Smoke Components Research Articles

Expression of transient receptor potential channels on peripheral blood leukocytes of patients with chronic obstructive pulmonary disease

It is known that transient receptor potential (TRP) channels are receptors for reactive oxygen species and components of cigarette smoke, and therefore may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).Aim: To investigate the expression of TRPV1, TRPV4, TRPM8 and TRPA1 channels on peripheral blood leukocytes of COPD patients and healthy individuals and to establish its possible relationships with inflammatory markers and lung function parameters.Methodology and Research Methods. 23 patients with COPD of varying severity and 17 individuals without bronchial obstruction were examined. The expression of TRP channels on monocytes, lymphocytes and granulocytes was determined by indirect flow cytometry. Plasma concentrations of cytokines were measured in a multiplex assay. Lung function parameters were assessed by spirometry.Results. Monocytes from COPD patients were characterized by increased expression of TRPV1 (98.8 (97.6; 99.6)% vs. 97.8 (96.3; 98.6)%, p = 0.03) and TRPA1 (99.2 (98.7; 99.8)% vs. 95.1 (94.2; 98.4)%, p = 0.003). In addition, COPD was associated with an increased ratio of TRPV4/TRPM8 expression on monocytes (0.66 (0.51, 0.90) vs. 0.27 (0.12, 0.70), p = 0.02) and granulocytes (0.97 (0.86; 0.92) vs. 0.29 (0.06; 0.89), p = 0.003). TRPV4 expression on monocytes showed correlation with CXCL10 level (ρ = 0.55, p = 0.01), and for TRPM8 inverse relationships were found with the concentrations of IL-6 (ρ = –0.56, p = 0.02) and IL-10 (ρ = –0.55, p = 0.02). We did not find any associations between the expression of TRP channels and lung function parameters.Conclusion. Increased expression of TRPV1 and TRPA1, as well as an increased TRPV4/TRPM8 ratio on peripheral blood monocytes of COPD patients may indicate the contribution of these receptors to the proinflammatory activation of the cells and indicate possible prospects of TRP channels pharmacological modulation for the purpose of the disease therapy.

Azadirachtin Attenuates Carcinogen Benzo(a) Pyrene-Induced DNA Damage, Cell Cycle Arrest, Apoptosis, Inflammatory, Metabolic, and Oxidative Stress in HepG2 Cells.

Azadirachtin (AZD), a limonoid from the versatile, tropical neem tree (Azadirachta indica), is well known for its many medicinal, and pharmacological effects. Its effects as an anti-oxidant, anti-inflammatory, and anti-cancer agent are well known. However, not many studies have explored the effects of AZD on toxicities induced by benzo(a)pyrene (B(a)P), a toxic component of cigarette smoke known to cause DNA damage and cell cycle arrest, leading to different kinds of cancer. In the present study, using HepG2 cells, we investigated the protective effects of Azadirachtin (AZD) against B(a)P-induced oxidative/nitrosative and metabolic stress and mitochondrial dysfunction. Treatment with 25 µM B(a)P for 24 h demonstrated an increased production of reactive oxygen species (ROS), followed by increased lipid peroxidation and DNA damage presumably, due to the increased metabolic activation of B(a)P by CYP 450 1A1/1A2 enzymes. We also observed intrinsic and extrinsic apoptosis, alterations in glutathione-dependent redox homeostasis, cell cycle arrest, and inflammation after B(a)P treatment. Cells treated with 25 µM AZD for 24 h showed decreased oxidative stress and apoptosis, partial protection from DNA damage, and an improvement in mitochondrial functions and bioenergetics. The improvement in antioxidant status, anti-inflammatory potential, and alterations in cell cycle regulatory markers qualify AZD as a potential therapeutic in combination with anti-cancer drugs.

Design, Synthesis, and Biological Studies of Flavone-Based Esters and Acids as Potential P450 2A6 Inhibitors.

