Cigarette smoking and alcohol drinking and esophageal cancer risk in Taiwan Residents women

AIM:To investigate the etiology of esophageal cancer among Taiwan Residents women.METHODS:This is a multi-center,hospital-based,case-control study.Case patients consisted of women who were newly diagnosed and pathology-proven to have esophageal squamous cell carcinoma(ESCC) from three large medical centers(one from Northern and two from Southern Taiwan,respectively)between August 2000 and December 2008.Each ESCC patient was matched with 4 healthy women based on age(within 3 years)and hospital of origin,from the Department of Preventive Medicine in each hospital.A total of 51 case patients and 204 controls,all women,were studied.RESULTS:Frequencies of smokers and drinkers among ESCC patients were 19.6%and 21.6%,respectively,which were significantly higher than smokers(4.4%) and drinkers(4.4%)among controls(OR=4.07,95%CI:1.36-12.16,P=0.01;OR=3.55,95%CI:1.03-12.27,P=0.04).Women who drank an amount of alcohol more than 158 g per week had a 20.58-fold greater risk(95%CI:1.72-245.62,P=0.02)of ESCC than those who never drank alcohol after adjusting for other covariates,although the sample size was small.CONCLUSION:Cigarette smoking and alcohol drinking,especially heavy drinking,are the major risks for developing ESCC in Taiwan Residents women.

The Impact of Cigarette Smoking on Metabolic Syndrome

Metabolic syndrome （MetS） is a constellation of interconnected cardiometabolic disorders, including obesity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is a precursor to type 2 diabetes mellitus （T2DM） and cardiovascular disease （CVD）; it increases the risk of T2DM by 3-4 times[11 and the risk of CVD by 1.4-fold[21, and is more prevalent in obese individuals. As the obesity rates increase, the prevalence of MetS in the population is increased. In 2006, the global prevalence of MetS in adults was estimated to be 20%-25%TM, and in China, in 2007-2008, using the criteria of the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults （JCDCG）, it reached 21.9% among the adult population aged 〉20 vears old[4].

Exercise Training Attenuated Chronic Cigarette Smoking-induced Up-regulation of FIZZ1/RELMα in Lung of Rats

FIZZ/RELM is a new gene family named ＂found in inflammatory zone＂ （FIZZ） or ＂re- sistin-like molecule＂ （RELM）. FIZZ1/RELMct is specifically expressed in lung tissue and associated with pulmonary inflammation. Chronic cigarette smoking up-regulates FIZZ 1/RELMct expression in rat lung tissues, the mechanism of which is related to cigarette smoking-induced airway hyperresponsive- ness. To investigate the effect of exercise training on chronic cigarette smoking-induced airway hyper- responsiveness and up-regulation of FIZZ1/RELMct, rat chronic cigarette smoking model was estab- lished. The rats were treated with regular exercise training and their airway responsiveness was meas- ured. Hematoxylin and eosin （HE） staining, immunohistochemistry and in situ hybridization of lung tissues were performed to detect the expression of FIZZ1/RELMct. Results revealed that proper exercise training decreased airway hyperresponsiveness and pulmonary inflammation in rat chronic cigarette smoking model. Cigarette smoking increased the mRNA and protein levels of FIZZ1/RELMct, which were reversed by the proper exercise. It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMct induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness.

Protection motivation theory and cigarette smoking among vocational high school students in China:a cusp catastrophe modeling analysis

