include developmental delays, addiction, mental health and behavioral changes, lung disease, cardiovascular disease, endocrine disorders, diabetes, immune system changes, and cancer. Increasing evidence suggests that nicotine-associated epigenetic changes may mediate or moderate the development and progression of a myriad of negative health outcomes. In addition, nicotine exposure may confer increased lifelong susceptibility to disease and mental health challenges through alteration of epigenetic signaling. This review examines the relationship between nicotine exposure (and smoking), epigenetic changes, and maladaptive outcomes that include developmental disorders, addiction, mental health challenges, pulmonary disease, cardiovascular disease, endocrine disorders, diabetes, immune system changes, and cancer. Overall, findings support the contention that nicotine (or smoking) associated altered epigenetic signaling is a contributing factor to disease and health challenges. [Display omitted] [ABSTRACT FROM AUTHOR]

Smoking can lead to several diseases and cause a reduction in fertility in men and women. Among the various components of cigarettes harmful during pregnancy, nicotine stands out. It can cause a reduction in placental blood flow, compromising the development of the baby with neurological, reproductive and endocrine consequences. Thus, we aimed to evaluate the effects of nicotine on the pituitary-gonadal axis of rats exposed during pregnancy and breastfeeding (1st generation - F1), and whether the possible damage observed would reach the 2nd generation (F2). Pregnant Wistar rats received 2 mg/kg/day of nicotine throughout the entire gestation and lactation. Part of the offspring was evaluated on the first neonatal day (F1) for macroscopic, histopathological and immunohistochemical analyses of brain and gonads. Another part of the offspring was kept until 90 days-old for mating and obtainment of progenies that had the same parameters evaluated at the end of pregnancy (F2). The occurrence of malformations was more frequent and diversified in nicotine-exposed F2. Brain alterations, including reduced size and changes in cell proliferation and death, were seen in both generations of nicotine-exposed rats. Male and female gonads of F1 exposed rats were also affected. The F2 rats showed reduced cellular proliferation and increased cell death on the pituitary and ovaries, besides increased anogenital distance in females. The number of mast cells was not enough altered to indicate an inflammatory process in brain and gonads. We conclude that prenatal exposure to nicotine causes transgenerational alterations in the structures of pituitary-gonadal axis in rats. • Maternal exposure to nicotine damaged the brain structure of F1 and F2 rats. • Pituitary damage was worse in F2 than in F1 rats exposed in intrauterine phase. • Nicotine-exposure caused alteration in ovarian and testicular cells of F1 and F2 rats. • F2 female rats present damage on pituitary, ovaries and increased AGD. • Nicotine causes transgerational damage in brain, pituitary and gonad of the offspring. [ABSTRACT FROM AUTHOR]

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are widely distributed both pre- and post-synaptically in the mammalian brain. By modulating cation flux across cell membranes, neuronal nAChRs regulate neuronal excitability and the release of a variety of neurotransmitters to influence multiple physiologic and behavioral processes including synaptic plasticity, motor function, attention, learning and memory. Abnormalities of neuronal nAChRs have been implicated in the pathophysiology of neurologic disorders including Alzheimer's disease, Parkinson's disease, epilepsy, and Tourette´s syndrome, as well as psychiatric disorders including schizophrenia, depression, and anxiety. The potential role of nAChRs in a particular illness may be indicated by alterations in the expression of nAChRs in relevant brain regions, genetic variability in the genes encoding for nAChR subunit proteins, and/or clinical or preclinical observations where specific ligands showed a therapeutic effect. Over the past 25 years, extensive preclinical and some early clinical evidence suggested that ligands at nAChRs might have therapeutic potential for neurologic and psychiatric disorders. However, to date the only approved indications for nAChR ligands are smoking cessation and the treatment of dry eye disease. It has been argued that progress in nAChR drug discovery has been limited by translational gaps between the preclinical models and the human disease as well as unresolved questions regarding the pharmacological goal (i.e., agonism, antagonism or receptor desensitization) depending on the disease. [Display omitted] • Nicotinic receptors are ligand-gated ion channels widely distributed in the brain. • Nicotinic receptors influence synaptic plasticity, motor function, and behavior. • Nicotinic receptor alterations are implicated in multiple neuropsychiatric disorders. • Nicotinic receptors are therapeutic targets for multiple neuropsychiatric disorders. • This review discusses these topics, current challenges, and future directions. [ABSTRACT FROM AUTHOR]

