Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

BACKGROUND: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. METHODS: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R-) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. RESULTS: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R- HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. CONCLUSIONS: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Development of Opioid Use Disorder After Breast Reconstruction: Effects of Nicotine Exposure.

INTRODUCTION: After undergoing breast reconstructive surgery, patients are typically prescribed opioids. Smoking tobacco increases rate of opioid metabolism and is associated with development of opioid use disorder (OUD). The aim of this study was to determine whether patients who smoke have an increased risk of OUD after breast reconstructive surgery. Given that OUD is a known risk factor for injection drug use and intravenous drug use increases risk of acquiring blood-borne diseases including human immunodeficiency virus (HIV) and hepatitis, the secondary aim was to determine if these patients are also at increased risk of acquiring these communicable diseases associated with OUD. METHODS: A retrospective analysis was conducted using TriNetX, a multi-institutional deidentified database. Individuals included underwent a breast reconstructive surgery and received postoperative opioid treatment. The exposed group included patients who smoke. The control group did not smoke. Risk of developing OUD, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV from 12 to 36 months after surgery was compared between groups. Patients with preexisting OUD or associated diseases were excluded. Cohorts were matched to control for confounding factors including age, sex, race, mental health history, and concomitant substance use. RESULTS: There were 8648 patients included in the analysis. After matching, 4324 patients comprised the exposure group, and 4324 patients remained in the control group. Preoperative smoking was significantly associated with increased risk of OUD at 12, 24, and 36 months after breast reconstruction (36 months: odds ratio [OR], 2.722; confidence interval [CI], 2.268-6.375). Smoking was also associated with increased risk of HIV and HCV at all time points after surgery (36 months HIV: OR, 2.614; CI, 1.977-3.458; 36 months HCV: OR, 3.718; CI, 2.268-6.375) and increased risk of HBV beginning at 24 months after surgery (36 months HBV: OR, 2.722; CI, 1.502-4.935). CONCLUSIONS: Individuals who smoke have an increased risk of developing OUD, HIV, HCV, and HBV after breast reconstructive surgery. This risk persists for at least 3 years after surgery. Additional research and clinical interventions focusing on early identification of OUD, prevention efforts, and harm reduction strategies for patients who smoke or have nicotine dependence undergoing breast reconstruction are warranted.

Preventive effects of crocin, a natural compound from saffron, against nicotine­induced oxidative stress and neurobehavioral disturbances.

Nicotine is a psychostimulant that induces neurochemical and behavioral changes upon chronic administration, leading to neurodegenerative conditions associated with smoking. As of now, no preventive or therapeutic strategies are known to counteract nicotine­induced neurodegeneration. In this study, we explore the neuroprotective effects of crocin, a bioactive agent commonly found in saffron - a spice derived from the flower of Crocus sativus - using a rat model. The dose­dependent effects of crocin were evaluated in nicotine­induced neurodegeneration and compared with a control group. Neurobehavioral changes, assessed through the elevated plus maze, the open field test, the forced swim test, and the Morris water maze, as well as oxidative stress in the hippocampus, were evaluated. Interestingly, nicotine administration resulted in depression, anxiety, and abnormal motor and cognitive functions, while crocin treatment protected the rat brain from these abnormalities. The beneficial effects of crocin were associated with reduced oxidative stress biomarkers such as malondialdehyde, along with increases in superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. These results demonstrate that crocin can mitigate nicotine­induced neurodegeneration by reducing oxidative stress, potentially offering a protective measure against neurodegenerative effects in smokers.

An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence.

