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Selenium, a crucial antioxidant in the body, has been linked to all-cause and cause-specific mortality. However, the relationship between selenium and mortality in the general population remains unclear. A total of 5449 participants in the National Health and Nutrition Examination Survey (NHANES) (2003-2004, 2011-2016) were analyzed to track participant mortality until December 31, 2019. The COX proportional hazard model, Kaplan‒Meier survival analysis and restricted cubic spline regression analysis were used to investigate the associations. Subgroup analysis was conducted on the basis of age (≤ 60, > 60), sex (male, female), and smoking status (nonsmoker, former smoker, and current smoker). The second quartile was associated with lower all-cause mortality and noncardiovascular mortality (HR and 95% CI 0.61,0.45-0.83;0.59,0.42-0.83, respectively). The third quartile was associated with lower cardiovascular-related mortality (HR and 95% CI 0.49, 0.32-0.76). Elevated serum selenium concentrations were associated with lower all-cause mortality, noncardiovascular mortality (range ≤ 129.82 μg/L), and cardiovascular mortality (range ≤ 129.08 μg/L). Subgroup analysis revealed a positive correlation between the serum selenium concentration (range ≥ 129.82 μg/L) and all-cause mortality among the subgroup of current smokers (p < 0.001). This study indicates that the protective effect of the serum selenium concentration on cause-specific mortality decreases beyond a certain range in the general population, potentially increasing the risk of death among current smokers., (© 2024. The Author(s).)

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

Stainless steel welders are exposed to heavy filler metals. We evaluated the concentration of these metals in whole blood and urine, and the relevant biochemical parameters in relation to the total chromosomal aberrations (CAs), chromatid-type (CTA-type, CTAs) and chromosome-type (CSA-type, CSAs), in 117 welders and control individuals. Statistically higher concentrations of the total Cr, Ni and Mn were observed in whole blood and urine of welders, and the concentrations were higher in welders who smoked. On the contrary, concentrations of urinary heavy metals Cr and Mn adjusted for creatinine were significantly higher in the control groups. A statistically higher frequency of total CAs was observed in the whole group of welders, and also in the non-smoking welders, as compared to controls. The frequency of total CAs significantly correlated with the concentration of Cr, Ni and Mn in whole blood (R=0.61, P˂0.0001, R=0.33, P˂0.0001 and R=0.66, P˂0.0001, respectively), with urinary concentrations of Ni and Mn (R=0.27, P=0.003 and R=0.28, P=0.003, respectively) and with urinary concentrations of Cr, Ni and Mn adjusted for creatinine (R=0.22, P=0.029, R=0.26, P=0.005 and R=0.20, P=0.030, respectively). Likewise, the frequency of CTA-types significantly correlated with the concentration of Cr and Mn in whole blood (R=0.31, P=0.0007 and R=0.34, P=0.0002). The frequency of CSA-types significantly correlated with concentrations of Cr, Ni and Mn in whole blood (R=0.43, P˂0.0001, R=0.38, P˂0.0001 and R=0.46, P˂0.0001, respectively). The statistically higher values of serum creatinine and total bilirubin were detected in all welders, as well as in smokers when compared to the corresponding controls. The exposure to heavy metals in welders increased the frequencies of CAs and altered the balance between urinary excretion of heavy metals and their possible accumulation., Competing Interests: Declaration of Competing Interest To our best knowledge neither of the co-authors has any actual or potential competing interests regarding this manuscript. The study was conducted in agreement with ethical principles on strictly coded samples and the identity of the participants was not disclosed., (Copyright © 2024. Published by Elsevier B.V.)

It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exposure to tobacco smoke (ETS) is one of the main risk factors for cardiovascular disease (CVD). Renalase is a protein that may play a role in the pathogenesis of CVD. The aim of the study was to assess the relationship between ETS and serum renalase concentration. A group of 109 patients was recruited for this study (49.7 ± 14.7 years). In accordance with the questionnaire, patients were divided into the following subgroups: subgroup A- declaring themselves active smokers (n = 36), subgroup B- declaring themselves non-smokers and exposed to environmental tobacco smoke (n = 35), subgroup C- declaring themselves non-smokers and not exposed to environmental tobacco smoke (n = 38). The same patients were divided based on cotinine concentration into the following subgroups: subgroup D- active smokers (n = 42), subgroup E- non-smokers exposed to environmental tobacco smoke (n = 66), and subgroup F- non-smokers not exposed to environmental tobacco smoke (n = 1). Serum cotinine concentration and serum renalase concentration were measured using ELISA tests. Serum renalase concentration was statistically significantly higher in subgroup C than in subgroups A and B and in subgroup E and F than in D. There was a negative correlation between serum cotinine concentration and serum renalase concentration (r = -0.41, p < 0.05). Regression analysis showed that higher BMI, higher diastolic blood pressure, coronary artery disease and higher serum cotinine concentration are independent risk factors of lower serum renalase concentration. The questionnaire method of assessing exposure to tobacco smoke was characterized by high sensitivity, but only moderate specificity, especially in terms of assessing environmental exposure to tobacco smoke. In summary, the study showed an independent relationship between exposure to tobacco smoke and lower serum renalase concentration., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis., Methods: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers., Results: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p =  < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03)., Conclusion: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable., (© 2024. The Author(s).)

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers., (© 2024 UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis., Methods: Serum samples from 98,737 subjects from two prospective population studies, HUNT2 and HUNT3, were considered initially. Inclusion criteria for cases were: ever-smokers; no known cancer at study entrance; 0-8 years from blood sampling to LC diagnosis. Each future LC case had one control matched to sex, age at study entrance, pack-years, smoking cessation time, and similar HUNT Lung Cancer Model risk score. A total of 240 and 72 serum samples were included in the discovery (HUNT2) and validation (HUNT3) datasets, respectively, and analysed by next-generation sequencing. The validated serum microRNAs were also tested in two pre-diagnostic plasma datasets from the prospective population studies NOWAC (n = 266) and NSHDS (n = 258). A new model adding clinical variables was also developed and validated., Results: Fifteen unique microRNAs were discovered and validated in the pre-diagnostic serum datasets when all cases were contrasted against all controls, all with AUC > 0.60. In combination as a 15-microRNAs signature, the AUC reached 0.708 (discovery) and 0.703 (validation). A non-small cell lung cancer signature of six microRNAs showed AUC 0.777 (discovery) and 0.806 (validation). Combined with clinical variables of the HUNT Lung Cancer Model (age, gender, pack-years, daily cough parts of the year, hours of indoor smoke exposure, quit time in years, number of cigarettes daily, body mass index (BMI)) the AUC reached 0.790 (discovery) and 0.833 (validation). These results could not be validated in the plasma samples., Conclusion: There were a few significantly differential expressed microRNAs in serum up to eight years before diagnosis. These promising microRNAs alone, in concert, or combined with clinical variables have the potential to serve as early diagnostic LC biomarkers. Plasma is not suitable for this analysis. Further validation in larger prospective serum datasets is needed., (© 2024. The Author(s).)

