{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:53Z","timestamp":1792166333305,"version":"4.4.0"},"reference-count":98,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["#2020\/10362-0"],"award-info":[{"award-number":["#2020\/10362-0"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["#2020\/10322-9"],"award-info":[{"award-number":["#2020\/10322-9"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["#2022\/16249-7"],"award-info":[{"award-number":["#2022\/16249-7"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)","award":["#2020\/10362-0"],"award-info":[{"award-number":["#2020\/10362-0"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)","award":["#2020\/10322-9"],"award-info":[{"award-number":["#2020\/10322-9"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)","award":["#2022\/16249-7"],"award-info":[{"award-number":["#2022\/16249-7"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In recent years, the use of electronic cigarettes (e-cigs) has increased. However, their long-term effects on oral health and saliva remain poorly understood. Therefore, this study aimed to evaluate the saliva of e-cig users and investigate possible biomarkers. Participants were divided into two groups: the Electronic Cigarette Group (EG)\u201425 regular and exclusive e-cig users\u2014and Control Group (CG)\u201425 non-smokers and non-e-cig users, matched in sex and age to the EG. The clinical analysis included the following parameters: age, sex, heart rate, oximetry, capillary blood glucose, carbon monoxide (CO) concentration in exhaled air, and alcohol use disorder identification test (AUDIT). Qualitative and quantitative analyses of saliva included sialometry, viscosity, pH, and cotinine concentrations. Furthermore, the EG and CG salivary metabolomes were compared using gas chromatography coupled with mass spectrometry (GC-MS). Data were analyzed using the Mann\u2013Whitney test. The MetaboAnalyst 6.0 software was used for statistical analysis and biomarker evaluation. The EG showed high means for exhaled CO concentration and AUDIT but lower means for oximetry and salivary viscosity. Furthermore, 10 metabolites (isoleucine, 2-hydroxyglutaric acid, 3-phenyl-lactic acid, linoleic acid, 3-hydroxybutyric acid, 1,6-anhydroglucose, glucuronic acid, valine, stearic acid, and elaidic acid) were abundant in EG but absent in CG. It was concluded that e-cig users had high rates of alcohol consumption and experienced significant impacts on their general health, including increased cotinine and CO concentration in exhaled air, decreased oximetry, and low salivary viscosity. Furthermore, they showed a notable increase in salivary metabolites, especially those related to inflammation, xenobiotic metabolism, and biomass-burning pathways.<\/jats:p>","DOI":"10.3390\/ijms252111750","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:59:54Z","timestamp":1730437194000},"page":"11750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Salivary Metabolic Pathway Alterations in Brazilian E-Cigarette Users"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2064-5220","authenticated-orcid":false,"given":"Bruna Fernandes do Carmo","family":"Carvalho","sequence":"first","affiliation":[{"name":"Instituto de Ci\u00eancia e Tecnologia, Universidade Estadual Paulista (UNESP), C\u00e2mpus S\u00e3o Jos\u00e9 dos Campos, Av. Eng. Francisco Jos\u00e9 Longo, 777, S\u00e3o Dimas, S\u00e3o Jos\u00e9 dos Campos 12245-000, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia de Carvalho","family":"Faria","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancia e Tecnologia, Universidade Estadual Paulista (UNESP), C\u00e2mpus S\u00e3o Jos\u00e9 dos Campos, Av. Eng. Francisco Jos\u00e9 Longo, 777, S\u00e3o Dimas, S\u00e3o Jos\u00e9 dos Campos 12245-000, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kethilyn Chris Sousa","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancia e Tecnologia, Universidade Estadual Paulista (UNESP), C\u00e2mpus S\u00e3o Jos\u00e9 dos Campos, Av. Eng. Francisco Jos\u00e9 Longo, 777, S\u00e3o Dimas, S\u00e3o Jos\u00e9 dos Campos 12245-000, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Greenfield","sequence":"additional","affiliation":[{"name":"Technology Research Center (NPT), Universidade Mogi das Cruzes, Mogi das Cruzes 08780-911, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica Ghislaine Oliveira","family":"Alves","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancia e Tecnologia, Universidade Estadual Paulista (UNESP), C\u00e2mpus S\u00e3o Jos\u00e9 dos Campos, Av. Eng. Francisco Jos\u00e9 Longo, 777, S\u00e3o Dimas, S\u00e3o Jos\u00e9 dos Campos 12245-000, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriellen","family":"Dias","sequence":"additional","affiliation":[{"name":"Dempster MS Lab, Department of Chemical Engineering, Polytechnic School, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-040, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-9286","authenticated-orcid":false,"given":"Maria Anita","family":"Mendes","sequence":"additional","affiliation":[{"name":"Dempster MS Lab, Department of Chemical Engineering, Polytechnic School, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-040, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-9868","authenticated-orcid":false,"given":"Mario","family":"P\u00e9rez-Say\u00e1ns","sequence":"additional","affiliation":[{"name":"Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"ORALRES Group, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), 15782 Santiago de Compostela, Spain"},{"name":"Instituto de los Materiales de Santiago de Compostela (iMATUS), 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-9715","authenticated-orcid":false,"given":"Janete Dias","family":"Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancia e Tecnologia, Universidade Estadual Paulista (UNESP), C\u00e2mpus S\u00e3o Jos\u00e9 dos Campos, Av. Eng. Francisco Jos\u00e9 Longo, 777, S\u00e3o Dimas, S\u00e3o Jos\u00e9 dos Campos 12245-000, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1590\/S1806-37132014000500013","article-title":"The electronic cigarette: The new cigarette of the 21st century?","volume":"40","author":"Knorst","year":"2014","journal-title":"J. Bras. De Pneumol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100143","DOI":"10.1016\/j.dadr.2023.100143","article-title":"The role of flavored electronic nicotine delivery systems in smoking cessation: A systematic review","volume":"7","author":"Liber","year":"2023","journal-title":"Drug Alcohol Depend. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.18332\/tid\/116988","article-title":"Harmful chemicals emitted from electronic cigarettes and potential deleterious effects in the oral cavity","volume":"18","author":"Ebersole","year":"2020","journal-title":"Tob. Induc. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Travis, N., Knoll, M., Cook, S., Oh, H., Cadham, C.J., S\u00e1nchez-Romero, L.M., and Levy, D.T. (2023). Chemical Profiles and Toxicity of Electronic Cigarettes: An Umbrella Review and Methodological Considerations. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20031908"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36001","DOI":"10.1289\/EHP5686","article-title":"Metal\/Metalloid Levels in Electronic Cigarette Liquids, Aerosols, and Human Biosamples: A Systematic Review","volume":"128","author":"Zhao","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1067\/mpr.2001.113778","article-title":"A review of saliva: Normal composition, flow, and function","volume":"85","author":"Humphrey","year":"2001","journal-title":"J. Prosthet. Dent."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0003-9969(01)00003-6","article-title":"Relationships between medication intake, complaints of dry mouth, salivary flow rate and composition, and the rate of tooth demineralization in situ","volume":"46","author":"Bardow","year":"2001","journal-title":"Arch. Oral Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"077014","DOI":"10.1289\/EHP1011","article-title":"The Saliva Exposome for Monitoring of Individuals\u2019 Health Trajectories","volume":"125","author":"Bessonneau","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Washio, J., and Takahashi, N. (2016). Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060870"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1007\/s12010-012-9891-5","article-title":"Saliva Metabolomics Opens Door to Biomarker Discovery, Disease Diagnosis, and Treatment","volume":"168","author":"Zhang","year":"2012","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_11","unstructured":"World Health Organization (WHO) (2024, May 15). WHO Report on the Global Tobacco Epidemic, 2021: Addressing New and Emerging Products. 2021. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/326043."