{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:19:56Z","timestamp":1788311996388,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Platform, Dicle University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This study investigated the effects of zonisamide treatment on cerebellar tissues in an experimental alcohol addiction (AA) model and its potential mechanisms of action, particularly regarding apoptotic protease activating factor-1 (APAF-1) and tumor necrosis factor-alpha (TNF-\u03b1) expression. Thirty rats were divided into three groups: sham, ethanol (EtOH), and EtOH + zonisamide. AA was induced by administering 6 cc of EtOH orally every 8 h for 4 days. Zonisamide (100 mg\/kg) was given to rats once daily before EtOH administration. Motor defects were evaluated using an open field maze. Serum TNF-\u03b1 levels were measured from blood samples. Cerebellar sections were processed for histological examination and immunostained for APAF-1 and TNF-\u03b1. Protein interaction networks were constructed using Cytoscape, and functional annotations were performed with ShinyGO (version 0.80) software. The traveled area in the EtOH group was significantly reduced compared to the sham group (p = 0.0005). Rats in the EtOH + zonisamide group covered a larger area, with zonisamide treatment significantly improving locomotor ability compared to the EtOH group (p = 0.0463). Serum TNF-\u03b1 levels were significantly elevated in the EtOH group compared to the sham group (p &lt; 0.0001) and were significantly decreased in the EtOH + zonisamide group compared to the EtOH group (p = 0.0309). Regular cerebellar histological layers were observed in the sham group, while EtOH induction caused loss of cerebellar tissue integrity, neuronal degeneration, vascular dilatation and congestion, reduced myelin density, and neuropils in the EtOH group. Zonisamide treatment improved these pathologies, enhancing myelination and neuropil formation. Negative APAF-1 and TNF-\u03b1 expressions were observed across cerebellar layers in the sham group. Due to EtOH toxicity, APAF-1 and TNF-\u03b1 expression were upregulated in the EtOH group compared to the sham group (p &lt; 0.001 for both). Zonisamide treatment downregulated these protein expressions in the EtOH + zonisamide group compared to the EtOH group (p &lt; 0.001 and p = 0.0087, respectively). APAF-1 was primarily associated with AA through antifolate resistance, endopeptidases, and the interleukin-1 pathway, while TNF-\u03b1 was predominantly enriched in infections and choline-binding, indicating zonisamide\u2019s impact on immune and inflammatory pathways. In conclusion, zonisamide treatment significantly mitigated ethanol-induced cerebellar damage and inflammation in an AA model. Zonisamide improved locomotor function and reduced serum TNF-\u03b1 levels, as well as APAF-1 and TNF-\u03b1 expression in cerebellar tissues. These findings suggest that zonisamide exerts its protective effects by modulating immune and inflammatory pathways, thereby preserving cerebellar integrity and function.<\/jats:p>","DOI":"10.3390\/life14070795","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T10:41:12Z","timestamp":1719225672000},"page":"795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Zonisamide Ameliorated the Apoptosis and Inflammation in Cerebellar Tissue of Induced Alcohol Addiction Animal Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-9146","authenticated-orcid":false,"given":"F\u0131rat","family":"A\u015f\u0131r","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fikri","family":"Erdemci","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhal","family":"\u00c7ank\u0131r\u0131","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011fcan","family":"Korak","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical Faculty, Kocaeli University, 41001 Kocaeli, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00fcreyya \u00d6zdemir","family":"Ba\u015faran","sequence":"additional","affiliation":[{"name":"Department of Andrology, Gazi Yasargil Education and Research Hospital, Health Sciences University, 21090 Diyarbakir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zge","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Andrology, Gazi Yasargil Education and Research Hospital, Health Sciences University, 21090 Diyarbakir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zkan","family":"Y\u00fckselmi\u015f","sequence":"additional","affiliation":[{"name":"Division of Physical Medicine and Rehabilitation, Diyarbak\u0131r Da\u011f Kap\u0131 State Hospital, 21100 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil\u00fcfer","family":"D\u00f6nmezdil","sequence":"additional","affiliation":[{"name":"Department of Audiology, Faculty of Health Sciences, Mardin Artuklu University, 47200 Mardin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayat","family":"Ayaz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eehmus","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sel\u00e7uk","family":"Tunik","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.ncl.2014.07.013","article-title":"The human cerebellum: A review of physiologic neuroanatomy","volume":"32","author":"Roostaei","year":"2014","journal-title":"Neurol. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s12311-008-0074-4","article-title":"Cerebellum: Connections and functions","volume":"7","author":"Glickstein","year":"2008","journal-title":"Cerebellum"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1176\/jnp.12.2.193","article-title":"The role of the cerebellum in cognition and behavior: A selective review","volume":"12","author":"Rapoport","year":"2000","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_4","first-page":"138","article-title":"Alcohol and the Cerebellum: Effects on Balance, Motor Coordination, and Cognition","volume":"19","author":"Sullivan","year":"1995","journal-title":"Alcohol. Health Res. World"},{"key":"ref_5","first-page":"1922","article-title":"The effects of alcohol on gastrointestinal tract, liver and pancreas: Evidence-based suggestions for clinical management","volume":"19","author":"Federico","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/0471142301.ns0928s44","article-title":"The Majchrowicz binge alcohol protocol: An intubation technique to study alcohol dependence in rats","volume":"44","author":"Faingold","year":"2008","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/01.ALC.0000113416.65546.01","article-title":"Alcohol-induced neurodegeneration: When, where and why?","volume":"28","author":"Crews","year":"2004","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1046\/j.1471-4159.2002.01214.x","article-title":"Binge ethanol exposure decreases neurogenesis in adult rat hippocampus","volume":"83","author":"Nixon","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/alcalc\/agn079","article-title":"Mechanisms of neurodegeneration and regeneration in alcoholism","volume":"44","author":"Crews","year":"2009","journal-title":"Alcohol. Alcohol."},{"key":"ref_10","first-page":"403","article-title":"Influence of long-term drinking alcohol on the cytokines in the rats with endogenous and exogenous lung injury","volume":"17","author":"Liu","year":"2013","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.alcohol.2014.08.003","article-title":"TNF-alpha and IL-6 serum levels: Neurobiological markers of alcohol consumption in alcohol-dependent patients?","volume":"48","author":"Heberlein","year":"2014","journal-title":"Alcohol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1111\/acer.13078","article-title":"A Mechanistic Review of Cell Death in Alcohol-Induced Liver Injury","volume":"40","author":"Wang","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_13","first-page":"1258","article-title":"MiR-221 affects the proliferation and apoptosis of laryngeal cancer cells through the PI3K\/AKT signaling pathway","volume":"24","author":"Shi","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.bbrc.2014.12.012","article-title":"High-dose alcohol induces reactive oxygen species-mediated apoptosis via PKC-\u03b2\/p66Shc in mouse primary cardiomyocytes","volume":"456","author":"Wang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/01.ALC.0000163493.45344.7A","article-title":"Alcohol and mitochondria in cardiac apoptosis: Mechanisms and visualization","volume":"29","author":"Buzas","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/add.15647","article-title":"Clinical management of the alcohol withdrawal syndrome","volume":"117","author":"Day","year":"2022","journal-title":"Addiction"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s40263-015-0240-4","article-title":"Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders","volume":"29","author":"Hammond","year":"2015","journal-title":"CNS Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.13172\/2053-0285-1-1-446","article-title":"Novel anticonvulsants for reducing alcohol consumption: A review of evidence from preclinical rodent drinking models","volume":"1","author":"Padula","year":"2013","journal-title":"OA Alcohol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/JCP.0000000000000246","article-title":"Zonisamide, topiramate, and levetiracetam: Efficacy and neuropsychological effects in alcohol use disorders","volume":"35","author":"Knapp","year":"2015","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_20","first-page":"RA1","article-title":"Targets for antiepileptic drugs in the synapse","volume":"13","author":"Landmark","year":"2007","journal-title":"Med. Sci. Monit."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/JCP.0b013e3181db38bb","article-title":"Placebo-controlled trial of zonisamide for the treatment of alcohol dependence","volume":"30","author":"Arias","year":"2010","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1530-0277.2007.00592.x","article-title":"Effects of topiramate on urge to drink and the subjective effects of alcohol: A preliminary laboratory study","volume":"32","author":"Miranda","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1007\/s00701-013-1726-9","article-title":"Study the effects of zonisamide on fine structure of rabbit basilar artery and hippocampus in rabbit subarachnoid hemorrhage model","volume":"155","author":"Demirci","year":"2013","journal-title":"Acta Neurochir."