Objective:To assess the hepatoprotective effects of flavone on nicotine-induced liver damage.Methods:Thirty-six rats were allocated into six groups:the control group,the nicotine group,the flavone alone groups(10 and ...Objective:To assess the hepatoprotective effects of flavone on nicotine-induced liver damage.Methods:Thirty-six rats were allocated into six groups:the control group,the nicotine group,the flavone alone groups(10 and 25 mg/kg/body weight),and the nicotine groups treated with flavone(10 and 25 mg/kg/body weight).Liver function,oxidative stress,Nrf2 pathway(HO-1,Nrf2,and Keap-1),and inflammatory markers(IL-17,TNF-α,and NF-κB)were evaluated.Additionally,a histopathological examination of liver tissues was performed.Results:Nicotine increased liver damage,inflammation,and oxidative stress.However,flavone suppressed nicotine-induced liver enzymes,oxidative stress,and inflammation,as manifested by increased antioxidants and decreased malondialdehyde level,liver enzymatic activities,and inflammatory markers.Flavone(10 and 25 mg/kg/body weight)also reduced the level of Keap-1 and increased HO-1 and Nrf2 levels in the liver of nicotine-exposed rats.Conclusions:Flavone has hepatoprotective properties and may slow the progression of liver injury by reducing oxidative stress,liver enzymes,and inflammation possibly via the Nrf2 pathway.展开更多
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 subje...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.展开更多
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 we...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.展开更多
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 ...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.展开更多
Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smo...Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.展开更多
[Objective] This study aimed to investigate the variation dynamics of total nitrogen and nicotine of burtey tobacco at various growing stages under different ni- trogen nutrition levels to provide reference for optimi...[Objective] This study aimed to investigate the variation dynamics of total nitrogen and nicotine of burtey tobacco at various growing stages under different ni- trogen nutrition levels to provide reference for optimizing fertilization technologies for burley tobacco. [Method] Fresh burley tobacco leaves were collected at various growing stages and dried to measure the content of total nitrogen, protein and nico- tine by using INTEGRAL automated chemical analyzer and analyze the correlation with nitrogen application level. [Result] Regardless of the nitrogen application level, the content of total nitrogen and protein showed a downward trend since root ex- tending stage and reached the minimum at mature stage; the content of nicotine showed an upward trend since early vigorous growing stage and increased to the maximum at mature stage; the content of total nitrogen, protein and nicotine all in- creased after air curing; the content of total nitrogen, protein and nicotine showed positive correlation with nitrogen application level, while total nitrogen/nicotine was negatively correlated. The results indicate that nitrogen level is closely related to the total nitrogen and nicotine of burley tobacco at growing period and post-air curing, rational application of nitrogen is an important measure to regulate the content of total nitrogen and nicotine of tobacco. [Conclusion] This study provides scientific ba- sis for rational fertilization of burley tobacco.展开更多
In this study, toxicity and control efficiency of three nicotine biopesticides against pomegranate aphids were determined via indoor toxicity test and field effica- cy test, aiming at screening the appropriate reagent...In this study, toxicity and control efficiency of three nicotine biopesticides against pomegranate aphids were determined via indoor toxicity test and field effica- cy test, aiming at screening the appropriate reagent for prevention and control of pomegranate aphids. The results of indoor toxicity test showed that LC^o of reagent 1, reagent 2 and reagent 3 reached 10 270, 12 810 and 13 040 mg/L, respectively. The results of field efficacy test showed that control efficacy of reagent 1, reagent 2 and reagent 3 reached 60.52%, 34.60% and 46.99%, respectively. Overall, reagent 1 （91% ultrafine powder of tobacco leaves, 3% silicone oil, 2% sasangua cake, 2% emulsifier, 2% ascorbic acid） exhibited the highest control efficiency against pomegranate aphids, which can be further popularized and utilized.展开更多
Nitrogen(N)supply is the most important factor affecting yield and quality of flue-cured tobacco(FCT).A field experiment and an in situ incubation method were used to study the effects of soil N mineralization in the ...Nitrogen(N)supply is the most important factor affecting yield and quality of flue-cured tobacco(FCT).A field experiment and an in situ incubation method were used to study the effects of soil N mineralization in the later stages of growth on yield and nicotine content of FCT in Fenggang and Jinsha,Guizhou Province.The yield and market value of FCT at Fenggang were much lower than those at Jinsha.However,the nicotine content of middle and upper leaves was much higher at Fenggang than at Jinsha when the same rate of fertilizer N was applied,which might be due to a higher N supply capacity at the Fenggang site.At later stages of growth(7-16 weeks after transplanting),the soil net N mineralization at Fenggang(56 kg N ha^(-1))was almost double that at Jinsha(30 kg N ha^(-1)).While soil NH_4-N and NO_3-N were almost exhausted by the plants or leached 5 weeks after transplanting,the N taken up at the later growth stages at Fenggang were mainly derived from soil N mineralization,which contributed to a high nicotine content in the upper leaves.The order of soil N contribution to N buildup in different leaves was:upper leaves>middle leaves>lower leaves.Thus,soil N mineralization at late growth stages was an important factor affecting N accumulation and therefore the nicotine content in the upper leaves.展开更多
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 emp...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.展开更多
