Periodontal Pathogens and Neuropsychiatric Health

Abhishek   Wadhawan,  Mark  A.  Reynolds,  Hina   Makkar,  Alison  J.  Scott,  Eileen   Potocki,  Andrew  J.  Hoisington,  Lisa  A.  Brenner,  Aline   Dagdag,  Christopher  A.  Lowry,  Yogesh   Dwivedi and   Teodor  T.  Postolache*
Review Article
Periodontal Pathogens and Neuropsychiatric Health

Author(s): Abhishek Wadhawan, Mark A. Reynolds, Hina Makkar, Alison J. Scott, Eileen Potocki, Andrew J. Hoisington, Lisa A. Brenner, Aline Dagdag, Christopher A. Lowry, Yogesh Dwivedi, Teodor T. Postolache*
Journal Name: Current Topics in Medicinal Chemistry
Volume 20 , Issue 15 , 2020
DOI : 10.2174/1568026620666200110161105
Journal Home
Graphical Abstract:

Abstract:

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.
Keywords: Chronic periodontitis, Porphyromonas gingivalis, Dementia, Cardiovascular disease, Metabolic syndrome, Suicidal behavior, Mood disorders, micro-RNAs.
[1] 
Page, R.C.; Schroeder, H.E. Periodontitis in man and other animals. A comparative review; S. karger: Basel, 1982. 
[2] 
Lang, N.P.; Lindhe, J. Clinical Periodontology and Implant Dentistry; John Wiley & Sons: New York, 2015, 2, . 
[3] 
Armitage, G.C. Development of a classification system for periodontal diseases and conditions. Ann. Periodontol.,  1999, 4(1), 1-6.
[http://dx.doi.org/10.1902/annals.1999.4.1.1] [PMID: 10863370] 
[4] 
Motedayyen, H.; Ghotloo, S.; Saffari, M.; Sattari, M.; Amid, R. Evaluation of microRNA-146a and its targets in gingival tissues of patients with chronic periodontitis. J. Periodontol.,  2015, 86(12), 1380-1385.
[http://dx.doi.org/10.1902/jop.2015.150319] [PMID: 26313020] 
[5] 
Ghotloo, S.; Motedayyen, H.; Amani, D.; Saffari, M.; Sattari, M. Assessment of microRNA-146a in generalized aggressive periodontitis and its association with disease severity. J. Periodontal Res.,  2019, 54(1), 27-32.
[http://dx.doi.org/10.1111/jre.12538] [PMID: 30328616] 
[6] 
Hung, Y.Y.; Wu, M.K.; Tsai, M.C.; Huang, Y.L.; Kang, H.Y. Aberrant expression of intracellular let-7E, MIR-146a, and MIR-155 correlates with severity of depression in patients with major depressive disorder and is ameliorated after antidepressant treatment. Cells,  2019, 8(7), E647
[http://dx.doi.org/10.3390/cells8070647] [PMID: 31252530] 
[7] 
Jiang, S.Y.; Xue, D.; Xie, Y.F.; Zhu, D.W.; Dong, Y.Y.; Wei, C.C.; Deng, J.Y. The negative feedback regulation of microRNA-146a in human periodontal ligament cells after Porphyromonas gingivalis lipopolysaccharide stimulation. Inflamm. Res.,  2015, 64(6), 441-451.
[http://dx.doi.org/10.1007/s00011-015-0824-y] [PMID: 25948157] 
[8] 
Xie, Y.F.; Shu, R.; Jiang, S.Y.; Liu, D.L.; Ni, J.; Zhang, X.L. MicroRNA-146 inhibits pro-inflammatory cytokine secretion through IL-1 receptor-associated kinase 1 in human gingival fibroblasts. J. Inflamm. (Lond.),  2013, 10(1), 20.
[http://dx.doi.org/10.1186/1476-9255-10-20] [PMID: 23680172] 
[9] 
Makkar, H.; Reynolds, M.A.; Wadhawan, A.; Dagdag, A.; Merchant, A.T.; Postolache, T.T. Periodontal, metabolic, and cardiovascular disease: Exploring the role of inflammation and mental health. Pteridines,  2018, 29(1), 124-163.