BACKGROUND: As well as being associated with serious negative health outcomes, smoking has been reported to have an array of physiological and psychological effects, including effects on mood and cognitive function. Post-cessation, loss of such effects (including temporary deficits in cognitive function) have been cited as reasons for resumption of smoking. The effects of e-cigarettes and nicotine delivered by e-cigarettes on these functions have not been widely researched but may play a role in the effectiveness of e-cigarettes as a satisfactory alternative to combustible cigarettes for people who smoke, and in encouraging individuals who would otherwise continue to smoke, to transition to e-cigarettes. METHODS: The study was an exploratory, randomised, partially-blinded, single-centre, five-arm crossover trial that recruited 40 healthy male and female people who smoke. At 5 study sessions, following a 12-h period of nicotine abstinence, participants were randomly assigned to use either a combustible cigarette, an e-cigarette of three varying nicotine strengths (18 mg/mL, 12 mg/mL or 0 mg/mL respectively) or observe a no product usage session. Participants completed pre- and post-product usage assessments to examine the product usage effect on cognitive performance (using the Cambridge Neuropsychological Test Automated Battery (CANTAB)), subjective mood and smoking urges. RESULTS: A significant improvement in sustained attention task performance was observed following use of both the nicotine containing e-cigarettes and combustible cigarette compared to no product use. Additionally, there were no significant differences between the nicotine containing products, indicating that nicotine use enhanced sustained attention regardless of delivery format. Nicotine containing e-cigarette and combustible cigarette use also significantly improved overall mood of participants compared to no product use, with no significant differences observed between the nicotine containing products. Nicotine containing e-cigarette and combustible cigarette use significantly reduced smoking urges compared to no product use, though combustible cigarette use elicited the greatest reduction in smoking urges. CONCLUSIONS: Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke. Trial registration ISRCTN (identifier: ISRCTN35376793).

[The role of ROS/JNK/caspase 3 axis in apoptosis induction by menthol-favored electronic cigarette liquid in human periodontal ligament stem cells].

PURPOSE: To explore the cytotoxic effect of a menthol-favored E-liquid on human periodontal ligament stem cells (hPDLSCs), as well as the underlying mechanism of electronic cigarette (E-cig)-induced cell apoptosis. METHODS: PDLSCs were isolated and cultured from periodontal ligament tissues of healthy premolars extracted for orthodontic reasons. Cells in passage 3 were used to detect the surface markers of stem cells by flow cytometry. Then the cells were exposed to different doses of menthol-favored E-liquid (at 59 mg/L nicotine concentration) in the culture median (the final nicotine concentrations were 0.1 µg/mL, 1.0 µg/mL, 10 µg/mL, 50 µg/mL, 0.1 mg/mL, 0.2 mg/mL and 0.5 mg/mL, respectively) for different period of times (24, 48 and 72 h). The cell viability was analyzed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry (7-AAD and Annexin V staining) and TUNEL assay. Reactive oxygen species (ROS) production was detected with fluorescence probe DCFH-DA by confocal microscopy and flow cytometry. The protein expression levels associated with ROS/JNK/caspase 3 axis(p-JNK, JNK, c-Jun, p-c-Jun, Bcl-2, Bax and cleaved-caspase 3) were analyzed by Western blot. Immunocytofluorescense staining was applied to evaluate the expression level of p-JNK. After addition of NAC, a ROS scavenger, and MAPK/JNK specific blocker SP600125, their effects on E-cig-induced cell apoptosis were evaluated. Statistical analysis was performed with Graph Pad 5.0 software package. RESULTS: Human PDLSCs were successfully isolated and cultured and flow cytometry assay showed the mesenchymal stem cell surface biomarkers (CD73, CD90 and CD105) were positively expressed. CCK8 assay indicated cell viability was significantly(P＜0.001) different among all concentration groups at various time points (24, 48 or 72 h), and the difference in apoptosis rate among all concentration groups was also statistically significant (P＜0.001). After exposure to E-liquid with nicotine concentration ≥50 µg/mL, cell viability was significantly reduced, and the proportion of apoptotic cells and the cellular ROS level was significantly increased in a dose-dependent manner as compared with the control group(0.0 mg/mL). Western blot assay showed E-cig exposure could promote MAPK/JNK phosphorylation in a dose-dependent and time-dependent manner. Either NAC or SP600125 could partially rescue the E-cig-induced cell apoptosis via reversing up-regulation of p-JNK and cleaved caspase 3. CONCLUSIONS: ROS/JNK/caspase 3 axis is involved in menthol-favored E-liquid-induced apoptosis of hPDLSCs.