Background:Tobacco use is one of the greatest public health problems worldwide and the hazards of cigarette smoking to public health call for better recognition of cigarette smoking behaviors to guide evidence-based policy.Protection motivation theory(PMT)provides a conceptual framework to investigate tobacco use.Evidence from diverse sources implies that the dynamics of smoking behavior may be quantum in nature,consisting of an intuition and an analytical process,challenging the traditional linear continuous analytical approach.In this study,we used cusp catastrophe,a nonlinear analytical approach to test the dual-process hypothesis of cigarette smoking.Methods:Data were collected from a random sample of vocational high school students in China(n=528).The multivariate stochastic cusp modeling was used and executed with the Cusp Package in R.The PMT-based Threat Appraisal and Coping Appraisal were used as the two control variables and the frequency of cigarette smoking(daily,weekly,occasional,and never)in the past month was used as the outcome variable.Results:Consistent with PMT,the Threat Appraisal(asymmetry,α1=0.1987,p<0.001)and Coping Appraisal(bifurcation,β2=0.1760,p<0.05)significantly predicted the smoking behavior after controlling for covariates.Furthermore,the cusp model performed better than the alternative linear and logistic regression models with regard to higher R2(0.82 for cusp,but 0.21 for linear and 0.25 for logistic)and smaller AIC and BIC.Conclusion:Study findings support the conclusion that cigarette smoking in adolescents is a quantum process and PMT is relevant to guide studies to understand smoking behavior for smoking prevention and cessation.

THE STUDY ON RELATIONSHIP BETWEEN CIGARETTE SMOKING AND THE p53 PROTEIN AND P21 PROTEIN EXPRESSION IN NON-SMALL LUNG CANCER

This paper discusses the relationship between cigarette smoking and the p53 protein and P21 protein expression by the immunohistochemical analysis in 93 cases with lung cancer in which squamous cell carcinoma accounted for 45 cases, adenocarcinoma 48 cases. The results showed that positive proportion of p53 protein expression was 74.20% (28 of 37 squamous cell carcinoma, 21 of 30 adenocarcinomas) in cigarette smoking group with lung cancers, and 38.46% (3 of 8 squamous cell carcinoma, 7 of 18 adenocarcinomas) in nonsmoking group with lung cancers. The difference was statistically significant. Odds ratio was 4.14 and confidence limits for OR was 1.42-12.52. A dose-related presents in the p53 protein expression for the smoking amount and smoking years. The positive proportion of P21 protein expression was 79.31% (21 of 28 squamous cell carcinoma, 25 of 30 adenocarcinomas) in cigarette smoking group with lung cancers, and 82.75% (10 of 11 squamous, 14 of 18 adenocarcinomas) in nonsmoking group with lung cancers, the difference was not statistically significant. But their positive proportion of P21 protein expression were very high in both groups. It was indicated that no relationship between cigarette smoking and the P21 protein expression. We suggest that the p53 gene could be a common target of tobacco-associated carcinogenesis in lung cancer.

Cigarette Smoking is Associated with Decreased Sperm Density

Objectives To study the association between cigarette smoking and sperm density in men of reproductive age. Methods We enrolled 224 male employees of a modern petrochemical plant in Nanjing, China. These men had no prior history of infertility or other reproductive diseases. Epidemiologic data, including information on smoking and other occupational and lifestyle exposures were obtained by a questionnaire interview. Semen specimens were collected from each participant and analyzed according to the WHO guidelines. Regression analyses were performed to estimate the effect of smoking on sperm density. Results Approximately 67% of the subjects had ever smoked cigarettes. Different measurements of smoking behavior were each associated with decreased sperm density. There was a significant dose-response trend between the tertites of total smoking amount in pack-years and sperm density. As compared to men who never smoked, current smokers had a significant reduction in sperm density (-13.3×106/ml; 95% CI, - 24. 1, -2. 5) ,while ex-smokers had only a small decrement in sperm density ( -2. 6×106/ml; 95%CI, -18. 7,13. 5). Starting smoking at less than 20 years of age was associated with significant reduction in sperm density (- 14.8×106/ml; 95% CI, - 27. 4, -2. 2). Starting smoking at 20 years or older was associated with a slightly smaller decrease ( -10.1×106/ml; 95% CI,-21.7,1.4). Conclusions Cigarette smoking is associated with decreased sperm density, showing an evident dose-response trend in this population.

