Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials.

Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.

Tobacco, nicotine, and cannabis use and exposure in an Australian Indigenous population during pregnancy: A protocol to measure parental and foetal exposure and outcomes.

BACKGROUND: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported. The 2021 report shows the rate of smoking for Australian Indigenous mothers was 42% compared with 11% for Australian non-Indigenous mothers. Evidence shows that Indigenous babies exposed to maternal smoking have a higher rate of adverse outcomes compared to non-Indigenous babies exposed to maternal smoking (S1 File). OBJECTIVES: The reasons for the differences in health outcome between Indigenous and non-Indigenous pregnancies exposed to tobacco and nicotine is unknown but will be explored in this project through a number of activities. Firstly, the patterns of parental and household tobacco, nicotine and cannabis use and exposure will be mapped during pregnancy. Secondly, a range of biological samples will be collected to enable the first determination of Australian Indigenous people's nicotine and cannabis metabolism during pregnancy; this assessment will be informed by pharmacogenomic analysis. Thirdly, the pharmacokinetic and pharmacogenomic findings will be considered against maternal, placental, foetal and neonatal outcomes. Lastly, an assessment of population health literacy and risk perception related to tobacco, nicotine and cannabis products peri-pregnancy will be undertaken. METHODS: This is a community-driven, co-designed, prospective, mixed-method observational study with regional Queensland parents expecting an Australian Indigenous baby and their close house-hold contacts during the peri-gestational period. The research utilises a multi-pronged and multi-disciplinary approach to explore interlinked objectives. RESULTS: A sample of 80 mothers expecting an Australian Indigenous baby will be recruited. This sample size will allow estimation of at least 90% sensitivity and specificity for the screening tool which maps the patterns of tobacco and nicotine use and exposure versus urinary cotinine with 95% CI within ±7% of the point estimate. The sample size required for other aspects of the research is less (pharmacokinetic and genomic n = 50, and the placental aspects n = 40), however from all 80 mothers, all samples will be collected. CONCLUSIONS: Results will be reported using the STROBE guidelines for observational studies. FORWARD: We acknowledge the Traditional Custodians, the Butchulla people, of the lands and waters upon which this research is conducted. We acknowledge their continuing connections to country and pay our respects to Elders past, present and emerging. Notation: In this document, the terms Aboriginal and Torres Strait Islander and Indigenous are used interchangeably for Australia's First Nations People. No disrespect is intended, and we acknowledge the rich cultural diversity of the groups of peoples that are the Traditional Custodians of the land with which they identify and with whom they share a connection and ancestry.

Oxytocin decreases alcohol self-administration in male baboons.

The neurohormone oxytocin (OT) has been proposed as a treatment for alcohol and nicotine use disorders. The aim of the present study was to examine whether intravenous (IV) OT decreases alcohol oral self-administration and consumption in nonhuman primates under a 6-h alcohol access procedure as well as alcohol and nicotine (IV) self-administration under 6-h concurrent access conditions. The subjects were five male baboons (Papio anubis) that self-administered oral alcohol (4% w/v) during 6-h sessions under a fixed ratio 3 (FR3) schedule per drink. Baseline levels of alcohol self-administration were established and then OT treatment was initiated. A single dose of OT (20, 40, 80, 120 IU, IV) or its vehicle (saline) was administered before and again in the middle of the 6-h drinking session for 5 consecutive days (total oxytocin dose of 40, 80, 160, 240 IU/day). After each 5-day treatment, baseline levels of alcohol self-administration were reestablished before the next 5-day OT treatment. In addition, the effect of OT on concurrent alcohol and IV nicotine self-administration was explored in 3 of the baboons where alcohol and nicotine were concurrently available during the 6-hr session each under an FR3 schedule for each drug. Establishment of baseline self-administration and 5-day OT treatments were completed as in the alcohol only study. There was a significant overall reduction in alcohol consumption with OT compared to placebo. On post-hoc analysis, after correcting for multiple comparisons, the 40 and 80 IU doses of OT significantly reduced alcohol consumption compared with vehicle, and consumption did not vary significantly within each 5-day treatment period. OT, qualitatively, also reduced the coadministration of both alcohol and nicotine in each baboon for at least one of the OT doses administered. These results underscore the therapeutic potential of oxytocin as a treatment of alcohol use disorder and possibly, co-use of nicotine.