Multi-endpoint in vitro toxicological assessment of snus and tobacco-free nicotine pouch extracts.

'Modern' oral tobacco-free nicotine pouches (NPs) are a nicotine containing product similar in appearance and concept to Swedish snus. A three-step approach was taken to analyse the biological effects of NPs and snus extracts in vitro. ToxTracker was used to screen for biomarkers for oxidative stress, cell stress, protein damage and DNA damage. Cytotoxicity, mutagenicity, and genotoxicity were assessed in the following respective assays: Neutral Red Uptake (NRU), Ames and Mouse Lymphoma Assay (MLA). Targeted analysis of phosphorylation signalling and inflammatory markers under non-toxic conditions was used to investigate any potential signalling pathways or inflammatory response. A reference snus (CRP1.1) and four NPs with various flavours and nicotine strengths were assessed. Test article extracts was generated by incubating one pouch in 20 mL of media (specific to each assay) with the inclusion of the pouch material. NP extracts did not induce any cytotoxicity or mutagenic response, genotoxic response was minimal and limited signalling or inflammatory markers were induced. In contrast, CRP1.1 induced a positive response in four toxicological endpoints in the absence of S9: Srxn1 (oxidative stress), Btg2 (cell stress), Ddit3 (protein damage) and Rtkn (DNA damage), and three endpoints in presence of S9: Srxn1, Ddit3 and Rtkn. CRP1.1 was genotoxic when assessed in MLA and activated signalling pathways involved in proliferation and cellular stress and specifically induced phosphorylation of c-JUN, CREB1, p53, p38 MAPK and to a lesser extent AKT1S1, GSK3α/ß, ERK1/2 and RSK1 in a dose-dependent manner. CRP 1.1 extracts resulted in the release of several inflammatory mediators including cytokines IL-1α, IL5, IL6, IL8, IL-1RA, MIF and TNF-ß, receptor IL-2RA, and growth factors FGF-basic, VEGF and M-CSF. In conclusion these assays contribute to the weight of evidence assessment of the potential comparative health risks of NPs and snus.

Using Project Extension for Community Healthcare Outcomes to Enhance Substance Use Disorder Care in Primary Care: Mixed Methods Study.

BACKGROUND: Substance use and overdose deaths make up a substantial portion of injury-related deaths in the United States, with the state of Ohio leading the nation in rates of diagnosed substance use disorder (SUD). Ohio's growing epidemic has indicated a need to improve SUD care in a primary care setting through the engagement of multidisciplinary providers and the use of a comprehensive approach to care. OBJECTIVE: The purpose of this study was to assess the ability of the Weitzman Extension for Community Healthcare Outcomes (ECHO): Comprehensive Substance Use Disorder Care program to both address and meet 7 series learning objectives and address substances by analyzing (1) the frequency of exposure to the learning objective topics and substance types during case discussions and (2) participants' change in knowledge, self-efficacy, attitudes, and skills related to the treatment of SUDs pre- to postseries. The 7 series learning objective themes included harm reduction, team-based care, behavioral techniques, medication-assisted treatment, trauma-informed care, co-occurring conditions, and social determinants of health. METHODS: We used a mixed methods approach using a conceptual content analysis based on series learning objectives and substances and a 2-tailed paired-samples t test of participants' self-reported learner outcomes. The content analysis gauged the frequency and dose of learning objective themes and illicit and nonillicit substances mentioned in participant case presentations and discussions, and the paired-samples t test compared participants' knowledge, self-efficacy, attitudes, and skills associated with learning objectives and medication management of substances from pre- to postseries. RESULTS: The results of the content analysis indicated that 3 learning objective themes-team-based care, harm reduction, and social determinants of health-resulted in the highest frequencies and dose, appearing in 100% (n=22) of case presentations and discussions. Alcohol had the highest frequency and dose among the illicit and nonillicit substances, appearing in 81% (n=18) of case presentations and discussions. The results of the paired-samples t test indicated statistically significant increases in knowledge domain statements related to polysubstance use (P=.02), understanding the approach other disciplines use in SUD care (P=.02), and medication management strategies for nicotine (P=.03) and opioid use disorder (P=.003). Statistically significant increases were observed for 2 self-efficacy domain statements regarding medication management for nicotine (P=.002) and alcohol use disorder (P=.02). Further, 1 statistically significant increase in the skill domain was observed regarding using the stages of change theory in interventions (P=.03). CONCLUSIONS: These findings indicate that the ECHO program's content aligned with its stated learning objectives; met its learning objectives for the 3 themes where significant improvements were measured; and met its intent to address multiple substances in case presentations and discussions. These results demonstrate that Project ECHO is a potential tool to educate multidisciplinary providers in a comprehensive approach to SUD care.

