Resting-state electroencephalography theta predicts neurofeedback treatment 4-month follow-up response in nicotine addiction

Background The high rate of long-term relapse is a major cause of smoking cessation failure.Recently,neurofeedback training has been widely used in the treatment of nicotine addiction;however,approximately 30%of subjects fail to benefit from this intervention.Our previous randomised clinical trial(RCT)examined cognition-guided neurofeedback and demonstrated a significant decrease in daily cigarette consumption at the 4-month follow-up.However,significant individual differences were observed in the 4-month follow-up effects of decreased cigarette consumption.Therefore,it is critical to identify who will benefit from pre-neurofeedback.Aims We examined whether the resting-state electroencephalography(EEG)characteristics from pre-neurofeedback predicted the 4-month follow-up effects and explored the possible mechanisms.Methods This was a double-blind RCT.A total of 60 participants with nicotine dependence were randomly assigned to either the real-feedback or yoked-feedback group.They underwent 6 min closed-eye resting EEG recordings both before and after two neurofeedback sessions.A follow-up assessment was conducted after 4 months.Results The frontal resting-state theta power spectral density(PSD)was significantly altered in the real-feedback group after two neurofeedback visits.Higher theta PSD in the real-feedback group before neurofeedback was the only predictor of decreased cigarette consumption at the 4-month follow-up.Further reliability analysis revealed a significant positive correlation between theta PSD pre-neurofeedback and post-neurofeedback.A leave-one-out cross-validated linear regression of the theta PSD pre-neurofeedback demonstrated a significant correlation between the predicted and observed reductions in cigarette consumption at the 4-month follow-up.Finally,source analysis revealed that the brain mechanisms of the theta PSD predictor were located in the orbital frontal cortex.Conclusions Our study demonstrated changes in the resting-state theta PSD following neurofeedback training.Moreover,the resting-state theta PSD may serve as a prognostic marker of neurofeedback effects.A higher resting-state theta PSD predicts a better long-term response to neurofeedback treatment,which may facilitate the selection of individualised interventions.

Comparison of protective effects of electroacupuncture and moxibustion at Zusanli(ST 36)on perinatal nicotine exposure-induced lung phenotype in rat offspring

Objective:To compare the effects of electroacupuncture(EA)and moxibustion at Zusanli(ST 36)on the lung phenotype of rat offspring exposed to nicotine during the perinatal period.Methods:Pregnant Sprague-Dawley rats were randomly divided into 4 groups:the control group(saline only),the model group(nicotine only),the EA group(nicotine+EA at ST 36 acupoints bilaterally),and the moxibustion group(nicotine+moxibustion at ST 36 acupoints bilaterally).n=6 rats per group.On postnatal day 21,the body weight,lung weight,and pulmonary function were determined and lung morphometry was performed.Peroxisome proliferator-activated receptor gamma andβ-catenin levels in the lung tissue of offspring were also determined.Results:Perinatal nicotine exposure(PNE)results in decreased body and lung weights of offspring rats,abnormal lung tissue morphology,and significantly altered pulmonary function,showing an increase in total airway resistance and a decrease in tidal volume,minute ventilation,total airway compliance,and peak expiratory flow.Bilateral EA at ST 36 acupoints could block all of these perinatal nicotine-induced effects.Although moxibustion also had protective effects in nicotine-induced offspring lungs,some of these effects did not reach statistical significance,e.g.,protection against the upregulation ofβ-catenin,the downregulation of PPARγsignaling,and the increase in peak expiratory flow.Conclusion:Maternal EA at ST 36 blocked the PNE-induced changes in key developmental signaling pathways,prevented the PNE-induced changes in lung morphology,and protected pulmonary function.Moxibustion at ST 36 showed similar but weaker protective effects against the PNE-induced changes in the exposed offspring.It is important to note that the mechanism underlying the protective effects of moxibustion at ST 36 may be different from those of EA at ST 36,and further research is needed to understand these differences.