Cannabis is among the most widely consumed psychoactive drugs around the world and cannabis use disorder (CUD) has no current approved pharmacological treatment. Nicotine and cannabis are commonly co-used which suggests there to be overlapping neurobiological actions supported primarily by the co-distribution of both receptor systems in the brain. There appears to be strong rationale to explore the role that nicotinic receptors play in cannabinoid dependence. Preclinical studies suggest that the ɑ7 nAChR subtype may play a role in modulating the reinforcing and discriminative stimulus effects of cannabinoids, while the ɑ4β2 * nAChR subtype may be involved in modulating the motor and sedative effects of cannabinoids. Preclinical and human genetic studies point towards a potential role of the ɑ5, ɑ3, and β4 nAChR subunits in CUD, while human GWAS studies strongly implicate the ɑ2 subunit as playing a role in CUD susceptibility. Clinical studies suggest that current smoking cessation agents, such as varenicline and bupropion, may also be beneficial in treating CUD, although more controlled studies are necessary. Additional behavioral, molecular, and mechanistic studies investigating the role of nAChR in the modulation of the pharmacological effects of cannabinoids are needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Developmental periods such as gestation and adolescence have enhanced plasticity leaving the brain vulnerable to harmful effects from nicotine use. Proper brain maturation and circuit organization is critical for normal physiological and behavioral outcomes. Although cigarette smoking has declined in popularity, noncombustible nicotine products are readily used. The misperceived safety of these alternatives lead to widespread use among vulnerable populations such as pregnant women and adolescents. Nicotine exposure during these sensitive developmental windows is detrimental to cardiorespiratory function, learning and memory, executive function, and reward related circuitry. In this review, we will discuss clinical and preclinical evidence of the adverse alterations in the brain and behavior following nicotine exposure. Time-dependent nicotine-induced changes in reward related brain regions and drug reward behaviors will be discussed and highlight unique sensitivities within a developmental period. We will also review long lasting effects of developmental exposure persisting into adulthood, along with permanent epigenetic changes in the genome which can be passed to future generations. Taken together, it is critical to evaluate the consequences of nicotine exposure during these vulnerable developmental windows due to its direct impact on cognition, potential trajectories for other substance use, and implicated mechanisms for the neurobiology of substance use disorders. [Display omitted] • Developmental exposure to nicotine has long-term effects that are highly time sensitive. • Gestational nicotine exposure negatively effects cardiorespiratory function and disrupts normal cholinergic development. • Perinatal/postnatal nicotine exposure impairs hippocampal dependent learning/memory and sensory cortical processing. • Adolescent nicotine exposure impairs cognition and alters reward processing in the nucleus accumbens. • Nicotine-induced epigenetic alterations cause long-term deficits that can be passed to later generations. [ABSTRACT FROM AUTHOR]