Changes in the use of nicotine-containing products during and after the COVID-19 pandemic in a representative sample of the Italian adult population.

INTRODUCTION: To assess nicotine-containing products (NCPs; heated tobacco products and/or electronic cigarettes) use in relation to conventional smoking. METHODS: "LOST IN ITALY" ("LOckdown and Lifestyles IN ITALY") and "LOST IN TOSCANA" cross-sectional surveys estimated lifestyles changes before, during, and after the lockdown in a representative sample of the Italian population. A Poisson regression model was used to estimate prevalence ratios of NCP use according to socio-demographic, mental distress, and smoking variables. RESULTS: The prevalence of conventional cigarette smokers did not decrease, remaining stable at 23%. Exclusive conventional cigarette smokers decreased from 21% before the lockdown in 2020 to 15% in 2023 but dual users, representing the large majority of NCP users, increased by 4 times, and exclusive NCP users decreased from 7% in 2020 to 5% in 2023. CONCLUSIONS: NCPs are mostly accompanying instead of replacing conventional cigarettes. A targeted campaign should be developed in Italy to raise awareness on that.

Notes from the Field: E-Cigarette and Nicotine Pouch Use Among Middle and High School Students - United States, 2024.

Current e-cigarette use among U.S. youth has declined considerably since 2019*; however, approximately 2.13 million youths used e-cigarettes in 2023 (1). As sales of nicotine pouches (small, dissolvable, flavored pouches containing nicotine derived from tobacco that users place in the mouth between the lip and gum)† have continued to rise nationally since 2016, their use among U.S. youths has become concerning (2,3). All pouches and most e-cigarettes contain nicotine,§ which is highly addictive and can harm the developing adolescent brain (4,5).

Applications of an Electrochemical Sensory Array Coupled with Chemometric Modeling for Electronic Cigarettes.

This study investigates the application of an eNose (electrochemical sensory array) device as a rapid and cost-effective screening tool to detect increasingly prevalent counterfeit electronic cigarettes, and those to which potentially hazardous excipients such as vitamin E acetate (VEA) have been added, without the need to generate and test the aerosol such products are intended to emit. A portable, in-field screening tool would also allow government officials to swiftly identify adulterated electronic cigarette e-liquids containing illicit flavorings such as menthol. Our approach involved developing canonical discriminant analysis (CDA) models to differentiate formulation components, including e-liquid bases and nicotine, which the eNose accurately identified. Additionally, models were created using e-liquid bases adulterated with menthol and VEA. The eNose and CDA model correctly identified menthol-containing e-liquids in all instances but were only able to identify VEA in 66.6% of cases. To demonstrate the applicability of this model to a commercial product, a Virginia Tobacco JUUL product was adulterated with menthol and VEA. A CDA model was constructed and, when tested against the prediction set, it was able to identify samples adulterated with menthol 91.6% of the time and those containing VEA in 75% of attempts. To test the ability of this approach to distinguish commercial e-liquid brands, a model using six commercial products was generated and tested against randomized samples on the same day as model creation. The CDA model had a cross-validation of 91.7%. When randomized samples were presented to the model on different days, cross-validation fell to 41.7%, suggesting that interday variability was problematic. However, a subsequently developed support vector machine (SVM) identification algorithm was deployed, increasing the cross-validation to 84.7%. A prediction set was challenged against this model, yielding an accuracy of 94.4%. Altered Elf Bar and Hyde IQ formulations were used to simulate counterfeit products, and in all cases, the brand identification model did not classify these samples as their reference product. This study demonstrates the eNose's capability to distinguish between various odors emitted from e-liquids, highlighting its potential to identify counterfeit and adulterated products in the field without the need to generate and test the aerosol emitted from an electronic cigarette.

Health Warnings on Instagram Advertisements for Synthetic Nicotine E-Cigarettes and Engagement.

