Inhibition of the NF-κB Signaling Pathway Improves Cigarette Mainstream Smoke-Induced Lung Injury and Gut Microbiota Disturbance

Currently,cigarette smoke(CS)remains a major contributor to disease morbidity and mortality.CS can be divided into cigarette mainstream smoke(CMS)and side-stream smoke,depending on where it is produced by burning tobacco^([1]).CMS is inhaled by smokers from the filter end during cigarette combustion and is strongly associated with the development of several diseases^([2-4]).

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.

Research on the Relationship Between Average Cigarette Price per Box and Government Procurement in City A Based on a Regression Model

This study aims to analyze and predict the relationship between the average price per box in the cigarette market of City A and government procurement,providing a scientific basis and support for decision-making.By reviewing relevant theories and literature,qualitative prediction methods,regression prediction models,and other related theories were explored.Through the analysis of annual cigarette sales data and government procurement data in City A,a comprehensive understanding of the development of the tobacco industry and the economic trends of tobacco companies in the county was obtained.By predicting and analyzing the average price per box of cigarette sales across different years,corresponding prediction results were derived and compared with actual sales data.The prediction results indicate that the correlation coefficient between the average price per box of cigarette sales and government procurement is 0.982,implying that government procurement accounts for 96.4%of the changes in the average price per box of cigarettes.These findings offer an in-depth exploration of the relationship between the average price per box of cigarettes in City A and government procurement,providing a scientific foundation for corporate decision-making and market operations.

Analysis of four tobacco-specific nitrosamines in mainstream cigarette smoke of Virginia cigarettes by LC-MS/MS

An improved method was developed for the determination of the four major tobacco-specific nitrosamines（TSNAs） in mainstream cigarette smoke. The new method offers decreased sample preparation and analysis time as compared to traditional methods. This method uses isotope dilution liquid chromatography coupled with a tandem mass spectrometer with electrospray ionization and is significantly more sensitive than traditional methods. It also shows no evidence of artifactual formation of TSNAs. Sample concentrations were determined for four TSNAs in mainstream smoke using two isotopically labeled TSNAs analogues as internal standards. Mainstream smoke was collected on an industry standard 44-ram Cambridge filter pad, extracted with 0.1 mol/L ammonium acetate, purified by solid-phase extraction, and analyzed without further sample cleanup. The analytical column is a 3.9 mm×150 mm Waters Symmertry Shield RP18 column and volume fraction of the mobile phase is 50% methanol, 50% water containing 0.1% acetic acid. The results show that the linear range is 0.5-100.0 mg/L except for N-nitrosoanabasine （NAB） from 0.25 to 50.0 mg/L. The limits of detection are 0.1 mg/L for N-nitrosonornicotine （NNN）, 0.08 mg/L for 4-（methylnitrosamino）-1- （3-py-ridyl）-1-butanone （NNK）, 0.05 mg/L for N-nitrosoanatabine （NAT） and 0.06 mg/L for NAB. The recoveries of the four TSNAs are from 90.2% to 105.7%.

Study on Deliver Analysis Method of Heavy Metal Elements during Cigarette Smoking

[Objective] The deliver amount and deliver rate of heavy metal elements during smoking were studied, which could provide a reference for reducing the damage of cigarette products. [Method] Two pretreatment methodsof microwave di- gestion and acid extraction were used to process the ash content, the total particu- late matter of mainstream smoke （TPM） and cigarette filter. Detection results of heavy metal elements were compared by the two methods. [Result] The microwave digestion method was better than acid solution extraction method on analysis of TPM, but presented disadvantages on analysis of ash and filter. Meanwhile, the migration amount and rate were studied and resultsshowed that most heavy metal elements were escaped along with sidestream smoke between 66.89% and 95.48%, and almost all Hg escaped through sidestream smoke. Other heavy metal elements, except Hg, were separately found in ash, TPM and filter. Cr, Ni, As and Se were mostly residual in ash, followed by TPM, and filter had the least, while Cd and Pb were just in the reverse order. Normally, 5% or less heavy metal elements were transferred to TPM, only a small part of which could reach 5%-10%. [Conclusion] Most of the heavy metal elements are taken by sidestream smoke, ash and filter, while the migration amounts to mainstream smoke are extremely low.