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/alcalc\/agx003","article-title":"The Impact of Zonisamide on the Development and Course of Alcohol Dependence in Rabbits. A pharmaco-EEG study","volume":"52","author":"Zwierzynska","year":"2017","journal-title":"Alcohol Alcohol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.pbb.2007.04.001","article-title":"Zonisamide decreases ethanol intake in rats and mice","volume":"87","author":"Knapp","year":"2007","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.parkreldis.2007.05.008","article-title":"Effects of zonisamide on experimental tremors in rats","volume":"14","author":"Miwa","year":"2008","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s10787-018-0478-9","article-title":"A mechanistic approach to explore the neuroprotective potential of zonisamide in seizures","volume":"26","author":"Kumar","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_28","first-page":"e52434","article-title":"Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice","volume":"96","author":"Seibenhener","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.3390\/cimb46020102","article-title":"The Effects of Ellagic Acid on Experimental Corrosive Esophageal Burn Injury","volume":"46","author":"Ayaz","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Crowe, A.R., and Yue, W. (2019). Semi-quantitative Determination of Protein Expression using Immunohistochemistry Staining and Analysis: An Integrated Protocol. Bio Protoc., 9.","DOI":"10.21769\/BioProtoc.3465"},{"key":"ref_31","first-page":"219","article-title":"WIPI-2 protein expression increases in the placentas of patients with preeclampsia","volume":"31","author":"Deveci","year":"2023","journal-title":"Perinat. J."},{"key":"ref_32","unstructured":"Oliveros, J.C. (2024, February 15). Venny: An Interactive Tool for Comparing Lists with Venn\u2019s Diagrams. Available online: http:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_34","first-page":"135","article-title":"The risks associated with alcohol use and alcoholism","volume":"34","author":"Rehm","year":"2011","journal-title":"Alcohol. Res. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2018.11.005","article-title":"Gut-brain axis and addictive disorders: A review with focus on alcohol and drugs of abuse","volume":"196","author":"Jerlhag","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/B978-0-444-64189-2.00022-6","article-title":"Toxic-induced cerebellar syndrome: From the fetal period to the elderly","volume":"Volume 155","author":"Manto","year":"2018","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mitoma, H., Manto, M., and Shaikh, A.G. (2021). Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18168678"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/978-3-319-98788-0_14","article-title":"Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer","volume":"1032","author":"Marshall","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104584","DOI":"10.1016\/j.neuint.2019.104584","article-title":"Neurochemical mechanisms underlying acute and chronic ethanol-mediated responses in zebrafish: The role of mitochondrial bioenergetics","volume":"131","author":"Nunes","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0006-8993(87)90168-5","article-title":"Zonisamide enhances slow sodium inactivation in Myxicola","volume":"413","author":"Schauf","year":"1987","journal-title":"Brain Res."},{"key":"ref_41","first-page":"416","article-title":"Inhibitory effect of zonisamide on human carbonic anhydrase in vitro","volume":"43","author":"Masuda","year":"1993","journal-title":"Arzneimittelforschung"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1080\/00952990903060150","article-title":"The anticonvulsant zonisamide reduces ethanol self-administration by risky drinkers","volume":"35","author":"Knapp","year":"2009","journal-title":"Am. J. Drug Alcohol. Abuse"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"102024","DOI":"10.1016\/j.tice.2023.102024","article-title":"Zonisamide improves Fas\/FasL-mediated apoptosis and inflammation in a degenerative cervical myelopathy rat model","volume":"81","author":"Wang","year":"2023","journal-title":"Tissue Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0006-8993(97)00789-0","article-title":"Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: A histological, in vivo microdialysis and behavioral study","volume":"770","author":"Owen","year":"1997","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0014-2999(94)90704-8","article-title":"Zonisamide reduces hypoxic-ischemic brain damage in neonatal rats irrespective of its anticonvulsive effect","volume":"257","author":"Hayakawa","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.biochi.2017.02.001","article-title":"Apaf-1: Regulation and function in cell death","volume":"135","author":"Shakeri","year":"2017","journal-title":"Biochimie"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1007\/s12311-014-0591-2","article-title":"Apoptosis of Purkinje and granular cells of the cerebellum following chronic ethanol intake","volume":"13","author":"Oliveira","year":"2014","journal-title":"Cerebellum"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113849","DOI":"10.1016\/j.fct.2023.113849","article-title":"Alcohol induces apoptosis and autophagy in microglia BV-2 cells","volume":"177","author":"Wang","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/alcalc\/agm166","article-title":"Alcohol exposure alters cell cycle and apoptotic events during early neurulation","volume":"43","author":"Anthony","year":"2008","journal-title":"Alcohol Alcohol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s12311-015-0674-8","article-title":"Effects of Ethanol on the Cerebellum: Advances and Prospects","volume":"14","author":"Luo","year":"2015","journal-title":"Cerebellum"},{"key":"ref_51","first-page":"9370","article-title":"Alcohol consumption promotes colorectal cancer by altering intestinal permeability","volume":"24","author":"Diao","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.alcohol.2008.04.008","article-title":"Serum TNF-alpha levels in relation to alcohol consumption and common TNF gene polymorphisms","volume":"42","author":"Campos","year":"2008","journal-title":"Alcohol"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1002\/hep.510260622","article-title":"Dietary saturated fatty acids down-regulate cyclooxygenase-2 and tumor necrosis factor alfa and reverse fibrosis in alcohol-induced liver disease in the rat","volume":"26","author":"Nanji","year":"1997","journal-title":"Hepatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000104236","article-title":"Effect of ethanol on inflammatory responses. Implications for pancreatitis","volume":"7","author":"Szabo","year":"2007","journal-title":"Pancreatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.bbi.2020.08.002","article-title":"Alcohol use disorder and circulating cytokines: A systematic review and meta-analysis","volume":"89","author":"Adams","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Czerwinska-Blaszczyk, A., Pawlak, E., and Pawlowski, T. (2021). The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.797123"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bbi.2023.02.020","article-title":"Chronic ethanol induces a pro-inflammatory switch in interleukin-1beta regulation of GABAergic signaling in the medial prefrontal cortex of male mice","volume":"110","author":"Varodayan","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/mnfr.201200077","article-title":"Folate, alcohol, and liver disease","volume":"57","author":"Medici","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12995-018-0209-6","article-title":"Olfactory dysfunction revisited: A reappraisal of work-related olfactory dysfunction caused by chemicals","volume":"13","author":"Werner","year":"2018","journal-title":"J. Occup. Med. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Teixeira, M.C., Pacheco, F.T., Souza, J.N., Silva, M.L., Ines, E.J., and Soares, N.M. (2016). Strongyloides stercoralis Infection in Alcoholic Patients. Biomed. Res. Int., 2016.","DOI":"10.1155\/2016\/4872473"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"de Souza, J.N., Oliveira, C.L., Araujo, W.A.C., Souza, A.B.S., Silva, M.L.S., da Cruz, I.D.R., Sampaio, L.M., Dos Santos, J.S.B., Teixeira, M.C.A., and Soares, N.M. (2020). Strongyloides stercoralis in Alcoholic Patients: Implications of Alcohol Intake in the Frequency of Infection and Parasite Load. Pathogens, 9.","DOI":"10.3390\/pathogens9060422"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/2211-5463.12270","article-title":"A G protein-coupled alpha7 nicotinic receptor regulates signaling and TNF-alpha release in microglia","volume":"7","author":"King","year":"2017","journal-title":"FEBS Open Bio"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, X., Korner, H., and Liu, X. (2020). Susceptibility to Intracellular Infections: Contributions of TNF to Immune Defense. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01643"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"100645","DOI":"10.1016\/j.bbih.2023.100645","article-title":"IL-6, but not TNF-alpha, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers","volume":"31","author":"Blaine","year":"2023","journal-title":"Brain Behav. Immun. Health"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/7\/795\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:03:29Z","timestamp":1760108609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/7\/795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,24]]},"references-count":64,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["life14070795"],"URL":"https:\/\/doi.org\/10.3390\/life14070795","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,24]]}}}