[http://dx.doi.org/10.1515/pteridines-2018-0013] [PMID: 30705520] 
[10] 
Mariotti, A. Dental plaque-induced gingival diseases. Ann. Periodontol.,  1999, 4(1), 7-19.
[http://dx.doi.org/10.1902/annals.1999.4.1.7] [PMID: 10863371] 
[11] 
Oliver, R.C.; Brown, L.J.; Löe, H. Periodontal diseases in the United States population. J. Periodontol.,  1998, 69(2), 269-278.
[http://dx.doi.org/10.1902/jop.1998.69.2.269] [PMID: 9526927] 
[12] 
Eke, P.I.; Page, R.C.; Wei, L.; Thornton-Evans, G.; Genco, R.J. Update of the case definitions for population-based surveillance of periodontitis. J. Periodontol.,  2012, 83(12), 1449-1454.
[http://dx.doi.org/10.1902/jop.2012.110664] [PMID: 22420873] 
[13] 
Eke, P.I.; Dye, B.A.; Wei, L.; Thornton-Evans, G.O.; Genco, R.J. CDC Periodontal Disease Surveillance workgroup: James Beck (University of North Carolina, Chapel Hill, USA); Gordon Douglass (Past President, American Academy of Periodontology); Roy Page (University of Washington). Prevalence of periodontitis in adults in the United States: 2009 and 2010. J. Dent. Res.,  2012, 91(10), 914-920.
[http://dx.doi.org/10.1177/0022034512457373] [PMID: 22935673] 
[14] 
Eke, P.I.; Dye, B.A.; Wei, L.; Slade, G.D.; Thornton-Evans, G.O.; Borgnakke, W.S.; Taylor, G.W.; Page, R.C.; Beck, J.D.; Genco, R.J. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. J. Periodontol.,  2015, 86(5), 611-622.
[http://dx.doi.org/10.1902/jop.2015.140520] [PMID: 25688694] 
[15] 
Eke, P.I.; Wei, L.; Borgnakke, W.S.; Thornton-Evans, G.; Zhang, X.; Lu, H.; McGuire, L.C.; Genco, R.J. Periodontitis prevalence in adults ≥ 65 years of age, in the USA. Periodontol. 2000,  2016, 72(1), 76-95.
[http://dx.doi.org/10.1111/prd.12145] [PMID: 27501492] 
[16] 
Bersell, C.H. Access to Oral Health Care: A national crisis and call for reform. J. Dent. Hyg.,  2017, 91(1), 6-14.
[PMID: 29118145] 
[17] 
Saremi, A.; Nelson, R.G.; Tulloch-Reid, M.; Hanson, R.L.; Sievers, M.L.; Taylor, G.W.; Shlossman, M.; Bennett, P.H.; Genco, R.; Knowler, W.C. Periodontal disease and mortality in type 2 diabetes. Diabetes Care,  2005, 28(1), 27-32.
[http://dx.doi.org/10.2337/diacare.28.1.27] [PMID: 15616229] 
[18] 
Friedewald, V.E.; Kornman, K.S.; Beck, J.D.; Genco, R.; Goldfine, A.; Libby, P.; Offenbacher, S.; Ridker, P.M.; Van Dyke, T.E.; Roberts, W.C. The American Journal of Cardiology and Journal of Periodontology editors’ consensus: periodontitis and atherosclerotic cardiovascular disease. J. Periodontol.,  2009, 80(7), 1021-1032.
[http://dx.doi.org/10.1902/jop.2009.097001] [PMID: 19563277] 
[19] 
Genco, R.J.; Borgnakke, W.S. Risk factors for periodontal disease. Periodontol. 2000,  2013, 62(1), 59-94.
[http://dx.doi.org/10.1111/j.1600-0757.2012.00457.x] [PMID: 23574464] 
[20] 
Mehta, A. Risk factors associated with periodontal diseases and their clinical considerations. Int. J. Contemp. Dent. Med. Rev.,  2015, 2015, 1-5.
[21] 
Komatsu, T. Oxidative stress and periodontal disease in Down Syndrome. InStudies on Periodontal Disease; Springer: Berlin, 2014, pp. 211-223.
