Component Of Tobacco Smoke Research Articles

The impacts of tobacco and nicotine on HIV-1 infection, inflammation, and the blood-brain barrier in the central nervous system

Human immunodeficiency virus (HIV-1) remains a persistent global health crisis. Even while successfully virologically suppressed, people with HIV (PWH) experience a higher risk for inflammatory disorders such as HIV-associated neurocognitive disorder (HAND). Tobacco use puts PWH at higher risk for neurocognitive symptoms resulting from HIV-associated neuroinflammation. The NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated as a driver of HIV-associated inflammation, including HAND. Nicotine, the psychoactive component of tobacco smoke, has also been shown to signal through the NLRP3 inflammasome and modulate inflammatory signaling in the CNS. Here, we explore the impacts of nicotine and tobacco on the complex neurobiology of HAND, including effects on cognition, inflammation, viral latency, and blood-brain barrier integrity. We outline nicotine’s role in the establishment of active and latent infection in the brain and posit the NLRP3 inflammasome as a common pathway by which HIV-1 and nicotine promote neuroinflammation in PWH.

Effect and investigating of oxygen / nitrogen on modified glassy carbon electrode chitosan/carbon nanotube and best detection of nicotine using Cyclic voltammetry measurement technique

Nicotine, a component of tobacco smoke, is a neurotoxin. It exerts its effects by stimulating nicotine-containing acetylcholine receptors. Nicotine, one of over 4,700 components in tobacco smoke, was previously used as an insecticide in agriculture. Although the use of nicotine in agriculture has been banned in many countries, nicotine poisoning due to accidental or intentional ingestion of nicotine products remains a problem for smoking workers as well as children and adults. Understanding the mechanisms of nicotine poisoning is important for both prevention and treatment, as well as for appropriate regulatory approaches. We study the pharmacological properties of nicotine and the cellular mechanisms underlying acute and persistent nicotine addiction that appear to be related to the central and peripheral nervous systems. The electrochemical properties of nicotine were studied using a glassy carbon-chitosan/multiwalled carbon nanotubes-COOH electrode. Nicotine-COOH via chitosan/multiwalled carbon nanotubes was irreversibly reduced in the presence of oxygen and nitrogen gas. Oxidation signals at lower potentials and higher currents were obtained for nicotine via the modified electrode compared to the glassy carbon electrode. This condition proliferated in the presence of oxygen gas, suggesting that nanotubes, including carbon nanotubes, facilitate electron transfer and form the basis for electrocatalytic nicotine applications. Under optimal conditions, cyclic voltammetry (CV) shows oxidation of nicotine in the presence of oxygen at 0.74 V and nitrogen at 0.81 V in phosphate buffer solution at pH = 7.4. Linear calibration curves range from 0.1 to 200 μM for oxygen and 0.05 to 200 μM for nitrogen conditions, both with R2 = 0.99, and detection limits of 7.1 for oxygen and 9.2 nM for nitrogen.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study

BackgroundVolatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. MethodsIn a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40–75 years, 58% women, enrollment: 2004–2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. ResultsThere were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. ConclusionOur findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.

Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.

Summary of Regulatory Methods and Procedures for Determination of Harmful and Potentially Harmful Components in Tobacco Smoke

Summary Tobacco smoke consists of over 5000 chemical components, most of them are carcinogenic, respiratory toxicants, cardiovascular toxicants, addictive, etc. In 2006 the Working Group on Tobacco Control identified substances in tobacco smoke, which are harmful and potentially harmful for human health (Priority List) and encouraged the development of methods for the analysis of these components. This review focuses on the different methods of evaluation of harmful and potentially harmful components in tobacco smoke used by the International Agency for Research on Cancer (IARC) and the U.S. Food and Drug Administration (FDA) and furthermore on the official methods proposed by the World Health Organization (WHO) and the Cooperation Center for Scientific Research Relative to Tobacco (CORESTA) for analysing these constituents. The various methods for the determination of the substances in tobacco smoke included in the Priority List are compared. In addition, the different evaluation of components from the Priority List is presented. The authors hope that this review will acquaint readers with the harmful components in tobacco smoke. Also, that it will help accredited or scientific laboratories to compare the different methods and to choose appropriate methods depending on their laboratory equipment and laboratory chemicals available.

Estimating the health impact of nicotine exposure by dissecting the effects of nicotine versus non-nicotine constituents of tobacco smoke: A multivariable Mendelian randomisation study.

