14,838 results on '"NICOTINE"'
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2. Effect and investigating of oxygen / nitrogen on modified glassy carbon electrode chitosan/carbon nanotube and best detection of nicotine using Cyclic voltammetry measurement technique
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Abolfazl Mirani, Ahmed Mahdi Rheima, Zainab talib turki, Sabrean Farhan Jawad, Duaa Mohammed Athair, Zainab T. Al-Sharify, Mohammadreza Esmaili, Hamidreza Sayadi, and Ehsan kianfar
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Nicotine ,Electrochemical properties cyclic voltammetry ,Nanofibers ,Chitosan ,Multi-functionalized carbon nanotube ,Nicotine pathways ,Chemistry ,QD1-999 - Abstract
Nicotine, a component of tobacco smoke, is a neurotoxin. It exerts its effects by stimulating nicotine-containing acetylcholine receptors. Nicotine, one of over 4,700 components in tobacco smoke, was previously used as an insecticide in agriculture. Although the use of nicotine in agriculture has been banned in many countries, nicotine poisoning due to accidental or intentional ingestion of nicotine products remains a problem for smoking workers as well as children and adults. Understanding the mechanisms of nicotine poisoning is important for both prevention and treatment, as well as for appropriate regulatory approaches. We study the pharmacological properties of nicotine and the cellular mechanisms underlying acute and persistent nicotine addiction that appear to be related to the central and peripheral nervous systems. The electrochemical properties of nicotine were studied using a glassy carbon-chitosan/multiwalled carbon nanotubes-COOH electrode. Nicotine-COOH via chitosan/multiwalled carbon nanotubes was irreversibly reduced in the presence of oxygen and nitrogen gas. Oxidation signals at lower potentials and higher currents were obtained for nicotine via the modified electrode compared to the glassy carbon electrode. This condition proliferated in the presence of oxygen gas, suggesting that nanotubes, including carbon nanotubes, facilitate electron transfer and form the basis for electrocatalytic nicotine applications. Under optimal conditions, cyclic voltammetry (CV) shows oxidation of nicotine in the presence of oxygen at 0.74 V and nitrogen at 0.81 V in phosphate buffer solution at pH = 7.4. Linear calibration curves range from 0.1 to 200 μM for oxygen and 0.05 to 200 μM for nitrogen conditions, both with R2 = 0.99, and detection limits of 7.1 for oxygen and 9.2 nM for nitrogen.
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- 2024
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3. Systematic Review of Naturally Derived Substances That Act as Inhibitors of the Nicotine Metabolizing Enzyme Cytochrome P450 2A6
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Haralampos Tzoupis, Konstantinos D. Papavasileiou, Stavros Papatzelos, Angelos Mavrogiorgis, Lefteris C. Zacharia, Georgia Melagraki, and Antreas Afantitis
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cytochrome P450 ,CYP450 inhibition ,natural products ,nicotine ,replacement therapy ,smoking cessation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Tobacco smoking has been highlighted as a major health challenge in modern societies. Despite not causing death directly, smoking has been associated with several health issues, such as cardiovascular diseases, respiratory disorders, and several cancer types. Moreover, exposure to nicotine during pregnancy has been associated with adverse neurological disorders in babies. Nicotine Replacement Therapy (NRT) is the most common strategy employed for smoking cessation, but despite its widespread use, NRT presents with low success and adherence rates. This is attributed partially to the rate of nicotine metabolism by cytochrome P450 2A6 (CYP2A6) in each individual. Nicotine addiction is correlated with the high rate of its metabolism, and thus, novel strategies need to be implemented in NRT protocols. Naturally derived products are a cost-efficient and rich source for potential inhibitors, with the main advantages being their abundance and ease of isolation. This systematic review aims to summarize the natural products that have been identified as CYP2A6 inhibitors, validated through in vitro and/or in vivo assays, and could be implemented as nicotine metabolism inhibitors. The scope is to present the different compounds and highlight their possible implementation in NRT strategies. Additionally, this information would provide valuable insight regarding CYP2A6 inhibitors, that can be utilized in drug development via the use of in silico methodologies and machine-learning models to identify new potential lead compounds for optimization and implementation in NRT regimes.
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- 2024
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4. Neurological Disorders Induced by Drug Use: Effects of Adolescent and Embryonic Drug Exposure on Behavioral Neurodevelopment
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Olga Karatayev, Adam D. Collier, Stella R. Targoff, and Sarah F. Leibowitz
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maternal ,alcohol ,nicotine ,cannabis ,substance use disorders ,neurological disorders ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, are observed not only in adults but also with drug use during adolescence and after prenatal exposure to these drugs, and they are accompanied by long-lasting disturbances in brain development. This report provides overviews of clinical and preclinical studies, which confirm these adverse effects in adolescents and the offspring prenatally exposed to the drugs and include a more in-depth description of specific neuronal systems, their neurocircuitry and molecular mechanisms, affected by drug exposure and of specific techniques used to determine if these effects in the brain are causally related to the behavioral disturbances. With analysis of further studies, this review then addresses four specific questions that are important for fully understanding the impact that drug use in young individuals can have on future pregnancies and their offspring. Evidence demonstrates that the adverse effects on their brain and behavior can occur: (1) at low doses with short periods of drug exposure during pregnancy; (2) after pre-conception drug use by both females and males; (3) in subsequent generations following the initial drug exposure; and (4) in a sex-dependent manner, with drug use producing a greater risk in females than males of developing SUDs with emotional conditions and female offspring after prenatal drug exposure responding more adversely than male offspring. With the recent rise in drug use by adolescents and pregnant women that has occurred in association with the legalization of cannabis and increased availability of vaping tools, these conclusions from the clinical and preclinical literature are particularly alarming and underscore the urgent need to educate young women and men about the possible harmful effects of early drug use and to seek novel therapeutic strategies that might help to limit drug use in young individuals.
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- 2024
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5. HINT1 Gene Polymorphisms, Smoking Behaviour, and Personality Traits: A Haplotype Case-Control Study
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Aleksandra Suchanecka, Agnieszka Boroń, Krzysztof Chmielowiec, Aleksandra Strońska-Pluta, Jolanta Masiak, Milena Lachowicz, Jolanta Chmielowiec, Grzegorz Trybek, and Anna Grzywacz
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HINT1 gene ,haplotype ,smoking ,nicotine ,personality ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The factors influencing the development and maintenance of nicotine dependence are numerous and complex. Recent studies indicate that smokers exhibit distinct genetic predispositions to nicotine dependence. We aimed to analyse (1) the association between rs2551038 and cigarette smoking, (2) the association of between the rs3864236–rs2526303–rs2551038 haplotype and cigarette smoking, and (3) the personality traits measured by the NEO Five-Factor Inventory in cigarette users and never-smokers. No significant differences were present in the frequency of rs2551038 genotypes and alleles in the studied cigarette users compared to the control group. Cigarette users, compared to the control group, had higher scores on the NEO-FFI Extraversion scale (p = 0.0011), and lower scores were obtained by the cigarette users for the NEO-FFI Openness (p = 0.0060), Agreeability (p ≤ 0.000), and Conscientiousness (p ≤ 0.000) scales. There was a significant positive Pearson’s linear correlation between the age and the Fagestrom test (r = 0.346; p < 0.0001) and the NEO-FFI Openness scale (r = 0.180; p < 0.0001) in the group of cigarette users. We observed significant linkage disequilibrium between rs2526303 and rs3864236 (D’ = 0.3581; p < 2.2204 × 10−16) and between rs2526303 and rs2551038 (D’ = 0.9993; p < 2.2204 × 10−16) in the tested sample. The sex-stratified haplotype analysis revealed that in the group of male never-smokers, the GTC haplotype was significantly more frequent than in the group of cigarette users (38% vs. 22%; p = 0.0039). The presented study reveals significant differences in personality trait scores between cases and controls. Moreover, the sex-stratified analysis showed significant differences in haplotype distribution. These results underscore the interplay between genetic predisposition, sex, and personality in nicotine-using individuals.
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- 2024
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6. Self-assembled core-shell nanoparticles with embedded internal standards for SERS quantitative detection and identification of nicotine released from snus products
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Yongfeng Tian, Lu Zhao, Xiaofeng Shen, Shanzhai Shang, Yonghua Pan, Gaofeng Dong, Wang Huo, Donglai Zhu, and Xianghu Tang
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nicotine ,snus ,SERS (surface enhanced Raman spectroscopy) ,internal standards ,liquid-liquid interface ,Chemistry ,QD1-999 - Abstract
Surface enhanced Raman spectroscopy (SERS) is a unique analytical technique with excellent performance in terms of sensitivity, non-destructive detection and resolution. However, due to the randomness and poor repeatability of hot spot distribution, SERS quantitative analysis is still challenging. Meanwhile, snus is a type of tobacco product that can release nicotine and other components in the mouth without burning, and the rapid detection technique based on SERS can reliably evaluate the amount of nicotine released from snus, which is of great significance for understanding its characteristics and regulating its components. Herein, the strategy was proposed to solve the feasibility of SERS quantitative detection based on self-assembled core-shell nanoparticles with embedded internal standards (EIS) due to EIS signal can effectively correct SERS signal fluctuations caused by different aggregation states and measurement conditions, thus allowing reliable quantitative SERS analysis of targets with different surface affinity. By means of process control, after the Au nanoparticles (Au NPs) were modified with 4-Mercaptobenzonitrile (4-MBN) as internal standard molecules, Ag shell with a certain thickness was grown on the surface of the AuNP@4-MBN, and then the Au@4-MBN@Ag NPs were used to regulate and control the assembly of liquid-liquid interface. The high-density nano-arrays assembled at the liquid-liquid interface ensure high reproducibility as SERS substrates, and which could be used for SERS detection of nicotine released from snus products. In addition, time-mapping research shows that this method can also be used to dynamically monitor the release of nicotine. Moreover, such destruction-free evaluation of the release of nicotine from snus products opens up new perspectives for further research about the impact of nicotinoids-related health programs.