Background and Objectives : One of the members of the neurotrophin (NT) family is the brain-derived neurotrophic factor (BDNF). In addition to its role in the nerve system, it has been found to play a role in lung health and diseases. Materials and Methods : The serum concentrations of BDNF were assessed in 57 patients with COPD and in 19 control individuals and the possible associations of BDNF with the spirometric indexes and disease stages were explored. Results : We did not find a significant difference between the serum concentrations of BDNF of patients and controls ( p = 0.521). A significant negative correlation of the serum BDNF levels with the age of the patients (Rho = -0.279, p = 0.036) was observed. In addition, a borderline negative correlation with the age of disease onset (Rho= -0.244, p = 0.063) was also found. When analyzing these correlations in different genders, we found stronger statistical significance in male patients (Rho = -0.398, p = 0.009; and Rho = -0.419, p = 0.006), while no such significance was found in females ( p = 0.574 and p = 0.342). The analyses of the possible relations of serum BDNF concentration with the spirometric parameters in the whole group of patients did not reveal any significance ( p = 0.231 for FEV1%pr. and p = 0.271 for FEV1/FVC%). However, when the patients were dichotomized on the basis of smoking habits, we obtained a strong positive correlation between BDNF and FEV1%pr. (Rho = 0.501, p = 0.048) in non-smokers, but strong negative correlations with FEV1%pr. (Rho = -0.468, p = 0.003) and with FEV1/FVC% (Rho = -0.331, p = 0.040) in ex/current smokers. Non-smokers with moderate disease (GOLD II) had higher BDNF serum concentrations than patients with GOLD stage III/IV ( p = 0.031). In ex/current smokers, there was an opposite association ( p = 0.045). Conclusions : The results of our study suggest that the expression and secretion of BDNF are changed in COPD, but its effects and functions may differ according to the smoking history of the patients.

Tobacco smoking is the main etiological factor of lung cancer (LC), which can also cause metabolome disruption. This study aimed to investigate whether the observed metabolic shift in LC patients was also associated with their smoking status. Untargeted metabolomics profiling was applied for the initial screening of changes in serum metabolic profile between LC and chronic obstructive pulmonary disease (COPD) patients, selected as a non-cancer group. Differences in metabolite profiles between current and former smokers were also tested. Then, targeted metabolomics methods were applied to verify and validate the proposed LC biomarkers. For untargeted metabolomics, a single extraction-dual separation workflow was applied. The samples were analyzed using a liquid chromatograph-high resolution quadrupole time-of-flight mass spectrometer. Next, the selected metabolites were quantified using liquid chromatography-triple-quadrupole mass spectrometry. The acquired data confirmed that patients' stratification based on smoking status impacted the discriminating ability of the identified LC marker candidates. Analyzing a validation set of samples enabled us to determine if the putative LC markers were truly robust. It demonstrated significant differences in the case of four metabolites: allantoin, glutamic acid, succinic acid, and sphingosine-1-phosphate. Our research showed that studying the influence of strong environmental factors, such as tobacco smoking, should be considered in cancer marker research since it reduces the risk of false positives and improves understanding of the metabolite shifts in cancer patients., (© 2024. The Author(s).)

Introduction: Smoking is a public health threat because of its well-described link to increased oxidative stress-related diseases including peripheral vascular disease and coronary artery disease. Tobacco use has been linked to risk of inpatient trauma morbidity including acute respiratory distress syndrome; however, its mechanistic effect on comprehensive metabolic heterogeneity has yet to be examined., Methods: Plasma was obtained on arrival from injured patients at a Level 1 trauma center and analyzed with modern mass spectrometry-based metabolomics. Patients were stratified by nonsmoker, passive smoker, and active smoker by lower, interquartile, and upper quartile ranges of cotinine intensity peaks. Patients were substratified by high injury/high shock (Injury Severity Score, ≥15; base excess, <-6) and compared with healthy controls. p Value of <0.05 following false discovery rate correction of t test was considered significant., Results: Forty-eight patients with high injury/high shock (7 nonsmokers [15%], 25 passive smokers [52%], and 16 active smokers [33%]) and 95 healthy patients who served as controls (30 nonsmokers [32%], 43 passive smokers [45%], and 22 active smokers [23%]) were included. Elevated metabolites in our controls who were active smokers include enrichment in chronic inflammatory and oxidative processes. Elevated metabolites in active smokers in high injury/high shock include enrichment in the malate-aspartate shuttle, tyrosine metabolism, carnitine synthesis, and oxidation of very long-chain fatty acids., Conclusion: Smoking promotes a state of oxidative stress leading to mitochondrial dysfunction, which is additive to the inflammatory milieu of trauma. Smoking is associated with impaired mitochondrial substrate utilization of long-chain fatty acids, aspartate, and tyrosine, all of which accentuate oxidative stress following injury. This altered expression represents an ideal target for therapies to reduce oxidative damage toward the goal of personalized treatment of trauma patients., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Male infertility along with altered semen parameters have been related to smoking. Smoking-related elevations in serum and seminal lead (Pb) and arsenic (As) may play a role in mediating the toxic effects of smoking on seminogram. This research aims to determine whether smoking has any significant impact on Pb and As levels in the seminal plasma and serum, as well as on the various semen parameters, when compared to nonsmokers. In total, 80 adult males were included: 60 smokers and 20 age-matched nonsmokers. Based on the number of cigarettes smoked/day (CPD), the smokers were categorized into mild (1-10), moderate (11-20), and severe (> 20). The analysis of semen was conducted in accordance with the 2010 WHO laboratory manual. Using an atomic absorption spectrophotometer, Pb and As concentrations in the serum and seminal plasma of all groups were determined. Compared to nonsmokers, smokers had a significantly reduced sperm count, motility, and viability, as well as a larger percentage of aberrant forms (P = 0.001, 0.025, 0.034, 0.002 respectively). Smokers had higher Pb concentrations in their serum and seminal fluid than nonsmokers (P = 0.002, 0.001 respectively). Seminal Pb had a significant negative correlation with sperm count (P = 0.004, r = -0.320). Serum Pb levels were found to positively correlate with seminal Pb levels (P 0.001, r = 0.648), and cigarette smokers had substantially greater seminal As levels than nonsmokers (P = 0.024). Sperm viability was strongly inversely related to seminal As (P = 0.042, r = -0.264). Seminal As levels and aberrant sperm shapes were found to be significantly correlated (P = 0.001, r = 0.414). In smokers, a significant positive relationship between seminal As and seminal Pb was observed. Therefore, semen parameters could be adversely affected by smoking through high levels of Pb and As (P = 0.012, r = 0.298)., (© 2024. The Author(s).)

Purpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity., Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤50 mmHg) and non-mild (PASP >50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve., Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P =0.009) and SI ( P =0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628)., Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Sun et al.)

Selenium (Se) is an essential trace element for humans and its low or high concentration in vivo is associated with the high risk of many diseases. It is important to identify influential factors of Se status. The present study aimed to explore the association between several factors (Se intake, gender, age, race, education, body mass index (BMI), income, smoking and alcohol status) and blood Se concentration using the National Health and Nutrition Examination Survey 2017-2020 data. Demographic characteristics, physical examination, health interviews and diets were compared among quartiles of blood Se concentration using the Rao-Scott χ 2 test. Se levels were compared between the different groups of factors studied, measuring the strength of their association. A total of 6205 participants were finally included. The normal reference ranges of blood Se concentration were 142.3 (2.5th percentile) and 240.8 μg/L (97.5th percentile), respectively. The mean values of dietary Se intake, total Se intake and blood Se concentration of the participants were 111.5 μg/day, 122.7 μg/day and 188.7 μg/L, respectively, indicating they were in the normal range. Total Se intake was the most important contributor of blood Se concentration. Gender, race, education status, income, BMI, smoking and alcohol status were associated with blood Se concentration.

Background: Levels of anti-Müllerian hormone (AMH) are known to be associated with lifestyle determinants such as smoking and oral contraception (OC) use. When measuring AMH in clinical practice, it is essential to know which factors may influence circulating levels or ovarian reserve in general., Objective and Rationale: To date, there is no systematic review or summarizing consensus of the nature and magnitude of the relation between AMH and modifiable lifestyle factors. The purpose of this review was to systematically assess the evidence on association of lifestyle behaviors with circulating AMH levels., Search Methods: We performed a pre-registered systematic review of publications in Embase and PubMed on the lifestyle factors BMI, smoking, OC use, alcohol consumption, caffeine consumption, physical activity, and waist-hip ratio (WHR) in relation to circulating AMH levels up to 1 November 2023. The search strategy included terms such as 'Anti-Mullerian hormone', 'lifestyle', and 'women'. Studies were considered eligible if the association between at least one of the lifestyle factors of interest and AMH was assessed in adult women. The quality of included studies was assessed using the Study Quality Assessment Tools of the National Heart, Lung, and Blood Institute. The results were presented as ranges of the most frequently used association measure for studies that found a significant association in the same direction., Outcomes: A total of 15 072 records were identified, of which 65 studies were eligible for inclusion, and 66.2% of the studies used a cross-sectional design. The majority of studies investigating BMI, smoking, OC use, and physical activity reported significant inverse associations with AMH levels. For WHR, alcohol, and caffeine use, the majority of studies did not find an association with AMH. For all determinants, the effect measures of the reported associations were heterogeneous. The mean difference in AMH levels per unit increase in BMI ranged from -0.015 to -0.2 ng/ml in studies that found a significant inverse association. The mean difference in AMH levels for current smokers versus non-smokers ranged from -0.4 to -1.1 ng/ml, and -4% to -44%, respectively. For current OC use, results included a range in relative mean differences in AMH levels of -17% to -31.1%, in addition to a decrease of 11 age-standardized percentiles, and an average decrease of 1.97 ng/ml after 9 weeks of OC use. Exercise interventions led to a decrease in AMH levels of 2.8 pmol/l to 13.2 pmol/l after 12 weeks in women with polycystic ovary syndrome or a sedentary lifestyle., Wider Implications: Lifestyle factors are associated with differences in AMH levels and thus should be taken into account when interpreting individual AMH measurements. Furthermore, AMH levels can be influenced by the alteration of lifestyle behaviors. While this can be a helpful tool for clinical and lifestyle counseling, the nature of the relation between the observed differences in AMH and the true ovarian reserve remains to be assessed., Registration Number: PROSPERO registration ID: CRD42022322575., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aimed to evaluate the association of serum zinc with periodontitis in non-diabetics based on smoking status, using a representative sample of adults in the United States., Methods: A total of 1051 participants who underwent full-mouth periodontal examination and serum zinc testing were enrolled from NHANES 2011 to 2014. The covariate-adjusted association of serum zinc concentrations with periodontitis was explored using multivariable logistic regression, restricted cubic spines, and sensitivity analysis., Results: The mean age of the 1051 adults was 54.5 years, 59.37% were male, and 20.65% had periodontitis. Analysis of the results showed that serum zinc was associated with periodontitis. The overall adjusted odds of periodontitis were 9% (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83-1.00) and 14% (OR: 0.86; 95% CI: 0.75-0.98) for nonsmokers and smokers, respectively. Smokers with T3 serum zinc exhibited a 53% reduction in the fully adjusted odds of periodontitis (OR: 0.47; 95% CI: 0.23-0.96), when compared to the reference group (T1 serum zinc), with serum zinc as the categorical variable., Conclusions: Serum zinc levels were associated with the risk of periodontitis in non-diabetic smokers but not non-smokers., (© 2023 Wiley Periodicals LLC.)

Cadmium (Cd) is a known carcinogen, but its impact on cancer risk at lower concentrations is poorly understood. Previous studies on Cd and cancer risk in men show inconsistent results, prompting further investigation. A prospective cohort study involving 2956 men was conducted. Blood Cd levels were measured, and participants were followed for 78 months to assess cancer incidence. Men with high blood Cd levels (>0.71 µg/L) had a significantly increased risk of cancer compared to those with low levels (<0.19 µg/L) (HR 3.42, p < 0.001), particularly among non-smokers (HR 3.74, p = 0.003), individuals aged < 60 years (HR 2.79, p = 0.017), and ≥60 (HR 4.63, p = 0.004). The influence of smoking on cancer risk based on Cd levels was not significant in this study. Blood Cd levels may influence cancer risk in men, emphasizing the importance of minimizing Cd exposure to reduce risk. Confirmation of these results in other populations is essential for effective preventive measures against Cd-related cancers.

Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability 1-6 . However, the variables that drive such differences in cytokine secretion-a crucial component of the host response to immune challenges-remain poorly defined. Here we investigated 136 variables and identified smoking, cytomegalovirus latent infection and body mass index as major contributors to variability in cytokine response, with effects of comparable magnitudes with age, sex and genetics. We find that smoking influences both innate and adaptive immune responses. Notably, its effect on innate responses is quickly lost after smoking cessation and is specifically associated with plasma levels of CEACAM6, whereas its effect on adaptive responses persists long after individuals quit smoking and is associated with epigenetic memory. This is supported by the association of the past smoking effect on cytokine responses with DNA methylation at specific signal trans-activators and regulators of metabolism. Our findings identify three novel variables associated with cytokine secretion variability and reveal roles for smoking in the short- and long-term regulation of immune responses. These results have potential clinical implications for the risk of developing infections, cancers or autoimmune diseases., (© 2024. The Author(s).)