Variability and Correlation in Biomarkers of Exposure from Two Randomized Controlled Studies of JUUL Electronic Nicotine Delivery Systems

The data included in this analysis were from two clinical studies (Study A and Study B), which evaluated JUUL electronic nicotine delivery systems (ENDS) against combustible cigarettes. In both studies, biomarkers of exposure including nicotine equivalents, NNAL, 3-HPMA, MHBMA, S-PMA and COHb were measured. Coefficients of variation (CV) of the biomarkers were calculated and compared. Pearson correlation analysis was used to examine the correlation between the biomarkers. Seven out of the nine biomarkers of exposure in Study A were highly variable (CV > 30%). Higher variability was observed in NNAL, MHBMA and S-PMA than in other biomarkers. After adult cigarette smokers switched from combustible cigarettes to JUUL ENDS, the correlation between nicotine equivalents and other biomarkers became weaker. A similar trend was observed between NNAL and other biomarkers. In Study B, the participants in the 5% ENDS group had higher nicotine equivalent levels than those in the 3% ENDS group. The higher nicotine levels did not result in a substantial increase in the levels of other biomarkers (except 1-OHP). The correlations between nicotine equivalents and 3-HPMA, MHBMA, S-PMA, COHb, HMPMA, and 1-OHP were weak in both the 5% and 3% ENDS groups.

EGCG抑制Nicotine诱导肺腺癌H1299细胞JAK2/STAT3 mRNA的表达研究

为探索EGCG对Nicotine诱导肺癌细胞增殖的抑制作用,本研究通过MTT实验筛选出EGCG、Nicotine对肺腺癌细胞H1299的最佳作用浓度,利用实时荧光定量PCR技术检测EGCG、Nicotine对H1299细胞中Bax、Bcl-2、Jak2和Stat3基因mRNA相对表达量的变化。实验结果表明,EGCG对H1299细胞的半抑制浓度IC50值约为32μmol·L-1(24 h)、15μmol·L-1(48 h);1μmol·L-1的Nicotine对H1299细胞促增殖作用明显;以15μmol·L-1的EGCG预处理H1299细胞24 h可显著下调1μmol·L-1 Nicotine的促增殖作用(P<0.05)。1μmol·L-1的Nicotine处理H1299细胞可明显降低JAK2/STAT3信号通路中Bax基因mRNA的表达,增加Bcl-2、Jak2、Stat3基因的mRNA表达;15μmol·L-1 EGCG预处理H1299细胞可反向调控Nicotine诱导所致JAK2/STAT3信号通路中Jak2、Stat3和Bax、Bcl-2基因表达量的变化,结果具有显著性差异(P<0.05)。由此可知,EGCG对Nicotine诱导的肺腺癌H1299细胞增殖及JAK2/STAT3信号通路中促增殖基因mRNA的表达起抑制作用。

Distribution of ^3H—nicotine in Rat Tissues Under the Influence of Simulated Microgravity

Rat tail suspension offers a useful model to reproduce physiologic responses to weightlessness.The present study was conducted in the head-down-tilt(HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30°for two weeks on a 12/12 light/dark cycle. During this period,body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected IV withe a solution contaming 4 microuries of micotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain,blood,trachea,salivary gland,lung,heart,esophagus,spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determinded and ealeulated as percent of total injected radioactivity. Final body weights of suspended ammals were significantly (P < 0.0 5) lower than those of eontrols(309±21 vs 350±11g). 3HNicotine waw retained in greatest amounts by the kindneys, followed inorder by salivary glands, spleen, and gastrointestinal tissues. compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues:esphyagus (25 %), aorta (25%). fundus (25%), trachea (22%), adrenals (18%), spleen (17 %), and pancreas (12 %). The decreased retention of mcotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differnces in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.

Regular nicotine intake increased tooth movement velocity,osteoclastogenesis and orthodontically induced dental root resorptions in a rat model

Orthodontic forces have been reported to significantly increase nicotine-induced periodontal bone loss. At present, however, it is unknown, which further （side） effects can be expected during orthodontic treatment at a nicotine exposure corresponding to that of an average European smoker. 63 male Fischer344 rats were randomized in three consecutive experiments of 21 animals each （A/B/C） to 3 experimental groups （7 rats, 112/3）. （A） cone-beam-computed tomography （CBCT）; （B） histology/serology; （C） reverse- transcription quantitative real-time polymerase chain reaction （RT-qPCR）/cotinine serology--（1） control; （2） orthodontic tooth movement （OTM） of the first and second upper left molar （NiTi closed coil spring, 0.25 N）; （3） OTM with 1.89 mg-kg- 1 per day s.c. of L（- ）-nicotine. After 14 days of OTM, serum cotinine and IL-6 concentration as well as orthodontically induced inflammatory root resorption （OIIRR）, osteoclast activity （histology）, orthodontic tooth movement velocity （CBCT, within 14 and 28 days of OTM） and relative gene expression of known inflammatory and osteoclast markers were quantified in the dental-periodontal tissue （RT-qPCR）. Animals exposed to nicotine showed significantly heightened serum cotinine and IL-6 levels corresponding to those of regular European smokers. Both the extent of root resorption, osteoclast activity, orthodontic tooth movement and gene expression of inflammatory and osteoclast markers were significantly increased compared to controls with and without OTM under the influence of nicotine. We conclude that apart from increased periodontal bone loss, a progression of dental root resorption and accelerated orthodontic tooth movement are to be anticipated during orthodontic therapy, if nicotine consumption is present. Thus patients should be informed about these risks and the necessity of nicotine abstinence during treatment.