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- 2024
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7. Regenerative potential of platelet derived growth factor in nicotine induced intervertebral disc degenerative model – In vivo study
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Daqiang Zheng, Zhiming Wu, Xiaoming Guan, Yannan Zhang, Haoyu Feng, and Jianjun Chang
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Nicotine ,Platelet derived growth factor ,Intervertebral disc ,Nucleus pulposus ,Calcium deposition ,Cartilage regeneration ,Chemistry ,QD1-999 - Abstract
Intervertebral disc (IVD) degeneration is an age-related disease affecting the elderly population worldwide. The disease is contributed by degeneration of the cartilage tissue in the vertebral column. The current study explores the possibility of exploiting platelet derived growth factor (PDGF), a growth factor secreted by platelets, as a therapeutic agent against the IVD degeneration. BALB/c mice were exposed to nicotine at higher concentrations to induce IVD degeneration. Three different concentrations of PDGF (1 ng/mL, 2 ng/mL, 3 ng/mL) were used in the study. Oxidative stress parameters were assessed through Lipid peroxidation (LPO), Myeloperoxidase (MPO) and Nitric oxide (NO). Histopathology was done for assessing the extent of degeneration, collagen II, mucin, and calcium deposition by Haematoxylin and Eosin staining, immunohistochemistry, Alcian blue and Alizarin red staining respectively. Gene expression studies were carried out by quantitative real-time Polymerase chain reaction (RT-PCR) for Aggrecan, alkaline phosphatase, RUNX2, Collagen I alpha and osteocalcin. IVD degeneration was prominent and PDGF treatment restored the tissue as evidenced by H&E staining. Oxidative stress was induced by the nicotine treatment and all the biomarkers of oxidative stress were restored back to normal by PDGF in a dose dependent manner. Biomarkers of endochondral bone formation (aggrecan, alkaline phosphatase, RUNX2, Collagen I alpha and osteocalcin) was observed to be normalized by exposing to PDGF in mRNA level though RT-PCR. Mucin, calcium contents were also brought back to normal by PDGF treatment. In conclusion, current work strongly supports that PDGF could be used as a therapeutic agent for the treatment of IVD degeneration.
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- 2024
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8. Utilizing molecular geometry, pKa, NMR, and IR data to assess the accuracy of quantum mechanics-derived thermodynamic parameters in evaluating antioxidant activity
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Mert Metin and Tomonori Kawano
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Antioxidant ,DFT ,IR ,Molecular geometry ,Nicotine ,NMR ,Chemistry ,QD1-999 - Abstract
In the current scientific milieu, a plethora of studies explores the intricacies of unravelling the antioxidant capacities inherent in novel compounds, employing the sophisticated tool of quantum chemistry. However, despite the strides made in this field, it is widely acknowledged that quantum chemical computations are not immune to imperfections, particularly when applied to a diverse array of chemical systems. The challenges extend to the critical task of discerning the reliability of suspected thermodynamic data, a pivotal aspect in the assessment of antioxidant candidates.This report endeavours to address the pressing question of how to establish the trustworthiness of thermodynamic data derived from quantum mechanical computations. Rather than solely relying on quantum mechanical approaches, our proposed methodology advocates for an inclusive strategy that incorporates additional experimental parameters to bolster the overall credibility assessment. With a specific focus on nicotine and Trolox, we aim to transcend the limitations of singular computational methods. By juxtaposing quantum-derived data with supplementary experimental evidence, we aspire to forge a comprehensive framework capable of robustly evaluating antioxidant candidates.
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- 2024
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9. Nornicotine-typed insecticides: The potential insecticides with strong activity against Diaphorina citri
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Pengfei Hu, Xiaoping Ye, Xiaoping Song, Mingxin Yang, Yunsheng Zhong, Yijing Cen, Yanxin Zhang, Yiming Song, and Qingchao Liu
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Nornicotine-typed compounds ,Nicotine ,Insecticide ,Diaphorina citri Kuwayama ,Synthesis ,Agriculture (General) ,S1-972 ,Biochemistry ,QD415-436 ,Chemistry ,QD1-999 - Abstract
Nicotine and nornicotine-typed compounds are well-known for its potential as insecticide. Some researches have shown that nicotine was highly toxic to Diaphorina citri Kuwayama, an invasive and fast spreading pest. Here we report the effects of nornicotine-typed insecticide against D. citri. Novel compounds A1-A8, B1–B28, C1–C18 and D1-D12 were synthesized by reported procedure. And bioassays indicated that some of these compounds exhibited good effects against D. citri. Compounds B2, B3, B8, B12, B13, B22, C5, C7, D5, and D9 exhibited the mortality up to 100% within 120 h in 50 mg/L. And further data shows that A2-5, A7, B1, B8, B20 and B22 showed rapid insecticidal activities against D. citri in 24 h with the low LC50 (LC50
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- 2023
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10. Corrigendum: Analytical approaches for the evaluation of data deficient simulated leachable compounds in ENDS products: a case study
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Cameron Smith, Matthew Lyndon, Lena Jeong, Danielle Lehman, J. Brian Jameson, Harish Chevva, Felix Ayala-Fierro, David Cook, Karen Carter, Michael Oldham, and I. Gene Gillman
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ENDS ,e-cigarette ,electronic cigarette ,nicotine ,leachables ,risk assessment ,Chemistry ,QD1-999 - Published
- 2023
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11. Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmitters in vivo
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Lulu Guo, Jian Mao, Qidong Zhang, Wu Fan, Dingzhong Wang, Zhonghao Li, Jiaqiang Huang, and Jianping Xie
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nicotine ,neurotransmitters ,brain metabolism ,online-microdialysis ,UHPLC-HRMS/MS ,Chemistry ,QD1-999 - Abstract
Introduction: The body’s ability to metabolize nicotine and the disposition of nicotine in the brain are important determinants of its exposure. Limited knowledge about the near real-time changes of neurochemicals during the brain nicotine metabolic process hinders the recognition of its multiple neuropharmacological effects.Methods: An online microdialysis coupled with UHPLC-HRMS/MS method for the in vivo multi-analysis of nicotine metabolites and several neurotransmitters in rat brain was developed. Whether the systemic modulation of metabolic enzyme CYP2B would modulate nicotine pharmacokinetics and local neurochemical effects was further investigated.Results: The dynamic profiles of over 10 nicotine metabolites and neurotransmitters were simultaneously obtained after a single injection of nicotine (2 mg·kg−1, i.p.) using the new method. Proadifen pretreatment (50 mg·kg−1·d−1, i.p., 4 days) caused significant inhibition of brain CYP2B1 activity. When exposed to nicotine, the brain Cmax of nicotine was 1.26 times higher and the levels of nicotine metabolites, nornicotine, and nicotine-N-oxide, were decreased by 85.3% and 34.4% in proadifen-pretreated rats. The higher level of brain nicotine induced a greater release of dopamine, serotonin, glutamate, and γ-amino-butyric acid in the nucleus accumbens. The concentrations of nicotine and dopamine were positively correlated, and the average levels of γ-amino-butyric acid and serotonin were 2.7 and 1.2 times higher, respectively, under the inhibition of nicotine metabolism.Discussion: These results demonstrated that inhibiting nicotine metabolism in rats can enhance the residence of brain nicotine and its local neurotransmitter effects. The metabolic activity of nicotine under different physiological conditions could regulate nicotine’s bioavailability and its resulting pharmacology.
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- 2023
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12. Determination of nicotine content in locally produced smokeless tobacco (Shammah) samples from Jazan region of Saudi Arabia using a convenient HPLC-MS/MS method
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Alhazmi Hassan A.
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lc-ms/ms ,jazan ,nicotine ,saudi arabia ,shammah ,smokeless tobacco ,Chemistry ,QD1-999 - Abstract
Shammah is one of the forms of smokeless tobacco (SLT) prepared by mixing tobacco powder with other ingredients to increase its acceptability. Nicotine (NT) is the main alkaloid present in tobacco and is a precursor for carcinogenic metabolites including tobacco specific nitrosamines (TSNAs). In this study, eight varieties of Shammah samples, collected from Jazan region of Saudi Arabia, were analyzed for NT content by a validated high performance liquid chromatography-mass spectrometry/mass spectrometry method. Electrospray ionization was used with the multiple reaction monitoring in the positive mode for data acquisition. The method was fast and short retention times (RT) of 1.4 and 3.1 min were observed for NT and lapatinib used as internal standard (IS), respectively. The inter- and intra-day accuracy and precision results met the acceptance criteria of United States Food and Drug Administration and International Council for Harmonisation validation guidelines. The developed method was successfully applied for the detection of NT contents in various Shammah samples. NT concentration was found to be in the range of 6.94 ± 0.16 to 31.69 ± 0.79% with the maximum level detected in special Shammah from Ahad Al Masarihah and the lowest level in Khadrah Shammah from Samtah city. The results of this investigation have warranted further research to determine the minor Shammah contents including additive materials and assessment of associated health effects.