[http://dx.doi.org/10.1007/978-1-4614-9557-4_15] 
[22] 
Ali, T.B.; Abidin, K.Z. Relationship of periodontal disease to pre-term low birth weight infants in a selected population--a prospective study. Community Dent. Health,  2012, 29(1), 100-105.
[PMID: 22482259] 
[23] 
Leng, W.D.; Zeng, X.T.; Kwong, J.S.; Hua, X.P. Periodontal disease and risk of coronary heart disease: An updated meta-analysis of prospective cohort studies. Int. J. Cardiol.,  2015, 201, 469-472.
[http://dx.doi.org/10.1016/j.ijcard.2015.07.087] [PMID: 26313869] 
[24] 
Sfyroeras, G.S.; Roussas, N.; Saleptsis, V.G.; Argyriou, C.; Giannoukas, A.D. Association between periodontal disease and stroke. J. Vasc. Surg.,  2012, 55(4), 1178-1184.
[http://dx.doi.org/10.1016/j.jvs.2011.10.008] [PMID: 22244863] 
[25] 
Mattila, K.J.; Valle, M.S.; Nieminen, M.S.; Valtonen, V.V.; Hietaniemi, K.L. Dental infections and coronary atherosclerosis. Atherosclerosis,  1993, 103(2), 205-211.
[http://dx.doi.org/10.1016/0021-9150(93)90263-T] [PMID: 8292096] 
[26] 
Soto-Barreras, U.; Olvera-Rubio, J.O.; Loyola-Rodriguez, J.P.; Reyes-Macias, J.F.; Martinez-Martinez, R.E.; Patiño-Marin, N.; Martinez-Castañon, G.A.; Aradillas-Garcia, C.; Little, J.W. Peripheral arterial disease associated with caries and periodontal disease. J. Periodontol.,  2013, 84(4), 486-494.
[http://dx.doi.org/10.1902/jop.2012.120051] [PMID: 22680302] 
[27] 
Chen, Y.W.; Umeda, M.; Nagasawa, T.; Takeuchi, Y.; Huang, Y.; Inoue, Y.; Iwai, T.; Izumi, Y.; Ishikawa, I. Periodontitis may increase the risk of peripheral arterial disease. Eur. J. Vasc. Endovasc. Surg.,  2008, 35(2), 153-158.
[http://dx.doi.org/10.1016/j.ejvs.2007.08.016] [PMID: 17964192] 
[28] 
Lockhart, P.B.; Bolger, A.F.; Papapanou, P.N.; Osinbowale, O.; Trevisan, M.; Levison, M.E.; Taubert, K.A.; Newburger, J.W.; Gornik, H.L.; Gewitz, M.H.; Wilson, W.R.; Smith, S.C., Jr; Baddour, L.M. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation,  2012, 125(20), 2520-2544.
[http://dx.doi.org/10.1161/CIR.0b013e31825719f3] [PMID: 22514251] 
[29] 
Humphrey, L.L.; Fu, R.; Buckley, D.I.; Freeman, M.; Helfand, M. Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J. Gen. Intern. Med.,  2008, 23(12), 2079-2086.
[http://dx.doi.org/10.1007/s11606-008-0787-6] [PMID: 18807098] 
[30] 
Rutger Persson, G.; Ohlsson, O.; Pettersson, T.; Renvert, S. Chronic periodontitis, a significant relationship with acute myocardial infarction. Eur. Heart J.,  2003, 24(23), 2108-2115.
[http://dx.doi.org/10.1016/j.ehj.2003.10.007] [PMID: 14643271] 
[31] 
Cueto, A.; Mesa, F.; Bravo, M.; Ocaña-Riola, R. Periodontitis as risk factor for acute myocardial infarction. A case control study of Spanish adults. J. Periodontal Res.,  2005, 40(1), 36-42.
[http://dx.doi.org/10.1111/j.1600-0765.2004.00766.x] [PMID: 15613077] 
[32] 
Andriankaja, O.M.; Genco, R.J.; Dorn, J.; Dmochowski, J.; Hovey, K.; Falkner, K.L.; Scannapieco, F.; Trevisan, M. The use of different measurements and definitions of periodontal disease in the study of the association between periodontal disease and risk of myocardial infarction. J. Periodontol.,  2006, 77(6), 1067-1073.