Proteomics Identification of Differentially Expressed Proteins Relevant for Nicotine Synthesis in Flue-Cured Tobacco Roots Before and After Decapitation

Nicotine is a secondary substance synthesized in tobacco roots. In flue-cured tobacco planting, tobacco decapitation is an effective practice to promote nicotine biosynthesis by regulation of the redistribution of total nitrogen amounts. However, proteins relevant to nicotine synthesis in tobacco roots has not been identified and characterized yet. It is important to explore the regulation of nicotine biosynthesis in tobacco roots. To identify the proteins relevant to nicotine synthesis, the protein patterns in roots of flue-cured tobacco （cv. K326） before and after decapitation were analyzed. In the present study, the protein patterns in roots of flue-cured tobacco were analyzed by two-dimensional electrophoresis （2-DE）, and the differentially-expressed spots were identified by matrix assisted laser desorption ionization time of flight mass spectrometry （MALDI-TOF-MS）. Paired comparison of 2-DE maps revealed 26 spots of differentially-expressed proteins in roots before and after decapitation. Furthermore, nine differentially-expressed spots were identified. There were four proteins which were enzymes possibly involved in nicotine biosynthesis. In addition, the roles of the four enzymes in nicotine biosynthesis were discussed in a putative network. Our results would contribute to the understanding of the regulation pathway of nicotine biosynthesis and further to the molecular manipulation on the nicotine contents in flue-cured tobacco.

Determination of Nicotine in Tobacco by Capillary Electrophoresis with Electrochemical Detection

A sensitive, simple and low-cost method based on capillary electrophoresis（CE） with electrochemical（EC） detection at a carbon fiber microdisk electrode（CFE） was developed for the determination of nicotine. Effects of de- tection potential, concentration and pH value of the phosphate buffer, and injection time as well as separation voltage were investigated. Under the optimized conditions： a detection potential of 1.20 V, 40 rnmol/L phosphate buffer（pH 2.0）, a sample injection time of 10 s at 10 kV and a separation voltage of 16 kV, the linear range obtained was from 5.0×10^-7 mol/L to 1.0×10^-4 mol/L with a correlation coefficient of 0.9989 and the limit of detection（LOD, S/N=3） obtained was 5.0×10^-8 mol/L. The method was also used to determine the nicotine in cigarettes. Nicotine amount ranged from 0.211 mg/g to 0.583 mg/g in the pipe tobacco of seven brands of cigarette and the amount in one ciga- rette varied from 0.136 mg/cigarette to 0.428 mg/cigarette.

Analysis of effect of nicotine on microbial community structure in sediment using PCR-DGGE fingerprinting

Solid or liquid waste containing a high concentration of nicotine can pollute sediment in rivers and lakes, and may destroy the ecological balance if it is directly discharged into the environment without any treatment. In this study, the polymerase chain reaction （PCR） and denaturing gradient gel electrophoresis （DGGE） method was used to analyze the variation of the microbial community structure in the control and nicotinecontaminated sediment samples with nicotine concentration and time of exposure. The results demonstrated that the growth of some bacterial species in the nicotine-contaminated sediment samples was inhibited during the exposure. Some bacteria decreased in species diversity and in quantity with the increase of nicotine concentration or time of exposure, while other bacteria were enriched under the effect of nicotine, and their DGGE bands changed from undertones to deep colors. The microbial community structure, however, showed a wide variation in the nicotine- contaminated sediment samples, especially in the sediment samples treated with high-concentration nicotine. The Jaccard index was only 35.1% between the initial sediment sample and the sediment sample with a nicotine concentration of 0.030 μg/g after 28 d of exposure. Diversity indices showed that the contaminated groups had a similar trend over time. The diversity indices of contaminated groups all decreased in the first 7 d after exposure, then increased until day 42. It has been found that nicotine decreased the diversity of the microbial community in the sediment.