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- 2023
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13. Neurobiology of Stress-Induced Nicotine Relapse
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Xinyu Wang, Yun Chen, Jing Dong, Jing Ge, Xiaoliu Liu, and Jianfeng Liu
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nicotine ,stress ,relapse ,reinstatement ,neurobiology ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, the relapse rate remains very high. Among the factors that could induce nicotine relapse, stress might be the most important one. In the last decades, preclinical studies have generated many new findings that lead to a better understanding of stress-induced relapse of nicotine-seeking. Several molecules such as α3β4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated receptor 1, and neuropeptide systems (corticotropin-releasing factor and its receptors, dynorphine and kappa opioid receptor) have been linked to stress-induced nicotine relapse. In this review, we discuss recent advances in the neurobiology, treatment targets, and potential therapeutics of stress-induced nicotine relapse. We also discuss some factors that may influence stress-induced nicotine relapse and that should be considered in future studies. In the final section, a perspective on some research directions is provided. Further investigation on the neurobiology of stress-induced nicotine relapse will shed light on the development of new medicines for controlling smoking and will help us understand the interactions between the stress and reward systems in the brain.
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- 2024
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14. Nicotine Motivated Behavior in C. elegans
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Chinnu Salim, Enkhzul Batsaikhan, Ann Ke Kan, Hao Chen, and Changhoon Jee
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nicotine ,motivated behavior ,C. elegans ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
To maximize the advantages offered by Caenorhabditis elegans as a high-throughput (HTP) model for nicotine dependence studies, utilizing its well-defined neuroconnectome as a robust platform, and to unravel the genetic basis of nicotine-motivated behaviors, we established the nicotine conditioned cue preference (CCP) paradigm. Nicotine CCP enables the assessment of nicotine preference and seeking, revealing a parallel to fundamental aspects of nicotine-dependent behaviors observed in mammals. We demonstrated that nicotine-elicited cue preference in worms is mediated by nicotinic acetylcholine receptors and requires dopamine for CCP development. Subsequently, we pinpointed nAChR subunits associated with nicotine preference and validated human GWAS candidates linked to nicotine dependence involved in nAChRs. Functional validation involves assessing the loss-of-function strain of the CACNA2D3 ortholog and the knock-out (KO) strain of the CACNA2D2 ortholog, closely related to CACNA2D3 and sharing human smoking phenotypes. Our orthogonal approach substantiates the functional conservation of the α2δ subunit of the calcium channel in nicotine-motivated behavior. Nicotine CCP in C. elegans serves as a potent affirmation of the cross-species functional relevance of GWAS candidate genes involved in nicotine seeking associated with tobacco abuse, providing a streamlined yet comprehensive system for investigating intricate behavioral paradigms within a simplified and reliable framework.
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- 2024
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15. Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis
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J. Brian Jameson, Jiaming Wang, Patrick C. Bailey, Michael J. Oldham, Cameron R. Smith, Lena N. Jeong, David K. Cook, Austin L. Bates, Sifat Ullah, Alexander S. C. Pennington, and I. Gene Gillman
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ENDS ,nicotine ,tobacco ,carbonyls ,formaldehyde ,metals ,Chemistry ,QD1-999 - Abstract
Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50–100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.
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- 2023
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16. Analytical approaches for the evaluation of data deficient simulated leachable compounds in ENDS products: a case study
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Cameron Smith, Matthew Lyndon, Lena Jeong, Danielle Lehman, J. Brian Jameson, Harish Chevva, Felix Ayala-Fierro, David Cook, Karen Carter, Michael Oldham, and I. Gene Gillman
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ENDS ,e-cigarette ,electronic cigarette ,nicotine ,leachables ,risk assessment ,Chemistry ,QD1-999 - Abstract
Leachable investigations are routinely undertaken across a range of sectors (e.g., pharmaceuticals, medical devices, etc.) to determine whether chemicals from a container closure system transfer into a product under normal conditions of use. For Electronic Nicotine Delivery Systems (ENDS) the container closure system includes all materials in contact with the e-liquid that is aerosolized and subsequently inhaled by the user. Currently, there is no guidance for conducting leachable studies for ENDS products, however, there are relevant guidance documents for orally inhaled drug products that can be applied to an ENDS container closure system. We present a case study of the analytical investigation of two leachable compounds identified in simulated leachable studies using aged JUULpods filled with unflavored e-liquid (PG/VG/nicotine/benzoic acid). Both compounds had limited toxicological information and were considered data deficient. A qualitative analysis of the aerosol collected from aged commercial JUULpods (Virginia Tobacco and Menthol), using a similar analytical method (LC-MS/MS) used in the simulated leachable studies, showed no trace or detectable levels of either leachable compound. Therefore, this qualitative analysis did not provide semi-quantitative values for the data-deficient leachable compounds necessary to support toxicological risk assessment. Further, no commercial authentic standards or reasonable synthetic route were available due to the molecular size and structural complexity of the compounds. Instead, method limits were established using an alternative approach to standard ICH guidelines. The experimentally determined method limit of quantitation, using spiked samples of simulated leachable e-liquid, provided conservative semi-quantitative values for each data deficient leachable compound in the aerosol that enabled a transfer efficiency from e-liquid to aerosol to be estimated. The transfer efficiency of each leachable compound was experimentally determined to be less than 3% based on the limit of quantitation, which then could be used to define a relevant exposure limit for the toxicological risk assessment. This work details a novel analytical approach for determining the transfer efficiency of data deficient leachable compounds from ENDS container closure systems into the ENDS aerosol to support toxicological health risk assessments.
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- 2023
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17. Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice
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Matthew Zammit, Chien-Min Kao, Hannah J. Zhang, Hsiu-Ming Tsai, Nathanial Holderman, Samuel Mitchell, Eve Tanios, Mohammed Bhuiyan, Richard Freifelder, Anna Kucharski, William N. Green, Jogeshwar Mukherjee, and Chin-Tu Chen
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kinetic modeling ,nicotine ,addiction ,PET ,Nifene ,2-FA85380 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Positron emission tomography (PET) radioligands that bind with high-affinity to α4β2-type nicotinic receptors (α4β2Rs) allow for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. Here, we investigate the use of an image-derived arterial input function and the cerebellum for kinetic analysis of radioligand binding in mice. Two radioligands were explored: 2-[18F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [18F]Nifene, displaying similar pKa and binding affinity to nicotine. Time–activity curves of the left ventricle of the heart displayed similar distribution across wild type mice, mice lacking the β2-subunit for ligand binding, and acute nicotine-treated mice, whereas reference tissue binding displayed high variation between groups. Binding potential estimated from a two-tissue compartment model fit of the data with the image-derived input function were higher than estimates from reference tissue-based estimations. Rate constants of radioligand dissociation were very slow for 2-FA and very fast for Nifene. We conclude that using an image-derived input function for kinetic modeling of nicotinic PET ligands provides suitable results compared to reference tissue-based methods and that the chemical properties of 2-FA and Nifene are suitable to study receptor response to nicotine addiction and smoking cessation therapies.
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- 2023
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18. ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization
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Tu Lu, Fangfang Xie, Chuangxin Huang, Lijun Zhou, Kunbei Lai, Yajun Gong, Zijing Li, Longhui Li, Jiandong Liang, Qifeng Cong, Weihua Li, Rong Ju, Sarah X. Zhang, and Chenjin Jin
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ERp29 ,nicotine ,endoplasmic reticulum stress ,macrophage polarization ,choroidal neovascularization ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.
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- 2023
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19. Nicotine Impairs the Anti-Contractile Function of Perivascular Adipose Tissue by Inhibiting the PPARγ–Adiponectin–AdipoR1 Axis
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Afifah Zahirah Abd Rami, Amilia Aminuddin, Adila A. Hamid, Mohd Helmy Mokhtar, and Azizah Ugusman
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adiponectin ,anti-contractile ,nicotine ,perivascular adipose tissue ,PPARγ ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ–adiponectin–adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ–adiponectin–adipoR1 axis.
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- 2023
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20. Quercetin Derivatives as Potential Therapeutic Agents: An Updated Perspective on the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer
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Naser A. Alsharairi
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flavonoids ,flavonols ,quercetin derivatives ,non-small cell lung cancer ,nicotine ,molecular mechanisms ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Flavonoids are the largest group of polyphenols, represented by many compounds that exhibit high anticancer properties. Quercetin (Q) and its main derivatives (rutin, quercitrin, isoquercitrin, isorhamnetin, tamarixetin, rhamnetin, and hyperoside) in the class of flavonols have been documented to exert anticancer activity. Q has been shown to be useful in the treatment of non-small cell lung cancer (NSCLC), as demonstrated by in vitro/in vivo studies, due to its antitumor, anti-inflammatory, anti-proliferative, anti-angiogenesis, and apoptotic properties. Some flavonoids (flavone, anthocyanins, and proanthocyanidins) have been demonstrated to be effective in nicotine-induced NSCLC treatment. However, the molecular mechanisms of quercetin derivatives (QDs) in nicotine-induced NSCLC treatment remain unclear. Thus, this review aims to summarize the available literature on the therapeutic effects of QDs in nicotine-induced NSCLC.