[http://dx.doi.org/10.1902/jop.2006.050276] [PMID: 16734583] 
[33] 
Andriankaja, O.M.; Genco, R.J.; Dorn, J.; Dmochowski, J.; Hovey, K.; Falkner, K.L.; Trevisan, M. Periodontal disease and risk of myocardial infarction: the role of gender and smoking. Eur. J. Epidemiol.,  2007, 22(10), 699-705.
[http://dx.doi.org/10.1007/s10654-007-9166-6] [PMID: 17828467] 
[34] 
Renvert, S.; Ohlsson, O.; Pettersson, T.; Persson, G.R. Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years. J. Periodontol.,  2010, 81(7), 992-1000.
[http://dx.doi.org/10.1902/jop.2010.090105] [PMID: 20350154] 
[35] 
Holmlund, A.; Hedin, M.; Pussinen, P.J.; Lerner, U.H.; Lind, L. Porphyromonas gingivalis (Pg) a possible link between impaired oral health and acute myocardial infarction. Int. J. Cardiol.,  2011, 148(2), 148-153.
[http://dx.doi.org/10.1016/j.ijcard.2009.10.034] [PMID: 19913930] 
[36] 
Khosravi Samani, M.; Jalali, F.; Seyyed Ahadi, S.M.; Hoseini, S.R.; Dabbagh Sattari, F. The relationship between acute myocardial infarction and periodontitis. Caspian J. Intern. Med.,  2013, 4(2), 667-671.
[PMID: 24009957] 
[37] 
Li, P.; He, L.; Sha, Y.; Luan, Q. [Periodontal status of patients with post-acute myocardial infarction]. Beijing Da Xue Xue Bao Yi xue ban,  2013, 45(1), 22-26.
[38] 
Kodovazenitis, G.; Pitsavos, C.; Papadimitriou, L.; Vrotsos, I.A.; Stefanadis, C.; Madianos, P.N. Association between periodontitis and acute myocardial infarction: a case-control study of a nondiabetic population. J. Periodontal Res.,  2014, 49(2), 246-252.
[http://dx.doi.org/10.1111/jre.12101] [PMID: 23713486] 
[39] 
Rydén, L.; Buhlin, K.; Ekstrand, E.; de Faire, U.; Gustafsson, A.; Holmer, J.; Kjellström, B.; Lindahl, B.; Norhammar, A.; Nygren, Å. Periodontitis increases the risk of a first myocardial infarction: a report from the PAROKRANK study. Circulation,  2016, 133(6), 576-583.
[40] 
Yu, Y.H.; Chasman, D.I.; Buring, J.E.; Rose, L.; Ridker, P.M. Cardiovascular risks associated with incident and prevalent periodontal disease. J. Clin. Periodontol.,  2015, 42(1), 21-28.
[http://dx.doi.org/10.1111/jcpe.12335] [PMID: 25385537] 
[41] 
Holmlund, A.; Holm, G.; Lind, L. Severity of periodontal disease and number of remaining teeth are related to the prevalence of myocardial infarction and hypertension in a study based on 4,254 subjects. J. Periodontol.,  2006, 77(7), 1173-1178.
[http://dx.doi.org/10.1902/jop.2006.050233] [PMID: 16805679] 
[42] 
Bazile, A.; Bissada, N.F.; Nair, R.; Siegel, B.P. Periodontal assessment of patients undergoing angioplasty for treatment of coronary artery disease. J. Periodontol.,  2002, 73(6), 631-636.
[http://dx.doi.org/10.1902/jop.2002.73.6.631] [PMID: 12083536] 
[43] 
Buhlin, K.; Gustafsson, A.; Håkansson, J.; Klinge, B. Oral health and cardiovascular disease in Sweden. J. Clin. Periodontol.,  2002, 29(3), 254-259.
[http://dx.doi.org/10.1034/j.1600-051x.2002.290312.x] [PMID: 11940146] 
[44] 
Parkar, S.M.; Modi, G.N.; Jani, J. Periodontitis as risk factor for acute myocardial infarction: A case control study. Heart Views,  2013, 14(1), 5-11.