As a potential means for smoking cessation and consequently prevention of smoking-related diseases and mortality, in this study, our goal was to investigate the inhibition of nicotine metabolism by P450 2A6. Smoking is the main cause of many diseases and disabilities and harms nearly every organ of the body. As reported by the Centers for Disease Control and Prevention (CDC), more than 16 million Americans are living with diseases caused by smoking. On average, the life expectancy of a smoker is about 10 years less than a nonsmoker. Smoking cessation can substantially reduce the incidence of smoking-related diseases, including cancer. At least, 70 of the more than 7000 cigarette smoke components, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are known carcinogens. Nicotine is the compound responsible for the addictive and psychopharmacological effects of tobacco. Cytochrome P450 enzymes are responsible for the phase I metabolism of many tobacco components, including nicotine. Nicotine is mainly metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism decreases the amount of available nicotine in the bloodstream, leading to increased smoking behavior and thus exposure to tobacco toxicants and carcinogens. Here, we report the syntheses and P450 2A6 inhibitory activities of a number of new flavone-based esters and acids. Three of the flavone derivatives studied were found to be potent competitive inhibitors of the enzyme. Docking studies were used to determine the possible mechanisms of the activity of these inhibitors.

GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio=2.04, 95% CI=1.30-3.20, P=0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio=2.90, 95% CI=1.43-5.87, P=0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

Abstract 14071: Plasma Protein Concentrations and Risk of Incident Cardiovascular Diseases in the UK Biobank

Introduction: Profiling of plasma proteins has the potential to improve diagnosis, predict disease and reveal new biologic pathways for cardiovascular disease (CVD). Objectives: We tested the associations of circulating proteins with new-onset coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), and aortic stenosis (AS) in the UK Biobank. Methods: The initial dataset consisted of 52,705 individuals and 1,463 proteins measured using the Olink platform. A total of 47,665 unrelated individuals without prevalent CVD and 1,459 proteins were retained after quality control. Cox proportional hazards models were used to evaluate associations of protein levels at baseline with incident CAD, AF, HF, and AS. Models were adjusted for age, age 2 , race, first ten principal components of genetic ancestry, sex, smoking, BMI, SBP, antihypertensive and lipid-lowering medication use, DMII, serum creatinine, LDL and HDL cholesterol, and Townsend deprivation index. The four outcomes were incorporated as time-varying covariates. Results: Among the 47,665 individuals, mean (SD) age was 56.8 (8.2) years, 25,674 (53.9%) were female, and 44,691 (93.8%) white. Over a median follow-up of 11.1 years, there were 2,941 (6.2%), 2,502 (5.2%), 1,470 (3.1%) and 420 (0.9%) incident cases of CAD, AF, HF, and AS, respectively. Multivariable-adjusted Cox regression revealed 270, 156, 385, and 21 significant associations (P < 8.6 x 10-6) for CAD, AF, HF, and AS, respectively. Fifteen biomarkers overlapped across all outcomes. The strongest associations for CAD, AF, HF, and AS were with GDF-15 (HR = 1.33, 95% CI = 1.28 - 1.39), NT-proBNP (HR = 1.83, 95% CI = 1.75 - 1.91), HE4 (encoded by WFDC2; HR = 1.67, 95% CI = 1.57 - 1.77), and GDF-15 (HR = 1.51, 95% CI = 1.43 - 1.59), respectively. NT-proBNP, IGFBP-4 and HE4 were the strongest overlapping associations. Conclusions: High-throughput proteomics may offer new mechanistic insights and improve risk prediction for common CVDs.

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Evidence from epidemiological studies suggests an association between cigarette smoking and a low risk of Parkinson’s disease. Other data indicate a rapid worsening of the disease and an exacerbation of the disease after smoking cessation. To prevent the risk of Parkinson’s disease as the main component of cigarette smoke, nicotine is proposed as a alkaloid that has a fundamental role in the regulation of the behavior and activity of the striatum mediated by the dopaminergic system. Animal studies have also shown that nicotine can regulate dopamine transmission and reduce levodopa-induced dyskinesia. However, previous clinical trials have shown conflicting results regarding nicotine treatment. Epidemiological, preclinical, clinical updates and studies on dietary nicotine are presented. The suggestion to quit smoking for health reasons, as it reduces the risk of cancer and cardiovascular disease, should be accepted as an essential health procedure, however, in the case of Parkinson’s disease, a nicotine replacement supplement should be provided. Since small amounts of nicotine can lead to stimulation of a large portion of the brain’s nicotinic receptors, nicotine from other sources, such as less harmful advanced smoking devices, as well as diet, may be promising therapeutic agents to support motor function and protect against Parkinson’s disease.