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cca.2013.03.033","article-title":"Metabolomics in chronic kidney disease","volume":"422","author":"Zhao","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1177\/1535370220941258","article-title":"Electronic nicotine delivery system-induced alterations in oral health via saliva assessment","volume":"245","author":"Alqahtani","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"de S\u00e1 Alves, M., de S\u00e1 Rodrigues, N., Bandeira, C.M., Chagas, J.F.S., Pascoal, M.B.N., Nepomuceno, G.L.J.T., Martinho, H.d.S., Alves, M.G.O., Mendes, M.A., and Dias, M. (2021). Identification of Possible Salivary Metabolic Biomarkers and Altered Metabolic Pathways in South American Patients Diagnosed with Oral Squamous Cell Carcinoma. Metabolites, 11.","DOI":"10.3390\/metabo11100650"},{"key":"ref_15","unstructured":"World Health Organization (WHO) (2024, June 10). WHO Report on the Global Tobacco Epidemic 2023: Protect People from Tobacco Smoke. 2023. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240077164."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3949\/ccjm.86a.19118","article-title":"Vaping: The new wave of nicotine addiction","volume":"86","author":"Dinardo","year":"2019","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_17","first-page":"381","article-title":"Tobacco use among middle and high school students\u2014United States, 2011\u20132014","volume":"64","author":"Arrazola","year":"2015","journal-title":"Morb. Mortal. Wkly. Rep. (MMWR)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.oooo.2022.07.019","article-title":"Global frequency and epidemiological profile of electronic cigarette users: A systematic review","volume":"134","author":"Martins","year":"2022","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/ntr\/ntv237","article-title":"Patterns of Electronic Cigarette Use Among Adults in the United States","volume":"18","author":"Delnevo","year":"2016","journal-title":"Nicotine Tob. Res."},{"key":"ref_20","unstructured":"Action on Smoking and Health (ASH) (2024, August 23). Use of e-Cigarettes (Vapes) Among Adults in Great Britain. 2021. Available online: https:\/\/ash.org.uk\/uploads\/Use-of-e-cigarettes-vapes-among-adults-in-Great-Britain-2021.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.jadohealth.2019.02.019","article-title":"Adolescents\u2019 E-Cigarette Use: Increases in Frequency, Dependence, and Nicotine Exposure Over 12 Months","volume":"64","author":"Vogel","year":"2019","journal-title":"J. Adolesc. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1921513","DOI":"10.1001\/jamanetworkopen.2019.21513","article-title":"Prevalence of Electronic Cigarette Dependence Among Youth and Its Association With Future Use","volume":"3","author":"Vogel","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ypmed.2014.10.009","article-title":"A systematic review of health effects of electronic cigarettes","volume":"69","author":"Pisinger","year":"2014","journal-title":"Prev. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/ntr\/nts145","article-title":"FDA Summary of Adverse Events on Electronic Cigarettes","volume":"15","author":"Chen","year":"2013","journal-title":"Nicotine Tob. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1007\/s00508-020-01711-z","article-title":"Health effects of electronic cigarette (e-cigarette) use on organ systems and its implications for public health","volume":"133","author":"Sandner","year":"2021","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Espinoza-Derout, J., Shao, X.M., Lao, C.J., Hasan, K.M., Rivera, J.C., Jordan, M.C., Echeverria, V., Roos, K.P., Sinha-Hikim, A.P., and Friedman, T.C. (2022). Electronic Cigarette Use and the Risk of Cardiovascular Diseases. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.879726"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1164\/rccm.201604-0804OC","article-title":"Electronic Cigarette Use and Respiratory Symptoms in Adolescents","volume":"195","author":"McConnell","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/15563650.2022.2160342","article-title":"E-cigarette or vaping-associated lung injury (EVALI): A review of international case reports from outside the United States of America","volume":"61","author":"Sund","year":"2023","journal-title":"Clin. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1136\/tc.2010.037614","article-title":"The effect of S\u00e3o Paulo\u2019s smoke-free legislation on carbon monoxide concentration in hospitality venues and their workers","volume":"20","author":"Issa","year":"2011","journal-title":"Tob. Control"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.oooo.2020.11.009","article-title":"E-cig might cause cell damage of oral mucosa","volume":"131","author":"Schwarzmeier","year":"2021","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_31","first-page":"1","article-title":"Smoking cessation decreases arterial blood pressure in hypertensive smokers: A subgroup analysis of the randomized controlled trial, GENTSMOKING","volume":"22","author":"Gaya","year":"2024","journal-title":"Tob. Induc. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/prd.12102","article-title":"Salivary changes in oral mucosal diseases","volume":"70","author":"Hassona","year":"2016","journal-title":"Periodontology 2000"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/joor.12664","article-title":"Salivary secretion in health and disease","volume":"45","author":"Pedersen","year":"2018","journal-title":"J. Oral Rehabil."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cicho\u0144ska, D., Kusiak, A., Kocha\u0144ska, B., Ochoci\u0144ska, J., and \u015awietlik, D. (2022). Influence of Electronic Cigarettes on Selected Physicochemical Properties of Saliva. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19063314"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1600-0722.1984.tb00897.x","article-title":"Stimulated salivary flow rate, pH and lactobacillus and yeast concentrations in non-smokers and smokers","volume":"92","author":"Parvinen","year":"1984","journal-title":"Eur. J. Oral Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5152\/balkanmedj.2021.20125","article-title":"Effects of Oral pH Changes on Smoking Desire","volume":"38","author":"Kilinc","year":"2021","journal-title":"Balk. Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"ii36","DOI":"10.1136\/tobaccocontrol-2013-051470","article-title":"Electronic cigarettes: Human health effects","volume":"23","year":"2014","journal-title":"Tob. Control"},{"key":"ref_38","first-page":"1","article-title":"Profile of Brazilian Undergraduates Who Use Electronic Cigarettes: A Cross-Sectional Study on Forbidden Use","volume":"2023","author":"Andrade","year":"2023","journal-title":"Int. J. Ment. Health Addict."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e210007","DOI":"10.1590\/1980-549720210007.supl.2","article-title":"Prevalence of electronic nicotine delivery systems and waterpipe use in Brazil: Where are we going?","volume":"24","author":"Bertoni","year":"2021","journal-title":"Rev. Bras. Epidemiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.12669\/pjms.294.3696","article-title":"Effects of alcohol on the morphological and structural changes in oral mucosa","volume":"29","author":"Feng","year":"2013","journal-title":"Pak. J. Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hoes, L., Dok, R., Verstrepen, K.J., and Nuyts, S. (2021). Ethanol-Induced Cell Damage Can Result in the Development of Oral Tumors. Cancers, 13.","DOI":"10.3390\/cancers13153846"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41568-021-00423-4","article-title":"Smokeless tobacco and cigarette smoking: Chemical mechanisms and cancer prevention","volume":"22","author":"Hecht","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1111\/odi.14196","article-title":"Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium","volume":"29","author":"Goyal","year":"2023","journal-title":"Oral Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Fan, X., Peters, B.A., Jacobs, E.J., Gapstur, S.M., Purdue, M.P., Freedman, N.D., Alekseyenko, A.V., Wu, J., Yang, L., and Pei, Z. (2018). Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults. Microbiome, 6.","DOI":"10.1186\/s40168-018-0448-x"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"108496","DOI":"10.1016\/j.drugalcdep.2020.108496","article-title":"Bidirectional associations between e-cigarette use and alcohol use across adolescence","volume":"220","author":"Lozano","year":"2021","journal-title":"Drug Alcohol Depend."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1056\/NEJMsr2306723","article-title":"The IARC Perspective on Alcohol Reduction or Cessation and Cancer Risk","volume":"389","author":"Gapstur","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.addbeh.2018.08.025","article-title":"Relative influence of perceived peer and family substance use on adolescent alcohol, cigarette, and marijuana use across middle and high school","volume":"88","author":"Schuler","year":"2019","journal-title":"Addict. Behav."