Bilateral Pneumonia and Pleural Effusions Subsequent to Electronic Cigarette Use

Electronic nicotine delivery systems also known as electronic cigarettes (or e-cigarettes) are marketed by their manufactures as a safer alternative to tobacco cigarettes because of potentially reduced delivery of toxins. However, the scientific evidence and the long-term health effects of e-cigarettes are limited. We describe a case of a 43-year-old man who had been smoking electronic cigarettes excessively for three days and presented with acute dyspnea, increased work of breathing and tachycardia. Subsequent chest x-ray revealed bilateral pleural effusions. In addition, the patient had a new oxygen requirement and was thus admitted with a diagnosis of pneumonia and bilateral pleural effusions. The case and the potential harmful effects of electronic cigarettes are discussed herein.

Toxicology of Commonly Found Ingredients in E-Cigarettes: A Brief Review

Electronic cigarettes (EC) have gained popularity among smokers due to their taste, smell, appearance, and easy availability compared to traditional cigarettes, as well as the perception that they are safer than traditional cigarettes. These devices result in aerosols containing nicotine, propylene glycol, glycerin, ethylene glycol, vitamin E, and chemical flavors inhaled into the lungs. Other components found in these vapors include heavy metals such as nickel, chromium, lead, manganese, and tin. In addition, some ingredients volatilization leads to toxic aldehydes formation such as formaldehyde, acetaldehyde, and acrolein. Smoking cigarettes is addictive and has been associated with many health issues such as heart disease, lung cancer, etc. Rising awareness of these dangers moves more people towards these electronic delivery systems, reducing the health effects of cigarettes. The toxicity of EC’s ingredients is well studied when ingested;however, their toxicity through inhalation remains unclear. Consequently, the use of ECs has become a significant concern worldwide and raises whether it is indeed safe to use. This paper will serve as a literature review paper to discuss the toxicity of commonly found ingredients in ECs and their associated health issues. Our conclusion emphasizes that even though smoking EC is less risker than smoking traditional cigarettes, it is still not safe due to the potentially harmful effect these E-cig’s ingredients have on the human’s health. In addition, E-cigarette’s aerosol could also contain toxic compounds such as formaldehyde, acetaldehyde, and acrolein due to glycerin’s thermo-degradation.

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.

Berberine Attenuates Cigarette Smoke Extract-induced Airway Inflammation in Mice:Involvement of TGF-β1/Smads Signaling Pathway

Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease(COPD),its underlying mechanisms were not clear until now.We aimed to establish an experiment mouse model for COPD and to investigate the effects of berberine on airway inflammation and its possible mechanism in COPD model mice induced by cigarette smoke extract(CSE).Twenty SPF C57BL/6 mice were randomly divided into PBS control group,COPD model group,low-dose berberine group and high-dose berberine group,5 mice in each group.The neutrophils and macrophages were examined by Wright's staining.The levels of inflammatory cytokines TNF-α and IL-6 in bronchoalveolar lavage fluid(BALF)were detennined by enzyme-linked immunosorbent assay.The expression levels of TGF-β1,Smad2 and Smad3 mRNA and proteins in lung tissues were respectively detected by quantitative real-time polymerase chain reaction and Western blotting.It was found that CSE increased the number of inflammation cells in BALF,elevated lung inflammation scores,and enhanced the TGF-β1/Smads signaling activity in mice.High-dose berberine restrained the alterations in the COPD mice induced by CSE.It was concluded that high-dose berberine ameliorated CSE-induced airway inflammation in COPD mice.TGF-β1/Smads signaling pathway might be involved in the mechanism.These findings suggested a therapeutic potential of high-dose berberine on the CSE-induced airway inflammation.

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.

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.

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.

Comparison of volatile and semivolatile compounds from commercial cigarette by supercritical fluid extraction and simultaneous distillation extraction

Supercritical carbon dioxide fluid extraction (SFE) was studied as a rapid method for extraction of volatile and semivolatile compounds of Chinese commercial cigarettes. The method was compared with simultaneous distillation and extraction (SDE). Temperature and pressure for the SFE were optimized. The extracts obtained by the two methods showed different characters in composition and represented differently the flavor characteristics of tobacco; compared to SDE, SFE can extract compounds within a shorter time and avoid the thermal degradation and solvent contamination of samples. The extracts by the two extraction methods are complementary for investigating the flavor characteristic of tobacco products.

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.

Research on cigarette during smoking based on reverse engineering and numerical simulation

The three-dimensional(3 D)model of cigarette was accurately constructed through reverse engineering as the research object of numerical simulation.The combustion process of cigarette was studied with computational fluid dynamics(CFD).Standard Laminar models with species transport approach were applied,and numerical simulation of the cigarette was analyzed with semi-implicit method for pressure–velocity coupling.The results showed that the model could predict velocity of cigarette smoke,the distributions of temperature and pressure at different times.In order to verify the correctness of model,it was found that the relationship between the velocity of smoke and pressure according to Darcy’s law on z position(x=4 mm,y=0,0 mm≤z≤50.61 mm).