A Study on the Antibacterial, Antispasmodic, Antipyretic, and Anti-Inflammatory Activity of ZnO Nanoparticles Using Leaf Extract from Jasminum sambac (L. Aiton).

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using plants has grown in significance in recent years. ZnO NPs were synthesized in this work via a chemical precipitation method with Jasminum sambac (JS) leaf extract serving as a capping agent. These NPs were characterized using UV-vis spectroscopy, FT-IR, XRD, SEM, TEM, TGA, and DTA. The results from UV-vis and FT-IR confirmed the band gap energies (3.37 eV and 3.50 eV) and the presence of the following functional groups: CN, OH, C=O, and NH. A spherical structure and an average grain size of 26 nm were confirmed via XRD. The size and surface morphology of the ZnO NPs were confirmed through the use of SEM analysis. According to the TEM images, the ZnO NPs had an average mean size of 26 nm and were spherical in shape. The TGA curve indicated that the weight loss starts at 100 °C, rising to 900 °C, as a result of the evaporation of water molecules. An exothermic peak was seen during the DTA analysis at 480 °C. Effective antibacterial activity was found at 7.32 ± 0.44 mm in Gram-positive bacteria (S. aureus) and at 15.54 ± 0.031 mm in Gram-negative (E. coli) bacteria against the ZnO NPs. Antispasmodic activity: the 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by (78.19%), acetylcholine (at a concentration of 1 µM) by (67.57%), and nicotine (at a concentration of 2 µg/mL) by (84.35%). The antipyretic activity was identified using the specific Shodhan vidhi method, and their anti-inflammatory properties were effectively evaluated with a denaturation test. A 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by 78.19%, acetylcholine (at a concentration of 1 µM) by 67.57%, and nicotine (at a concentration of 2 µg/mL) by 84.35%. These results underscore the sample solution's potential as an effective therapeutic agent, showcasing its notable antispasmodic activity. Among the administered doses, the 150 mg/kg sample dose exhibited the most potent antipyretic effects. The anti-inflammatory activity of the synthesized NPs showed a remarkable inhibition percentage of (97.14 ± 0.005) at higher concentrations (250 µg/mL). Furthermore, a cytotoxic effect was noted when the biologically synthesized ZnO NPs were introduced to treated cells.

Dopamine and Norepinephrine Tissue Levels in the Developing Limbic Brain Are Impacted by the Human CHRNA6 3'-UTR Single-Nucleotide Polymorphism (rs2304297) in Rats.

We previously demonstrated that a genetic single-nucleotide polymorphism (SNP, rs2304297) in the 3' untranslated region (UTR) of the human CHRNA6 gene has sex- and genotype-dependent effects on nicotine-induced locomotion, anxiety, and nicotine + cue-induced reinstatement in adolescent rats. This study aims to investigate how the CHRNA6 3'-UTR SNP influences dopaminergic and noradrenergic tissue levels in brain reward regions during baseline and after the reinstatement of drug-seeking behavior. Naïve adolescent and adult rats, along with those undergoing nicotine + cue reinstatement and carrying the CHRNA6 3'-UTR SNP, were assessed for dopamine (DA), norepinephrine (NE), and metabolites in reward pathway regions. The results reveal age-, sex-, and genotype-dependent baseline DA, NE, and DA turnover levels. Post-reinstatement, male α6GG rats show suppressed DA levels in the Nucleus Accumbens (NAc) Shell compared to the baseline, while nicotine+ cue-induced reinstatement behavior correlates with neurotransmitter levels in specific brain regions. This study emphasizes the role of CHRNA6 3'-UTR SNP in the developmental maturation of the dopaminergic and noradrenergic system in the adolescent rat brain, with tissue levels acting as predictors of nicotine + cue-induced reinstatement.