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Trucco, E.M. (2020). A review of psychosocial factors linked to adolescent substance use. Pharmacol. Biochem. Behav., 196.","DOI":"10.1016\/j.pbb.2020.172969"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.5993\/AJHB.43.1.1","article-title":"Adolescent Tobacco Uptake and Other Substance Use: A Latent Class Analysis","volume":"43","author":"Delk","year":"2019","journal-title":"Am. J. Health Behav."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1038\/npp.2015.139","article-title":"Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling","volume":"40","author":"Spoelder","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_51","first-page":"100690","article-title":"The impact of colonialism on head and neck cancer in Brazil: A historical essay focussing on tobacco, alcohol and slavery","volume":"31","author":"Martins","year":"2024","journal-title":"Lancet Reg. Health-Am."},{"key":"ref_52","unstructured":"Vigitel (2024, July 10). Vigitel Brazil 2006\u20132023: Smoking and Alcohol Abuse. Surveillance of Risk and Protective Factors for Chronic Diseases by Telephone Survey: Estimates of Frequency and Sociodemographic Distribution of Smoking and Alcohol abuse in the Capitals of the 26 Brazilian States and the Federal District Between 2006 and 2023. 2023, Available online: https:\/\/www.gov.br\/saude\/pt-br\/centrais-de-conteudo\/publicacoes\/svsa\/vigitel\/vigitel-brasil-2006-2023-tabagismo-e-consumo-abusivo-de-alcool\/view."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.15585\/mmwr.mm6937e1","article-title":"E-cigarette Use Among Middle and High School Students\u2014United States, 2020","volume":"69","author":"Wang","year":"2020","journal-title":"Morb. Mortal. Wkly. Rep. (MMWR)"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1080\/17425247.2020.1814736","article-title":"Nicotine forms: Why and how do they matter in nicotine delivery from electronic cigarettes?","volume":"17","author":"Gholap","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_55","unstructured":"Brazilian Health Regulatory Agency (Anvisa) (2024, July 10). Resolution RDC 14\/2012. 2012, Available online: https:\/\/antigo.anvisa.gov.br\/legislacao#\/visualizar\/28843."},{"key":"ref_56","unstructured":"World Health Organization (WHO) (2023). Study Group on Tobacco Product Regulation; Report on the Scientific Basis of Tobacco Product Regulation: Ninth Report of a WHO Study Group, WHO."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.etap.2018.05.016","article-title":"Clinical and radiographic periodontal status and whole salivary cotinine, IL-1\u03b2 and IL-6 levels in cigarette- and waterpipe-smokers and E-cig users","volume":"61","author":"Mokeem","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/ntr\/ntz232","article-title":"Characterization of Nicotine Salts in 23 Electronic Cigarette Refill Liquids","volume":"22","author":"Harvanko","year":"2020","journal-title":"Nicotine Tob. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/10408444.2020.1794443","article-title":"A review of toxic effects of electronic cigarettes\/vaping in adolescents and young adults","volume":"50","author":"Overbeek","year":"2020","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Morean, M.E., Butler, E.R., Bold, K.W., Kong, G., Camenga, D.R., Cavallo, D.A., Simon, P., O\u2019malley, S.S., and Krishnan-Sarin, S. (2018). Preferring more e-cigarette flavors is associated with e-cigarette use frequency among adolescents but not adults. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204349"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.jadohealth.2015.01.022","article-title":"Tripling Use of Electronic Cigarettes Among New Zealand Adolescents Between 2012 and 2014","volume":"56","author":"White","year":"2015","journal-title":"J. Adolesc. Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"a012120","DOI":"10.1101\/cshperspect.a012120","article-title":"Short- and Long-Term Consequences of Nicotine Exposure during Adolescence for Prefrontal Cortex Neuronal Network Function","volume":"2","author":"Goriounova","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.drugalcdep.2016.09.014","article-title":"Effects of sweet flavorings and nicotine on the appeal and sensory properties of e-cigarettes among young adult vapers: Application of a novel methodology","volume":"168","author":"Goldenson","year":"2016","journal-title":"Drug Alcohol Depend."