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 a...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.展开更多
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 tot...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.展开更多
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. Effec...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.展开更多
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 treatmen...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.展开更多
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, mov...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.展开更多
AIM： To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine.METHODS： The esophageal squamo...AIM： To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine.METHODS： The esophageal squamous carcinoma cell line （TE-13） was treated with different concentrations of nicotine （100 μg/mL and 200 μg/mL） or 200 μg/mL nicotine plus 100 μmol/L nimesulide. Cell migration and invasion were measured using migration and invasion chamber systems. COX-2 expression was determined by Western blotting. Matrix metalloproteinase-2 （MMP-2） was analyzed by zymography and ELISA.RESULTS： Nicotine （100 μg/mL, 200 μg/mL） enhanced TE-13 cells migration and invasion, and increased the protein expression of COX-2 and the activity of MMP-2. Nicotine （200 μ/mL） stimulated TE-13 cells migration and invasion which were partly blocked by nimesulide. This was associated with decreased protein expression of COX-2 and decreased activity and protein expression of MMP-2. CONCLUSION： Nicotine enhances the migration and invasion of the esophageal squamous carcinoma cell line, and nimesulide partly blocks the effect ofnicotine-enhanced esophageal squamous carcinoma cell migration and invasion.展开更多
Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of ni...Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.展开更多
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 fro...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.展开更多
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 G...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.展开更多
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 inh...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.展开更多
文摘Objective:To assess the hepatoprotective effects of flavone on nicotine-induced liver damage.Methods:Thirty-six rats were allocated into six groups:the control group,the nicotine group,the flavone alone groups(10 and 25 mg/kg/body weight),and the nicotine groups treated with flavone(10 and 25 mg/kg/body weight).Liver function,oxidative stress,Nrf2 pathway(HO-1,Nrf2,and Keap-1),and inflammatory markers(IL-17,TNF-α,and NF-κB)were evaluated.Additionally,a histopathological examination of liver tissues was performed.Results:Nicotine increased liver damage,inflammation,and oxidative stress.However,flavone suppressed nicotine-induced liver enzymes,oxidative stress,and inflammation,as manifested by increased antioxidants and decreased malondialdehyde level,liver enzymatic activities,and inflammatory markers.Flavone(10 and 25 mg/kg/body weight)also reduced the level of Keap-1 and increased HO-1 and Nrf2 levels in the liver of nicotine-exposed rats.Conclusions:Flavone has hepatoprotective properties and may slow the progression of liver injury by reducing oxidative stress,liver enzymes,and inflammation possibly via the Nrf2 pathway.
基金This work was supported by the National Natural Science Foundation of China(32000750,32171080,71942003,and 32161143022)Grants for Scientific Research of BSKY(XJ201907)from Anhui Medical University+4 种基金Scientific Research Improvement Project of Anhui Medical University(2021xkjT018)Research Fund of Anhui Institute of Translational Medicine(2022zhyx-C02)Basic and Clinical Collaborative Research Improvement Project of Anhui Medical University(2020xkjT020)The Chinese National Programs for Brain Science and Brain-like Intelligence Technology(2021ZD0202101)CAS-VPST Silk Road Science Fund 2021(GLHZ202128).The numerical calculations in this paper have been done on the Medical Big Data Supercomputing Center System of Anhui Medical University and Bioinformatics Center of the University of Science and Technology of China.
文摘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.
基金supported by the National Natural Science Foundation of China(81674059 and 82174505)the Postgraduate Project of Beijing University of Chinese Medicine(2018-JYB22-XS116)+1 种基金the Tobacco-Related Disease Research Program(27IP-0050,and T29IR0737)the National Institutes of Health(HL151769)。
文摘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.
文摘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.
文摘Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.
基金Supported by Scientific and Research Project of Yunnan Tobacco Monopoly Bureau(Company)(07A06)~~
文摘[Objective] This study aimed to investigate the variation dynamics of total nitrogen and nicotine of burtey tobacco at various growing stages under different ni- trogen nutrition levels to provide reference for optimizing fertilization technologies for burley tobacco. [Method] Fresh burley tobacco leaves were collected at various growing stages and dried to measure the content of total nitrogen, protein and nico- tine by using INTEGRAL automated chemical analyzer and analyze the correlation with nitrogen application level. [Result] Regardless of the nitrogen application level, the content of total nitrogen and protein showed a downward trend since root ex- tending stage and reached the minimum at mature stage; the content of nicotine showed an upward trend since early vigorous growing stage and increased to the maximum at mature stage; the content of total nitrogen, protein and nicotine all in- creased after air curing; the content of total nitrogen, protein and nicotine showed positive correlation with nitrogen application level, while total nitrogen/nicotine was negatively correlated. The results indicate that nitrogen level is closely related to the total nitrogen and nicotine of burley tobacco at growing period and post-air curing, rational application of nitrogen is an important measure to regulate the content of total nitrogen and nicotine of tobacco. [Conclusion] This study provides scientific ba- sis for rational fertilization of burley tobacco.