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- 2023
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21. Determination of nicotine in newborn meconium by high-Resolution ambient mass spectrometry using wooden-Tip spray
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Xinrong Wang, Mingyu Yang, Hui Xiao, Danping Liu, Lu Pan, Liuyang Zhang, Yan Yang, Qing Lu, Yanqiu Liu, Xiao Yang, and Bicheng Yang
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wooden tip ,meconium ,nicotine ,ambient mass spectrometry ,electrospray ionization ,Chemistry ,QD1-999 - Abstract
Prenatal exposure to nicotine that are mainly produced from tobacco smoke has been reported to affect infants. Therefore, nicotine exposure is one of important health concerns for newborn screening. Detecting nicotine and its metabolites such as cotinine in meconium were widely used to evaluate the tobacco exposure of pregnancy. In this study, disposable wooden tips were applied for touch sampling of meconium from newborn infants, and then were directly mounted on mass spectrometer (MS) to perform rapid screening of nicotine and cotinine. Choice of extraction/spray solvents was optimized. The limits of detection, reproducibility, linear response for direct analysis of meconium were also investigated. It is found the limits of detection (S/N = 3) to be as low as 0.36 ng/mg and 1.18 ng/mg for nicotine and cotinine, respectively, while the limits of quantitation (S/N = 10) to be 1.19 ng/mg and 3.94 ng/mg for nicotine and cotinine, respectively. The relative standard deviations (RSD) were found to be at 8.4%–19.8% (n = 6) for nicotine and cotinine, a good linear range from 5–500 ng/mL (R2 > 0.99). These analytical performances are well-accepted levels for ambient mass spectrometer analysis. In this study, evaluation of nicotine and cotinine in 22 puerpera volunteers were conducted by the established wooden-tip spray mass spectrometry (WTS-MS). These results showed that wooden-tip spray mass spectrometry would be useful for newborn screening of nicotine and cotinine in meconium with high reproducibility, speed, sensitivity, and specificity. Owing to the use of disposable wooden tips that involves no sample preparation and no chromatographic separation, our results show that wooden-tip spray mass spectrometry is a powerful tool for determination of nicotine in newborn meconium.
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- 2023
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22. Harmful Components in Tobacco Smoke and Factors Affecting Their Content
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Margarita Docheva, Yovcho Kochev, Maria Kasheva, and Hristo Bozukov
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tobacco smoke ,tar ,nicotine ,carbon monoxide ,smoking regimes ,filter ventilation ,Chemistry ,QD1-999 - Abstract
The aim of this study was to determine the influence of the smoking regime on thе content of tar, nicotine and CO, and to establish the decreasing content of tar, nicotine and CO with increasing the filter ventilation by 10, 20, and 30 %. The smoking regime and filter ventilation were investigated as the factors influencing the components of tobacco smoke. The intensive smoking regimes increased the content of tar, nicotine, and CO between 57 and 164 %. The filter ventilation was the other most significant factor on the increased content of components in tobacco smoke. Tar, nicotine and CO in non-ventilation cigarettes increased between 36 and 92 % compared to the same cigarettes with 30 % ventilation. The greatest increase was observed in intensive smoking regimes and closed ventilation.
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- 2022
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23. Nicotine: From Discovery to Biological Effects
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Luigi Sansone, Francesca Milani, Riccardo Fabrizi, Manuel Belli, Mario Cristina, Vincenzo Zagà, Antonio de Iure, Luca Cicconi, Stefano Bonassi, and Patrizia Russo
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nicotine ,nicotinic receptor ,tobacco ,dependence ,cell proliferation ,neo-angiogenesis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Nicotine, the primary psychoactive agent in tobacco leaves, has led to the widespread use of tobacco, with over one billion smokers globally. This article provides a historical overview of tobacco and discusses tobacco dependence, as well as the biological effects induced by nicotine on mammalian cells. Nicotine induces various biological effects, such as neoangiogenesis, cell division, and proliferation, and it affects neural and non-neural cells through specific pathways downstream of nicotinic receptors (nAChRs). Specific effects mediated by α7 nAChRs are highlighted. Nicotine is highly addictive and hazardous. Public health initiatives should prioritize combating smoking and its associated risks. Understanding nicotine’s complex biological effects is essential for comprehensive research and informed health policies. While potential links between nicotine and COVID-19 severity warrant further investigation, smoking remains a significant cause of morbidity and mortality globally. Effective public health strategies are vital to promote healthier lifestyles.
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- 2023
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24. The Influence of Nicotine on Trophoblast-Derived Exosomes in a Mouse Model of Pathogenic Preeclampsia
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Ayane Kubo, Keiichi Matsubara, Yuko Matsubara, Hirotomo Nakaoka, and Takashi Sugiyama
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preeclampsia ,exosomes ,nicotine ,proteomics ,bioinformatics ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Because the risk of PE is actually decreased by cigarette smoking, we considered the possibility that nicotine, a critical component of tobacco smoke, might protect against PE by modifying the content of exosomes from EVTs. We investigated the effects of nicotine on our PE model mouse and evaluated blood pressure. Next, exosomes were extracted from nicotine-treated extravillous trophoblasts (HTR-8/SVneo), and the peptide samples were evaluated by DIA (Data Independent Acquisition) proteomic analysis following nano LC-MS/MS. Hub proteins were identified using bioinformatic analysis. We found that nicotine significantly reduced blood pressure in a PE mouse model. Furthermore, we identified many proteins whose abundance in exosomes was modified by nicotine treatment of EVTs, and we used bioinformatic annotation and network analysis to select five key hub proteins with potential roles in the pathogenesis or prevention of PE. EVT-derived exosomes might influence the pathogenesis of PE because the cargo delivered by exosomes can signal to and modify the receiving cells and their environment.
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- 2023
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25. Molecular and docking studies of tetramethoxy hydroxyflavone compound from Artemisia absinthium against carcinogens found in cigarette smoke
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Aldakheel Fahad M., Alduraywish Shatha A., Mateen Ayesha, Alqahtani Mohammed S., and Syed Rabbani
- Subjects
artemisia absinthium ,docking studies ,mirna ,nicotine ,smoking ,Chemistry ,QD1-999 - Abstract
Artemisia absinthium (AA) is an indigenous medicine used for treatment of inflammation of the liver and chronic fever, and is studied as an antimalarial and anticancer agent. The focus of the current investigation was to determine the action and effect of AA on microRNAs (miRNAs) from breast cancer cell lines. Molecular docking is a structure-based drug design process that studies the interaction of small molecule ligands with receptor biomacromolecules to predict binding mechanism and affinity. MiRNA expression profiling was done using microarray technology. Validation of transcripts with regulated expression pattern was done by SYBR-based quantitative real time PCR (qRT-PCR). AutoDock 4.2 programming allots polar hydrogens, bound together total Kollman charges, solvation borders, and fragmental volumes to the protein using auto dock devices in docking research (ADT). As confirmed by SYBR-based RT-PCR, our investigation discovered an upregulation of the miRNA-22 articulation and a downregulation of miRNA-199a*. These findings support and demonstrate the role of AA as a miRNA articulation-influencing factor in human breast cancer progression. AA’s tetramethoxy hydroxyflavone (p7F) molecule was found to be effective in the treatment of cancer. Changes in miRNA expression patterns could be a key pathogenic component in AA’s physiological action on cancer cells.
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- 2021
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26. Determination of Nicotine in Cigarette Tobacco Smuggled to Brazil by Modified QuEChERS Methodology
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Cinthia Eloise Domingues, Januário Kordiak, Carlos R. Pedroso, Tatiana R. de Oliveira Stremel, Rosimara Zittel, Patrícia Los Weinert, Carlos M. de Sousa Vidal, and Sandro X. de Campos
- Subjects
Doehlert matrix ,Nicotine ,QuEChERS ,Smuggled cigarettes ,Science ,Chemistry ,QD1-999 - Abstract
The study of cigarette authenticity in Brazil is important due to increasing consumption of contraband cigarettes. Nicotine concentration is an important parameter reflecting the quality of tobacco used in the production of these cigarettes. Simple methods for this determination, which produce reduced waste, are environmentally and industrially important. The nicotine concentration of smuggled cigarette tobacco was determined by the QuEChERS method, requiring some modifications, such as decreasing the volume of the extractor solvent, changes in pH, and removal of the sample hydration step. Quantification was performed by gas chromatography using a flame ionization detector. The Doehlert matrix design was used to optimize the method. The extraction recoveries ranged from 97.5% to 99.6%, with relative standard deviation (RSD) ≤ 2.5% and limits of detection and quantification of 0.6 mg L-1 and 2.5 mg L-1, respectively. The method was sensitive and accurate for the detection and quantification of nicotine. The nicotine concentration in contraband cigarettes was found to be lower than that observed in legal cigarettes. The method was successfully applied to real samples of smuggled and legal cigarettes, providing a robust method for routine analysis and proving the need for more studies on quality control of smuggled cigarettes in Brazil.