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"ii32","DOI":"10.1136\/tobaccocontrol-2016-053192","article-title":"Flavour preferences in youth versus adults: A review","volume":"25","author":"Hoffman","year":"2016","journal-title":"Tob. Control"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11306-023-02038-2","article-title":"Metabolomics of head and neck cancer in biofluids: An integrative systematic review","volume":"19","author":"Chuchueva","year":"2023","journal-title":"Metabolomics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/nbm.1369","article-title":"Understanding the human salivary metabolome","volume":"22","author":"Takeda","year":"2009","journal-title":"NMR Biomed."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.fct.2003.08.009","article-title":"The effect of tobacco ingredients on smoke chemistry. Part II Casing Ingred","volume":"42","author":"Baker","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"207S","DOI":"10.1093\/jn\/136.1.207S","article-title":"Branched-Chain Amino Acids: Enzyme and Substrate Regulation","volume":"136","author":"Brosnan","year":"2006","journal-title":"J. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.arr.2014.05.004","article-title":"Krebs cycle intermediates regulate DNA and histone methylation: Epigenetic impact on the aging process","volume":"16","author":"Salminen","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/bbb\/zbad169","article-title":"Valine improves mitochondrial function and protects against oxidative stress","volume":"88","author":"Sharma","year":"2024","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2303489","DOI":"10.1002\/advs.202303489","article-title":"Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype","volume":"11","author":"Liang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s11306-009-0178-y","article-title":"Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles","volume":"6","author":"Sugimoto","year":"2010","journal-title":"Metabolomics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1002\/ijc.25881","article-title":"Salivary metabolite signatures of oral cancer and leukoplakia","volume":"129","author":"Wei","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1161\/CIRCRESAHA.120.317828","article-title":"Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers","volume":"129","author":"Gupta","year":"2021","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1001\/jamacardio.2016.5303","article-title":"Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users","volume":"2","author":"Moheimani","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1017\/S0007114508992576","article-title":"Bioactive dietary long-chain fatty acids: Emerging mechanisms of action","volume":"100","author":"Chapkin","year":"2008","journal-title":"Br. J. Nutr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1161\/CIRCULATIONAHA.118.038908","article-title":"Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality","volume":"139","author":"Marklund","year":"2019","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Mercola, J., and D\u2019Adamo, C.R. (2023). Linoleic Acid: A Narrative Review of the Effects of Increased Intake in the Standard American Diet and Associations with Chronic Disease. Nutrients, 15.","DOI":"10.3390\/nu15143129"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Liu, H., Nan, B., Yang, C., Li, X., Yan, H., and Yuan, Y. (2022). Elaidic acid induced NLRP3 inflammasome activation via ERS-MAPK signaling pathways in Kupffer cells. Biochim. Et Biophys. Acta (BBA)-Mol. Cell Biol. Lipids, 1867.","DOI":"10.1016\/j.bbalip.2021.159061"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"114060","DOI":"10.1016\/j.fct.2023.114060","article-title":"Elaidic acid induced hepatocyte pyroptosis via autophagy-CTSB-NLRP3 pathway","volume":"181","author":"Lu","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.atherosclerosis.2017.09.004","article-title":"Stearic acid at physiologic concentrations induces in vitro lipotoxicity in circulating angiogenic cells","volume":"265","author":"Spigoni","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e20220598","DOI":"10.36660\/abc.20220598","article-title":"\u00c1cido Este\u00e1rico (mas n\u00e3o o \u00c1cido Palm\u00edtico) est\u00e1 Associado a