文摘In this study, toxicity and control efficiency of three nicotine biopesticides against pomegranate aphids were determined via indoor toxicity test and field effica- cy test, aiming at screening the appropriate reagent for prevention and control of pomegranate aphids. The results of indoor toxicity test showed that LC^o of reagent 1, reagent 2 and reagent 3 reached 10 270, 12 810 and 13 040 mg/L, respectively. The results of field efficacy test showed that control efficacy of reagent 1, reagent 2 and reagent 3 reached 60.52%, 34.60% and 46.99%, respectively. Overall, reagent 1 （91% ultrafine powder of tobacco leaves, 3% silicone oil, 2% sasangua cake, 2% emulsifier, 2% ascorbic acid） exhibited the highest control efficiency against pomegranate aphids, which can be further popularized and utilized.
基金the Program for Changjiang Scholars and Innovation Research Team in University(No.IRT0511)
文摘Nitrogen(N)supply is the most important factor affecting yield and quality of flue-cured tobacco(FCT).A field experiment and an in situ incubation method were used to study the effects of soil N mineralization in the later stages of growth on yield and nicotine content of FCT in Fenggang and Jinsha,Guizhou Province.The yield and market value of FCT at Fenggang were much lower than those at Jinsha.However,the nicotine content of middle and upper leaves was much higher at Fenggang than at Jinsha when the same rate of fertilizer N was applied,which might be due to a higher N supply capacity at the Fenggang site.At later stages of growth(7-16 weeks after transplanting),the soil net N mineralization at Fenggang(56 kg N ha^(-1))was almost double that at Jinsha(30 kg N ha^(-1)).While soil NH_4-N and NO_3-N were almost exhausted by the plants or leached 5 weeks after transplanting,the N taken up at the later growth stages at Fenggang were mainly derived from soil N mineralization,which contributed to a high nicotine content in the upper leaves.The order of soil N contribution to N buildup in different leaves was:upper leaves>middle leaves>lower leaves.Thus,soil N mineralization at late growth stages was an important factor affecting N accumulation and therefore the nicotine content in the upper leaves.
文摘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.
基金the ReForM-A-research funding programme of the Faculty of Medicine(University of Regensburg)for their financial supportsupported by a ReForM-A grant from the ReForM research funding programme of the Faculty of Medicine of the University of Regensburg,Germany(Kirschneck 31 March 2015)the German Research Foundation(DFG)within the funding programme Open Access Publishing
文摘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.
基金Natural Science Foundation of Henan Province, China (0624050013)Inovation Foundation of Tobacco Profession Cultivation Key Laboratory,China (06 TCIF 006)
文摘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.
基金Supported by the National Natural Science Foundation of China(No.20875085)
文摘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.
基金supported by the National Natural Science Foundation of China(Grants No.51378175 and 41323001)the Special Fund of the State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering(Grant No.20145028212)
文摘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.
基金The National Natural Science Foundation of China Research Fund for Doctoral Program of Higher EducationProfessor Yuan Fa
文摘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.
基金Supported by Beijing Municipal Commission of Education, Science and Technology Program, No. KM200610025029Beijing Municipal Natural Science Foundation, No. 7072022
文摘AIM： To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine.METHODS： The esophageal squamous carcinoma cell line （TE-13） was treated with different concentrations of nicotine （100 μg/mL and 200 μg/mL） or 200 μg/mL nicotine plus 100 μmol/L nimesulide. Cell migration and invasion were measured using migration and invasion chamber systems. COX-2 expression was determined by Western blotting. Matrix metalloproteinase-2 （MMP-2） was analyzed by zymography and ELISA.RESULTS： Nicotine （100 μg/mL, 200 μg/mL） enhanced TE-13 cells migration and invasion, and increased the protein expression of COX-2 and the activity of MMP-2. Nicotine （200 μ/mL） stimulated TE-13 cells migration and invasion which were partly blocked by nimesulide. This was associated with decreased protein expression of COX-2 and decreased activity and protein expression of MMP-2. CONCLUSION： Nicotine enhances the migration and invasion of the esophageal squamous carcinoma cell line, and nimesulide partly blocks the effect ofnicotine-enhanced esophageal squamous carcinoma cell migration and invasion.
文摘Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.
文摘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.
文摘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.
基金supported by National Natural Science Foundation of China(81273606,81473259 to XL,81603116 to YS)National Science and Technology Major Project(2014ZX09J14103-08C to XL)
文摘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.