Association of Cigarette Smoking with Hyperlipidemia in Male Individuals

Cigarette smoking is one of the major modifiable and environmental risk factors which can alter the lipid profile that leads to the progression of atherosclerosis and cardiovascular diseases. The aim of the current study is to explore the association of cigarette smoking with Hyperlipidemia in male individuals. A cross-sectional study was carried out from March 2017 to Au-gust 2018 in Xuzhou, Jiangsu, China. A total of 1561 male individuals were enrolled in the study with a mean age (years) of 55.33 ± 14.41. We collected data on demographic, anthropometric and lifestyle indices. Total cholesterol (TC), triglyceride (TGL), and high-density lipoprotein cholesterol (HDL-C) were determined by the enzymatic colorimetric method. The mean level of serum TC, TG, and HDL-C were 4.85 ± 0.91, 1.69 ± 1.45 and 1.27 ± 0.32 mmol/L respectively. We found that age, body mass index, pack-years, marital status, annual household income, alcohol consumption, smoking status, education level, and occupational status have significant association with Hyperlipidemia. Adjusted multiple logistic regressions showed that in old age, smoking behavior can significantly increase the risk of Hyperlipidemia. With an increase in pack-years, a significant increase is found only in TC while decreasing trend noticed in HDL-C level. Current smokers showed a significant increase in the risk of Hyperlipidemia compared to those who never smoked while smoking cessation decreases the risk of Hyperlipidemia. This study concluded that cigarette smoking along with increased age and pack-years can significantly increase the risk of Hyperlipidemia that further leads to heart diseases.

Passive cigarette smoking induces inflammatory injury in human arterial walls

Background Epidemiological studies have shown that both active and passive cigarette smoking increase the risk of atherosclerosis. But very little is known about the biological processes induced by passive cigarette smoking that contribute to atherosclerosis. We observe the expression of a few of biological and inflammatory markers in human arterial walls in vitro which were treated with the second-hand smoke solution （sidestream whole, SSW）, and discuss the possible mechanism of inflammatory injury induced by second-hand smoke. Methods The biological markers （platelet endothelial cell adhesion molecule-I, PECAM-1; a-smooth muscle actin, a-SMA; collagen IV, Col IV） and inflammatory markers （vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1 ; interleukin-8, IL-8） of human aortat wall were tested by immunofluorescence staining. The levels of MCP-1 and IL-8 mRNA expression were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results No distinct difference was observed between SSW and the control group on the expression of biological markers as assessed by the light microscope. But the inflammatory markers VCAM-1, MCP-1 and IL-8 on the subendothelial layer and smooth muscle cell layers, which are near the endothelium of arterial wall, were strongly stained in the SSW group compared with the control group. Their fluorescence intensities in the 1：40 SSW group （VCAM-1： 0.35±0.04, MCP-1： 0.34±0.05, IL-8： 0.37±0.05） and the 1：20 SSW group （VCAM-I： 0.40±0.04, MCP-1： 0.52±0.09, IL-8： 0.51±0.07） were significantly stronger than the control group （VCAM-1： 0.12±0.04, MCP-1： 0.06±0.02, IL-8： 0.24±0.03） by semi-quantitative analysis of immunofluorescence （P 〈0.001 vs control）. MCP-1 mRNA expression in the 1：40 SSW （0.15±0.04） and the 1：20 SSW （0.19±0.06） group was significantly higher than in the control group （0.09±0.03） （P 〈0.05, P 〈0.01 vs control）; IL-8 mRNA expression in the 1：40 SSW （0.64±0.12） and 1：20 SSW （0.72±0.13） groups was also significantly higher than that in the control group （0.49±0.13） （P 〈0.05, P 〈0.01 vs control） by RT-PCR. Conclusions It is implied that a second-hand smoke solution induces the inflammatory reaction of the arterial wall by release of inflammatory factors even though there is no distinct structural change on the arterial walls under light microscope, indicating that passive cigarette smoking is related to inflammatory injury in human arterial wall and could be closely related to the early inflammatory stage of atherosclerosis.

Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease

Background： Many studies have suggested that cigarette smoking and polymorphisms of resi stin and glutathione peroxidase-1 （GPx-1） genes are closely correlated with tile pathogenesis of nonalcoholic lhtty liver disease （NAFLD）. However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, exalnined the distribution of polymorphisms in GPx-l and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. Methods： Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter- 420C/G and GPx- 1 gene Pro 198Leu were analyzed by polymorphism-polymerase chain reaction （PCR） in DNA extracted from peripheral blood leukocytes. Interactions between tile two mutants and the gene-environment interaction with cigarette smoking were also analyzed. Results： Genotype frequencies of 420C/G （GG） and Pro198Leu （LL） were significantly higher in NAFLD cases （49.56% and 50.11%, respectively） compared with healthy controls （23.67% and 24.22%, respectively） （P = 0.0069： P= 0.0072）. Moreover, the risk of NAFLD with 420C/G （GGJ was significantly higher than in controls （odds ratio [OR] =3.1685, 95% confidence interval （（7） 1.9366-5.2073）. Individuals carrying Pro198Leu （LL） had a high risk of NAFLD （OR - 3.1424, 95% C/= 1.7951 5.2367）. Combined analysis of the polymorphisms showed that the -420C/G （GG）/Pro198Leu （LL） genotype was significantly more common in the NAFLD group than in the control group （39.44% vs. 12.78%, respectively, P 0.0054）, while individuals with -420C/G （GG）/Pro198Leu （LL） had a high risk of NAFLD （OR = 5.（1357, 95% CI= 3.1852 7.8106）. Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in tile control group （OR = 1.8990, P = 0.0083 in the smoking index （SI） _〈400 subgroup： OR = 5.0937, P = 0.0051 in the SI 〉400 subgroup）, and statistical analysis suggested a positive interaction between cigarette smoking and 420C/G （GG） （y = 5.6018 in tile SI≤400 subgroup; γ - 4.4770 in the SI 〉400 subgroup） and Pro198Leu （LL） （y = 5.7715 in the SI ≤400 subgroup： γ 4.5985 in the SI 〉400 subgroup） in increasing the risk of NAFLD. Conclusion： NAFLD risk factors include -420C/G （GG）, Pro198Leu （LL） and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.

Unveiling the dynamic role of innate and adaptive immune cells in COPD pathogenesis induced by cigarette smoke

Chronic obstructive pulmonary disease(COPD)is a multifaceted syndrome characterized by a dysregulated inflammatory cascade within the respiratory system,primarily triggered by exposure to harmful particles and gases,notably from cigarette smoke.This inflammatory response is orchestrated by innate immune cells like macrophages and epithelial cells,which recognize danger signals released from damaged cells.Prolonged inflammation prompts an adaptive immune reaction mediated by dendritic cells,culminating in the formation of lymphoid follicles and involving a complex interplay of T and B cells,as well as cytotoxic activity.Additionally,both viral and bacterial infections exacerbate COPD by further igniting inflammatory pathways,perpetuating the chronic inflammatory state.This comprehensive review encapsulates the intricate interplay between innate and adaptive immunity in COPD,with a particular focus on the role of cigarette smoke in its pathogenesis and potential therapeutic targets.

Parkinson's Disease and Smoking: An Integral Part of PD's Etiological Study

To explore the association of Parkinson抯 disease (PD) with cigarette smoking. Methods One hundred of fourteen PD patients were compared with 205 control subjects who were matched by gender, race and residency. A previously validated questionnaire including smoking, alcohol/tea consumption as well as some other environmental exposure data was administered. Results With never-smokers as the reference category, we observed reduced risk for PD among ever smokers (OR=0.49, 95% CI: 0.30 to 0.79) current smokers (OR=0.44, 95% CI: 0.23 to 0.86) and ex-smokers (OR=0.54, 95% CI: 0.30 to 0.96). When ever smokers were stratified by years of smoking, there was an inverse correlation between those whose smoking history was longer than 20 years (OR=0.40 95% CI: 0.21 to 0.81) and an even mild protective correlation between those who smoked less than 20 years (OR=0.57, 95% CI: 0.33 to 0.99). Those who had quitted smoking for more than 20 years were less likely to have the disease than never smokers, and those who had quitted for less than 20 years were least likely to have PD, while those who were current smokers were still least likely to have the disease. We found significant inverse gradient with pack-day smoking (trend P<0.05), and the inverse correlation between cigarette smoking and PD was not confounded by alcohol/tea consumption and other confounding bias. Conclusions The inverse correlation between Parkinson抯 disease risk and smoking as well as the trend of gradient dose response is again observed in our study. More future researches are needed to confirm these correlations and to explore further biochemical evidence.