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Photochemical Degradation of the New Nicotine Pesticide Acetamiprid in Water.

Acetamiprid is a novel nicotinic pesticide widely used in modern agriculture because of its low toxicity and specific biological target properties. The objective of this study was to understand the photolysis pattern of acetamiprid in the water column and elucidate its degradation products and mechanism. It was observed that acetamiprid exhibited different photolysis rates under different light source conditions in pure water, with ultraviolet > fluorescence > sunlight; furthermore, its photolysis half-life ranged from 17.3 to 28.6 h. In addition, alkaline conditions (pH 9.0) accelerated its photolysis rate, which increased with pH. Using gas chromatography-mass spectrometry, five direct photolysis products generated during the exposure of acetamiprid to pure water were successfully separated and identified. The molecular structure of acetamiprid was further analyzed using density functional theory, and the active photodegradation sites of acetamiprid were predicted. The mechanism of the photolytic transformation of acetamiprid in water was mainly related to hydroxyl substitution and oxidation. Based on these findings, a comprehensive transformation pathway for acetamiprid was proposed.

Neuronal nicotinic acetylcholine receptor of the central amygdala modulates the ethanol-induced tolerance to anxiolysis and withdrawal-induced anxiety in male rats.

The nicotine acetylcholinergic receptor (nAchR) in the central nucleus of the amygdala (CeA) is known to modulate anxiety traits as well as ethanol-induced behavioral effects. Therefore, the present study investigated the role of CeA nAChR in the tolerance to ethanol anxiolysis and withdrawal-induced anxiety-related effects in rats on elevated plus maze (EPM). To develop ethanol dependence, rats were given free access to an ethanol-containing liquid diet for 10 days. To assess the development of tolerance, separate groups of rats were challenged with ethanol (2 g/kg, i.p.) on days 1, 3, 5, 7 and 10 during the period of ethanol exposure, followed by an EPM assessment. Moreover, expression of ethanol withdrawal was induced after switching ethanol-dependent rats to a liquid diet on day 11, and withdrawal-induced anxiety-like behavior was noted at different post-withdrawal time points using the EPM test. The ethanol-dependent rats were pretreated with intra-CeA (i.CeA) (bilateral) injections of nicotine (0.25 µg/rat) or mecamylamine (MEC) (5 ng/rat) before the challenge dose of ethanol on subthreshold tolerance on the 5th day or on peak tolerance day, that is, 7th or 10th, and before assessment of postwithdrawal anxiety on the 11th day on EPM. Bilateral i.CeA preadministration of nicotine before the challenge dose of ethanol on days 5, 7 and 10 exhibited enhanced tolerance, while injection of MEC, completely mitigated the tolerance to the ethanol-induced antianxiety effect. On the other hand, ethanol-withdrawn rats pretreated i.CeA with nicotine exacerbated while pretreatment with MEC, alleviated the ethanol withdrawal-induced anxiety on all time points. Thus, the present investigation indicates that stimulation of nAChR in CeA negatively modulates the ethanol-induced chronic behavioral effects on anxiety in rats. It is proposed that nAChR antagonists might be useful in the treatment of alcohol use disorder and ethanol withdrawal-related anxiety-like behavior.

Extraction and Purification of Nicotine from Tobacco Rhizomes by Supercritical CO2.