Smoking and alcohol consumption impact on development and distribution of ulcerative colitis in adult patients among West Siberia Region population

Despite the prolonged history of study of ulcerative colitis (UC) its precise aetiology is still unknown. Smoking impact on UC development has been revealed several decades ago and is being discussed due to the exact mechanism of tobacco smoke components to affect colonic mucosa hasn’t been discovered. Alcohol consumption role in UC development isn’t completely understood as well. Researches into the potential risk factors including pernicious habits are of interest as it allows the development of preventive measures and early diagnosis.Objective. To evaluate the correlation between smoking, alcohol consumption and UC development in adult patients among West Siberia region populationMaterial and methods. It has been conducted a case-control study from 2017 to 2022. The case series and matched controls included 157 UC patients and 56 healthy respondents respectively. Information was obtained through a written questionnaire.Results. Ulcerative colitis development odds in patients who quit smoking is 3.8 times higher. Disease debut in 48 % of patients occurred 5 or more years after quitting smoking. Extensive colitis was observed more often in patients with smoking history and left-sided colitis predominated in nonsmoking patients. There's no correlation between smoking history duration and UC distribution. Average amount of wine consumed in controls was almost three times higher than in UC patients.Conclusions. Smoking is not only considered as a trigger that can potentially cause UC regardless the number of cigarettes. Extensive colitis has been observed more often in smoking patients and the ones who quit smoking. Wine consumption up to 20 ml per day may have a protective effect against UC.

Supporting drug and alcohol service users to cut down or stop smoking: review and evidence.gaps

Abstract Background Globally, drug and alcohol service users are underserved by smoking cessation and tobacco control services despite their high rates of smoking, smoking-related disease and interest in quitting or cutting down. DASHES (drug and alcohol users help to exit smoking) is developing and evaluating a tobacco harm reduction intervention with service users and staff of specialist third sector and NHS services, public health, and policymakers. It combines NHS Scotland behavioural change, pharmacotherapy, NRT delivered as vapes and tailored support. We sought evidence of approaches on which to build and assess our model. Methods Rapid review of smoking cessation interventions for drugs and/or alcohol service users. Papers screened by title and abstract, extracted using Covidence and appraised by 4 researchers using CASP guidance. Included papers were quality reviewed. We used PROGRESS-PLUS to assess consideration of equity. Narrative synthesis explored components of smoking cessation/reduction interventions. Results We quality reviewed 29 eligible studies. Heterogeneity and lack of power precluded meta-analysis and limited estimation of effect sizes. Some interventions fell short of existing, evidence-based practice. Despite funders and authorities requiring commitment to increasing equity and diversity of research participation, few studies monitored or addressed equity of participation, barriers to smoking cessation or provision of trauma-informed care explicitly. Promising interventions included designs and supportive features that mitigate healthcare inequities for other conditions. Conclusions Our review identified promising components for inclusion in DASHES but effective and equitable delivery of smoking cessation/reduction services for people using drug and alcohol services remains understudied. Lack of attention contributes to the ongoing burden of avoidable disease and death associated with tobacco-related harm in this population. Key messages • Smoking-related inequities will continue and drug and alcohol service users remain underserved by smoking cessation/tobacco control services until gaps in the evidence base are addressed. • Action to assure equity in research participation, quality and design of interventions remains limited and must be addressed by policymakers funders, researchers and services.

Environmental carcinogen benzo[a]pyrene alters neutral lipid storage via a cyp-35A2 mediated pathway in Caenorhabditis elegans

Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.