Effects of chronic smoking on color vision in young subjects

AIM: To evaluate the effects of chronic smoking on color vision in young subjects.METHODS: This study included 91 smokers and 88non-smokers(a total of 179 volunteers) without any ophthalmologic and systemical disorders. The subjects were between 18-40 years of age with a best corrected visual acuity(BCVA) of 20/20, normal anterior and posterior segment examinations and normal intraocular pressure. The color vision of the subjects were evaluated with Farnsworth-Munsell 100 Hue test(FMHT). The total error scores and axis calculation were performed for each subject and the results correlated.RESULTS: Mean age and the standard deviation was28±5y in the smokers group, and 26.7±5.5y in the control group(P =0.101). Sex distribution was similar in the two groups(P =0.365). There was no significant correlation between age and FMHT total error scores(P =0.069).Median of FMHT total error scores of smokers and non-smokers were 65 and 50.50, respectively. FMHT total error scores was found significantly higher in smokers than non-smokers(P =0.004). There was no statisticaly significant difference between smoker and non-smoker groups with respect to axis ratio calculation(P =0.611).There was no significant correlation with FMHT total error scores with neither smoking duration nor number of cigarettes smoked per day(P =0.405, P =0.454,respectively).· CONCLUSION: This study suggested that chronic smoking affects the color vision of young smokers but this may not be sector selective.

The Effects of Smoking Ban in Closed Public Spaces on the Status of Smoking

Smoking Ban in Closed Public Spaces went into effect in Turkey on May 19, 2008. We aimed at investigating the status of smoking among hospital staff following the ban. The study was conducted with the staff of the university hospital other than physicians. A questionnaire form investigating the status of smoking among hospital staff, the effects of the ban on smoking in closed public spaces, their thoughts that might affect their decisions to quit smoking or to decrease the number of cigarettes smoked was implemented. Prior to each interview, the participants read and signed the informed consent form. Mean and percentage distributions were used in the evaluation of the data. Of 60 individuals, 68% were female, mean age was 40.72 ~ 7.25. Of them 50% were active smokers. After the ban 55% of the smokers declared a decrease in the number of cigarettes they smoked, 37% said no change. The ban had no effect on smokers＇ decisions about quitting smoking. Social leadership and role model characteristics of healthcare professionals should be taken into consideration and the habit of smoking should be handled as a disease, and medical approaches including behavioral therapy should be given the necessary significance they deserve.

Membrane and Subcellular Muscle Injury Are Induced by Single or Multiple Exposure to Cigarette Smoke

Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD). Diaphragm injury is observed in patients with COPD. However, the potential role of smoking in triggering or perpetuating muscle injury is unknown. The present study was aimed at evaluating the potential role of commercial tobacco smoke as a direct cause of skeletal muscle injury in experimental conditions. Seventy Wistar rats (170 - 250 g) were assigned to smoking (n = 49) or non-smoking (n = 21) groups. The smoking groups were submitted to a single or multiple (i.e., five or thirty) daily sessions of cigarette smoking in an inhalatory chamber (time length: 2 h each session). The level of exposure was constant and assessed by CO concentrations (50 ppm) and serum cotinine analysis. Animals submitted to a single smoke exposure and the corresponding controls were euthanized in groups at 0 h, 2 h, 4 h, 24 h or 48 h after completing the exposure. Animals submitted to multiple exposures were euthanized at 0 h after smoking. Samples from vastus lateralis muscle were obtained and processed for assessing cell injury and selected protein expression. Monoclonal anti-albumin antibodies were used to identify muscle fibers with sarcolemmal (membrane) injury. Subcellular muscle injury was assessed using transmission electron microscopy (EM). MyoD, myogenin and α-tubulin were immunodetected using western blot techniques. Exposure to cigarette smoke associated with significant membrane damage (mean relative difference (MRD) with controls: +181%, p = 0.004) and sarcomere disruptions (MRD: +226%, p = 0.001). Expression of MyoD and myogenin (normalized to α-tubulin) were significantly increased at 4 h and remained increased at 48 h post-exposure. We conclude that not only a single but also consecutive exposure to tobacco smoke have acute deleterious effects on peripheral muscle structure. A rapid induction of subrogate markers of skeletal muscle stress and repair processes associates to sarcolemmal and sarcomere damage.