Interaction of Nicotine and Bovine Serum Albumin

The binding of nicotine to bovine serum albumin (BSA) was studied by UV absorption. fluorescence, and H-1 NMR methods. With the addition of nicotine, the absorption band of BSA at about 210 nm decreased gradually, moved to longer wavelengths, and narrowed. BSA fluorescence of tryptophan residue was quenched by nicotine. The H-1 NMR peaks of nicotine moved to downfield by the addition of BSA. The experimental results showed that nicotine was capable of binding with BSA to form a 1:1 complex. BSA's high selectivity for nicotine binding suggests a unique role for this protein in the detoxification and/or transport of nicotine.

Aqueous extract of Ocimum gratissimum Linn and ascorbic acid ameliorate nicotine-induced cellular damage in murine peritoneal macrophage

Objective:To test the in vitro protective role of aqueous extract of Ocimum gratissimum Linn. (0.gratissimum) and ascorbic acid against nicotine-induced murine peritoneal macrophage. Methods:Peritoneal macrophages from mice were treated with nicotine(10 mM),nicotine (10 mM) with aqueous extract of O.gratissimum(1 to 25μg/mL),and nicotine(10 mM) with ascorbic acid(0.01 mM) for 12 h in cell culture media,while the control group was treated with culture media.Levels of free radical generation,lipid peroxidation,protein carbonyls,oxidized glutathione levels and DNA damage were observed and compared.Results:Phytochemical analysis of aqueous extract has shown high amount of phenolics and flavonoids compound present in it.The significantly increased free radical generation,lipid peroxidation,protein carbonyls,oxidized glutathione levels and DNA damage were observed in nicotine-treated group as compared to the control group:those were significantly reduced in aqueous extract of O. gratissimum and ascorbic acid supplemented groups.Moreover,significantly reduced antioxidant status in nicotine exposed murine peritoneal macrophage was effectively ameliorated by these two products.Among the different concentration of aqueous extract of O.gratissimum,the maximum protective effect was observed at 10μg/mL which does not produce any significant change in the normal cell.Conclusions:These findings suggest the potential use and beneficial role of O.gratissimum as a modulator of nicotine-induced cellular damage in murine peritoneal macrophage.

Role of sortase in Streptococcus mutans under the effect of nicotine

Streptococcus mutans is a common Gram-positive bacterium and plays a significant role in dental caries. Tobacco and/or nicotine have documented effects on S. mutans growth and colonization. Sortase A is used by many Gram-positive bacteria, including S. mutans, to facilitate the insertion of certain cell surface proteins, containing an LPXTGX motif such as antigen 1/11. This study examined the effect of nicotine on the function of sortase A to control the physiology and growth of S. mutans using wild-type S. mutans NG8, and its isogenic sortase-defective and -complemented strains. Briefly, the strains were treated with increasing amounts of nicotine in planktonic growth, biofilm metabolism, and sucrose-induced and saliva-induced antigen I/ll-dependent biofilm formation assays. The strains exhibited no significant differences with different concentrations of nicotine in planktonic growth assays. However, they had significantly increased （P~〈 0.05） biofilm metabolic activity （2- to 3-fold increase） as the concentration of nicotine increased. Furthermore, the sortase-defective strain was more sensitive metabolically to nicotine than the wild-type or sortase-complemented strains. All strains had significantly increased sucrose-induced biofilm formation （2- to 3-fold increase） as a result of increasing concentrations of nicotine. However, the sortase-defective strain was not able to make as much sucrose- and saliva-induced biofilm as the wild-type NG8 did with increasing nicotine concentrations. These results indicated that nicotine increased metabolic activity and sucrose-induced biofilm formation. The saliva-induced biofilm formation assay and qPCR data suggested that antigen 1/11 was upregulated with nicotine but biofilm was not able to be formed as much as wild-type NG8 without functional sortase A.

Nicotine protects against ulcerative colitis through regulating microRNA-124 and STAT3

OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.