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- 2022
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27. E-Cigarette Aerosol Condensate Leads to Impaired Coronary Endothelial Cell Health and Restricted Angiogenesis
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Michael Chhor, Esra Tulpar, Tara Nguyen, Charles G. Cranfield, Catherine A. Gorrie, Yik Lung Chan, Hui Chen, Brian G. Oliver, Lana McClements, and Kristine C. McGrath
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e-vaping ,cardiovascular disease ,smoking ,nicotine ,atherosclerosis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as an alternative smoking cessation device, which has been increasingly used by non-smokers; however, the cardiovascular effects surrounding the use of e-Cigs remains unclear. This study aimed to investigate the effects of e-Cig aerosol condensate (EAC) (0 mg and 18 mg nicotine) in vitro on human coronary artery endothelial cells (HCAEC) and in vivo on the cardiovascular system using a mouse model of ‘e-vaping’. In vitro results show a decrease in cell viability of HCAEC when exposed to EAC either directly or after exposure to conditioned lung cell media (p < 0.05 vs. control). Reactive oxygen species were increased in HCAEC when exposed to EAC directly or after exposure to conditioned lung cell media (p < 0.0001 vs. control). ICAM-1 protein expression levels were increased after exposure to conditioned lung cell media (18 mg vs. control, p < 0.01). Ex vivo results show an increase in the mRNA levels of anti-angiogenic marker, FKBPL (p < 0.05 vs. sham), and endothelial cell adhesion molecule involved in barrier function, ICAM-1 (p < 0.05 vs. sham) in murine hearts following exposure to electronic cigarette aerosol treatment containing a higher amount of nicotine. Immunohistochemistry also revealed an upregulation of FKBPL and ICAM-1 protein expression levels. This study showed that despite e-Cigs being widely used for tobacco smoking cessation, these can negatively impact endothelial cell health with a potential to lead to the development of cardiovascular disease.
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- 2023
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28. Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System
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Catherine Verhaeghe, Marja Talikka, Alain Sewer, Nicolas Sierro, Mehdi Auberson, Dariusz Peric, David Bornand, Remi Dulize, Emmanuel Guedj, Patrick Nef, Sebastien P. Tabruyn, Julia Hoeng, Manuel C. Peitsch, and Giuseppe Lo Sasso
- Subjects
ulcerative colitis ,alkaloids ,mouse model ,nicotine ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.
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- 2023
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29. Nicotine-Mediated Recruitment of GABAergic Neurons to a Dopaminergic Phenotype Attenuates Motor Deficits in an Alpha-Synuclein Parkinson’s Model
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Jessica IChi Lai, Alessandra Porcu, Benedetto Romoli, Maria Keisler, Fredric P. Manfredsson, Susan B. Powell, and Davide Dulcis
- Subjects
nicotine ,dopamine ,tyrosine-hydroxylase ,alpha-synuclein ,neurotransmitter-switching ,substantia nigra ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Previous work revealed an inverse correlation between tobacco smoking and Parkinson’s disease (PD) that is associated with nicotine-induced neuroprotection of dopaminergic (DA) neurons against nigrostriatal damage in PD primates and rodent models. Nicotine, a neuroactive component of tobacco, can directly alter the activity of midbrain DA neurons and induce non-DA neurons in the substantia nigra (SN) to acquire a DA phenotype. Here, we investigated the recruitment mechanism of nigrostriatal GABAergic neurons to express DA phenotypes, such as transcription factor Nurr1 and DA-synthesizing enzyme tyrosine hydroxylase (TH), and the concomitant effects on motor function. Wild-type and α-syn-overexpressing (PD) mice treated with chronic nicotine were assessed by behavioral pattern monitor (BPM) and immunohistochemistry/in situ hybridization to measure behavior and the translational/transcriptional regulation of neurotransmitter phenotype following selective Nurr1 overexpression or DREADD-mediated chemogenetic activation. We found that nicotine treatment led to a transcriptional TH and translational Nurr1 upregulation within a pool of SN GABAergic neurons in wild-type animals. In PD mice, nicotine increased Nurr1 expression, reduced the number of α-syn-expressing neurons, and simultaneously rescued motor deficits. Hyperactivation of GABA neurons alone was sufficient to elicit de novo translational upregulation of Nurr1. Retrograde labeling revealed that a fraction of these GABAergic neurons projects to the dorsal striatum. Finally, concomitant depolarization and Nurr1 overexpression within GABA neurons were sufficient to mimic nicotine-mediated dopamine plasticity. Revealing the mechanism of nicotine-induced DA plasticity protecting SN neurons against nigrostriatal damage could contribute to developing new strategies for neurotransmitter replacement in PD.
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- 2023
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30. Repellency and Toxicity of Eight Plant Extracts against the Western Flower Thrips, Frankliniella occidentalis
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Liyun Ren and Juang Horng Chong
- Subjects
botanical insecticides ,nicotine ,pest management ,pyrethrins ,rotenone ,stemonine ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
We investigated the repellency and toxicity of eight plant extracts containing celangulin, cnidium lactone, matrine, nicotine, pyrethrins, rotenone, stemonine and veratrine against the western flower thrips (Frankliniella occidentalis Pergande; Thysanoptera: Thripidae). Flowers treated with 0.05% nicotine, pyrethrins, stemonine and rotenone harbored fewer western flower thrips in two- and multiple-choice repellency bioassays. When evaluated at concentrations varying from 0.005% to 0.1% in two-choice repellency bioassays, pyrethrins and rotenone were most repellent at 0.01% to 0.1%, and nicotine was most repellent at 0.025%. Mortality was 76% with 0.1% nicotine at 48 h, 78% with 0.5% stemonine at 72 h, and 100% with 0.1% pyrethrins and 0.5% rotenone at 48 h after contact with fresh (
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- 2023
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31. Investigating the Modulation of the VTA Neurons in Nicotine-Exposed Pups during Early Maturation Using Optogenetics
- Author
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Austin Ganaway, Yoshinori Sunaga, Yasumi Ohta, Jun Ohta, Metin Akay, and Yasemin M. Akay
- Subjects
nicotine ,dopamine ,VTA ,optogenetics ,ChrimsonR ,microdialysis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Advancing the understanding of the relationship between perinatal nicotine addiction and the reward mechanism of the brain is crucial for uncovering and implementing new treatments for addiction control and prevention. The mesolimbic pathway of the brain, also known as the reward pathway, consists of two main areas that regulate dopamine (DA) and addiction-related behaviors. The ventral tegmental area (VTA) releases DA when stimulated, causing the propagation of neuronal firing along the pathway. This ends in the release of DA into the extracellular space of the nucleus accumbens (NAc), which is directly modulated by the uptake of DA. Much research has been conducted on the effects of nicotine addiction, but little research has been conducted concerning nicotine addiction and the mesolimbic pathway regarding maturation due to the small brain size. In this study, we apply our novel microstimulation experimental system to rat pups that have been perinatally exposed to nicotine. By using our self-fabricated photo-stimulation (PS) device, we can stimulate the VTA and collect dialysate, which is then used to estimate DA released into the NAc. The proposed platform has demonstrated the potential to monitor neural pathways as the pups mature.
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- 2023
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32. Forging of nicotine for the effective management of diabetic wounds: A hybrid of scaffold hopping and molecular dynamics simulation approaches
- Author
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Bharat Kumar Reddy. Sanapalli, Vidyasrilekha. Yele, Dilep Kumar. Sigalapalli, Nikhil Gadewal, Afzal B. Shaik, Richie R. Bhandare, Sivakumar. Annadurai, and Veera Venkata Satyanarayana Reddy. Karri
- Subjects
Diabetic wound ,Nicotine ,Scaffold hopping ,Molecular docking ,Molecular dynamics simulation ,Chemistry ,QD1-999 - Abstract
Diabetic wound (DW) is a huge threat to the health care community and is always challenging to treat. The main biochemical culprits in DW recalcitrance are elevated inflammatory mediators, proteases, cell proliferation and migration suppressors, anti-angiogenic factors, and bacterial infections. In this scenario, using a scaffold to target important factors at each stage of pathogenesis can accelerate the healing process. Many shreds of evidence disclosed the role of nicotine scaffold in handling inflammation, infection, proliferation, migration, and angiogenesis. All these factors made us forge nicotine by employing a scaffold hopping approach. The hops were then subjected to molecular docking and binding free energy calculations against Matrix metallopeptidase 9, Glycogen synthase kinase 3 beta, Tumor necrosis factor alpha, MurC and ParE enzymes. Gratifyingly, molecule H1 was found to possess significant inhibitory activity against the selected receptors as evidenced by their high negative glide score and binding energy. Furthermore, 100 ns of molecular dynamics simulation studies (MD) was performed for the five H1/4XCT, H1/5F95, H1/2AZ5, H1/4C13 and H1/4MOT complexes to get insight into the binding modes and stability. The MD results showed significant stability as evidenced by the low conformational changes of the H1 with the chosen receptors. Hence, H1 might be a druggable candidate in the therapeutic management of DW. However, further research is strongly recommended to advance the drug into the therapeutic pipeline.
- Published
- 2022
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33. Vitamin E Acetate Determination in Vaping Liquids and Non-targeted Analysis of Vaping Emissions of Diluents of Concern, Vitamin E Acetate and Medium-Chain Triglycerides Oil
- Author
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Ivana Kosarac, Cariton Kubwabo, Guru Prasad Katuri, Dora Petraccone, and Trevor K. Mischki
- Subjects
vaping ,vitamin E acetate ,medium chain triglycerides ,aerosol ,nicotine ,gc ms ,Chemistry ,QD1-999 - Abstract
During the summer of 2019, cases of lung injury associated with vaping emerged in North America, including among individuals who reported exclusive use of nicotine vaping liquids. Once vitamin E acetate was identified as a potential causative agent a quantitative method based on a simple sample dilution, separation by gas chromatography and analysis by triple quadrupole mass spectrometry (GC MSMS) was developed. Method detection limit (MDL) and limit of quantification (LOQ) were determined at 0.159 µg/mL and 0.505 µg/mL, respectively. The analysis was performed on a subset of 203 commercially sourced nicotine containing vaping liquids of various flavour profile and nicotine range (nicotine free-59 mg/mL) from an internal inventory. The target analyte, Vitamin E Acetate, was not detected in any samples analyzed, as expected, given the reported detection in literature and high association of the chemical with cannabis and not nicotine containing vaping products.