Dysregulation of gastric H,K-ATPase by cigarette smoke extract

AIM:To test whether the expression and activity of H,K-ATPase in parietal cells would be affected by cigarette smoke extract.METHODS: Extracts of cigarette smoke were administered into mice by gastric gavage (5 mg/kg body weight/day) for 3 d or in drinking water for 7 or 14 d. For the latter, each day a mouse consumed 5 mL water containing extracts of two cigarettes, on average. Control littermate mice received only vehicle. To compare the amount of H,K-ATPase in control and smoke-treated mice, the stomach was processed for Western blotting and immunohistochemical analysis using monoclonal antibodies specific for α- or β-subunits of H,K-ATPase. The p-nitrophenylphospatase activity assay was used as a measurement for K-dependent H,K-ATPase activity.RESULTS: Probed transblots showed an increase in the amount of H,K-ATPase in smoke-treated mice which was confirmed by immunohistochemistry and was found to be due to increased amounts of protein per parietal cell rather than an increased parietal cell number. The increase in the amount of H,K-ATPase was associated with an enhancement of its enzymatic activity. K-dependent activity in control and smoke-treated mice was significantly different (respectively, 0.12 μmol/mg vs 0.27 μmol/mg per minute, P<0.05).CONCLUSION: Administration of cigarette smoke extract is associated with an increase in the amount and activity of H,K-ATPase and hence, smokers are susceptible to development of peptic ulcer.

Simple Fluorimetric Determination of Benzo[a]pyrene in Cigarette Smoke without Preseparation Procedure

Constant-energy synchronous fluorimetry was used for the identification of benzo[a]pyrene in mixtures with a detection limit of 1.34 nmol/L. The recovery experiments in cigarette smoke samples have also obtained satisfactory results of 99.1-103.5% for benzo[a]pyrene.

Damaging Effect of Cigarette Smoke Extract on PrimaryCultured Human Umbilical Vein Endothelial Cells and Its Mechanism

Objective To investigate the cellular effects of cigarette smoke extract (CSE) on primarily cultured human umbilical vein endothelial cells (HUVEC). Methods The effects of CSE (5%-20%) and nicotine (10-4 mol/L) on HUVEC viability, proliferation, angiogenesis and apoptosis were observed. Results CSE decreased HUVEC survival rate and angiogenesis after 24 h as well as its proliferation after 48 h in a dose-dependent manner. Moreover, CSE induced apoptosis of HUVEC as indicated in condensation of nuclear chromatin and the presence of hypodiploid DNA. HUVEC incubated with CSE for 24 h gave a significant decrease in the expression of Bcl-2 as well as the decline in the Bcl-2/Bax ratio accompanied with the loss of mitochondrial membrane potential and excess cytosolic calcium. Our study also observed that p53 protein level decreased, rather than increased in cells treated with CSE. Nicotine had no discernible inhibitory effects on the above indices of HUVEC. Conclusion Exposure to CSE other than nicotine causes inhibition of viability, proliferation and differentiation of HUVEC. CSE-induced HUVEC injury is mediated in part through accelerated apoptosis but independent of p53 pathway. It appears that mitochondria have played a key role in the apoptosis of HUVEC induced by CSE.