Importance: Synthetic nicotine is increasingly used in e-cigarette liquids along with flavors to appeal to youths. Regulatory loopholes have allowed tobacco manufacturers to use social media to target youths. Objective: To analyze the extent to which synthetic nicotine e-cigarette brands have implemented US Food and Drug Administration (FDA) health warning requirements and to evaluate the association between health warnings and user engagement on Instagram. Design, Setting, and Participants: In this cross-sectional study, posts from 25 brands were analyzed across a 14-month period (August 2021 to October 2022). A content analysis was paired with Warning Label Multi-Layer Image Identification, a computer vision algorithm designed to detect the presence of health warnings and whether the detected health warning complied with FDA guidelines by (1) appearing on the upper portion of the advertisement and (2) occupying at least 20% of the advertisement's area. Data analysis was performed from March to June 2024. Exposure: Synthetic nicotine e-cigarette advertisement on Instagram. Main Outcomes and Measures: The outcome variables were user engagement (number of likes and comments). Negative binomial regression analyses were used to evaluate the association between the presence and characteristics of health warnings and user engagement. Results: Of a total of 2071 posts, only 263 (13%) complied with both FDA health warning requirements. Among 924 posts with health warnings, 732 (79%) displayed warnings in the upper image portion, and 270 (29%) had a warning covering at least 20% of the pixel area. Posts with warnings received fewer comments than posts without warnings (mean [SD], 1.8 [2.5] vs 5.4 [11.7] comments; adjusted incident rate ratio [aIRR], 0.70; 95% CI, 0.57-0.86; P < .001). For posts containing warnings, a larger percentage of the warning label's pixel area was associated with fewer comments (aIRR, 0.96; 95% CI, 0.93-0.99; P = .003). Flavored posts with health warnings placed in the upper image portion received more likes than posts with warnings in the lower portion (mean [SD], 34.6 [35.2] vs 19.9 [19.2] likes; aIRR, 1.48; 95% CI, 1.07-2.06; P = .02). Conclusions and Relevance: In this cross-sectional study of synthetic nicotine brand Instagram accounts, 87% of sampled posts did not adhere to FDA health warning requirements in tobacco promotions. Enforcement of FDA compliant health warnings on social media may reduce youth engagement with tobacco marketing.

Simultaneous Determination of Tobacco Smoke Exposure and Stress Biomarkers in Saliva Using In-Tube SPME and LC-MS/MS for the Analysis of the Association between Passive Smoking and Stress.

Passive smoking from environmental tobacco smoke not only increases the risk of lung cancer and cardiovascular disease but may also be a stressor triggering neuropsychiatric and other disorders. To prevent these diseases, understanding the relationship between passive smoking and stress is vital. In this study, we developed a simple and sensitive method to simultaneously measure nicotine (Nic) and cotinine (Cot) as tobacco smoke exposure biomarkers, and cortisol (CRT), serotonin (5-HT), melatonin (MEL), dopamine (DA), and oxytocin (OXT) as stress-related biomarkers. These were extracted and concentrated from saliva by in-tube solid-phase microextraction (IT-SPME) using a Supel-Q PLOT capillary as the extraction device, then separated and detected within 6 min by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a Kinetex Biphenyl column (Phenomenex Inc., Torrance, CA, USA). Limits of detection (S/N = 3) for Nic, Cot, CRT, 5-HT, MEL, DA, and OXT were 0.22, 0.12, 0.78, 0.39, 0.45, 1.4, and 3.7 pg mL-1, respectively, with linearity of calibration curves in the range of 0.01-25 ng mL-1 using stable isotope-labeled internal standards. Intra- and inter-day reproducibilities were under 7.9% and 14.6% (n = 5) relative standard deviations, and compound recoveries in spiked saliva samples ranged from 82.1 to 106.6%. In thirty nonsmokers, Nic contents positively correlated with CRT contents (R2 = 0.5264, n = 30), while no significant correlation was found with other biomarkers. The standard deviation of intervals between normal beats as the standard measure of heart rate variability analysis negatively correlated with CRT contents (R2 = 0.5041, n = 30). After passive smoke exposure, Nic levels transiently increased, Cot and CRT levels rose over time, and 5-HT, DA, and OXT levels decreased. These results indicate tobacco smoke exposure acts as a stressor in nonsmokers.

Unveiling microbial dynamics in lung adenocarcinoma and adjacent nontumor tissues: insights from nicotine exposure and diverse clinical stages via nanopore sequencing technology.

Background: Lung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer. Methods: Tumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms. Results: the microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively. Conclusion: Nanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.

Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch.

Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset and stereotyped focal or generalized hypermotor events occurring predominantly (but not exclusively) from sleep. Clinically, SHE can be challenging to distinguish from psychogenic nonepileptic events or sleep disorders. Up to 30% of SHE cases are drug-resistant, and SHE represents about 10% of drug-resistant surgical epilepsy cases. Although most cases have an unknown etiology, there is a subset of individuals with pathogenic variants in the subunits of n-acetylcholine receptors (nAChR). Furthermore, some individuals with nAChR variants are responsive to nicotine. We report a case of a 23-year-old man with SHE, but no pathogenic variant on testing, whose seizures were exquisitely responsive to removal and application of a nicotine patch. This suggests an alternative mechanism of nicotine in the suppression of seizures in individuals with SHE.

The Fat Body-Specific GST Gene SlGSTe11 Enhances the Tolerance of Spodoptera litura to Cyantraniliprole and Nicotine.

Spodoptera litura is a significant agricultural pest, and its glutathione S-transferase (GST) plays a crucial role in insecticide resistance. This study aimed to investigate the relationship between the SlGSTe11 gene of S. litura and resistance to cyantraniliprole and nicotine. Transcriptome analysis revealed that SlGSTe11 is highly expressed mainly in fat bodies, with a significant increase in SlGSTe11 gene expression under induction by cyantraniliprole and nicotine. The ectopic expression of the SlGSTe11 gene in transgenic fruit flies resulted in a 5.22-fold increase in the tolerance to cyantraniliprole. Moreover, compared to the UAS-SlGSTe11 line, the Act5C-UAS>SlGSTe11 line laid more eggs and had a lower mortality after nicotine exposure. RNAi-mediated inhibition of SlGSTe11 gene expression led to a significant increase in the mortality of S. litura under cyantraniliprole exposure. In vitro metabolism experiments demonstrated that the recombinant SlGSTe11 protein efficiently metabolizes cyantraniliprole. Molecular docking results indicated that SlGSTe11 has a strong affinity for both cyantraniliprole and nicotine. These findings suggest that SlGSTe11 is involved in the development of resistance to cyantraniliprole and nicotine in S. litura.

Adverse Cardiovascular Effects of Nicotine Delivered by Chronic Electronic Cigarettes or Standard Cigarettes Captured by Cardiovascular Intrinsic Frequencies.

BACKGROUND: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system. METHODS AND RESULTS: One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine-rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle-arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine. CONCLUSIONS: Our IF results suggest that nicotine-containing electronic cigarettes adversely affect vascular function and left ventricle-arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.

E-cigarette exposure disrupts antitumor immunity and promotes metastasis.

Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.

What Are E-Cigarettes?

This JAMA Patient Page describes e-cigarettes and the potential health effects of vaping.

Variability in Constituents of E-Cigarette Products Containing Nicotine Analogues.

This study characterizes and quantifies constituents in 2 e-cigarette products to assess product consistency and inform future risk assessments.

E-Cigarette Use in Adults.

This JAMA Insights explores the adverse effects and health outcomes of e-cigarettes vs combusted cigarettes and the effectiveness of using e-cigarettes as a smoking cessation aid among US adults.

Vitamin B12 supplementation improved memory impairment following nicotine withdrawal in adolescent male rats: The role of oxidative stress, inflammatory, BDNF, GFAP, and AChE activity.

The present study aimed to assess the potential effect of vitamin B12 (Vit B12) on cognition impairment caused by nicotine (Nic) cessation in adolescent male rats. Adolescent male rats were categorized into two main groups as vehicle (normal saline, intraperitoneally), and Nic group in which received Nic (2 mg/kg) from 21 to 42 days of ages and then the Nic group were divided into three groups as withdrawal (the animals returned to regular diet without treatment), second and third groups received bupropion (20 mg/kg), and Vit B12 at three different doses including 0.5,1, and 1.5 mg/kg by oral gavage as treatments to attenuate Nic withdrawal symptoms. The last group including normal animals received the highest doses of Vit B12 just in the Nic abstinence period to compare the effect of that with vehicle. In MWM, Vit B12and bupropion increased the time spent in the target quadrant that is strongly associated with spatial memory as well as the more time spent with the NORT. Vit B12 and bupropion modulated both oxidant/antioxidant and inflammatory/anti-inflammatory balance, alongside inhibitory effect on AChE, and GFAP. However, BDNF and amyloid-B showed insignificant difference as compared to Vit B12 and bupropion. Considering the present results and similar related studies, Vit B12 can be introduced as a strong anti-oxidant, and anti-inflammatory agent by which probably improved memory impairment caused by Nic addiction accompanied by withdrawal. Further, other mechanisms including activity reduction of AChE, and GFAP should be considered; however, it needs further investigation and larger-scale evidences.