- Published
- 2021
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34. An Automated Aerosol Collection and Extraction System to Characterize Electronic Cigarette Aerosols
- Author
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Yeongkwon Son and Andrey Khlystov
- Subjects
electronic cigarette ,carbonyl ,aldehyde ,nicotine ,testing ,denuder ,Chemistry ,QD1-999 - Abstract
Electronic cigarette (e-cigarette) market increased by 122% during 2014–2020 and is expected to continue growing rapidly. Despite their popularity, e-cigarettes are known to emit dangerous levels of toxic compounds (e.g., carbonyls), but a lack of accurate and efficient testing methods is hindering the characterization of e-cigarette aerosols emitted by a wide variety of e-cigarette devices, e-liquids, and use patterns. The aim of this study is to fill this gap by developing an automated E-cigarette Aerosol Collection and Extraction System (E-ACES) consisting of a vaping machine and a collection/extraction system. The puffing system was designed to mimic e-cigarette use patterns (i.e., power output and puff topography) by means of a variable power-supply and a flow control system. The sampling system collects e-cigarette aerosols using a combination of glass wool and a continuously wetted denuder. After the collection stage, the system is automatically washed with absorbing and extracting liquids (e.g., methanol, an acetaldehyde-DNPH solution). The entire system is controlled by a computer. E-ACES performance was evaluated against conventional methods during measurements of nicotine and carbonyl emissions from a tank type e-cigarette. Nicotine levels measured using glass fiber filters and E-ACES were not significantly different: 201.2 ± 6.2 and 212.5 ± 17 μg/puff (p = 0.377), respectively. Differences in formaldehyde and acetaldehyde levels between filter-DNPH cartridges and the E-ACES were 14% (p = 0.057) and 13% (p = 0.380), respectively. The E-ACES showed reproducible nicotine and carbonyl testing results for the selected e-cigarette vaping conditions.
- Published
- 2021
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35. Ultrasound-triggered nicotine release from nicotine-loaded cellulose hydrogel
- Author
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Harshani Iresha and Takaomi Kobayashi
- Subjects
Ultrasound ,Triggering ,Drug release ,Cellulose hydrogel ,Nicotine ,Chemistry ,QD1-999 ,Acoustics. Sound ,QC221-246 - Abstract
Ultrasound (US)-triggered nicotine release system in a cellulose hydrogel drug carrier was developed with three different cellulose concentrations of 0.45 wt%, 0.9 wt%, and 1.8 wt%. The nicotine-loaded cellulose hydrogels were fabricated by the phase inversion method when the nicotine and cellulose mixture in the 6 wt% LiCl/N, N-dimethylacetamide solvent was exposed to water vapor at room temperature. Nicotine was used as the medicine due to its revealed therapeutic potential for neurodegenerative diseases like Alzheimer's and Parkinson's diseases. The behavior of US-triggered nicotine release from nicotine-cellulose hydrogel was studied at 43 kHz US frequency at the changing US output powers of 0 W, 5 W, 10 W, 20 W, 30 W, and 40 W. The significant US-triggered nicotine release enhancement was noted for the hydrogels made with 0.9 wt% and 1.8 wt% cellulose loading. The matrix made with 0.9 wt% cellulose was exhibited the highest nicotine release at the 40 W US power, and differences in nicotine release at different US powers were noticeable than at 0.45 wt% and 1.8 wt% cellulose loadings. For the three cellulose hydrogel systems, the storage modulus (G′) values at the 0.01 wt% strain rate were dropped from their initial values due to the US irradiation. This reduction was proportionately decreased when the US power was increased. The deconvolution of FTIR spectra of nicotine-loaded cellulose films before and after US exposure was suggested breakage of cellulose-nicotine and cellulose-water in the matrix; thus, the stimulated nicotine release from the cellulose matrix was promoted by the US irradiation.
- Published
- 2021
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36. Open Characterization of Vaping Liquids in Canada: Chemical Profiles and Trends
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Ivana Kosarac, Cariton Kubwabo, Xinghua Fan, Shabana Siddique, Dora Petraccone, Wei He, Jun Man, Matthew Gagne, Kelly R. Thickett, and Trevor K. Mischki
- Subjects
vaping ,nicotine ,non-targeted analysis ,E-cigarettes ,gc ms ,flavours ,Chemistry ,QD1-999 - Abstract
Currently, there is a lack of comprehensive data on the diversity of chemicals present in vaping liquids. To address this gap, a non-targeted analysis of 825 vaping liquids collected between 2017 and 2019 from Canadian retailers was conducted. Prior to mass spectrometry analysis, samples were diluted 1:500 v/v with methanol or acetonitrile. Chemical compound separation and analysis was carried out using gas chromatography and triple quadrupole mass spectrometry (GC-MS/MS) systems operated in the full scan mode and mass range of 35–450 m/z. Mass spectrum for each sample was obtained in electron ionization at 70 eV and processed. Non-targeted identification workflow included use of automated mass spectral deconvolution and identification system (AMDIS), where required, as well as a number of commercially available spectral libraries. In order to validate identities, an in-house database of expected compounds previously detected in vaping liquids was used along with genuine analytical standards for compounds of interest. This resulted in a dataset of over 1,500 unique detected chemicals. Approximately half of these chemical compounds were detected only once in a single product and not in multiple products analyzed. For any sample analyzed, on average, 40% of the chemical constituents appeared to have flavouring properties. The remainder were nicotine and related alkaloids, processing, degradation or indirect additives, natural extractives and compounds with unknown roles. Data published here from the project on the Open Characterization of vaping liquids is unique as it offers a detailed understanding of products’ flavour chemical profiles, the presence and frequency of chemicals of potential health concern, as well as trends and changes in products’ chemical complexity over a three-year period. Non-targeted chemical surveillance such as this present valuable tools to public health officials and researchers in responding to emergent issues such as vaping associated lung injury or informing chemical based strategies which may be aimed at addressing product safety or appeal.
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- 2021
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37. The Impact of Nicotine along with Oral Contraceptive Exposure on Brain Fatty Acid Metabolism in Female Rats
- Author
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Shahil H. Patel, Alba Timón-Gómez, Hari Pradhyumnan, Berk Mankaliye, Kunjan R. Dave, Miguel A. Perez-Pinzon, and Ami P. Raval
- Subjects
nicotine ,oral contraceptive ,β-oxidation ,carnitine palmitoyltransferase enzymes 1 and 2 ,metabolomics ,phospholipids ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Smoking-derived nicotine (N) and oral contraceptive (OC) synergistically exacerbate ischemic brain damage in females, and the underlying mechanisms remain elusive. In a previous study, we showed that N + OC exposure altered brain glucose metabolism in females. Since lipid metabolism complements glycolysis, the current study aims to examine the metabolic fingerprint of fatty acids in the brain of female rats exposed to N+/−OC. Adolescent and adult Sprague–Dawley female rats were randomly (n = 8 per group) exposed to either saline or N (4.5 mg/kg) +/−OC (combined OC or placebo delivered via oral gavage) for 16–21 days. Following exposure, brain tissue was harvested for unbiased metabolomic analysis (performed by Metabolon Inc., Morrisville, NC, USA) and the metabolomic profile changes were complemented with Western blot analysis of key enzymes in the lipid pathway. Metabolomic data showed significant accumulation of fatty acids and phosphatidylcholine (PC) metabolites in the brain. Adolescent, more so than adult females, exposed to N + OC showed significant increases in carnitine-conjugated fatty acid metabolites compared to saline control animals. These changes in fatty acyl carnitines were accompanied by an increase in a subset of free fatty acids, suggesting elevated fatty acid β-oxidation in the mitochondria to meet energy demand. In support, β-hydroxybutyrate was significantly lower in N + OC exposure groups in adolescent animals, implying a complete shunting of acetyl CoA for energy production via the TCA cycle. The reported changes in fatty acids and PC metabolism due to N + OC could inhibit post-translational palmitoylation of membrane proteins and synaptic vesicle formation, respectively, thus exacerbating ischemic brain damage in female rats.
- Published
- 2022
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38. Regulation of Cisplatin Resistance in Lung Cancer Cells by Nicotine, BDNF, and a β-Adrenergic Receptor Blocker
- Author
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Ravel Ray, Hind Al Khashali, Ben Haddad, Jadziah Wareham, Kai-Ling Coleman, Danyah Alomari, Robert Ranzenberger, Jeffrey Guthrie, Deborah Heyl, and Hedeel Guy Evans
- Subjects
β-adrenergic receptors ,brain-derived neurotrophic factor ,lung cancer ,cisplatin ,nicotine ,EGFR ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
It is well-recognized that cigarette smoking is a primary risk factor in the development of non-small cell lung cancer (NSCLC), known to account for ~80% of all lung cancers with nicotine recognized as the major addictive component. In investigating the effect of nicotine, brain-derived neurotrophic factor (BDNF), and the β-adrenergic receptor blocker, propranolol, on sensitivity of NSCLC cell lines, A549 and H1299, to cisplatin, we found increased cell viability, and enhanced cisplatin resistance with nicotine and/or BDNF treatment while opposite effects were found upon treatment with propranolol. Cell treatment with epinephrine or nicotine led to EGFR and IGF-1R activation, effects opposite to those found with propranolol. Blocking EGFR and IGF-1R activation increased cell sensitivity to cisplatin in both cell lines. PI3K and AKT activities were upregulated by nicotine or BDNF and downregulated by cell treatment with inhibitors against EGFR and IGF-1R and by propranolol. Apoptosis and cell sensitivity to cisplatin increased upon co-treatment of cells with cisplatin and inhibitors against PI3K or AKT. Our findings shed light on an interplay between nicotine, BDNF, and β-Adrenergic receptor signaling in regulating survival of lung cancer cells and chemoresistance which can likely expand therapeutic opportunities that target this regulatory network in the future.