Analysis of Influence of Cigarette Smoke on Signaling Pathways of Innate Immune System in Monocytes of Peripheral Blood

INTRODUCTION: Tobacco smoking is an important medical problem since it has a significant impact on the development and progression of chronic obstructive pulmonary disease (COPD). The components of tobacco smoke can initiate and support local and systemic inflammation with participation of monocytes and macrophages.
 AIM: To study molecular mechanisms associated with the impact of cigarette smoke on signaling pathways of the innate immune system in monocytes of peripheral blood.
 MATERIALS AND METHODS: The methods of in silico analysis was used to identify genes associated with the impact of tobacco smoke. On the basis of the data obtained, a cellular model of inflammation was created in vitro using tobacco smoke extract and monocytes of peripheral blood isolated by immunomagnetic separation. An enzyme-linked immunoassay (ELISA) kit was used to measure the concentration of tumor necrosis factor- (TNF-), interleukin-1 (IL-1) in cell supernatants, and of Toll-like receptor 4 (TLR4), ATP-binding cassette A1 (ABCA1) in homogenates of cell membranes of native monocytes and monocytes exposed to 4% tobacco smoke extract. These data were compared with the levels of TNF-, IL-1, TLR4 and ABCA1 in monocytes of peripheral blood of patients with COPD with frequent exacerbation phenotype and with obliterating atherosclerosis of lower limb arteries (OALLA). For statistical processing and visualization of the data, MedCalc 20.1.4 and R (version 4.2.2) software was used.
 RESULTS: Tobacco smoke influences TLR4, TNF- signaling pathways and lipid metabolism. Cigarette smoke extract enhanced the expression of proinflammatory cytokines TNF- and IL-1 in cell supernatants, increased the level of TLR4 and decreased that of ABCA1 in plasmolemma of monocytes of peripheral blood. In patients with COPD with frequent exacerbation phenotype and with OALLA, there were shown increase in the levels of proinflammatory TNF- and IL-1 cytokines in cell supernatants, increase in the level of TLR4 and reduction of the level of ABCA1 in plasmolemma of monocytes of peripheral blood compared to native monocytes of healthy individuals.
 CONCLUSION: Cigarette smoke enhances the production of proinflammatory TNF- and IL-1 cytokines, increases the levels of TLR4 protein and reduces the amount of ABCA1 transporter in membranes of monocytes of peripheral blood. This may partially explain the cause of the influence of cigarette smoke on development of the pulmonary and cardiovascular diseases. COPD with frequent exacerbation phenotype and OALLA are characterized by enhancement of inflammation with participation of monocytes.

Crotonaldehyde induced structural alterations in Low-Density Lipoprotein: Immunogenicity of the modified protein in experimental animals and auto-antibodies generation in various cancers

Crotonaldehyde (CA), a prominent component of cigarette smoke (CS) is a pervasive environmental pollutant that is a highly toxic, unsaturated aldehyde. Exposure to CA-rich pollutants has been linked to the emergence of many malignancies in humans. To better understand the role of CA in biomolecule modification, this study investigated the detailed structural alterations in low-density lipoprotein (LDL) modified by CA, as well as the immunogenicity of the modified protein in experimental animals and the search for autoantibodies in various cancers patients.In vitro, results indicated alterations in secondary and tertiary structures; examined using UV–visible, fluorescence, far-UV circular dichroism, and Fourier transform infrared spectroscopy techniques. Changes in the oxidation status of LDL were studied by carbonyl content assay and NBT assay. ThT binding assay, scanning, and transmission electron microscopy were used to study aggregate formation. The findings revealed significant structural damage in LDL modified by CA. The modification resulted in the unmasking of hydrophobic clusters, the loss of the protein α-helix, and the formation of β-pleated sheet structure. The amyloid aggregate formation was confirmed through ThT microscopy and electron spectroscopy. Rabbits immunized with crotonaldehyde; lead to structural changes in the LDL; that acted as extra antigenic determinants, eliciting strong antibody response. Immunoglobulin response is highly specific for modified LDL as demonstrated by the ELISA. The presence of antibodies against CA-modified LDL was confirmed by the immunoglobulin content of blood sera from human subjects with lung cancer, and competitive ELISA demonstrated the specificity of these antibodies. This study offers insights into the CA-mediated LDL modification and immunogenicity in lung cancer that will have diagnostic importance.