[http://dx.doi.org/10.4103/1995-705X.107113] [PMID: 23580918] 
[45] 
Joshipura, K.J.; Rimm, E.B.; Douglass, C.W.; Trichopoulos, D.; Ascherio, A.; Willett, W.C. Poor oral health and coronary heart disease. J. Dent. Res.,  1996, 75(9), 1631-1636.
[http://dx.doi.org/10.1177/00220345960750090301] [PMID: 8952614] 
[46] 
Howell, T.H.; Ridker, P.M.; Ajani, U.A.; Hennekens, C.H.; Christen, W.G. Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians. J. Am. Coll. Cardiol.,  2001, 37(2), 445-450.
[http://dx.doi.org/10.1016/S0735-1097(00)01130-X] [PMID: 11216961] 
[47] 
Dorn, J.M.; Genco, R.J.; Grossi, S.G.; Falkner, K.L.; Hovey, K.M.; Iacoviello, L.; Trevisan, M. Periodontal disease and recurrent cardiovascular events in survivors of myocardial infarction (MI): the Western New York Acute MI Study. J. Periodontol.,  2010, 81(4), 502-511.
[http://dx.doi.org/10.1902/jop.2009.090499] [PMID: 20367093] 
[48] 
Willershausen, I.; Weyer, V.; Peter, M.; Weichert, C.; Kasaj, A.; Münzel, T.; Willershausen, B. Association between chronic periodontal and apical inflammation and acute myocardial infarction. Odontology,  2014, 102(2), 297-302.
[http://dx.doi.org/10.1007/s10266-013-0112-7] [PMID: 23604464] 
[49] 
Beck, J.; Garcia, R.; Heiss, G.; Vokonas, P.S.; Offenbacher, S. Periodontal disease and cardiovascular disease. J. Periodontol.,  1996, 67(10)(Suppl.), 1123-1137.
[http://dx.doi.org/10.1902/jop.1996.67.10.1123] 
[50] 
Rintala, E.M.; Aittoniemi, J.; Laine, S.; Nevalainen, T.J.; Nikoskelainen, J. Early identification of bacteremia by biochemical markers of systemic inflammation. Scand. J. Clin. Lab. Invest.,  2001, 61(7), 523-530.
[http://dx.doi.org/10.1080/003655101753218283] [PMID: 11763410] 
[51] 
Pierrakos, C.; Vincent, J-L. Sepsis biomarkers: a review. Crit. Care,  2010, 14(1), R15.
[http://dx.doi.org/10.1186/cc8872] [PMID: 20144219] 
[52] 
Sconyers, J.R.; Crawford, J.J.; Moriarty, J.D. Relationship of bacteremia to toothbrushing in patients with periodontitis. J. Am. Dent. Assoc.,  1973, 87(3), 616-622.
[http://dx.doi.org/10.14219/jada.archive.1973.0453] [PMID: 4516507] 
[53] 
Forner, L.; Larsen, T.; Kilian, M.; Holmstrup, P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J. Clin. Periodontol.,  2006, 33(6), 401-407.
[http://dx.doi.org/10.1111/j.1600-051X.2006.00924.x] [PMID: 16677328] 
[54] 
Lafon, A.; Tala, S.; Ahossi, V.; Perrin, D.; Giroud, M.; Béjot, Y. Association between periodontal disease and non-fatal ischemic stroke: a case-control study. Acta Odontol. Scand.,  2014, 72(8), 687-693.
[http://dx.doi.org/10.3109/00016357.2014.898089] [PMID: 24720864] 
[55] 
Sim, S.J.; Kim, H.D.; Moon, J.Y.; Zavras, A.I.; Zdanowicz, J.; Jang, S.J.; Jin, B.H.; Bae, K.H.; Paik, D.I.; Douglass, C.W. Periodontitis and the risk for non-fatal stroke in Korean adults. J. Periodontol.,  2008, 79(9), 1652-1658.
[http://dx.doi.org/10.1902/jop.2008.080015] [PMID: 18771365] 
[56] 
Pradeep, A.R.; Hadge, P.; Arjun Raju, P.; Shetty, S.R.; Shareef, K.; Guruprasad, C.N. Periodontitis as a risk factor for cerebrovascular accident: a case-control study in the Indian population. J. Periodontal Res.,  2010, 45(2), 223-228.