Background: Cadmium, a toxic metal, is widely encountered in diverse environmental contexts. Despite its pervasive exposure, there is limited research on the association between blood cadmium levels and depression, especially among females. This study aimed to investigate the relationship between blood cadmium levels and depression in adult women., Methods: Data spanning 2005-2016 from the National Health and Nutrition Examination Survey (NHANES) were selected. Depression was diagnosed with the Patient Health Questionnaire (PHQ-9, score ≥10). Multiple logistic regression, multiple linear regression, and smoothed curve fitting were used to investigate the relationship between blood cadmium and depression. Subgroup analyses and interaction tests were performed to evaluate the stability of this association across populations., Results: A total of 1,173 individuals were diagnosed with depression. The heightened prevalence of depression was linked to increased blood cadmium levels, a trend that persisted even after quartering blood cadmium. In the fully adjusted model, each incremental unit of blood cadmium was associated with a 33% rise in the prevalence of depression (OR = 1.33, 95% CI: 1.21-1.45). Participants in the highest quartile were 63% more likely to experience depression compared to those in the lowest quartile of blood cadmium (OR = 1.63, 95% CI: 1.15-2.30), and PHQ-9 score increased by 0.73 (β = 0.73, 95% CI: 0.30-1.17). This positive association may be relevant to the general population., Conclusions: Blood cadmium levels are associated with depression in adult women, and this association varies by age and smoking status.

Background: Indonesia, with its expansive territorial waters, hosts numerous fishing communities residing on various islands. Many of these communities rely on diving activities, predominantly free diving without standardized safety equipment. This practice poses risks, including the potential for hypoxia-induced oxidative stress, which plays a role in disease pathogenesis. This study aimed to investigate the levels of malondialdehyde (MDA) in freediving fishermen and explore potential influencing factors., Materials and Methods: The research involved 30 freediving fishermen, aged 20-60, who engaged in diving at least twice weekly over the last 3 months. Blood plasma MDA levels were assessed using the Will method., Results: Results revealed a median age of 40.5 years (range: 20-59), a body mass index of 23.1 ± 2.8, and a mean blood pressure of 132/85 mmHg. A significant portion of the subjects exhibited smoking habits (90%) and alcohol consumption (76.7%). The median MDA level among subjects was measured at 0.42 nmol/mL (range: 0.34-0.70). However, no discernible relationship was found between smoking habits, alcohol consumption, and MDA level categories, as determined by the Fisher exact test (p > 0.05)., Conclusions: While these findings shed light on the MDA levels in freediving fishermen, further research is warranted to explore additional factors that may influence these levels. This comprehensive understanding is crucial for addressing the health risks associated with free diving practices in this unique population.

The amount of smoking, level of smoking addiction and smoking cessation have effects on blood cells, blood lipid levels, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV)/lymphocyte ratio (MPVLR) and monocyte/high- density lipoprotein (HDL) ratio (MHR). Methods In this self-controlled experimental study, we included individuals who applied to a smoking cessation clinic and quit smoking. Their sociodemographic and clinical characteristics, the amount of cigarettes consumed (pack/year), their Fagerstrom test for nicotine dependence (FTND) results, haemogram values before and 6 months after quitting smoking, NLR, PLR, MPVLR, MHR and blood lipid levels before and after the treatment were compared retrospectively. Results The mean (SD) age of the 239 individuals who participated in the study was 41.7 (10.9) years and 55.2% of them were women. Their mean FTND score was 7.06 (2.0), and most of them (47.7%) had a very high level of addiction. After the smoking cessation treatment, their neutrophil, platelet, MPV, red cell distribution width, platelet distribution width (PDW), cholesterol, triglyceride, low- density lipoprotein, NLR, PLR, MPVLR, MHR and HDL values increased (p<0.05). The amount of smoking and level of dependence were negatively correlated with HDL, and positively correlated with other parameters. Conclusion After smoking cessation, in addition to dyslipidaemia, the NLR, PLR, MPVLR and MHR values also decreased, and the difference was found to correlate with the level of addiction and the amount of smoking.

Objective: Smoking is a common public problem leading to increases in oxidative stress and decreases in the levels of some micronutrients, finally affecting adipokine levels. The aim of this study was to compare the serum levels of omentin (intelectin-1), chemerin, TNF-α, and some micronutrient intakes in male smokers and non-smokers., Methods: 40 male smokers and 40 male non-smokers with a mean age of 38.6±14.1 years were included in this study. Serum levels of omentin, chemerin, and TNF-α were measured. To calculate the daily intake of energy, carbohydrate, protein, fat, and some of the micronutrients, the 24-h recall and semi-quantitative food frequency questionnaire (FFQ) was used., Results: Omentin, chemerin, and TNF-α levels in male smokers were lower than non-smokers, but these differences were not statistically significant. However, after adjustment for total and saturated fat intakes and age, omentin (β=138.4, p=0.027) and TNF-α (β=144.5, p=0.015) revealed significant differences., Conclusion: The serum levels of omentin, chemerin, TNF-α, and some micronutrient intakes were not significantly different between smokers and non-smokers. Further population studies are needed to clarify this subject., (Copyright © 2021 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Purpose of this prospective uncontrolled single-centre pilot study was to find an association of retinal oxygen saturation (SatO 2 ) with acid-base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions., Methods: Forty-one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1-36) years, BMI 29.4 ± 6.3 kg/m 2 , and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4-day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro ® 2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO 2 ., Results: Wilcoxon signed-rank test showed no SatO 2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO 2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO 2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO 2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found., Conclusion: This study confirmed the association of venous SatO 2 with long-term but not with short-term diabetes control, ABB and other conditions. The increased SatO 2 and questionable impact of PG variability on retinal SatO 2 is a research challenge., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The routine techniques currently applied for the determination of nicotine and its major metabolites, cotinine, and trans -3'-hydroxycotinine, in biological fluids, include spectrophotometric, immunoassays, and chromatographic techniques. The aim of this study was to develop, and compare two new chromatographic methods high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS), and RP-HPLC enriched with chaotropic additives, which would allow reliable confirmation of tobacco smoke exposure in toxicological and epidemiological studies. The concentrations of analytes were determined in human plasma as the sample matrix. The methods were compared in terms of the linearity, accuracy, repeatability, detection and quantification limits (LOD and LOQ), and recovery. The obtained validation parameters met the ICH requirements for both proposed procedures. However, the limits of detection (LOD) were much better for HPLC-QQQ-MS/MS (0.07 ng mL -1 for trans -3'-hydroxcotinine; 0.02 ng mL -1 for cotinine; 0.04 ng mL -1 for nicotine) in comparison to the RP-HPLC-DAD enriched with chaotropic additives (1.47 ng mL -1 for trans -3'-hydroxcotinine; 1.59 ng mL -1 for cotinine; 1.50 ng mL -1 for nicotine). The extraction efficiency (%) was concentration-dependent and ranged between 96.66% and 99.39% for RP-HPLC-DAD and 76.8% to 96.4% for HPLC-QQQ-MS/MS. The usefulness of the elaborated analytical methods was checked on the example of the analysis of a blood sample taken from a tobacco smoker. The nicotine, cotinine, and trans -3'-hydroxycotinine contents in the smoker's plasma quantified by the RP-HPLC-DAD method differed from the values measured by the HPLC-QQQ-MS/MS. However, the relative errors of measurements were smaller than 10% (6.80%, 6.72%, 2.04% respectively).