Royal-jelly-based apitherapy can attenuate damages to male reproductive parameter following nicotine administration

Background:Nicotine administration can generate severe oxidative stress and lipid peroxidation.Royal jelly,with its antioxidant properties,acts as a scavenger of reactive oxygen species.This study describes the apitherapy effects of royal jelly on testicular damage following nicotine administration.Methods:Forty-eight male BALB/c mice were divided into 8 groups(n=6):saline,3 different doses of royal jelly(100,150,and 200 mg/kg body weight(BW)per day),nicotine(1.5 mg/kg),and 3 different groups of Nic+Roy(1.5 mg/kg of Nic+100,150,and 200 mg/kg BW per day of royal jelly).Nicotine was administrated intraperitoneally,and royal jelly was prescribed orally for 10 consecutive days.Serum levels of hormones(testosterone,luteinizing hormone,and follicle-stimulating hormone),total antioxidant capacity,nitric oxide(NO)status,malondialdehyde levels,sperm DNA fragmentation,sperm parameters,histopathological changes(H&E staining),immunohistochemistry against apoptotic proteins,and gene expression of Bcl-2,p53,Caspase-3,and Nrf2(real-time PCR)were assessed to evaluate the molecular and histological changes.Results:Hormone levels,sperm parameters,and status of antioxidants were decreased significantly(p<.05)following nicotine administration.Moreover,royal jelly treatment normalized hormonal and antioxidant characteristics,decreased apoptotic gene expression,increased Nfr2 gene expression,and restored histopathological alteration to the physiological status significantly(p<.05).Conclusion:Royal jelly upregulates the antioxidant status,inhibits the mitochondrialdependent apoptosis pathway,and increases the rate of proliferation.This therapeutic agent effectively protected the testis against nicotine-associated damages by antioxidant and anti-apoptotic effects.

EFFECT OF NICOTINE ON GROWTH AND EXPRESSION OF APOPTOSIS-RELATED GENES OF SMALL CELL LUNG CANCER (SCLC) CELL

Objective: To investigate the effect of nicotine on growth and apoptosis-related gene expression of human small lung cancer cell. Methods: NCI-H446 cell line was cultured in the presence of various concentrations (1～1000 ng/ml) of nicotine for 48 h. MTT was applied to evaluate the effect of nicotine on the growth of NCL-H446, small cell lung carcinoma (SCLC) cell line. After NCI-H446 cells were treated with 100 ng/ml for 48 h, human apoptosis-related gene cDNA expression profile microarray was used to detect the expression of 451 apoptosis-related genes in NCL-H446 cell line. Results: Significant proliferation promotion of nicotine (1～10 ng/ml) on NCI-LH446 cells were observed, but with decreased promotion effect with increased concentration of nicotine in culture. Growth inhibition rates for 1, 10, 100 and 1000 ng/m1 nicotine were -91.0%, -41.8%, -40.0% and 27.3% respectively. Microarray detection showed that significantly different expressions were found in71 of 451 apoptosis-related genes. 38 apoptosis-promoting gene and 30 apoptosis-inhibiting genes were up-regulated significantly (cy3/cy5>2.0), and only 3 showed significant down-regulation (cy3/cy5<0.5). Conclusion: Nicotine may promote growth of human SCLC cell, and regulate expression of apoptosis-related genes.

Tissue Distribution of [^3H]—Nicotine in Rats

This study was conducted in adult male Sprague -- Dawley rats to determine the distribution of [3H]-nicotine in blood and tissues following a bolus injection and a constant infusion of pure nicotine. The animals were anesthetized and injected with either 0.5 ml of nicotine solution or given a constant infusion of the same nicotine solution with identical amounts of radioactive nicotine. After sacrifice, blood, brain, trachea, salivery gland, esophagus, lung, heart, liver, fundus, antrum, spleen, pancreas, duodenum, jejunum, ileum, cecum, colon, kidneys, adrenal gland, and testes were collected and measured for radioactivity by scintillation counting. The distribution of nicotine was found highest in kidneys by both routes of administration. Higher accumulations were also found in salivary and adrenal glands, fundus, antrum, duodenum, jejunum, ileum and colon. Retention of nicotine via constant infusion was significantly higher in esophagus, fundus antrum, spleen, cecum, pancreas, testes, heart and muscle when compared with bolus injection. Six-fold increase in retention of blood levels of nicotine were found with constant infusion. (P<0.05). The results indicate that longer retention of nicotine occurs in blood and other specific tissues such as esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle via constant exposure. These data may implicate the predisposition of these tissues to pathologic manifestations.