DNA fragmentation as a bioindicator of peat fires’ smoke exposure

Introduction. The impact of combustion products of organic substances on the body is known to be accompanied by the accumulation of DNA damage, which can lead to mutations and pathological changes in the cell and the whole organism. The prevalence and scale of this phenomenon poses an important task for studying the consequences that occur in smoke-exposed organisms and their offspring. 
 Materials and methods. The conditions of real peat smoke were reproduced for 40 minutes with a CO concentration of 99±2.5 mg/m3 with using of experimental bio modelling. The genotoxicity of peat fire smoke after exposure to male white rats was assessed by the occurrence of DNA damage in blood cells using the DNA comet method in the alkaline version. In the first part of the experiment, males were directly exposed to the smoke of a peat fire; in the second part – their sexually mature offspring of both sexes were examined for the occurrence of DNA damage in blood cells.
 Results. The males of the parental generation and offspring were found to be resistant to the effects of smoke components, which was confirmed by the absence of statistical significance in terms of «% DNA in the comet tail» compared with the control. At the same time, females of the received generation showed a statistically significant increase in blood cell DNA damage compared to the control group. 
 Limitations. The study was limited to the study of DNA fragmentation after a single 40-minute exposure to peat smoke in male white rats and their intact offspring. 
 Conclusion. The data obtained in this investigation indicate that damage to the DNA structure in the offspring of male rats exposed to peat smoke containing CO at a concentration of 99±2.5 mg/m3 can be considered as a bioindicator of genotoxic effects induced in the next generation.

3, 4-Benzopyrene (Bap) aggravated abdominal aortic aneurysm formation by targeting pyroptosis in smooth muscle cells through ET-1 mediated NLRP3-inflammasome activation

According to epidemiological studies, smoking is one of the leading causes of the high incidence of abdominal aortic aneurysms (AAA).3,4-Benzopyrene (Bap) is a by-product of coal tar and tobacco combustion produced by the incomplete combustion of organic fuels. It is an essential component of both automobile exhaust and tobacco smoke, it is also an important member of the air pollutants. However, the exact mechanism by which Bap can worsen the condition of patients with AAA and increase the mortality of patients with AAA remains unknown.This research aims to investigate the role of Bap in inducing pyroptosis in AAA. In vitro experiments, we revealed that pyroptosis-Gasdermin D (GSDMD) increased when Bap was used. Additionally, the release of inflammatory factors, such as IL-1β and IL-18 were also rising. An mRNA sequencing analysis revealed that macrophages expressed a high level of the endothelin gene when cells were stimulated by Bap. It seemed that smooth muscle cells pyroptosis was related to macrophages. Experiments revealed that endothelin could increase the calcium ion concentration in smooth muscle cells, resulting in a large amount of ROS and activation of NLRP3 inflammasomes. We discovered that treatment with endothelin receptor antagonist (ABT-546) in vivo and calcium ion chelator (BAPTA) in vitro decreased AAA diameter, downregulated NLRP3 inflammasomes and ROS, and significantly reduced the number of activated GSDMD. Inflammatory mediators were released at a lower level. These findings suggest that Bap-induced pyroptosis may be mediated by the ET-1-Ca2+-inflammasome pathway, providing a new way to reduce mortality in AAA patients.

Assessment of Nicotine Degradation in Cigarette Smoke under Different Storage Conditions (Light and Duration)