BAG3 is highly expressed in the heart and its functions are essential in maintaining cardiac muscle cells homeostasis. In the past, BAG3 was detected in serum from advanced heart failure patients and its higher levels were correlated to an increased death risk. Moreover, it has also been reported that BAG3 levels in serum are increased in patients with hypertension, a known cardiovascular risk marker. Evidence from different laboratories suggested the possibility to use BAG3-based strategies to improve the clinical outcome of cardiovascular disease patients. This review aims to highlight the biological roles of intracellular or secreted BAG3 in myocardiocytes and propose additional new data on the levels of sieric BAG3 in patients with acute myocardial infarction (AMI), never assessed before. We evaluated BAG3 serum levels in relation to cardiovascular risk parameters in 64 AMI patients aged ≥18 years of either sex. We observed significant (p < .01) correlations of BAG3 positivity with dyslipidemic status and diabetic disease. We did not observe any significant correlations of BAG3 levels with smoking habit, hypertension or familiarity for AMI, although BAG3-positive seemed to be more numerous than BAG3-negative patients among hypertensives and among patients with familiarity for AMI. Furthermore, a significant (p < .001) correlation of BAG3 positivity with diuretics assumption was also noted. In conclusion, 32.8% of the patients were BAG3-positive and were characterized by some particular features as comorbidity presence or concomitant therapies. The significance of these observations needs to be verified by more extensive studies and could help in the validation of the use of BAG3 as a biomarker in heart attack risk stratification., (© 2021 Wiley Periodicals LLC.)

Immune system functionality has been commonly assessed by a whole-blood or isolated-cell stimulation assay. The aim of this study was to determine whether cytokine production in whole-blood-stimulated samples is influenced by age, sex, and smoking. A descriptive cross-sectional study in 253 healthy participants aged 18-55 years was conducted. Whole blood samples were stimulated for 24 h with LPS and concentrations of IL-6, IL-10, and TNF-α were determined in the culture media. Among parameters considered, statistical regression analysis indicated that smoking (change in R 2 = 0.064, p < 0.001) and sex (change in R 2 = 0.070, p < 0.001) were the main predictors for IL-10 production, with higher values for women and non-smokers. Age was also found to be a significant predictor (change in R 2 = 0.021, p < 0.001), with higher values for younger ages. Age (change in R 2 = 0.089, p = 0.013) and smoking (change in R 2 = 0.037, p = 0.002) were found to be negative predictors for IL-6 production. Regarding TNF-α-stimulated production, age (change in R 2 = 0.029, p = 0.009) and smoking (change in R 2 = 0.022, p = 0.022) were found to be negative predictors. Furthermore, sex (change in R 2 = 0.016, p = 0.045) was found to be a significant predictor, with lower values for women. In conclusion, sex, age, and smoking were found to be independent determinants of stimulated cytokine production. While female sex is associated with higher IL-10 and lower TNF-α production, aging and smoking are associated with lower IL-6, IL-10, and TNF-α production.

This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements., Competing Interests: The authors have declared that no competing interests exist.

Objective: The scavenger receptor class B type 1 (SR-BI, SCARB1), which is a high-density lipoprotein (HDL) receptor that mediates selective cholesteryl ester uptake, plays an important role in reverse cholesterol transport. This study investigated the distribution of polymorphic variants of the SR-BI gene in patients with coronary heart disease (CHD) with a history of early myocardial infarction (MI) at an early age and their effects on their serum lipid levels., Methods: SR-BI rs5888(T>C), rs4238001(C>T), and rs10846744(G>C) were analyzed in 100 male patients with CHD with a history of MI (MI+) who were younger than 50 years and 89 male control subjects without MI history (MI-) using real-time polymerase chain reaction (PCR) and mutant-allele-specific PCR techniques., Results: SR-BI rs4238001 common-CC genotype was found to be more frequent in patients with MI+ than in control subjects (MI-; odds ratio 4.046, p<0.001). The rs10846744 rare-C allele showed a significant association with increased total cholesterol (p=0.014) and triglyceride (p=0.009) levels in the MI+ CHD group. Logistic regression analysis confirmed that there may be an association between the rs4238001-CC genotype (p=0.002), smoking (p=0.026), and MI+ CHD in the presence of other risk factors associated with CHD, whereas haplotype analysis confirmed that patients with MI+ CHD (rs5888-C, rs10846744-G, and rs4238001-C alleles) and CCC (rs5888-C, rs10846744-C, and rs4238001-C alleles) haplotypes were highly frequent (p<0.01 and p=0.027, respectively)., Conclusion: These results indicated that SR-BI gene variants show different distribution in patients with MI+ CHD compared with that in MI- control subjects, and these variants may have effects in favor of dyslipidemia.

The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist. We used the 1999-2014 National Health and Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality. All participants were followed up until 2015 except those younger than 18 years old, after excluding those who died within three years of follow-up, a total of 1619 deaths among 19,034 people were included in the analysis. In the age-adjusted model (model 1), it was found that the lowest LDL-C group had a higher risk of all-cause mortality (HR 1.708 [1.432-2.037]) than LDL-C 100-129 mg/dL as a reference group. The crude-adjusted model (model 2) suggests that people with the lowest level of LDL-C had 1.600 (95% CI [1.325-1.932]) times the odds compared with the reference group, after adjusting for age, sex, race, marital status, education level, smoking status, body mass index (BMI). In the fully-adjusted model (model 3), people with the lowest level of LDL-C had 1.373 (95% CI [1.130-1.668]) times the odds compared with the reference group, after additionally adjusting for hypertension, diabetes, cardiovascular disease, cancer based on model 2. The results from restricted cubic spine (RCS) curve showed that when the LDL-C concentration (130 mg/dL) was used as the reference, there is a U-shaped relationship between LDL-C level and all-cause mortality. In conclusion, we found that low level of LDL-C is associated with higher risk of all-cause mortality. The observed association persisted after adjusting for potential confounders. Further studies are warranted to determine the causal relationship between LDL-C level and all-cause mortality., (© 2021. The Author(s).)