Currently, in the ongoing development of the tobacco industry, a large amount of tobacco rhizomes is discarded as waste. These wastes are usually disposed of through incineration or burial. However, these tobacco wastes still have some economic value. High-purity nicotine has a promising market outlook as the primary raw material for electronic cigarette liquid. Nicotine is not only found in tobacco leaves but also in the rhizomes of tobacco plants. This study presents a method for treating tobacco waste and extracting high-purity nicotine from it. After mixing the raw material powder and entrainer in specific ratios, as much of the nicotine in tobacco roots can be extracted as possible using supercritical carbon dioxide extraction. The effects of temperature, the ratio of the entrainer, and the volume fraction of ethanol in the entrainer on the nicotine yield in supercritical fluid extraction (SFE) at 25 MPa for 120 min were discussed. By using 90% ethanol (a raw material mass-to-volume ratio of 1:5) as the entrainer, we obtained the highest nicotine yield of 0.49% at 65 °C. Meanwhile, the purity of the crude extract was 61.71%, and after purification, it increased to 97.57%. In this way, we can not only obtain nicotine with market value but also further reduce the harm to the environment caused by tobacco waste disposal.

Structural Impact Assessment of Cytochrome P450 2A13 Polymorphisms Using Molecular Dynamics Simulations.

One of the members of CYP, a monooxygenase, CYP2A13 is involved in the metabolism of nicotine, coumarin, and tobacco-specific nitrosamine. Genetic polymorphisms have been identified in CYP2A13, with reported loss or reduction in enzymatic activity in CYP2A13 allelic variants. This study aimed to unravel the mechanism underlying the diminished enzymatic activity of CYP2A13 variants by investigating their three-dimensional structures through molecular dynamics (MD) simulations. For each variant, MD simulations of 1000 ns were performed, and the obtained results were compared with those of the wild type. The findings indicated alterations in the interaction with heme in CYP2A13.4, .6, .8, and .9. In the case of CYP2A13.5, observable effects on the helix structure related to the interaction with the redox partner were identified. These conformational changes were sufficient to cause a decrease in enzyme activity in the variants. Our findings provide valuable insights into the molecular mechanisms associated with the diminished activity in the CYP2A13 polymorphisms.

Changes in distinct brain systems identified with fMRI during smoking cessation treatment with varenicline: a review.

BACKGROUND: Varenicline is considered one of the most effective treatment options for smoking cessation. Nonetheless, it is only modestly effective. A deeper comprehension of the effects of varenicline by means of the in-depth review of relevant fMRI studies may assist in paving the development of more targeted and effective treatments. METHODOLOGY: A search of PubMed and Google Scholar databases was conducted with the keywords "functional magnetic resonance imaging" or "fMRI", and "varenicline". All peer-reviewed articles regarding the assessment of smokers with fMRI while undergoing treatment with varenicline and meeting the predefined criteria were included. RESULTS: Several studies utilizing different methodologies and targeting different aspects of brain function were identified. During nicotine withdrawal, decreased mesocorticolimbic activity and increased amygdala activity, as well as elevated amygdala-insula and insula-default-mode-network functional connectivity are alleviated by varenicline under specific testing conditions. However, other nicotine withdrawal-induced changes, including the decreased reward responsivity of the ventral striatum, the bilateral dorsal striatum and the anterior cingulate cortex are not influenced by varenicline suggesting a task-dependent divergence in neurocircuitry activation. Under satiety, varenicline treatment is associated with diminished cue-induced activation of the ventral striatum and medial orbitofrontal cortex concomitant with reduced cravings; during the resting state, varenicline induces activation of the lateral orbitofrontal cortex and suppression of the right amygdala. CONCLUSIONS: The current review provides important clues with regard to the neurobiological mechanism of action of varenicline and highlights promising research opportunities regarding the development of more selective and effective treatments and predictive biomarkers for treatment efficacy.

The many enigmas of nicotine.

This review discusses the diverse effects of nicotine on the various nicotinic acetylcholine receptors of the central and peripheral nervous system and how those effects may promote the usage and addiction to tobacco products.