This study examines the demographic factors associated with youths' first product tried (i.e., cigarettes, e-cigarettes, cigars, hookah, or smokeless tobacco). This study also evaluates whether the first product tried is associated with future nicotine product use (i.e., no use, single product use, and multiple product use) and nicotine dependence. Participants were 1999 youths (ages 12–17 years) who had ever tried a nicotine product and completed the Population Assessment of Tobacco Health study's Wave 1 (2013–2014) and Wave 4 (2016–2018) assessments. Two separate multinomial logistic regression models examined the association between 1) demographic factors and the first product tried at Wave 1 and 2) the first product tried at Wave 1 and past-30-day product use status at Wave 4. A two-part multivariable model examined the association between the first product tried and nicotine dependence, with part 1 modeling the presence (or absence) of any symptom of dependence and part 2 modeling the degree of dependence among those with any symptom of dependence. The first product tried was associated with sex, race, urbanicity, and parent education. First trying smokeless tobacco (vs. e-cigarettes) was associated with a greater likelihood of multiple product use (vs. no use and vs. single product use). Regarding the degree of nicotine dependence (n = 713), first trying smokeless tobacco (vs. e-cigarettes) was associated with higher nicotine dependence scores among those with any symptom of dependence. Youths who first try smokeless tobacco (vs. e-cigarettes) may be at higher risk for future multiple product use and more symptoms nicotine dependence. Research should explore tailored interventions for smokeless tobacco users. • We examined first nicotine product tried and multiple product use (MPU). • First trying smokeless tobacco (FT-ST; vs. e-cigarettes) was associated with MPU. • FT-ST (vs. e-cigarettes) was associated with higher nicotine dependence scores. [ABSTRACT FROM AUTHOR]

This manuscript is a correspondence referencing an article published in Preventive Medicine. [ABSTRACT FROM AUTHOR]

As the global consumption of cigarettes has increased, the massive generation of cigarette butts (CBs) has led to critical environmental and health problems. Landfilling or incineration of CBs has been conventionally carried out, but such disposal protocols have suffered from the potential risks of the unwanted/uncontrolled release of leachates, carcinogens, and toxic chemicals into all environmental media. Thus, this study focuses on developing an environmentally dependable method for CB disposal. Littered CBs from filtered/electronic cigarettes were valorized into syngas (H 2 /CO). To seek a greener approach for the valorization of CBs, CO 2 was intentionally considered as a reaction intermediate. Prior to multiple pyrolysis studies, the toxic chemicals in the CBs were qualitatively determined. This study experimentally proved that the toxic chemicals in CBs were detoxified/valorized into syngas. Furthermore, this work demonstrated that CO 2 was effective in thermally destroying toxic chemicals in CBs via a gas-phase reaction. The reaction features and CO 2 synergistically enhance syngas production. With the use of a supported Ni catalyst and CO 2 , syngas production from the catalytic pyrolysis of CBs was greatly enhanced (approximately 4 times). Finally, the gas-phase reaction by CO 2 was reliably maintained owing to the synergistic mechanistic/reaction feature of CO 2 for coke formation prevention on the catalyst surface. [Display omitted] • Sustainable disposal/upgrading platform for cigarettes butts (CBs) was presented. • Toxic compounds in CBs such as nicotine and aromatics were examined. • CO 2 was used as a reactant to convert toxic matters in CBs into syngas (H 2 /CO). • A nickel catalyst more than tripled conversion of CBs into syngas. [ABSTRACT FROM AUTHOR]