Purpose: In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges., Methods: Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups., Results: We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P < .0001 for both). Women had lower IgA (beta: - 0.24; 95% confidence interval [95% CI]: - 0.29; - 0.20) and IgG (beta: - 0.33; 95% CI: - 0.44; - 0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between - 0.07 and - 1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking: - 0.70; 95% CI: - 0.91; - 0.48). Corticosteroid use was associated with lower IgG (beta: - 1.12; 95% CI: - 1.58; - 0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes., Conclusion: Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges., (© 2021. The Author(s).)

Reference intervals that indicate the anticipated results of clinical chemistry parameters in a healthy background population are essential for the proper interpretation of laboratory data. In the present study, we analysed major trace elements in blood samples from 400 randomly selected members of the general Danish population. Reference intervals were established for trace elements in both whole blood and serum, and associations with major plasma transport proteins were investigated. In the case of a statistically significant correlation, a corresponding protein-adjusted reference interval was established for comparison with the unadjusted interval. While several trace elements correlated with albumin, ferritin and transferrin, the overall impact of transport proteins was minor and resulted in only marginal changes in the reference intervals. In conclusion, the updated reference intervals for trace elements can be employed without adjusting for plasma protein concentrations.

Background: Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known., Methods: Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both., Results: There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor-based model were 0.015 (0.004-0.028) and 0.020 (0.001-0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033-0.109) and 0.051 (0.017-0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (-0.006 to 0.054) in CARDIA and 0.039 (0.0005-0.072) in FOS., Conclusions: Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.

Background: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population., Methods: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m 2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m 2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m 2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m 2 per year or > 30 % decrease in eGFR from baseline., Results: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04)., Conclusions: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population., (© 2021. The Author(s).)

Background: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up., Methods: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD., Results: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m 2 , and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015)., Conclusions: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant., (© 2021. The Author(s).)

Introduction: Women who smoke during pregnancy have a reduced risk of preeclampsia. The mechanism of this association is poorly understood. Preeclampsia is an anti-angiogenic and inflammatory state. Transforming growth factor beta 1 (TGF-β1) is a multi-functional anti-inflammatory cytokine that activates membrane bound endoglin on endothelial cells causing a myriad of vascular actions including vasorelaxation. The objective of the study was to determine serum levels of cytokines, angiogenic factors, placental growth factor (PlGF), TGF-β-1 and anti-angiogenic factors, soluble endoglin (sEng) and soluble vascular endothelial growth factor 1 (sVEGFR1) in smoking and non-smoking pregnant women., Methods: Using enzyme-linked immunosorbent and multiplex assays we prospectively analyzed serum levels of PIGF, TGF-β1, sEng, sVEGFR1 and cytokines in normotensive pregnant smokers and non-smokers. Exclusion criteria included maternal hypertension, autoimmune disorders, rupture of membranes, evidence of labor and drug use., Results: There were 59 women in the smoking and 66 in the non-smoking group. Compared to non-smoking mothers. maternal age was lower in smoking mothers with no significant difference in other demographic variables. There was no difference in levels of cytokines, anti-angiogenic factors and PlGF between the two groups. Median TGF-β1 levels were significantly higher in the smoking group (8120 pg/mL vs 6040 pg/mL, p < 0.001) and remained significant after controlling for confounders. TGF-β1 levels correlated positively with cotinine levels in the smoking group., Conclusions: We speculate that higher TGF-β1 levels may explain the reduced incidence of preeclampsia in mothers who smoke by being available for action on maternal endothelium even after inactivation by circulating maternal sEng., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Young adults receive health screenings at lower rates than other age groups, and it may be difficult to detect diseases in the early stages for this group. We examined differences in health status relative to smoking in a young age group using the results of health screenings conducted in engaged and newly married couples in a cross-sectional database., Methods: The participants in this study were 808 young adults who visited a municipal hospital health screening center from July 2017 to March 2019. They completed a self-administered questionnaire, and physical measurements and a blood test were taken. They were classified into non-cigarette smokers, past cigarette smokers, and current cigarette smokers according to smoking behavior. In this study, we compared metabolic syndrome, the main components of which include obesity, high blood pressure, high blood triglycerides, low levels of HDL cholesterol and insulin resistance, with smoking behavior., Results: The mean age of the participants was 30.9±3.3 years (males 32.0±3.2, females 29.8±3.1), and 13.9% were current cigarette smokers (males 22.8%, females 5.1%). The proportion of men in their 30s was 76.6% for male group and 50.0% for female group, indicating that the male group had a relatively higher proportion of older and current smokers. Significant differences were found in age, sex, blood pressure, metabolic abnormalities, and drinking status according to smoking status. Cigarette smokers had a 2.4-fold greater risk of metabolic syndrome (95% confidence interval [CI], 1.43-3.96) than non-cigarette smokers; in particular, they had a 2.6-fold (95% CI, 1.44-4.55) greater risk of hypertriglyceridemia and a three-fold (95% CI, 1.45-6.35) greater risk of low HDL cholesterol., Conclusions: In comparison with non-single, young and generally healthy city dwellers, the risk of metabolic syndrome was significantly higher in smokers than in non-smokers, and in particular, it was confirmed that the risk of hypertriglyceridemia and low HDL cholesterolemia was higher. Smoking cessation is necessary, even for the young, because smoking may cause changes in blood lipids even if the smoking duration is short., Competing Interests: The authors have declared that no competing interests exist.

Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks' gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24-34 weeks' gestation); two prospective cohorts collected on the day of delivery (36 + 3-41 + 3 weeks' gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses., (© 2021. The Author(s).)

Background: Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known., Methods: A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity., Results: Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%, P =0.005). Antilaminin-521 autoantibodies were predominantly of IgG1 and IgG4 subclasses and significantly associated with lung hemorrhage ( P =0.005), hemoptysis ( P =0.008), and smoking ( P =0.01), although not with proteinuria or serum creatinine at diagnosis., Conclusions: Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes., (Copyright © 2021 by the American Society of Nephrology.)

In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total n = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP; chemokine (C-C motif) ligand 18, CCL18; C-X3-C motif chemokine ligand 1, CX3CL1; interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22; epidermal growth factor, EGF; IL-17; periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFNγ and TNFα without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma- and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations.