The detrimental health effects of smoking are well-known, but the impact of regular nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing daily use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]). We used Genome-Wide Association Study (GWAS) summary statistics from Buchwald and colleagues, the GWAS and Sequencing Consortium of Alcohol and Nicotine, the International Lung Cancer Consortium, and UK Biobank. Increased nicotine metabolism increased the risk of COPD, lung cancer, and lung function in the univariable analysis. However, when accounting for smoking heaviness in the multivariable analysis, we found that increased nicotine metabolite ratio (indicative of decreased nicotine exposure per cigarette smoked) decreases heart rate (b = -0.30, 95% CI -0.50 to -0.10) and lung function (b = -33.33, 95% CI -41.76 to -24.90). There was no clear evidence of an effect on the remaining outcomes. The results suggest that these smoking-related outcomes are not due to nicotine exposure but are caused by the other components of tobacco smoke; however, there are multiple potential sources of bias, and the results should be triangulated using evidence from a range of methodologies.

When smoke meets gut: deciphering the interactions between tobacco smoking and gut microbiota in disease development.

Tobacco smoking is a prevalent and detrimental habit practiced worldwide, increasing the risk of various diseases, including chronic obstructive pulmonary disease (COPD), cardiovascular disease, liver disease, and cancer. Although previous research has explored the detrimental health effects of tobacco smoking, recent studies suggest that gut microbiota dysbiosis may play a critical role in these outcomes. Numerous tobacco smoke components, such as nicotine, are found in the gastrointestinal tract and interact with gut microbiota, leading to lasting impacts on host health and diseases. This review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and functionality. We also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host health. Furthermore, this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

Heated tobacco smoke components delay tooth movement in a rat model

ABSTRACT Purpose This study aimed to evaluate the effect of the components of tobacco smoke from heated tobacco products (HTPs), referred to as Tobacco Smoke Components (TSCs), on tooth movement and the number of osteoclasts in rat models. Materials and Methods Wistar rats were divided into the following groups: control, distilled water-administered, cigarette TSCs-administered, and HTP TSCs-administered. Tooth movement was experimentally induced within each group using the Waldo method. Measurements were performed for tooth movement and the number of osteoclasts. Results Both cigarette and HTP TSCs decreased the number of osteoclasts and delayed the rate of tooth movement. The TSCs of cigarettes were particularly shown to have a stronger effect than the HTPs. Conclusion HTP TSCs significantly affected the rate of tooth movement; thus, orthodontists should be aware of the patient’s smoking status, as well as smoking method (paper or heated), and encourage smoking cessation during treatment.

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.

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.&#x0D; 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.&#x0D; 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.&#x0D; 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.&#x0D; 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.

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.

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.

Abstract 4602: Differences in tumor vascular density between smoker and non-smoker cancer patients

Abstract Smoking is among the most significant preventable risk factors associated with cancer and other benign diseases. Cancer development is a multi-step process in which transforming cells gradually gain malignant properties through a series of oncogenic genetic alterations. Successful cancer progression also depends on the remodeling of the surrounding stroma, which feeds the cancer cells in a host-parasite interaction. Tumor angiogenesis, the process of blood vessel formation, is an essential feature of solid tumors that ensures that they have the needed supply of food and oxygen to sustain their proliferative growth. We previously demonstrated that nicotine, an addictive component of tobacco smoke, promoted tumor angiogenesis by impacting the growth of endothelial cells. In the present work, we examined the differences in tumor vasculature between smoker and non-smoker patients to find clinical support for our laboratory findings. After searching the available tumor cases in the repository for the patient’s smoking history, I selected 27 smokers (12 lung and 15 prostate adenocarcinomas) and 19 non-smokers (4 lung and 15 prostate adenocarcinomas) cases. The tissue blocks were sectioned and subjected to hematoxylin and eosin staining and immunohistochemistry using an antibody against CD31, a biomarker for endothelial cells. Following digital scanning, all slides were reviewed to identify tumor areas and CD31+ tubular structures (blood vessels). We observed that lung and prostate tumor tissues from smoker patients had a significantly higher number of blood vessels than those from non-smoker patients. Thus, increased tumor vascularization appears to be a common feature of smoking cancer patients providing clinical support for a novel mechanism by which smoking may contribute to tumor pathobiology. Citation Format: Shubhangi Singh, Mohammad Aslam Khan, Elba T. Herrera, Seema Singh, Ajay P. Singh, Santanu Dasgupta. Differences in tumor vascular density between smoker and non-smoker cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4602.

The Tobacco Smoke Component, Acrolein, as a Major Culprit in Lung Diseases and Respiratory Cancers: Molecular Mechanisms of Acrolein Cytotoxic Activity

Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant that seriously threatens human health and life. Due to its high reactivity, cytotoxicity and genotoxicity, acrolein is involved in the development of several diseases, including multiple sclerosis, neurodegenerative diseases such as Alzheimer's disease, cardiovascular and respiratory diseases, diabetes mellitus and even the development of cancer. Traditional tobacco smokers and e-cigarette users are particularly exposed to the harmful effects of acrolein. High concentrations of acrolein have been found in both mainstream and side-stream tobacco smoke. Acrolein is considered one of cigarette smoke's most toxic and harmful components. Chronic exposure to acrolein through cigarette smoke has been linked to the development of asthma, acute lung injury, chronic obstructive pulmonary disease (COPD) and even respiratory cancers. This review addresses the current state of knowledge on the pathological molecular mechanisms of acrolein in the induction, course and development of lung diseases and cancers in smokers.