Smoke-free policies are effective in preventing secondhand smoke (SHS) exposure, but their adoption at home remains largely voluntary. This study aimed to quantify SHS exposure in homes with residents who smoke in Europe according to households' characteristics, tobacco consumption habits, and national contextual factors. Cross-sectional study (March 2017–September 2018) based on measurements of air nicotine inside 162 homes with residents who smoke from nine European countries. We installed passive samplers for seven consecutive days to monitor nicotine concentrations. Through self-administered questionnaires, we collected sociodemographic information and the number of individuals who smoke, smoking rules, frequency, location, and quantity of tobacco use in households. Country-level factors included the overall score in the Tobacco Control Scale 2016, the smoking prevalence, and self-reported SHS exposure prevalence. Nicotine concentrations were analyzed as continuous and dichotomous variables, categorized based on the limit of quantification of 0.02 μg/m3. Overall, median nicotine concentration was 0.85 μg/m3 (interquartile range (IQR):0.15–4.42), and there was nicotine presence in 93% of homes. Participants reported that smoking was not permitted in approximately 20% of households, 40% had two or more residents who smoked, and in 79% residents had smoked inside during the week of sampling. We found higher nicotine concentrations in homes: with smell of tobacco smoke inside (1.45 μg/m3 IQR: 0.32–6.34), where smoking was allowed (1.60 μg/m3 IQR: 0.68–7.63), with two or more residents who smoked (2.42 μg/m3 IQR: 0.58–11.0), with more than 40 cigarettes smoked (2.92 μg/m3 IQR: 0.97–10.61), and where two or more residents smoked inside (4.02 μg/m3 IQR: 1.58–11.74). Household nicotine concentrations were significantly higher in countries with higher national smoking prevalence and self-reported SHS exposure prevalence (p < 0.05). SHS concentrations in homes with individuals who smoke were approximately twenty times higher in homes that allowed smoking compared to those reporting smoke-free household rules. Evidence-based interventions promoting smoke-free homes should be implemented in combination with strengthening other MPOWER measures. • We assess air nicotine and reported smoking habits in homes with smokers in 9 EU countries. • 93% of the homes had nicotine presence and 78% allowed smoking inside. • SHS exposure was similar in homes where smoking was totally and partially allowed. • SHS levels were over 60 times higher with 2 or more smokers smoking indoors than in homes where no one smoked inside. • SHS exposure at homes was influenced by tobacco-related national-level factors. [ABSTRACT FROM AUTHOR]

Non-therapeutic, novel oral nicotine products are convenient, discreet to use, and flavored, with increasing sales in the United States. It is unclear whether these products appeal predominantly to adolescents already susceptible to inhalable nicotine products, or whether they attract adolescents who would not otherwise use nicotine. This study examined prevalence and correlates of susceptibility to inhalable and oral nicotine product use among adolescents. Ninth- and tenth-grade students from Southern California who had never used any nicotine product (N = 3129) completed an online survey in Fall 2021 assessing susceptibility to inhalable (i.e., cigarettes, e-cigarettes) and oral (e.g., pouches, gum, gummies) nicotine products. Multinomial logistic regression analyses estimated associations of demographic characteristics with odds of susceptibility to oral, inhalable, or both products. Susceptibility was highest for e-cigarettes (19.7%), followed by cigarettes (15.0%) and nicotine gum, lozenges, tablets and/or gummies (15.0%), and nicotine pouches (8.7%). Dual susceptibility to oral and inhalable products (vs. neither product type) was higher in cisgender female and non-cisgender (vs. cisgender male) adolescents (odds ratios [ORs] = 1.36–2.02; ps < 0.05). Hispanic adolescents (vs. Asian) were more susceptible to both products (OR = 1.47; p <.05). Lower-socioeconomic status (SES) and sexual minority adolescents were more susceptible to oral (ORs = 1.76–1.87; ps < 0.05) and both products (ORs = 1.32–1.88; ps < 0.05), compared to higher-SES and heterosexual adolescents. Adolescents in Southern California may be more susceptible to e-cigarettes than other nicotine/tobacco products. However, appreciable numbers may be susceptible to oral nicotine products, including some youth who might not otherwise use nicotine and youth from populations historically impacted by tobacco-related health disparities. • Novel oral nicotine products may appeal to adolescents. • Susceptibility to oral nicotine products was equal to that of cigarettes. • Lower-income youth had greater odds of oral nicotine product susceptibility. • Sexual minority youth had greater odds of oral nicotine product susceptibility. • Oral nicotine products may entice adolescents who would not otherwise use nicotine. [ABSTRACT FROM AUTHOR]