Persistent inflammation, despite anti-retroviral therapy (ART), is an independent predictor of mortality and comorbidities in HIV infection. Multiple factors, including lifestyle and chronic viral coinfections, may contribute. Several of these factors are also associated with a chronic inflammation in the general population. Little is known about the degree to which these factors influence inflammation in HIV infection, particularly within the first year of ART. The purpose of this study was to distinguish the effects of factors (gender, body mass index, cholesterol and triglyceride levels, smoke habit and cytomegalovirus seropositivity), known to contribute to inflammation, on inflammation biomarkers over the first year of ART in HIV-infected patients. Linear mixed model analysis revealed significant biomarker decreases [soluble CD14 (s-CD14), soluble CD163 (s-CD163) and D-dimer (DD)], or increases [C Reactive Protein (CRP) and interleukin-6 (IL-6)] over time in the whole cohort, differences in most categories (genders for IL-6, smoke habit for s-CD14, cytomegalovirus infection for s-CD163 and IL-6) and in some category × time interactions [gender for interleukin-7 (IL-7)], cytomegalovirus infection for s-CD14 and cholesterol levels for s-CD14 and Tumor Necrosis Factor α (TNF-α)]. This explorative longitudinal study suggests further investigations on targeting inflammation pathophysiology in HIV-infected patients on ART., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention., Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker., Methods: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan-Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort., Results: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 -1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 -1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 -1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 -1.117], p = 0.017)., Conclusion: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Parkinson's disease (PD) is a neurodegenerative disease with multifactorial aetiology that influences the quality of life. However, the association of possible factors with PD is need to be investigated in Indian population, hence we aimed to determine the association of lifestyle, environmental factors, biochemical parameters and genetic insights of MT-ND1 gene in PD patients. Using a standardised questionnaire, PD patients and control group of about 146 subjects were interviewed on demographic, lifestyle and environmental factors. The subjects includes n = 73 Parkinson's patients [juvenile (n = 4); early-onset (n = 8); late-onset (n = 61)] with equal number of age and sex matched controls, further we had obtained institutional ethical clearance and informed consent from study participants. Biomarker investigations and MT-ND1 alterations were investigated by appropriate molecular techniques. During the average follow-up years of 5.1, significant association was observed among smoking, alcohol, caffeinated drinks, surgery, pesticide exposure at p < 0.05 in varied PD age groups. Occupational exposure to agriculture and industry showed an increased risk among the late-onset group. The biomarkers uric acid (UA) and dopamine (DA) were significant at p < 0.05 in all the three PD age groups. The MT-ND1 alteration with A3843 G variant was significant at p < 0.05 for AG allele in all the three PD groups but the highest prevalence was observed in late-onset group. From our study, smoking, alcohol, caffeinated drinks, occupational influence of agriculture and industry and pesticide exposure had more association with PD occurrence. Hence, to the best of our knowledge, this is the first kind of study in Tamil Nadu population, India to validate the various factors with PD. Therefore we suggest that further research is mandatory to detect other possible associations among PD, using comprehensive larger sample size., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Problem: Cigarette smoking during pregnancy is associated with reduced incidence of preeclampsia. Mechanisms of this association are poorly understood. Cytokines, angiogenic, and anti-angiogenic factors are involved in the pathogenesis of preeclampsia. During normal pregnancy, Fas ligand (FasL) present on trophoblasts induces apoptosis of Fas bearing maternal immune cells. In preeclampsia, trophoblasts show increased apoptosis with reduced expression of FasL. We determined serum levels of cytokines, angiogenic (placental growth factor), anti-angiogenic factors (soluble endoglin, soluble fms-like tyrosine kinase-1), soluble Fas (sFas), and soluble FasL (sFasL) in smoking and non-smoking pregnant women., Methods: Using enzyme-linked immunosorbent and multiplex assays, we prospectively analyzed serum levels of angiogenic, anti-angiogenic factors, cytokines, sFas and sFasL in normotensive smoking and non-smoking mothers. Exclusion criteria included maternal hypertension, auto-immune disorders, rupture of membranes, evidence of labor, and drug use., Results: Of 100 women recruited to the study, 51 were in the non-smoking and 49 in the smoking group. Except for lower maternal age in the smoking group, there was no difference in gestation, BMI, gravidity, or ethnicity between the two groups. Levels of angiogenic, anti-angiogenic factors, cytokines, and sFas were similar between the two groups but sFasL levels were significantly higher in smoking group (38 pg/ml vs. 16 pg/ml, p < .001) and remained significant after controlling for confounders., Conclusion: Our study demonstrates higher sFasL levels in pregnant women who smoke. Higher sFasL may explain the reduced incidence of preeclampsia in pregnant mothers who smoke by inducing apoptosis of immune cells which may otherwise induce trophoblast apoptosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Previous analyses within the National Health and Nutrition Examination Survey (NHANES) II and III cycles suggested an association between blood lead levels (BLLs) and lung cancer mortality, although the evidence was limited by small case numbers. To clarify this relationship, we conducted updated analyses of 4,182 and 15,629 participants in NHANES II and III, respectively, (extending follow-up 20 and 8 years) aged ≥20 with BLL measurements and mortality follow-up through 2014. We fit multivariable Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) relating BLLs and lung cancer with adjustment for smoking and other factors. We did not observe an overall association between BLLs and lung cancer after adjustment for smoking (both surveys) and serum cotinine and environmental tobacco smoke exposure (NHANES III), although suggestive associations were observed among women (NHANES II: HR 2.7, 95% CI 0.7, 10.0 for ≥20.0 µg/dl vs. <10.0 µg/dl, P trend = 0.07; NHANES III: HR 11.2, 95% CI 2.1, 59.4 for ≥10.0 µg/dl vs. <2.5 µg/dl, P trend = 0.04). After stratifying on smoking status, an association with elevated BLLs was observed in NHANES II only among former smokers (HR 3.2, 95% CI 1.3, 8.0 for ≥15 vs. <15 µg/dl) and in NHANES III only among current smokers (HR 1.7, 95% CI 1.1, 2.8 for ≥5 vs. <5 µg/dl). In summary, we found elevated BLLs to be associated with lung cancer mortality among women in both NHANES II and III. Given the absence of an association among non-smokers, we cannot rule out residual confounding as an explanation for our findings., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)