[http://dx.doi.org/10.1111/j.1600-0765.2009.01220.x] [PMID: 19778330] 
[57] 
Dörfer, C.E.; Becher, H.; Ziegler, C.M.; Kaiser, C.; Lutz, R.; Jörss, D.; Lichy, C.; Buggle, F.; Bültmann, S.; Preusch, M.; Grau, A.J. The association of gingivitis and periodontitis with ischemic stroke. J. Clin. Periodontol.,  2004, 31(5), 396-401.
[http://dx.doi.org/10.1111/j.1600-051x.2004.00579.x] [PMID: 15086623] 
[58] 
Grau, A.J.; Becher, H.; Ziegler, C.M.; Lichy, C.; Buggle, F.; Kaiser, C.; Lutz, R.; Bültmann, S.; Preusch, M.; Dörfer, C.E. Periodontal disease as a risk factor for ischemic stroke. Stroke,  2004, 35(2), 496-501.
[http://dx.doi.org/10.1161/01.STR.0000110789.20526.9D] [PMID: 14707235] 
[59] 
Jimenez, M.; Krall, E.A.; Garcia, R.I.; Vokonas, P.S.; Dietrich, T. Periodontitis and incidence of cerebrovascular disease in men. Ann. Neurol.,  2009, 66(4), 505-512.
[http://dx.doi.org/10.1002/ana.21742] [PMID: 19847898] 
[60] 
Wu, T.; Trevisan, M.; Genco, R.J.; Dorn, J.P.; Falkner, K.L.; Sempos, C.T. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch. Intern. Med.,  2000, 160(18), 2749-2755.
[http://dx.doi.org/10.1001/archinte.160.18.2749] [PMID: 11025784] 
[61] 
Leira, Y.; Seoane, J.; Blanco, M.; Rodríguez-Yáñez, M.; Takkouche, B.; Blanco, J.; Castillo, J. Association between periodontitis and ischemic stroke: a systematic review and meta-analysis. Eur. J. Epidemiol.,  2017, 32(1), 43-53.
[http://dx.doi.org/10.1007/s10654-016-0170-6] [PMID: 27300352] 
[62] 
Suvan, J.; D’Aiuto, F.; Moles, D.R.; Petrie, A.; Donos, N. Association between overweight/obesity and periodontitis in adults. A systematic review. Obes. Rev.,  2011, 12(5), e381-e404.
[http://dx.doi.org/10.1111/j.1467-789X.2010.00808.x] [PMID: 21348914] 
[63] 
Saito, T.; Shimazaki, Y.; Sakamoto, M. Obesity and periodontitis. N. Engl. J. Med.,  1998, 339(7), 482-483.
[http://dx.doi.org/10.1056/NEJM199808133390717] [PMID: 9705695] 
[64] 
Saito, T.; Shimazaki, Y.; Koga, T.; Tsuzuki, M.; Ohshima, A. Relationship between upper body obesity and periodontitis. J. Dent. Res.,  2001, 80(7), 1631-1636.
[http://dx.doi.org/10.1177/00220345010800070701] [PMID: 11597023] 
[65] 
Modeer, T.; Blomberg, C.; Wondimu, B.; Lindberg, T. Y.; Marcus, C. Association between obesity and periodontal risk indicators in adolescents. Int. J. Pediatr. Obes,  2011, 6(2-2), e264-e270.
[http://dx.doi.org/10.3109/17477166.2010.495779] 
[66] 
Wakai, K.; Kawamura, T.; Umemura, O.; Hara, Y.; Machida, J.; Anno, T.; Ichihara, Y.; Mizuno, Y.; Tamakoshi, A.; Lin, Y.; Nakayama, T.; Ohno, Y. Associations of medical status and physical fitness with periodontal disease. J. Clin. Periodontol.,  1999, 26(10), 664-672.