Nicotine, the primary component of cigarette smoke, is not only addictive but also indirectly contributes to lung diseases by increasing heart rate and blood pressure upon inhalation. Therefore, managing nicotine content in cigarette smoke necessitates accurate quantitative analysis. Nicotine from cigarette smoke is collected using a Cambridge filter, subjected to solvent extraction, and analyzed using instrumental techniques. However, since nicotine is susceptible to light-induced oxidation, losses may occur during pretreatment, reducing result reliability. This study assesses nicotine loss under various lighting conditions and storage durations. Nicotine collected in Cambridge filters is exposed to dark, visible radiation, and UV radiation (254 nm) for different time intervals (0–48 h), and the nicotine content is analyzed and compared. In dark conditions, a 1.6% decline in nicotine concentration occurs after 48 h. With visible radiation, a 9% reduction is observed, while under UV exposure, the concentration decreases by 16.9%. The UV radiation-associated decrease in nicotine concentration is −0.335% h−1, exhibiting strong linearity ( R 2 = 0.9465 ). Consequently, significant nicotine loss in Cambridge filter-collected samples is influenced by storage duration and lighting conditions. This study’s findings can enhance the accuracy of nicotine quantification in cigarette smoke, thereby improving the understanding of nicotine’s harmful effects in cigarette smoke.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08–2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11–8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

Effect of tetrapeptide Acetyl-(D-Lys)-Lys-Arg-Arg-amide on immunological and biochemical parameters of Wistar rats using passive smoking models

Tetrapeptides, the homologues of adrenocorticotropic hormone fragment (15-18), play a special role among the bioregulators of the immune system. These compounds have cerebroprotective, neuroprotective and antioxidant properties. However, no available studies concerned the immunotropic properties of tetrapeptides in the models with exposure to xenobiotics, thus making such research quite relevant. Our study concerned the effects of tetrapeptide Acetyl-(D-Lys)-Lys-Arg-Arg-amide (laboratory code KK1) on the immunological and biochemical parameters of 72 female Wistar rats exposed to passive smoking. The experimental animals were fumigated with tobacco smoke for 8 hours. Synthetic peptide KK1 was administered intranasally at a dose of 40 g/kg/day five times a day for 10 days. Cotinine was detected only in blood serum of rats from experimental groups, thus confirming a contribution of this tetrapeptide to the trend for normalization of some immunological parameters in experimental animals subjected to passive tobacco smoking, expressed as an increase in thymus mass and the number of splenocytes, and a decrease in the circulating immune complexes compared to the parameters of smoking rats of the group. We revealed that passive tobacco smoking in rats was accompanied by a general tendency to accumulation of iron, lead and nickel in peripheral blood. There was a marked increase in the concentration of cadmium, lead and cobalt in rats of the experimental group compared with the content of these trace elements in the liver of smoking animals injected with tetrapeptide KK1. The revealed shifts in immunological indices may be based, firstly, on hepatotoxic effect of ecotoxicants, The lymphoid lineage is mostly affected thus causing hypoplasia of the central and peripheral immunity organs. An evident sign of such pathology is a decreased cellularity of hematopoietic and lymphoid organs found in the present study. Secondly, the tobacco smoke components with prooxidant action may disrupt cellular redox homeostasis, causing damage to cell membranes, resulting in necrosis or apoptosis, thus explaining the revealed decrease in the number of thymocytes, splenic karyocytes and a decrease in the weight of organs. Thus, our results suggest usage of experimental passive smoking in order to evaluate efficiency of the tetrapeptides. Administration of Acetyl-(D-Lys)-Lys-Arg-Arg-amide peptide to the passively smoking rats is associated with tendency to normalize the mass of the thymus and spleen, the number of thymocytes and splenocytes, and a decrease in circulating immune complexes. Further studies are required to elucidate the effects of tetrapeptides upon the immune system.

Cigarette smoke and intestinal microbiota - what do we know?

The gut microbiota is a unique structure that is normally in an equilibrium state and performs a huge number of diverse functions. Cigarette smoke modifies the intestinal microbiota through a variety of mechanisms and affects the work of enzymes associated with oxidative stress, the mucin layer and the expression of proteins of dense contacts of the intestinal mucosa, the balance of acids and bases in the colon. And this is in addition to the direct toxic effects of many components of tobacco smoke and the spread of bacteria directly from cigarettes. The article examines the data of modern literature on the complex and ambiguous mechanisms of the influence of tobacco smoke and its individual components on the gut microbiota.

The Influence of Nicotine on Trophoblast-Derived Exosomes in a Mouse Model of Pathogenic Preeclampsia.

Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Because the risk of PE is actually decreased by cigarette smoking, we considered the possibility that nicotine, a critical component of tobacco smoke, might protect against PE by modifying the content of exosomes from EVTs. We investigated the effects of nicotine on our PE model mouse and evaluated blood pressure. Next, exosomes were extracted from nicotine-treated extravillous trophoblasts (HTR-8/SVneo), and the peptide samples were evaluated by DIA (Data Independent Acquisition) proteomic analysis following nano LC-MS/MS. Hub proteins were identified using bioinformatic analysis. We found that nicotine significantly reduced blood pressure in a PE mouse model. Furthermore, we identified many proteins whose abundance in exosomes was modified by nicotine treatment of EVTs, and we used bioinformatic annotation and network analysis to select five key hub proteins with potential roles in the pathogenesis or prevention of PE. EVT-derived exosomes might influence the pathogenesis of PE because the cargo delivered by exosomes can signal to and modify the receiving cells and their environment.

Nicotine promotes Mycobacterium tuberculosis H37Rv growth and overexpression of virulence genes.

Tobacco consumption increases the susceptibility to develop infectious diseases such as tuberculosis (TB). Nicotine (Nc) is the main component of cigarette smoke with immunomodulatory properties, however, its effect on Mycobacterium tuberculosis (Mtb) has been scarcely investigated. The present study evaluated the effect of nicotine on the growth of Mtb and on the induction of virulence-related genes. Mycobacteria were exposed to different concentrations of nicotine then Mtb growth was evaluated. Subsequently, the expression of the virulence-related genes lysX, pirG, fad26, fbpa, ompa, hbhA, esxA, esxB, hspx, katG, lpqh, and caeA was evaluated by RT-qPCR. The effect of nicotine on intracellular Mtb was also evaluated. The results showed that nicotine promotes the growth of Mtb both extracellularly and intracellularly and increases the expression of genes related to virulence. In summary, nicotine promotes the growth of Mtb and the expression of virulence-related genes that could be correlated with the increased the risk of smokers developing TB.

Learning discriminative feature representation with pixel-level supervision for forest smoke recognition

Existing vision-based smoke recognition methods still face the issues of low detection rates and high false alarm rates in complex scenes. One reason is that they label light smoke and heavy smoke as the same value, which ignores the differences in multiple attribute information involved in the smoke imaging process. To solve this issue, this paper presents a pixel-level supervision neural network (PSNet) to learn discriminative feature representations for forest smoke recognition. First, the pixel-level supervision information, including the background component, smoke component, fusion ratio, and class information, is cooperatively considered to effectively guide the model training process. To avoid negative transfer caused by the asynchronous optimization of shared layer parameters and achieve synchronous minimization of each loss term, a regularization term based on the smoke imaging principle and a weight dynamic updating method are proposed to balance the weight coefficients of different loss terms. Second, a detail-difference-aware module (DDAM) based on a detail-difference-aware block (DDAB) and a spatial attention block (SAB) is proposed to distinguish smoke and smoke-like targets by fusing xy-shared convolution and z-shared convolution, which adaptively allocates the weights over different positions to prioritize the most informative visual elements in the spatial domain. Third, an attention-based feature separation module (AFSM) is proposed to relieve mutual interference in extracting background features and smoke features by designing component interaction attention (CIA), background component attention (BCA), smoke component attention (SCA), and enhanced residual blocks (ERBs), which can guide the interaction and separation process of background information and smoke information to enhance the discriminative spatial features and suppress interference features. ERB effectively eliminates noise and enhances smoke edge information based on median filters. Finally, to further enhance the feature representation capability, a multiconnection aggregation method (MCAM) is proposed by fully aggregating local and global features simultaneously. Extensive experiments show that our method achieves better performance than existing smoke recognition methods.Extensive experiments show that our PSNet achieves better performance than existing smoke recognition methods. For smoke recognition, our PSNet achieves a 96.95% detection rate, 3.02% false alarm rate, and 0.9694 F1-score. The average calculation time for each image is only 0.0195. For smoke component separation, our PSNet also achieves 0.0014 on evaluation criteria mean square error between predicted smoke component images and labelled smoke component images. These key experimental results are better than those of previous methods.