A New Solid Sorbent System for Rapid Monitoring of Dehydrogenated Nicotine by Using Furfural-hydrochloric Acid

A new solid sorbent system is developed for the monitoring of dehydrogenated nicotine in the environment. The reagent system for the indicator tube consists of furfural-hydrochloric acid and phosphoric acid impregnated over a cellulose fibre （cotton） and a humectant calcium chloride. The reagent system has also been used for the preparation of reagent paper. After exposing the indicator tubes and test paper to dehydrogenated nicotine, for a constant time, the red-violet colour developed could be compared with those obtained from standards. Alternatively the coloured compound was extracted in water and the absorbance measured at 540 nm. The lower limit of detection is 0.03 μg/m^3 of nicotine for the reagent papers and indicator tubes. The lower limit of determination by spectrophotometric procedure is 0.001μg/m^3 of air. The preparation of indicator tubes, test papers and their applications for the detection and determination of nicotine in environmental tobacco smoke （ETS）, mainstream smoke （MS）, side stream smoke （SS） and biological samples is described in this paper.

Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart diseases.Among the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)activity.Nicotine,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in smokers.Aldosterone has various direct and indirect adverse cardiac effects.It is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 receptors.RAAS activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease development.METHODS We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and secretion.RESULTS In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R cells.Importantly,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 expression.CONCLUSION Adrenalβarrestin1 upregulation is one of the mechanisms by which tobacco compounds,like nicotine,promote cardio-toxic hyperaldosteronism in vitro and in vivo.Thus,adrenalβarrestin1 represents a novel therapeutic target for tobaccorelated heart disease prevention or mitigation.

Nicotine dependence in community-dwelling Chinese patients with schizophrenia

Background Smoking is a serious public health problem. Patients with schizophrenia usually have a higher prevalence of smoking than the general population, but the level of nicotine dependence is seldom studied, especially for patients living in the communities. Aims This study aimed to examine the level of nicotine dependence in Chinese community-dwelling patients with schizophrenia and explored its associated sociodemographic and clinical factors. Methods A total of 621 patients with schizophrenia treated in the primary care centres of Guangzhou were consecutively recruited. The level of nicotine dependence was assessed with the Chinese version of the Fagerstrom Test for Nicotine Dependence (FTND). Results 148 patients with schizophrenia were current smokers, and the mean (SD) score of FTND was 5.06 (2.55) for all the current smokers. The prevalence of nicotine addiction was 48.0%(95% Cl: 40.0%-56.0%) in patients with current smoking. The patients with schizophrenia had a significantly higher level of nicotine dependence than the Chinese general population. Multiple linear regression analysis revealed that male gender, being unemployed, having a family history of psychiatric disorders, having major medical conditions, first illness episode and less severe positive symptoms were significantly associated with a higher level of nicotine dependence. Conclusion Community-dwelling patients with schizophrenia in China, especially male patients, had a higher level of nicotine dependence than the general population.

Effects of Plant Secondary Metabolite Nicotine on Growth and Development of Frankliniella occidentalis

[Objective] The paper was to explore the chemical and molecular mechanisms of Frankliniella occidentalis, an important quarantine pest, against toxic substances. [Method] F. occidentalis were evaluated after continuous exposure to artificial diets containing nicotine from the 2^（nd） and the 3^（rd）instars for five generations, to determine the larval weight, pupal weight, and larval development duration. [Result] The larval development delayed and nicotine treatment significantly inhibited the weight gain of larvae. Compared to the control, the inhibition rates of larval weight and pupal weight were declined from 45% to 20% and from 25% to 4% respectively after feeding the 2^（nd）instars with nicotine for five generations.Nicotine delayed the larval growth and prolonged the generation duration of F. occidentalis. Nicotine showed more significant inhibitory effect on the lower instar larvae. With the increasing generations of secondary culture, the inhibitory effect of nicotine on larval weight and pupal weight was weakened. The developmental period of larvae was shortened, and the generation duration of F. occidentalis was shortened. [Conclusion] Nicotine affects the growth and development of F. occidentalis. F. occidentalis will gradually increase the adaptability to nicotine toxic substances after selfregulation for a few generations, and relieve the inhibitory effect of toxic substances.