Prophylactic Anti-inflammation Inhibits Cigarette Smoke-induced Emphysema in Guinea Pigs

In this study, the effect of prophylactic anti inflammation on the development of smoke induced emphysema was investigated. Young male guinea pigs aged 1.5 - 2 months (weighing 198.3±26.9 g) were randomly divided into 4 groups: group A (cigarette smoke exposure only), group B (cigarette smoke exposure plus pentoxifylline rich (PTX, 10 mg/d) forage feeding), group C (cigarette smoke exposure plus intermittent cortical steroid injection (Triamcinolone acetonide, 3 mg, im, every three weeks) and control group (group D: animals with sham smoke exposure, raised under the same conditions). Animals in group A, B and C were exposed to smoke of cigarettes for 1 to 1.5 h twice a day, 5 days a week. All animals were killed at the 16th week and followed by morphometrical analysis of the midsagittal sectioned lung slices. Smoke exposure of 16 weeks resulted in visible emphysematous development in Group A but not in Group B and C. It was evidenced by the indicator of air space size, mean linear intercept (L m): 120.6±16.0 μm in Group A; 89.8±9.2 μm in Group B and 102.4±17.7 μm in Group C. The average L m in either group B or group C was shorter than that in Group A (ANOVA and Newman Keuls test, F=8.80, P =0.0002) but comparable to that (94.8±13.2 μm) in group D ( P >0.05). It is concluded that long term prophylactic anti inflammation inhibits pulmonary emphysema induced by cigarette smoking in the guinea pigs.

Cigarette smoke‑induced malignant transformation via STAT3 signalling in pulmonary epithelial cells in a lung‑on‑a‑chip model

Background Chronic obstructive pulmonary disease(COPD)is a severe public health problem.Cigarette smoke(CS)is a risk factor for COPD and lung cancer.The underlying molecular mechanisms of CS-induced malignant transformation of bronchial epithelial cells remain unclear.In this study,we describe a lung-on-a-chip to explore the possible mechanistic link between cigarette smoke extract(CSE)-associated COPD and lung cancer.Methods An in vitro lung-on-a-chip model was used to simulate pulmonary epithelial cells and vascular endothelial cells with CSE.The levels of IL-6 and TNF-αwere tested as indicators of inflammation using an enzyme-linked immune sorbent assay.Apical junction complex mRNA expression was detected with qRT-PCR as the index of epithelial-to-mesenchymal transition(EMT).The effects of CSE on the phosphorylation of signal transduction and transcriptional activator 3(STAT3)were detected by Western blotting.Flow cytometry was performed to investigate the effects of this proto-oncogene on cell cycle distribution.Results Inflammation caused by CSE was achieved in a lung-on-a-chip model with a mimetic movement.CSE exposure induced the degradation of intercellular connections and triggered the EMT process.CSE exposure also activated the phosphorylation of proto-oncogene STAT3,while these effects were inhibited with HJC0152.Conclusions CSE exposure in the lung-on-a-chip model caused activation of STAT3 in epithelial cells and endothelial cells.HJC0152,an inhibitor of activated STAT3,could be a potential treatment for CS-associated COPD and lung cancer.

Effects of Puerarin on Pulmonary Vascular Remodeling and Protein Kinase C-α in Chronic Cigarette Smoke Exposure Smoke-exposed Rats

In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-α （PKC-α） in chronic exposure smoke rats, 54 male Wistar rats were randomly divided into 7 groups： control group （C group）, smoke exposure groups （S4w group, S8w group）, puerarin groups （P4w group, P8w group）, propylene glycol control groups （PC4w group, PC8w group）. Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puerarin. To evaluate vascular remodeling, alpha-smooth muscle actin （α-SM-actin） staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries （CMA/IAPA） which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell （PASMC） apoptosis was detected by in situ end labeling technique （TUNEL）, and proliferation by proliferating cell nuclear antigen （PCNA） staining. Reverse transcription-polymerase chain reaction （RT-PCR）, immunofluorescence staining and Western blot analysis were done to detect the PKC-α mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and α-SM-actin expression were increased greatly, PASMC apoptosis was increased and proliferation was markedly increased; Apoptosis indices （AI） and proliferation indices （PI） were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-α mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the percentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-α mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an effect of the imbalance of PASMC proliferation and apoptosis. Puerarin appears to be able to reduce cell proliferation and vascular remodeling possibly through PKC signaling transduction pathway.