Biomarcadores Inflamat\u00f3rios e de Disfun\u00e7\u00e3o Endotelial em Indiv\u00edduos em Risco Cardiovascular","volume":"120","author":"Sampaio","year":"2023","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"36845","DOI":"10.1021\/acsomega.3c03683","article-title":"Preliminary Findings on the Salivary Metabolome of Hookah and Cigarette Smokers","volume":"8","author":"Greenfield","year":"2023","journal-title":"ACS Omega"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Fujiwara, R., Yokoi, T., and Nakajima, M. (2016). Structure and Protein\u2013Protein Interactions of Human UDP-Glucuronosyltransferases. Front. Pharmacol., 7.","DOI":"10.3389\/fphar.2016.00388"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10334-009-0171-5","article-title":"Detection and quantification of d-glucuronic acid in human bile using 1H NMR spectroscopy: Relevance to the diagnosis of pancreatic cancer","volume":"22","author":"Bezabeh","year":"2009","journal-title":"Magn. Reson. Mater. Phys. Biol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e995","DOI":"10.1002\/ctm2.995","article-title":"Dysregulated glucuronic acid metabolism exacerbates hepatocellular carcinoma progression and metastasis through the TGF\u03b2 signalling pathway","volume":"12","author":"Gao","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"843","DOI":"10.18632\/oncotarget.28514","article-title":"UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology","volume":"14","author":"Price","year":"2023","journal-title":"Oncotarget"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1352-2310(98)00145-9","article-title":"Levoglucosan, a tracer for cellulose in biomass burning and atmospheric particles","volume":"33","author":"Simoneit","year":"1999","journal-title":"Atmos. Environ."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bano\u017ei\u0107, M., Joki\u0107, S., A\u010dkar, \u0110., Bla\u017ei\u0107, M., and \u0160ubari\u0107, D. (2020). Carbohydrates\u2014Key Players in Tobacco Aroma Formation and Quality Determination. Molecules, 25.","DOI":"10.3390\/molecules25071734"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"111790","DOI":"10.1016\/j.envres.2021.111790","article-title":"Inhalable cigarette-burning particles: Size-resolved chemical composition and mixing state","volume":"202","author":"Zhang","year":"2021","journal-title":"Environ. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1080\/02786826.2017.1300231","article-title":"Environmental pollution and emission factors of electronic cigarettes, heat-not-burn tobacco products, and conventional cigarettes","volume":"51","author":"Ruprecht","year":"2017","journal-title":"Aerosol Sci. Technol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0021-9673(99)00322-2","article-title":"Qualitative and quantitative evaluation of mono- and disaccharides in d-fructose, d-glucose and sucrose caramels by gas\u2013liquid chromatography\u2013mass spectrometry","volume":"844","author":"Ratsimba","year":"1999","journal-title":"J. Chromatogr. A"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/jes.2009.46","article-title":"Urinary levoglucosan as a biomarker of wood smoke: Results of human exposure studies","volume":"20","author":"Bergauff","year":"2010","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/168584","article-title":"Saliva: A Cutting Edge in Diagnostic Procedures","volume":"2014","author":"Sindhu","year":"2014","journal-title":"J. Oral Dis."},{"key":"ref_96","unstructured":"Brazilian Health Regulatory Agency (Anvisa) (2024, August 01). Resolution RDC 855\/2024. 2024, Available online: https:\/\/www.gov.br\/anvisa\/pt-br\/assuntos\/tabaco\/cigarro-eletronico."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1159\/000260369","article-title":"Individual Diagnosis, Prognosis and Counselling for Caries Prevention","volume":"12","author":"Ericsson","year":"1978","journal-title":"Caries Res."},{"key":"ref_98","first-page":"53","article-title":"Evaluation of total unstimulated saliva viscosity in complete edentulous patients","volume":"3","author":"Murineanu","year":"2011","journal-title":"Rom. J. Oral Rehabil."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:26:34Z","timestamp":1760113594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":98,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111750"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111750","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,1]]}}}