The role of ß2-AR/PI3K/AKT pathway in the proliferation, migration and invasion of THLE-2 cells induced by nicotine.

Nicotine, the primary constituent of tobacco, is one of the important factors that induce the occurrence of hepatocellular carcinoma (HCC). The ß2-adrenergic receptor (ß2-AR) is implicated in the growth and advancement of tumors. However, the role of ß2-AR and its mediated cascades in nicotine-induced HCC remains unclear. This present study aims to observe the effects of nicotine on the proliferation, migration, and invasion of immortalized human liver epithelial (THLE-2) cells, as well as to explore the underlying mechanisms of action. The results of cell counting kit-8 (CCK-8) assay showed that 0.3125 µM nicotine had the ability to promote the proliferation of THLE-2 cells with a significant time-dependent manner. Therefore, THLE-2 cells were mainly selected for chronic treatment with 0.3125 µM nicotine in the later stage to cause transformation. After 30 passages of THLE-2 cells with 0.3125 µM nicotine treatment, chronic exposure to nicotine significantly enhanced the proliferation, metastasis, and invasion of cells. Besides, it also upregulated the intracellular levels of ß2-AR, phosphoinositide 3-kinase (PI3K), AKT, matrix metalloproteinase-2 (MMP-2) and Cyclin D1, as well as downregulated the expression of p53. More importantly, the ß2-AR/PI3K/AKT pathway was found to mediate the expression of MMP-2, Cyclin D1, and p53 in THLE-2 cells, playing a crucial role in their proliferation, migration, and invasion after continuous exposure to nicotine. Simply put, it demonstrated the role of ß2-AR/PI3K/AKT pathway in the transformation of THLE-2 cells induced by nicotine. This study could provide valuable insights into the relationship between nicotine and HCC. Additionally, it lays the groundwork for investigating potential anticancer treatments for liver cancer linked to tobacco consumption.

Systemic allopurinol administration reduces malondialdehyde, interleukin 6, tumor necrosis factor α, and increases vascular endothelial growth factor in random flap Wistar rats exposed to nicotine.

INTRODUCTION: Smoking poses a risk to flap viability, with nicotine being a major contributor to the formation of free radicals. Allopurinol, known for its antioxidant properties, has been shown to enhance tissue survival in ischemic conditions by reducing the production of reactive oxygen species (ROS). This study aims to assess the impact of allopurinol on the viability and success of skin flaps in Wistar rats exposed to nicotine. METHODS: This study examined skin flap survival in nicotine-exposed rats treated with allopurinol. Twenty-eight rats were separated into two groups. During 1 month of nicotine exposure, the treatment group received systemic allopurinol 7 days before and 2 days after the flap procedure, while the control group received no allopurinol. Pro-angiogenic factors, proinflammatory factors, anti-inflammatory factors, and oxidative markers were assessed on the 7th day after the flap procedure using enzyme-linked immunosorbent assay method. Macroscopic flap viability was evaluated on the 7th day using Image J photos. RESULTS: As an oxidative marker, malondialdehyde levels were significantly lower in rats given allopurinol than in controls (P < 0.001). The levels of interleukin 6 and tumor necrosis factor α, as markers of inflammatory factors, were significantly lower in the group of rats given allopurinol compared to controls (P < 0.001). The level of angiogenesis in rats given allopurinol, measured by vascular endothelial growth factor levels, was also higher in the treatment group compared to controls (P < 0.001). Macroscopically, the percentage of distal flap necrosis in Wistar rats given allopurinol was lower and statistically significant compared to controls (P < 0.001). CONCLUSIONS: Xanthine oxidoreductase is part of a group of enzymes involved in reactions that produce ROS. Allopurinol, as an effective inhibitor of the xanthine oxidase enzyme, can reduce oxidative stress by decreasing the formation of ROS. This reduction in oxidative stress mitigates the risk of ischemic-reperfusion injury effects and significantly increases the viability of Wistar rat flaps exposed to nicotine.