Epigenome-wide mediation analysis aims to identify DNA methylation CpG sites that mediate the causal effects of genetic/environmental exposures on health outcomes. However, DNA methylations in the peripheral blood tissues are usually measured at the bulk level based on a heterogeneous population of white blood cells. Using the bulk level DNA methylation data in mediation analysis might cause confounding bias and reduce study power. Therefore, it is crucial to get fine-grained results by detecting mediation CpG sites in a cell-type-specific way. However, there is a lack of methods and software to achieve this goal. We propose a novel method (Mediation In a Cell-type-Specific fashion, MICS) to identify cell-type-specific mediation effects in genome-wide epigenetic studies using only the bulk-level DNA methylation data. MICS follows the standard mediation analysis paradigm and consists of three key steps. In step1, we assess the exposure-mediator association for each cell type; in step 2, we assess the mediator-outcome association for each cell type; in step 3, we combine the cell-type-specific exposure-mediator and mediator-outcome associations using a multiple testing procedure named MultiMed [Sampson JN, Boca SM, Moore SC, et al. FWER and FDR control when testing multiple mediators. Bioinformatics 2018;34:2418-24] to identify significant CpGs with cell-type-specific mediation effects. We conduct simulation studies to demonstrate that our method has correct FDR control. We also apply the MICS procedure to the Normative Aging Study and identify nine DNA methylation CpG sites in the lymphocytes that might mediate the effect of cigarette smoking on the lung function., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The triglyceride glucose (TyG) index is a noninsulin-based marker for insulin resistance (IR) in general practice. Although smoking and heavy drinking have been regarded as major risk factors for various chronic diseases, there is limited evidence regarding the combined effects of smoking and alcohol consumption on IR. This study aimed to investigate the relationship between the TyG index and smoking and alcohol consumption using two Korean population-based datasets., Methods: This study included 10,568 adults in the Korean National Health and Nutrition Examination Survey (KNHANES) and 9586 adults in the Korean Initiatives on Coronary Artery Calcification (KOICA) registry datasets. Multivariate logistic analysis was conducted to explore the relationship between smoking and alcohol consumption and the TyG index. To assess the predictive value of smoking and alcohol consumption on high TyG index, the area under the curve (AUC) were compared and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were derived., Results: The combined effect of smoking and alcohol consumption was an independent risk factor of a higher TyG index in the KNHANES (adjusted odds ratio: 4.33, P < .001) and KOICA (adjusted odds ratio: 1.94, P < .001) datasets. Adding smoking and alcohol consumption to the multivariate logistic models improved the model performance for the TyG index in the KNHANES (AUC: from 0.817 to 0.829, P < .001; NRI: 0.040, P < .001; IDI: 0.017, P < .001) and KOICA (AUC: from 0.822 to 0.826, P < .001; NRI: 0.025, P = .006; IDI: 0.005, P < .001) datasets., Conclusions: Smoking and alcohol consumption were independently associated with the TyG index. Concurrent smokers and alcohol consumers were more likely to have a TyG index that was ≥8.8 and higher than the TyG indices of non-users and those who exclusively consumed alcohol or smoking tobacco.

Aim: PD-L1 is an important immune intervention target for lung cancer treatment; however, its clinical significance and biological function in circulating tumor cells (CTCs) of lung cancer need to be explored in depth. Materials & methods: In this study, the CanPatrol method was used to detect three types of CTCs and PD-L1 in 271 lung cancer patients from December 2015 to October 2019. Results: Smoking index, pathological diagnosis and clinical stage are independent influencing factors of PD-L1 expression. The methods that affect the count of CTCs are first-line chemotherapy and targeted therapy; however, there is no difference in the expression of PD-L1 with different treatments. Conclusions: The detection of CTCs and PD-L1 in peripheral blood is helpful for the diagnosis of lung cancer patients.

Purpose: Cigarette smoking is a risk factor for developing nonmuscle invasive bladder cancer, and continued smoking exposure after diagnosis may increase the likelihood of adverse clinical outcomes. We compare self-reported vs biochemically verified nicotine exposure to determine the accuracy of self-report among recently diagnosed nonmuscle invasive bladder cancer patients., Materials and Methods: This cross-sectional analysis consisted of 517 nonmuscle invasive bladder cancer patients who contributed a urine or saliva specimen the same day as self-reporting their smoking, use of e-cigarettes, nicotine replacement therapy and whether they lived with a smoker. Cotinine, the primary metabolite of nicotine, was used as an objective biomarker of recent nicotine exposure., Results: The prevalence of high, low and no cotinine exposure was 13%, 54% and 33%, respectively. Overall, 7.3% of patients (38/517) reported being a current cigarette smoker, while 13% (65/517) had cotinine levels consistent with active smoking exposure. Of these 65 patients 27 denied current smoking, resulting in a sensitivity of self-reported current smoking of 58%. After considering other sources of nicotine exposure such as e-cigarettes, cigars, nicotine replacement therapy and living with a smoker, the sensitivity was higher, at 82%. Nearly all patients with low cotinine denied any smoking-related exposure., Conclusions: Our findings suggest either biochemical verification with cotinine or additional questions about other sources of nicotine are needed to accurately identify nonmuscle invasive bladder cancer patients who have smoking-related exposures. Accurate classification of active and passive smoking exposure is essential to allow clinicians to advise cessation and help researchers estimate the association between post-diagnosis smoking-related exposure and nonmuscle invasive bladder cancer recurrence risk.

Background: Studies have shown in vitro that cigarette smoke condensate stimulates monocytes to express toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1), and enhances their adhesion to the endothelium. However, the same effects of cigarette smoking have not been explored in vivo . This study is to investigate the effect of cigarette smoking and smoking cessation on their mRNA expression in human peripheral blood mononuclear cells (PBMCs)., Methods: A group of 97 smokers and 62 nonsmokers were enrolled. The RNA from PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of ICAM-1, TNF-α, and TLR4. The same markers in PBMCs of 87 quitters were examined before and at one week, one month, and two months after smoking cessation., Results: Of the 97 smokers, 85 (87.6%) were males, and 30 (48.4%) of the nonsmokers were males ( p < 0.0001). The mean (SD) age of the smokers was 43.24 (10.89) years, which was younger than 43.45 (11.41) years of nonsmokers ( p < 0.0001). The incidence of cardiovascular diseases was 13.4% in smokers, which was higher than 1.6% in nonsmokers ( p < 0.05). Both ICAM-1 and TNF-α mRNA levels in PBMCs were higher among the smokers ( p < 0.0001). In addition, TLR4 mRNA levels in PBMCs were statistically elevated in the smokers ( p < 0.0001) comparing with those in the nonsmokers. The mRNA levels of TLR4 and TNF-α in PBMCs decreased in those who had quit smoking for 2 months ( p < 0.0001)., Conclusions: ICAM-1, TNF-α, and TLR4 mRNA expression levels in PBMCs increased in smokers and decreased after being on a smoking cessation program for 2 months. This finding suggested that TLR4 expression may mediate the atherogenic inflammatory process induced by smoking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yeh, Hung, Chen, Guo, Huang, Peng, Lee and Tsai.)