Enhanced proliferation,invasion,and epithelial-mesenchymal transition of nicotine-promoted gastric cancer by periostin

AIM:To investigate the contribution of periostin in nicotine-promoted gastric cancer cell proliferation,survival,invasion,drug resistance,and epithelial-mesenchymal transition(EMT).METHODS:Gastric cancer cells were treated with nicotine and periostin protein expression was determined by immunoblotting.Periostin mRNA in gastric cancer cells was silenced using small interfering RNA(siRNA) techniques and periostin gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Gastric cancer cells transfected with control or periostin siRNA plasmid were compared in terms of cell proliferation using the methylthiazolyldiphenyl-tetrazolium bromide assay.Cell apoptosis was compared using annexin V-fluoresceine isothiocyanate and propidium iodine double staining.Tumor invasion was determined using the Boyden chamber invasion assay,and the EMT marker Snail expression was evaluated by immunoblotting.RESULTS:Nicotine upregulated periostin in gastric cancer cells through a COX-2 dependent pathway,which was blocked by the COX-2-specific inhibitor NS398.Periostin mRNA expression was decreased by ～87.2% by siRNA in gastric cancer cells,and stable periostinsilenced cells were obtained by G418 screening.Periostin-silenced gastric cancer cells exhibited reduced cell proliferation,elevated sensitivity to chemotherapy with 5-fluorouracil,and decreased cell invasion and Snail expression(P < 0.05).CONCLUSION:Periostin is a nicotine target gene in gastric cancer and plays a role in gastric cancer cell growth,invasion,drug resistance,and EMT facilitated by nicotine.

Ulcerative colitis in smokers,non-smokers and ex-smokers

Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit.

The genetics of nicotine dependence:Relationship to Pancreatic cancer

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.

Nicotine enhances migration and invasion of human esophageal squamous carcinoma cells which is inhibited by nimesulide

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.

A Method and a Surface Treatment Agent for Preventing Biofouling on Surfaces under Water

This paper presents an environm centally friendly method of inhibiting biofouling especially acorn barnacles on surfaces under water by using nicotine and selenium in the form of Se（0）, or such a substance which can be converted into them. Both of the substances are necessary to oxygen dependent organisms and will be used after conversion, but are toxic in high doses. By adding the substances to paint or other surface treatment agent which marine surfaces are treated with, organisms which are trying to establish themselves on the surfaces will be exposed to so high doses, the reactions which the settling is based on are disturbed. When the substances leak out into the seas, they will act as environment protectors, as they promote the development of organisms. Nicotine is transformed to nicotine amid which is the reactive part in NADH and one of the most important substances for the transference of hydrogen. Selenite is reduced to Se（0）, also involved in the transport chain of hydrogen to reducible oxygen. However, large quantities Se（0） may disturb the reactions of sulphur b＇./binding to it and impairing the formation of S-S-bridges.

Rapid Analysis of Nicotine in Mushrooms Using QuEChERS Extraction and Liquid Chromatography Tandem Mass Spectrometry

A procedure based on the QuEChERS methodology and Liquid Chromatography Tandem Mass Spectrometry （LC/MS/MS） is described, for the determination of Nicotine in mushrooms. QuEChERS methodology was used to determine Nicotine in dried and fresh mushrooms under basic conditions with primary secondary amino sorbent （PSA） clean up. The chromatography was performed on C 18 reversed phase column using a gradient of acetonitrile and ammonium formiate lmM pH = 3.4 as mobile phase at a flow rate of 0.3 mL min^-1. Nicotine was determined by using Nicotine-d3 as internal standard. Limit of quantification （LOQ） was 0.01 mg kg^-1 for both fresh and dried mushrooms. Calibration curve was linear over the concentration range of 0.01-2.3 mg mL^-1, with r2 〉 0.99. As for recoveries in dried mushrooms, spiking levels of 0.32 mg kg^-1 and 2 mg kg^-1 were considered whereas for the fresh mushrooms the recoveries were determined at 0.036 mg kg^-1 and 0.36 mg kg^-1. Satisfactory results were obtained for both matrices and the recoveries proved to range from 105% to 135%, with a standard deviation in the range 17-20. The method was applied to the analysis of Nicotine to assess the levels of nicotine in fresh and dried mushrooms.

Application of Y2O3 nanoparticles on reducing the content of tar in cigarettes

Y2O3 nanoparticles prepared in microemulsion, which were sprayed on cut tobacco, can reduce tar in cigarettes effectively. Reducing the content of tar in many brands of cigarettes was studied. The results show that Y2O3 nanoparticles can reduce tar in cigarettes effectively and have no influence on nicotine when the addition of Y2O3 nanoparticles is 0,5-1.2%. The smaller the grain size of Y2O3 nanoparticles is,the more effective tar reduction is. The principle of reducing tar in cigarettes is studied preliminarily.

Pharmacophore identification and validation for human nAChR α7 agonists

Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure ofα7 receptor has not been resolved, ligand-based drug design strategy was took in this work. A 3D QSAR pharmacophore model was built by HypoGen method, and its quality was evaluated by cost function. Furthermore, the pharmacophore model was validated with activity prediction of test set and was cross-validated based on Fisher＇s Randomization Method. By Enrichment Factor and AU-ROC analysis, the final pharmacophore, which is consisted of one HBA, two Hydrophobic and one PosIonizable, was selected and it fitted well with the docking result of α7 homology model and the ligand. The pharmacophore is expected for the following virtual screening and lead optimization of human nAChR α7 agonists, which is important for the development and discovery of novel antipsychotics.

L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway

In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a con- ditioned place preference （CPP） model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine （DHI3E）. Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly in- hibited nicotine-induced tyrosine hydroxylase （TH） expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the ~4,132 and c^7 nicotine acetylcholine receptor （nAChR） subunits induced by nico- tine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of to- bacco addiction.

Efficacy observation of depression in nicotine withdrawal treated with acupuncture

Objective To evaluate the clinical efficacy of acupuncture on depression in nicotine withdrawal. Methods Seventy-four cases of depression after nicotine withdrawal were selected as the subjects in observation and they were randomized into an acupuncture group （38 cases） and a western medicine group （36 cases）. In the acupuncture group, acupuncture was applied to Bǎihuì （百会 GV 20）, Yìntáng （印堂 EX-HN 3）, Sānyīnjiāo （三阴交 SP 6）, Tàichōng （太冲 LR 3）, Nèiguān （内关 PC 6） and Hégǔ （合谷 LI 4）. In the western medicine group, Fluoxetine was prescribed for oral administration, once per day. Hamilton Depression Scale （HAMD） was adopted for the evaluation before and after treatment separately and the changes in HAMD score as well as the efficacy were compared before and after treatment. Results HAMD score in either acupuncture group or western medicine group was improved significantly as compared with that before treatment （all P0.05）. The effective rate was 89.5% （34/38） in the acupuncture group and was 91.7% （33/36） in the western medicine group. There was no statistically significant difference between the two groups （all P0.05）. Conclusion The efficacy of acupuncture is similar to that of Fluoxetine in the treatment of depression in nicotine withdrawal.