A number of flavored capsule heat-not-burn (FC–HNB) tobacco products such as IQOS, Lil, and Glo have been introduced as a new generation of cigarettes. As they can release various types of volatile organic compounds (VOCs), it is important to assess the harmfulness associated with their use. Thus, the composition of VOCs in HNB cigarette vapor was evaluated to investigate the interactive roles of key variables controlling the relationships between VOC composition and capsule breaking, particularly the compositional changes induced by capsule breaking and release of flavor from FC-HNB cigarettes relative to regular products. As the capsules of FC-HNB cigarettes were broken, the total VOC concentrations increased by as high as eight times from 60.3 ± 0.48 to 488 ± 21.8 μg cig-1. The key VOC components released after breaking the flavored capsules were identified as ethyl butyrate (157 ± 13.6 μg cig-1; Lil), isoamyl acetate (76.9 ± 1.98 μg cig-1; Lil), and limonene (52.3 ± 3.29 μg cig-1; Glo). If the primary health risks of FC-HNB cigarette vapor are assessed using National Institute for Occupational Safety & Health (NIOSH) guidelines, 2,3-butanedinone exceeds the maximum daily intake limit (i.e., 0.05 mg day-1). Our study is expected to offer valuable insights into the harmful effects of direct and indirect exposure to various VOCs in FC-HNB products. • The concentration levels of VOCs in FC-HNB cigarette smoke were investigated. • Differences in VOC levels were evaluated between before and after breaking capsule. • FC-HNB cigarette released higher levels of TVOC than regular HNB cigarette. • The health risk of FC-HNB cigarette smoke was assessed based on the NIOSH guidelines. [ABSTRACT FROM AUTHOR]

Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple's older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother's urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old. We detected low but not negligible concentrations of e-cigarette–related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies. • No studies exist on passive exposure to e-cigarettes during pregnancy and childhood. • We detected e-cigarette pollutants in both the pregnant woman and the child. • The only pollutants we found in breast milk were nicotine metabolites. • Neither nicotine metabolites nor any other pollutants were detected in cord blood. • Passive exposure is not irrelevant in the pregnant woman, child, or newborn. [ABSTRACT FROM AUTHOR]

The Angiotensin-Converting Enzyme 2 (ACE2) is the main receptor of the SARS-CoV-2. There is contradictory evidence on how the exposure to nicotine may module the concentration of soluble ACE2 (sACE2). The aim of this study was to assess the association between nicotine and sACE2 concentrations in saliva samples. Pooled analysis performed with data retrieved from two studies (n = 634 and n = 302). Geometric mean (GM) concentrations of sACE2, both total and relative to the total amount of protein in the sample, were compared according to sociodemographic variables and variables associated to nicotine. Multivariable linear regression models were fitted to explore the associations of sACE2 with nicotine adjusting for sex, age and body mass index. Spearman's rank-correlation coefficients were estimated between the concentrations of nicotine and cotinine, and pack-years, the concentration of relative sACE2 and the isoforms of sACE2. We observed a significant increase of 0.108‰ and 0.087 ng/μl in the relative and absolute salivary sACE2 GM concentrations, respectively, between the lowest and highest nicotine levels. Similar results were observed for cotinine. These associations did not change in the multivariable linear models. There was a low correlation of nicotine and cotinine concentration with the concentration of relative salivary sACE2 (r s = 0.153 and r s = 0.132, respectively), pack-years (r s = 0.222 and r s = 0.235, respectively) and with the concentration of isoform 40 KDa (r s = 0.193 and r s = 0.140, respectively). Salivary nicotine concentration seems to be limitedly associated with the concentration of sACE2. • Analyzing sACE2 in saliva is less invasive and cheaper than blood testing. • There is an association between salivary nicotine concentration and sACE2. • 55 kDa isoform shows the highest correlation with nicotine in saliva. [ABSTRACT FROM AUTHOR]

Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3–17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 μg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 μg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003–2006) on 3–14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007–2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment. • Quantifiable concentrations of cotinine in more than half of the participants. • Significant reduction in cotinine concentration compared to GerES IV (2003–2006). • Results demonstrate success of non-smoker protection laws. • 42% of participants live with at least one smoker in the household. • Passive smoke at home was the strongest predictor of elevated cotinine levels. [ABSTRACT FROM AUTHOR]