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- 2022
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39. Isotope-Dilution Gas Chromatography-Mass Spectrometry Method for the Selective Detection of Nicotine and Menthol in E-Cigarette, or Vaping, Product Liquids and Aerosols
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José J. Pérez, Clifford H. Watson, Benjamin C. Blount, and Liza Valentín-Blasini
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e-cigarettes ,vapes ,nicotine ,menthol ,gas chromatography-mass spectrometry ,Chemistry ,QD1-999 - Abstract
We developed a quantitative method for analyzing nicotine and menthol in e-cigarette, or vaping, products (EVPs). These products may adversely impact health through inhalational exposure to addictive and harmful chemicals. The presence of unknown substances in do-it-yourself e-liquids, counterfeits, or unregulated products may increase exposure to harmful chemicals, as underscored by the 2019 EVP use-associated lung injury (EVALI) outbreak. To minimize these risks, it is important to accurately quantify nicotine and menthol in e-liquids and aerosol emissions to evaluate EVP authenticity, verify product label accuracy, and identify potentially hazardous products. We developed a simple, versatile, high-throughput method using isotope-dilution gas chromatography-mass spectrometry for quantifying nicotine and menthol concentrations in both e-liquid contents and machine-generated aerosol emissions of EVPs. Rigorous validation has demonstrated that the method is specific, precise (CV
- Published
- 2021
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40. Data on Chemistry Reported by Researchers at Technology Center (Direct Extraction and Determination of Free Nicotine in Cigarette Smoke).
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HOOKAHS ,CIGARETTE smoke ,SMOKING ,NICOTINE ,RESEARCH personnel - Abstract
A recent study conducted at the Technology Center has presented data on the direct extraction and determination of free nicotine in cigarette smoke. The accurate measurement of free nicotine content is important for assessing cigarette quality, studying harm and addiction, and reducing tar levels. The researchers developed a method using cyclohexane for direct extraction and gas chromatography-mass spectrometry for detection, which offers simplicity, improved precision, better detection limits, and reduced interference. The study found that the content of free nicotine in commercially available cigarette brands ranged from 0.376 to 0.716 mg/cig, with an average of 0.540 mg/cig, and accounted for 39.1%-88.8% of the total nicotine content. [Extracted from the article]
- Published
- 2024
41. Xenobiotics Delivered by Electronic Nicotine Delivery Systems: Potential Cellular and Molecular Mechanisms on the Pathogenesis of Chronic Kidney Disease
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Pablo Scharf, Felipe Rizzetto, Luana Filippi Xavier, and Sandra Helena Poliselli Farsky
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diabetes mellitus ,hypertension ,nicotine ,risk assessment ,flavoring agents ,volatiles organic compounds ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Chronic kidney disease (CKD) is characterized as sustained damage to the renal parenchyma, leading to impaired renal functions and gradually progressing to end-stage renal disease (ESRD). Diabetes mellitus (DM) and arterial hypertension (AH) are underlying diseases of CKD. Genetic background, lifestyle, and xenobiotic exposures can favor CKD onset and trigger its underlying diseases. Cigarette smoking (CS) is a known modified risk factor for CKD. Compounds from tobacco combustion act through multi-mediated mechanisms that impair renal function. Electronic nicotine delivery systems (ENDS) consumption, such as e-cigarettes and heated tobacco devices, is growing worldwide. ENDS release mainly nicotine, humectants, and flavorings, which generate several byproducts when heated, including volatile organic compounds and ultrafine particles. The toxicity assessment of these products is emerging in human and experimental studies, but data are yet incipient to achieve truthful conclusions about their safety. To build up the knowledge about the effect of currently employed ENDS on the pathogenesis of CKD, cellular and molecular mechanisms of ENDS xenobiotic on DM, AH, and kidney functions were reviewed. Unraveling the toxic mechanisms of action and endpoints of ENDS exposures will contribute to the risk assessment and implementation of proper health and regulatory interventions.
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- 2022
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42. Nicotine in Combination with SARS-CoV-2 Affects Cells Viability, Inflammatory Response and Ultrastructural Integrity
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Luigi Sansone, Antonio de Iure, Mario Cristina, Manuel Belli, Laura Vitiello, Federica Marcolongo, Alfredo Rosellini, Lisa Macera, Pietro Giorgio Spezia, Carlo Tomino, Stefano Bonassi, Matteo A. Russo, Fabrizio Maggi, and Patrizia Russo
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cytokines ,human lung adenocarcinoma A549 cells ,necroptosis ,nicotine ,poly(I:C) ,pyroptosis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The aims of our study are to: (i) investigate the ability of nicotine to modulate the expression level of inflammatory cytokines in A549 cells infected with SARS-CoV-2; (ii) elucidate the ultrastructural features caused by the combination nicotine+SARS-CoV-2; and (iii) demonstrate the mechanism of action. In this study, A549 cells pretreated with nicotine were either exposed to LPS or poly(I:C), or infected with SARS-CoV-2. Treated and untreated cells were analyzed for cytokine production, cytotoxicity, and ultrastructural modifications. Vero E6 cells were used as a positive reference. Cells pretreated with nicotine showed a decrease of IL6 and TNFα in A549 cells induced by LPS or poly(I:C). In contrast, cells exposed to SARS-CoV-2 showed a high increase of IL6, IL8, IL10 and TNFα, high cytopathic effects that were dose- and time-dependent, and profound ultrastructural modifications. These modifications were characterized by membrane ruptures and fragmentation, the swelling of cytosol and mitochondria, the release of cytoplasmic content in extracellular spaces (including osmiophilic granules), the fragmentation of endoplasmic reticulum, and chromatin disorganization. Nicotine increased SARS-CoV-2 cytopathic effects, elevating the levels of inflammatory cytokines, and inducing severe cellular damage, with features resembling pyroptosis and necroptosis. The protective role of nicotine in COVID-19 is definitively ruled out.
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- 2022
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43. Insights into the Mechanisms of Action of Proanthocyanidins and Anthocyanins in the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer
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Naser A. Alsharairi
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flavonoids ,proanthocyanidins ,anthocyanins ,nicotine ,NSCLC ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In traditional medicine, different parts of plants, including fruits, have been used for their anti-inflammatory and anti-oxidative properties. Plant-based foods, such as fruits, seeds and vegetables, are used for therapeutic purposes due to the presence of flavonoid compounds. Proanthocyanidins (PCs) and anthocyanins (ACNs) are the major distributed flavonoid pigments in plants, which have therapeutic potential against certain chronic diseases. PCs and ACNs derived from plant-based foods and/or medicinal plants at different nontoxic concentrations have shown anti-non-small cell lung cancer (NSCLC) activity in vitro/in vivo models through inhibiting proliferation, invasion/migration, metastasis and angiogenesis and by activating apoptosis/autophagy-related mechanisms. However, the potential mechanisms by which these compounds exert efficacy against nicotine-induced NSCLC are not fully understood. Thus, this review aims to gain insights into the mechanisms of action and therapeutic potential of PCs and ACNs in nicotine-induced NSCLC.
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- 2022
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44. A Novel Electrochemical Sensor for Detection of Nicotine in Tobacco Products Based on Graphene Oxide Nanosheets Conjugated with (1,2-Naphthoquinone-4-Sulphonic Acid) Modified Glassy Carbon Electrode
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M. Abd-Elsabour, Hesham M. Alsoghier, Abdulrahman G. Alhamzani, Mortaga M. Abou-Krisha, Tarek A. Yousef, and Hytham F. Assaf
- Subjects
adapted glassy carbon sensor ,cigarette ,differential pulse voltammetry ,graphene oxide nanosheets synthesis ,nicotine ,Chemistry ,QD1-999 - Abstract
A simple electrochemical sensor for nicotine (NIC) detection was performed. The sensor based on a glassy carbon electrode (GCE) was modified by (1,2-naphthoquinone-4-sulphonic acid)(Nq) decorated by graphene oxide (GO) nanocomposite. The synthesized (GO) nanosheets were characterized using X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscope (SEM), transmission electron microscope (TEM), FT-IR, and UV-Visible Spectroscopy. The insertion of Nq with GO nanosheets on the surface of GCE displayed high electrocatalytic activity towards NIC compared to the bare GCE. NIC determination was performed under the optimum conditions using 0.10 M of Na2SO4 as a supporting electrolyte with pH 8.0 at a scan rate of 100 mV/s using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). This electrochemical sensor showed an excellent result for NIC detection. The oxidation peak current increased linearly with a 6.5–245 µM of NIC with R2 = 0.9999. The limit of detection was 12.7 nM. The fabricated electrode provided satisfactory stability, reproducibility, and selectivity for NIC oxidation. The reliable GO/Nq/GCE sensor was successfully applied for detecting NIC in the tobacco product and a urine sample.
