{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:05:52Z","timestamp":1760299552408,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T00:00:00Z","timestamp":1489104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs\/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug\/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug\/compound\u2019s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs\/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.<\/jats:p>","DOI":"10.3390\/toxins9030099","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T09:39:55Z","timestamp":1489138795000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection"],"prefix":"10.3390","volume":"9","author":[{"given":"Jane","family":"Bai","sequence":"first","affiliation":[{"name":"Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore","family":"Sakellaropoulos","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA"},{"name":"School of Mechanical Engineering, National Technical University of Athens, Zografou 15780, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas","family":"Alexopoulos","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, National Technical University of Athens, Zografou 15780, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1017\/S0950268815001442","article-title":"Human anthrax outbreak associated with livestock exposure: Georgia, 2012","volume":"144","author":"Navdarashvili","year":"2016","journal-title":"Epidemiol. Infect."},{"key":"ref_2","unstructured":"(2011). Review of the Scientific Approaches Used during the FBI\u2019s Investigation of the 2001 Anthrax Letters, The National Academies Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1126\/science.7973702","article-title":"The Sverdlovsk anthrax outbreak of 1979","volume":"266","author":"Meselson","year":"1994","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1073\/pnas.90.6.2291","article-title":"Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979","volume":"90","author":"Abramova","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/modpathol.3880337","article-title":"Quantitative pathology of inhalational anthrax I: Quantitative microscopic findings","volume":"14","author":"Grinberg","year":"2001","journal-title":"Mod. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.tim.2014.02.012","article-title":"Anthrax lethal and edema toxins in anthrax pathogenesis","volume":"22","author":"Liu","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.3390\/toxins3091185","article-title":"The potential contributions of lethal and edema toxins to the pathogenesis of anthrax associated shock","volume":"3","author":"Hicks","year":"2011","journal-title":"Toxins (Basel)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/n35101999","article-title":"Identification of the cellular receptor for anthrax toxin","volume":"414","author":"Bradley","year":"2001","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1365-2958.1994.tb00500.x","article-title":"Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity","volume":"13","author":"Klimpel","year":"1994","journal-title":"Mol. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1042\/bj3520739","article-title":"Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor","volume":"352 Pt 3","author":"Vitale","year":"2000","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1046\/j.1365-2672.1999.00892.x","article-title":"Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase","volume":"87","author":"Duesbery","year":"1999","journal-title":"J. Appl. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1111\/j.1462-5822.2008.01220.x","article-title":"Heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin","volume":"10","author":"Levin","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_13","first-page":"332","article-title":"Anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome","volume":"10","author":"Wickliffe","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1073\/pnas.79.10.3162","article-title":"Anthrax toxin edema factor: A bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells","volume":"79","author":"Leppla","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.1128\/IAI.00275-06","article-title":"Anthrax lethal toxin impairs innate immune functions of alveolar macrophages and facilitates bacillus anthracis survival","volume":"74","author":"Ribot","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature01794","article-title":"Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin","volume":"424","author":"Agrawal","year":"2003","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1007\/s00018-004-4251-4","article-title":"Anthrax lethal toxin: A weapon of multisystem destruction","volume":"61","author":"Agrawal","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Popova, T.G., Espina, V., Zhou, W., Mueller, C., Liotta, L., and Popov, S.G. (2014). Whole proteome analysis of mouse lymph nodes in cutaneous anthrax. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110873"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.4049\/jimmunol.174.8.4934","article-title":"Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells","volume":"174","author":"Tournier","year":"2005","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8275","DOI":"10.1128\/IAI.73.12.8275-8281.2005","article-title":"Direct inhibition of T-lymphocyte activation by anthrax toxins in vivo","volume":"73","author":"Comer","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1128\/iai.62.10.4432-4439.1994","article-title":"Anthrax edema toxin differentially regulates lipopolysaccharide-induced monocyte production of tumor necrosis factor alpha and interleukin-6 by increasing intracellular cyclic AMP","volume":"62","author":"Hoover","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1128\/IAI.00905-08","article-title":"Bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase A and exchange protein activated by cyclic amp pathways","volume":"77","author":"Yeager","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1002\/jcp.22859","article-title":"Anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling","volume":"227","author":"Liu","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/S0002-9440(10)62496-0","article-title":"Anthrax lethal toxin induces endothelial barrier dysfunction","volume":"166","author":"Warfel","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.chom.2011.09.014","article-title":"cAMP signaling by anthrax edema toxin induces transendothelial cell tunnels, which are resealed by MIM via Arp2\/3-driven actin polymerization","volume":"10","author":"Maddugoda","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19781","DOI":"10.1074\/jbc.M700128200","article-title":"Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1","volume":"282","author":"Hong","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1039\/C4IB00294F","article-title":"Identification of drug-specific pathways based on gene expression data: Application to drug induced lung injury","volume":"7","author":"Melas","year":"2015","journal-title":"Integr. Biol. (Camb.)"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Levinsohn, J.L., Newman, Z.L., Hellmich, K.A., Fattah, R., Getz, M.A., Liu, S., Sastalla, I., Leppla, S.H., and Moayeri, M. (2012). Anthrax lethal factor cleavage of NLRP1 is required for activation of the inflammasome. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002638"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.micinf.2011.12.005","article-title":"Anthrax and the inflammasome","volume":"14","author":"Moayeri","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25030","DOI":"10.1074\/jbc.M112.378323","article-title":"Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inflammasome activity","volume":"287","author":"Finger","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/24884","article-title":"Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP","volume":"396","author":"Zwartkruis","year":"1998","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1128\/AAC.01184-06","article-title":"Amiodarone and bepridil inhibit anthrax toxin entry into host cells","volume":"51","author":"Sanchez","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1086\/424853","article-title":"Chloroquine enhances survival in bacillus anthracis intoxication","volume":"190","author":"Artenstein","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5139","DOI":"10.1016\/j.bmc.2009.05.054","article-title":"Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death","volume":"17","author":"Zhu","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1128\/iai.57.7.2107-2114.1989","article-title":"Calcium is required for the expression of anthrax lethal toxin activity in the macrophagelike cell line J774A.1","volume":"57","author":"Bhatnagar","year":"1989","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1128\/IAI.01005-08","article-title":"Inactivation of Rho gtpases by statins attenuates anthrax lethal toxin activity","volume":"77","author":"deCathelineau","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34260","DOI":"10.1074\/jbc.M705687200","article-title":"Proteasomes control caspase-1 activation in anthrax lethal toxin-mediated cell killing","volume":"282","author":"Squires","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0924-8579(02)00200-5","article-title":"The prophylaxis and treatment of anthrax","volume":"20","author":"Brook","year":"2002","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.1021\/ja0495359","article-title":"Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides","volume":"126","author":"Lee","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Agren, J., Finn, M., Bengtsson, B., and Segerman, B. (2014). Microevolution during an anthrax outbreak leading to clonal heterogeneity and penicillin resistance. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089112"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1755-5949.2012.00317.x","article-title":"Cotinine: A potential new therapeutic agent against Alzheimer\u2019s disease","volume":"18","author":"Echeverria","year":"2012","journal-title":"CNS Neurosci. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1172\/JCI10852","article-title":"Statin-induced inhibition of the Rho-signaling pathway activates PPAR\u03b1 and induces HDL apoA-I","volume":"107","author":"Martin","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.4161\/cc.8.17.9446","article-title":"Abnormal activation of the Akt-GSK3\u03b2 signaling pathway in peripheral blood T cells from patients with systemic lupus erythematosus","volume":"8","author":"Tang","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"C886","DOI":"10.1152\/ajpcell.00416.2008","article-title":"Amantadine inhibits platelet-activating factor induced clathrin-mediated endocytosis in human neutrophils","volume":"297","author":"Eckels","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.tiv.2007.02.008","article-title":"Effects of phenytoin and carbamazepine on calcium transport in Caco-2 cells","volume":"21","author":"Crofoot","year":"2007","journal-title":"Toxicol. In Vitro"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1007\/s11064-015-1749-0","article-title":"Effects of levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, oxcarbazepine, topiramate, vinpocetine and sertraline on presynaptic hippocampal Na+ and Ca2+ channels permeability","volume":"41","author":"Sitges","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/sj.bjp.0707238","article-title":"The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5-HT3 receptors","volume":"151","author":"Thompson","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/sj.bjp.0704979","article-title":"The antimigraine 5-HT 1B\/1D receptor agonists, sumatriptan, zolmitriptan and dihydroergotamine, attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain","volume":"137","author":"Kayser","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1159\/000054078","article-title":"Signalling pathways activated by 5-HT(1B)\/5-HT(1D) receptors in native smooth muscle and primary cultures of rabbit renal artery smooth muscle cells","volume":"37","author":"Hinton","year":"2000","journal-title":"J. Vasc. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1089\/dna.2006.25.312","article-title":"Mitogen-activated protein kinase pathway was significantly activated in human bronchial epithelial cells by nicotine","volume":"25","author":"Tsai","year":"2006","journal-title":"DNA Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/1477-3163.106680","article-title":"Nicotine and lung cancer","volume":"12","author":"Warren","year":"2013","journal-title":"J. Carcinog."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1002\/1097-0142(19951215)76:12<2557::AID-CNCR2820761223>3.0.CO;2-9","article-title":"A prospective evaluation of ifosfamide-related nephrotoxicity in children and young adults","volume":"76","author":"Ho","year":"1995","journal-title":"Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16657","DOI":"10.1073\/pnas.0707936104","article-title":"A unique mechanism of beta-blocker action: Carvedilol stimulates beta-arrestin signaling","volume":"104","author":"Wisler","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12658","DOI":"10.1074\/jbc.M413140200","article-title":"Monastrol inhibition of the mitotic kinesin Eg5","volume":"280","author":"Cochran","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1046\/j.1471-4159.2003.02096.x","article-title":"Ebselen inhibits NO-induced apoptosis of differentiated PC12 cells via inhibition of ASK1-p38 MAPK-p53 and JNK signaling and activation of p44\/42 MAPK and Bcl-2","volume":"87","author":"Sarker","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12964-016-0141-2","article-title":"Epigenetic regulation of transcription factor promoter regions by low-dose genistein through mitogen-activated protein kinase and mitogen-and-stress activated kinase 1 nongenomic signaling","volume":"14","author":"Yu","year":"2016","journal-title":"Cell Commun. Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/nature12688","article-title":"A melanocyte lineage program confers resistance to MAP kinase pathway inhibition","volume":"504","author":"Johannessen","year":"2013","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Varghese, F.S., Thaa, B., Amrun, S.N., Simarmata, D., Rausalu, K., Nyman, T.A., Merits, A., McInerney, G.M., Ng, L.F., and Ahola, T. (2016). The antiviral alkaloid berberine reduces chikungunya virus-induced mitogen-activated protein kinase (MAPK) signaling. J. Virol.","DOI":"10.1128\/JVI.01382-16"},{"key":"ref_59","first-page":"15652","article-title":"Withaferin a activates stress signalling proteins in high risk acute lymphoblastic leukemia","volume":"8","author":"Shi","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1086\/491477","article-title":"Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42\/44 and p38 mitogen-activated protein kinase pathways in the platelets","volume":"192","author":"Kau","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1016\/j.oraloncology.2009.04.004","article-title":"Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: Modulation by curcumin","volume":"45","author":"Deng","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"71","DOI":"10.32604\/biocell.2011.35.071","article-title":"Apigenin inhibits cell migration through MAPK pathways in human bladder smooth muscle cells","volume":"35","author":"Liu","year":"2011","journal-title":"Biocell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1113\/JP270502","article-title":"Membrane glucocorticoid receptors are localised in the extracellular matrix and signal through the MAPK pathway in mammalian skeletal muscle fibres","volume":"593","author":"Boncompagni","year":"2015","journal-title":"J. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Remy, K.E., Qiu, P., Li, Y., Cui, X., and Eichacker, P.Q. (2013). B. anthracis associated cardiovascular dysfunction and shock: The potential contribution of both non-toxin and toxin components. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-217"},{"key":"ref_65","first-page":"139","article-title":"Molecular determinants for a cardiovascular collapse in anthrax","volume":"6","author":"Brojatsch","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"728494","DOI":"10.1155\/2015\/728494","article-title":"Restoration of endothelial function in Ppar\u03b1\u2212\/\u2212 mice by tempol","volume":"2015","author":"Silswal","year":"2015","journal-title":"PPAR Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Tabernero, A., Schoonjans, K., Jesel, L., Carpusca, I., Auwerx, J., and Andriantsitohaina, R. (2002). Activation of the peroxisome proliferator-activated receptor alpha protects against myocardial ischaemic injury and improves endothelial vasodilatation. BMC Pharmacol., 2.","DOI":"10.1186\/1471-2210-2-10"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46261","DOI":"10.1074\/jbc.M307827200","article-title":"Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation","volume":"278","author":"Gardner","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Bergman, P., Linde, C., Putsep, K., Pohanka, A., Normark, S., Henriques-Normark, B., Andersson, J., and Bjorkhem-Bergman, L. (2011). Studies on the antibacterial effects of statins\u2014In vitro and in vivo. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024394"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1006\/taap.1999.8863","article-title":"Cotinine and nicotine inhibit each other\u2019s calcium responses in bovine chromaffin cells","volume":"163","author":"Vainio","year":"2000","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Beitzinger, C., Bronnhuber, A., Duscha, K., Riedl, Z., Huber-Lang, M., Benz, R., Hajos, G., and Barth, H. (2013). Designed azolopyridinium salts block protective antigen pores in vitro and protect cells from anthrax toxin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066099"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1111\/j.1462-5822.2006.00840.x","article-title":"Anthrax toxins inhibit immune cell chemotaxis by perturbing chemokine receptor signalling","volume":"9","author":"Tonello","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1084\/jem.20041557","article-title":"Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling","volume":"201","author":"Paccani","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rossi Paccani, S., Benagiano, M., Capitani, N., Zornetta, I., Ladant, D., Montecucco, C., D\u2019Elios, M.M., and Baldari, C.T. (2009). The adenylate cyclase toxins of Bacillus anthracis and bordetella pertussis promote TH2 cell development by shaping T cell antigen receptor signaling. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000325"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/j.jaci.2010.12.1104","article-title":"The adenylate cyclase toxin of Bacillus anthracis is a potent promoter of TH17 cell development","volume":"127","author":"Paccani","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/emmm.201303415","article-title":"Fibrates ameliorate the course of bacterial sepsis by promoting neutrophil recruitment via CXCR2","volume":"6","author":"Tancevski","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Fu, C.H., Tsai, W.C., Lee, T.J., Huang, C.C., Chang, P.H., and Su Pang, J.H. (2016). Simvastatin inhibits IL-5-induced chemotaxis and CCR3 expression of HL-60-derived and human primary eosinophils. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157186"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/rheumatology\/ken466","article-title":"Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes","volume":"48","author":"Montecucco","year":"2009","journal-title":"Rheumatology (Oxford)"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Dozmorov, M., Wu, W., Chakrabarty, K., Booth, J.L., Hurst, R.E., Coggeshall, K.M., and Metcalf, J.P. (2009). Gene expression profiling of human alveolar macrophages infected by B. Anthracis spores demonstrates TNF-alpha and NF-kappab are key components of the innate immune response to the pathogen. BMC Infect. Dis., 9.","DOI":"10.1186\/1471-2334-9-152"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chauncey, K.M., Lopez, M.C., Sidhu, G., Szarowicz, S.E., Baker, H.V., Quinn, C., and Southwick, F.S. (2012). Bacillus anthracis\u2019 lethal toxin induces broad transcriptional responses in human peripheral monocytes. BMC Immunol., 13.","DOI":"10.1186\/1471-2172-13-33"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/3\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:30:10Z","timestamp":1760207410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/3\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,10]]},"references-count":80,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["toxins9030099"],"URL":"https:\/\/doi.org\/10.3390\/toxins9030099","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2017,3,10]]}}}