Effects of Cigarette Auxiliary Material Parameters on Release Amounts of Tar, CO and Free Radicals in Cigarette Mainstream Smoke

[Objective] This study aimed to investigate the effects of cigarette auxiliary material parameters on release amounts of tar, CO and free radicals in cigarette mainstream smoke. [Method] The effects of cigarette paper air-permeability, cigarette paper gram weight, filter rod pressure drop and filter tip ventilating strength parameters on the release amounts of tar, CO and free radicals in cigarette mainstream smoke were investigated by single factor experiment and orthogonal experiment. [Result] The cigarette paper air-permeability, filter rod pressure drop and filter tip ventilating strength showed significantly negative correlation with the release amounts of tar, CO and free radicals in cigarette mainstream smoke, to be specific, the cigarette paper air-permeability showed the greatest effect on the release amounts of tar and CO, filter tip ventilating strength showed the greatest effect on the release amounts of gaseous-phase free radicals and particulate-phase free radicals, while cigarette paper gram weight showed relatively slight effect on the release amounts of tar, CO and free radicals. Within the orthogonal experimental range, the optimal program is identified as cigarette paper airpermeability of 70 CU, filter rod pressure drop of 4500 Pa/unit, and filter tip ventilating strength of 60 CU. Compared to the results without optimization, the release amounts of tar, CO and free radicals after optimization were all reduced. [Conclusion] This study laid the foundation for the research of cigarette tar reduction and harm reduction.

Chitosan Removes Toxic Heavy Metal Ions from Cigarette Mainstream Smoke

This study investigated the removal of heavy metal ions from cigarette mainstream smoke using chitosan. Chitosan of various deacetylation degrees and molecular weights were manually added to cigarette filters in different dosages. The mainstream smoke particulate matter was collected by a Cambridge filter pad, digested by a microwave digestor, and then analyzed for contents of heavy metal ions, including As（Ill/V）, Pb（II）, Cd（II）, Cr（III/VI） and Ni（II）, by graphite furnace atomic absorption spectrometry （GFAAS）. The results showed that chitosan had a removal effect on Pb（II）, Cd（II）, Cr（III/VI） and Ni（II）. Of these, the percent re- moval of Ni（II） was elevated with an increasing dosage of chitosan. Chitosan of a high deace tylation degree exhibited good binding performance toward Cd（II）, Cr（III/VI） and Ni（II）, though with poor efficiency for Pb（II）. Except As（III/V）, all the tested metal ions showed similar tendencies in the growing contents with an increasing chitosan molecular weight. Nonetheless, the percent removal of Cr（III/VI） peaked with a chitosan molecular weight of 200 kDa, followed by a dramatic decrease with an increasing chitosan mo- lecular weight. Generally, chitosan had different removal effects on four out of five tested metal ions, and the percent removal of Cd（II）, Pb（II）, Cr（III/VI） and Ni（II） was approximately 55%, 45%, 50%, and 16%, respectively. In a word, chitosan used in cigarette filter can remove toxic heavy metal ions in the mainstream smoke, improve cigarette safety, and reduce the harm to smokers.

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.

Vascular and Morphogenetic Abnormalities Associated with Exposure of Cigarette Smoke Condensate during Chicken and Murine Embryogenesis

Objective Embryonic movements （EM） and angiogenesis pathways are evolutionarily conserved mechanisms which are essential for proper embryonic development. Deviations in these processes by exposure to cigarette smoke condensate （CSC） may cause vascular and morphogenetic disorders. Methods Using chicken and mouse embryos, we have demonstrated the in vivo effects of CSC on EM, vascular development, and organogenesis. Results Examination of the CSC exposed chicken embryos revealed a significant reduction in EM, stunted growth, deviated pattern of blood vessels, hemorrhages, and localized necrosis. Likewise, mouse embryos that were exposed to CSC at E8.5 and E9.5 died between E11.5 and E12.5, respectively. These mouse embryos showed defects in morphogenesis and remodeling of the embryonic vasculature, while littermate controls showed normal development. Conclusion Cigarette smoking during pregnancy is fatal for growing embryos. CSC may induce the remodeling of embryonic vasculature, leading to various pathologies.