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- 2022
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45. The Regulatory Role of H19/miR-181a/ATG5 Signaling in Perinatal Nicotine Exposure-Induced Development of Neonatal Brain Hypoxic-Ischemic Sensitive Phenotype
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Yong Li, Yanyan Zhang, Andrew Walayat, Yingjie Fu, Bailin Liu, Lubo Zhang, and Daliao Xiao
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nicotine ,neonatal HIE ,miR-181a ,ATG5 ,lncRNA H19 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Nicotine exposure either from maternal cigarette smoking or e-cigarette vaping is one of the most common risk factors for neurodevelopmental disease in offspring. Previous studies revealed that perinatal nicotine exposure programs a sensitive phenotype to neonatal hypoxic-ischemic encephalopathy (HIE) in postnatal life, yet the underlying mechanisms remain undetermined. The goal of the present study was to determine the regulatory role of H19/miR-181a/ATG5 signaling in perinatal nicotine exposure-induced development of neonatal brain hypoxic-ischemic sensitive phenotype. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps. All experiments were conducted in offspring pups at postnatal day 9 (P9). Perinatal nicotine exposure significantly enhanced expression of miR-181a but attenuated autophagy-related protein 5 (ATG5) mRNA and protein levels in neonatal brains. Of interest, miR-181a mimicking administration in the absence of nicotine exposure also produced dose-dependent increased hypoxia/ischemia (H/I)-induced brain injury associated with a decreased ATG5 expression, closely resembling perinatal nicotine exposure-mediated effects. Locked nucleic acid (LNA)-miR-181a antisense reversed perinatal nicotine-mediated increase in H/I-induced brain injury and normalized aberrant ATG5 expression. In addition, nicotine exposure attenuated a long non-coding RNA (lncRNA) H19 expression level. Knockdown of H19 via siRNA increased the miR-181a level and enhanced H/I-induced neonatal brain injury. In conclusion, the present findings provide a novel mechanism that aberrant alteration of the H19/miR-181a/AGT5 axis plays a vital role in perinatal nicotine exposure-mediated ischemia-sensitive phenotype in offspring and suggests promising molecular targets for intervention and rescuing nicotine-induced adverse programming effects in offspring.
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- 2022
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46. Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells
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Shinan Li, Pham Ngoc Khoi, Hong Yin, Dhiraj Kumar Sah, Nam-Ho Kim, Sen Lian, and Young-Do Jung
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sulforaphane ,nicotine ,metalloproteinase-9 ,gastric cancer ,cell invasion ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Sulforaphane, a natural phytochemical compound found in various cruciferous vegetables, has been discovered to present anti-cancer properties. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in gastric cancer metastasis. However, the role of sulforaphane in MMP-9 expression in gastric cancer is not yet defined. Nicotine, a psychoactive alkaloid found in tobacco, is associated with the development of gastric cancer. Here, we found that sulforaphane suppresses the nicotine-mediated induction of MMP-9 in human gastric cancer cells. We discovered that reactive oxygen species (ROS) and MAPKs (p38 MAPK, Erk1/2) are involved in nicotine-induced MMP-9 expression. AP-1 and NF-κB are the critical transcription factors in MMP-9 expression. ROS/MAPK (p38 MAPK, Erk1/2) and ROS functioned as upstream signaling of AP-1 and NF-κB, respectively. Sulforaphane suppresses the nicotine-induced MMP-9 by inhibiting ROS-mediated MAPK (p38 MAPK, Erk1/2)/AP-1 and ROS-mediated NF-κB signaling axes, which in turn inhibit cell invasion in human gastric cancer AGS cells. Therefore, the current study provides valuable evidence for developing sulforaphane as a new anti-invasion strategy for human gastric cancer therapy.
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- 2022
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47. Electrochemical Determination of Nicotine in Tobacco Products Based on Biosynthesized Gold Nanoparticles
- Author
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Yanqiu Jing, Shanghui Ning, Yu Guan, Mingfeng Cao, Junju Li, Li Zhu, Qili Zhang, Chuance Cheng, and Yong Deng
- Subjects
biosynthesis ,nicotine ,gold nanoparticle ,electrochemical sensor ,Plectranthus amboinicus ,Chemistry ,QD1-999 - Abstract
In this work, gold nanoparticles were biosynthesized via Plectranthus amboinicus leaf extract as the reducing agent. A series of techniques were used for sample analysis. The biosynthesized gold nanoparticles (bAuNPs) are a uniform size with a spherical shape. The FTIR analysis reveals the presence of many oxygen-containing functional groups on the bAuNP surface. The cyclic voltammetry and electrochemical impedance spectroscopic characterizations reveal that while the bAuNPs have a slightly lower conductivity than chemically synthesized AuNPs (cAuNPs). However, the bAuNPs have a superior electrocatalytic performance toward nicotine reduction. After optimization, the bAuNP-modified SPE could detect nicotine linearly from 10 to 2,000 μM with a low detection limit of 2.33 μM. In addition, the bAuNPs/SPE have been successfully used for nicotine-containing-product analysis.
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- 2020
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48. Expression and Function of Nicotinic Acetylcholine Receptors in Induced Regulatory T Cells
- Author
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Yuichiro Nakata, Kento Miura, Norimasa Yamasaki, Sawako Ogata, Shuka Miura, Naohisa Hosomi, and Osamu Kaminuma
- Subjects
acetylcholine receptors ,histone modification ,immune regulation ,nicotine ,T cell ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
A contribution of the cholinergic system to immune cell function has been suggested, though the role of nicotine and its receptors in T cells, especially regulatory T (Treg) cells, is unclear. We herein investigated the expression and function of nicotinic acetylcholine receptors (nAChRs) in murine-induced Treg (iTreg) cells. Upon differentiation of naive BALB/c T cells into iTreg cells and other T-cell subsets, the effect of nicotine on cytokine production and proliferation of iTreg cells was examined. The expression of nAChRs and its regulatory mechanisms were comparatively analyzed among T-cell subsets. Stimulation-induced transforming growth factor-β1 (TGF-β1) production of iTreg cells was suppressed by nicotine, whereas interleukin (IL)-10 production and proliferation was not affected. α2-, α5-, α9-, and β2-nAChRs were differentially expressed in naive, Th1, Th2, Th9, Th17, and iTreg cells. Among these cell types, the α9-nAChR was particularly upregulated in iTreg cells via its gene promoter, but not through tri-methylation at the 4th lysine residue of the histone H3-dependent mechanisms. We conclude that the immunoregulatory role of Treg cells is modified by the cholinergic system, probably through the characteristic expression of nAChRs.
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- 2022
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49. Injectable In Situ Gelling System for Sustained Nicotine Delivery as a Replacement Therapy for Smoking Cessation
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Eileen Hulambukie, Hani Abdeltawab, Sanjukta Duarah, Darren Svirskis, and Manisha Sharma
- Subjects
nicotine ,sustained release ,prolonged release ,poloxamers ,design expert ,factorial design ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Nicotine replacement therapy (NRT) is widely used to limit the withdrawal symptoms associated with cigarette smoking cessation. However, the available NRT formulations are limited by their short release profiles, requiring frequent administrations along with local side effects. Thus, the objective of this study is to develop an NRT formulation that offers prolonged, sustained nicotine release. Thermoresponsive in situ gelling systems containing nicotine were prepared using poloxamer 407 (P407) and poloxamer 188 (P188). The system was optimized using a three-factor, two-level full factorial design (23). A formulation composed of P407 (20% w/w), P188 (5% w/w), and loaded with nicotine (0.5% w/w) exhibited sol-to-gel transition at a suitable temperature close to physiological temperature (30 °C). The rheological analysis demonstrated a Newtonian-like flow at room temperature, suggesting ease of administration via injection, and semisolid gel status at physiological temperature. The optimized formulation successfully sustained nicotine in vitro release over 5 days following single administration. The findings suggest that poloxamer based in situ gelling systems are promising platforms to sustain the release of nicotine.
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- 2022
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50. Increased Risky Choice and Reduced CHRNB2 Expression in Adult Male Rats Exposed to Nicotine Vapor
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Priscilla Giner, Liliana Maynez-Anchondo, Anna E. Liley, Kevin P. Uribe, Gabriel A. Frietze, Nicholas W. Simon, and Ian A. Mendez
- Subjects
nicotine ,e-cigarette ,risky choice ,cholinergic ,dopaminergic ,rat ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
While the cognitive enhancing effects of nicotine use have been well documented, it has also been shown to impair decision making. The goal of this study was to determine if exposure to nicotine vapor increases risky decision making. The study also aims to investigate possible long-term effects of nicotine vapor exposure on the expression of genes coding for cholinergic and dopaminergic receptors in brain. Thirty-two adult male Sprague Dawley rats were exposed to 24 mg/mL nicotine vapor or vehicle control, immediately followed by testing in the probability discounting task for 10 consecutive days. Fifty-four days after the 10-day vapor exposure, animals were sacrificed and expression of genes coding for the α4 and β2 cholinergic receptor subunits, and dopamine D1 and D2 receptors, were analyzed using RT-PCR. Exposure to nicotine vapor caused an immediate and transient increase in risky choice. Analyses of gene expression identified significant reductions in CHRNB2 and DRD1 in the nucleus accumbens core and CHRNB2 and DRD2 in the medial prefrontal cortex of rats previously exposed to nicotine vapor, relative to vehicle controls. Results provide data on the negative cognitive effects of nicotine vapor exposure and identify cholinergic and dopaminergic mechanisms that may affected with repeated use.
- Published
- 2022
- Full Text
- View/download PDF
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