Smoking Cessation after Cancer Diagnosis and Enhanced Therapy Response: Mechanisms and Significance

The adverse effects of smoking on human health have been recognized for several decades, especially in the context of cancer. The ability of tobacco smoke components, including tobacco-specific carcinogens and additive compounds such as nicotine, to initiate or promote tumor growth have been described in hundreds of studies. These investigations have revealed the tumor-promoting activities of nicotine and other tobacco smoke components and have also recognized the ability of these agents to suppress the efficacy of cancer therapy; it is now clear that smoking can reduce the efficacy of most of the widely used therapeutic modalities, including immunotherapy, radiation therapy, and chemotherapy. Several studies examined if continued smoking after cancer diagnosis affected therapy response; it was found that while never smokers or non-smokers had the best response to therapy, those who quit smoking at the time of diagnosis had higher overall survival and reduced side-effects than those who continued to smoke. These studies also revealed the multiple mechanisms via which smoking enhances the growth and survival of tumors while suppressing therapy-induced cell death. In conclusion, smoking cessation during the course of cancer therapy markedly increases the chances of survival and the quality of life.

Abstract A007: Assessing immunoprevention efficacy of an agonist of CD137 pathway in a tobacco carcinogen-induced lung cancer preclinical model

Abstract Purpose: Lung cancer is the leading cause of cancer-related deaths worldwide. Cigarette smoking is the primary risk factor for lung cancer and is linked to 80-90% of lung cancer deaths according to the Centers for Disease Control (CDC). The most carcinogenic component of tobacco smoke is NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). SA-4-1BBL is a novel CD137 receptor agonist that has shown cancer immunoprevention efficacy in transplantable preclinical tumor models by invoking an innate immune surveillance mechanism involving CD4+ CD44+ T and NK cells. As a preclinical model for high-risk populations, we evaluated the immunoprevention efficacy of SA-4-1BBL in lung tumor formation induced by NNK. Experimental Procedures: A/J female mice were used as a preclinical model for lung cancer immunoprevention due to their susceptibility to tobacco-carcinogen-induced lung cancer. A/J mice were i.p. injected with NNK weekly for eight consecutive treatments. The mice were also treated s.c. with 100 µg SA-4-1BBL twice, two weeks apart on weeks 6 and 8 of NNK treatment. Animals were monitored for 21 weeks and euthanized to harvest the lung and lung-draining lymph nodes for histology (H&amp;E staining and PCNA immunofluorescence staining). In separate groups, mice were treated with a depleting antibody to CD4 twice two weeks apart on weeks 6 and 8 of NNK treatment to investigate the role of CD4+ immune cells in cancer immunoprevention. Results: NNK treatment resulted in lung tumor formation as assessed by PCNA immunofluorescence staining in all saline-injected control mice by the 21-week experimental end-point. Treatment with SA-4-1BBL resulted in significantly fewer macroscopic and microscopic tumor numbers than the control group (p &amp;lt; 0.01). Animals treated with SA-4-1BBL and subjected to CD4+ cell depletion showed similar numbers of macroscopic and microscopic lung tumors to the vehicle group. Conclusions: Prophylactic treatment with SA-4-1BBL significantly prevents NNK-induced lung tumor formation and CD4+ immune cells play a critical role in the observed immunoprevention efficacy of SA-4-1BBL. Supported by a grant from DOD LC190524 to Esma S. Yolcu. Citation Format: Ayse Ece Gulen, Mohammad Tarique, Vahap Ulker, Evrim Agca, Haval Shirwan, Esma S. Yolcu. Assessing immunoprevention efficacy of an agonist of CD137 pathway in a tobacco carcinogen-induced lung cancer preclinical model [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A007.

Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is an eye disease, which causes impaired vision that can lead to blindness. The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide-binding domain, leucine-rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85-90%) and wet (10-15%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti-vascular endothelial growth factor (anti-VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option. Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro-oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone-induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE-19 cells). An age-related eye disease study (AREDS) formulation (incl. omega-3 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone-induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance. The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). Hydroquinone induced an NLRP3-independent IL-18 release and NLRP3 accumulation inside the IL-1α-primed cells. Resvega treatment reduced the extent of hydroquinone-induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone- and impaired protein clearance-induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.