[http://dx.doi.org/10.1034/j.1600-051X.1999.261006.x] [PMID: 10522778] 
[67] 
Merchant, A.T.; Pitiphat, W.; Rimm, E.B.; Joshipura, K. Increased physical activity decreases periodontitis risk in men. Eur. J. Epidemiol.,  2003, 18(9), 891-898.
[http://dx.doi.org/10.1023/A:1025622815579] [PMID: 14561049] 
[68] 
Gortmaker, S.L.; Dietz, W.H., Jr; Cheung, L.W. Inactivity, diet, and the fattening of America. J. Am. Diet. Assoc.,  1990, 90(9), 1247-1252, 1255.
[PMID: 2398216] 
[69] 
Ching, P.L.; Willett, W.C.; Rimm, E.B.; Colditz, G.A.; Gortmaker, S.L.; Stampfer, M.J. Activity level and risk of overweight in male health professionals. Am. J. Public Health,  1996, 86(1), 25-30.
[http://dx.doi.org/10.2105/AJPH.86.1.25] [PMID: 8561237] 
[70] 
Khader, Y.S.; Dauod, A.S.; El-Qaderi, S.S.; Alkafajei, A.; Batayha, W.Q. Periodontal status of diabetics compared with nondiabetics: a meta-analysis. J. Diabetes Complications,  2006, 20(1), 59-68.
[http://dx.doi.org/10.1016/j.jdiacomp.2005.05.006] [PMID: 16389170] 
[71] 
D’Aiuto, F.; Sabbah, W.; Netuveli, G.; Donos, N.; Hingorani, A.D.; Deanfield, J.; Tsakos, G. Association of the metabolic syndrome with severe periodontitis in a large U.S. population-based survey. J. Clin. Endocrinol. Metab.,  2008, 93(10), 3989-3994.
[http://dx.doi.org/10.1210/jc.2007-2522] [PMID: 18682518] 
[72] 
Khader, Y.; Khassawneh, B.; Obeidat, B.; Hammad, M.; El-Salem, K.; Bawadi, H.; Al-akour, N. Periodontal status of patients with metabolic syndrome compared to those without metabolic syndrome. J. Periodontol.,  2008, 79(11), 2048-2053.
[http://dx.doi.org/10.1902/jop.2008.080022] [PMID: 18980512] 
[73] 
Shimazaki, Y.; Saito, T.; Yonemoto, K.; Kiyohara, Y.; Iida, M.; Yamashita, Y. Relationship of metabolic syndrome to periodontal disease in Japanese women: the Hisayama Study. J. Dent. Res.,  2007, 86(3), 271-275.
[http://dx.doi.org/10.1177/154405910708600314] [PMID: 17314261] 
[74] 
Cutler, C.W.; Shinedling, E.A.; Nunn, M.; Jotwani, R.; Kim, B.O.; Nares, S.; Iacopino, A.M. Association between periodontitis and hyperlipidemia: cause or effect? J. Periodontol.,  1999, 70(12), 1429-1434.
[http://dx.doi.org/10.1902/jop.1999.70.12.1429] [PMID: 10632517] 
[75] 
Nishimura, F.; Murayama, Y. Periodontal inflammation and insulin resistance--lessons from obesity. J. Dent. Res.,  2001, 80(8), 1690-1694.
[http://dx.doi.org/10.1177/00220345010800080201] [PMID: 11669476] 
[76] 
Al-Zahrani, M.S.; Borawski, E.A.; Bissada, N.F. Periodontitis and three health-enhancing behaviors: maintaining normal weight, engaging in recommended level of exercise, and consuming a high-quality diet. J. Periodontol.,  2005, 76(8), 1362-1366.
[http://dx.doi.org/10.1902/jop.2005.76.8.1362] [PMID: 16101370] 
[77] 
Chaffee, B.W.; Weston, S.J. Association between chronic periodontal disease and obesity: a systematic review and meta-analysis. J. Periodontol.,  2010, 81(12), 1708-1724.
[http://dx.doi.org/10.1902/jop.2010.100321] [PMID: 20722533] 
[78] 
Marchetti, E.; Monaco, A.; Procaccini, L.; Mummolo, S.; Gatto, R.; Tetè, S.; Baldini, A.; Tecco, S.; Marzo, G. Periodontal disease: the influence of metabolic syndrome. Nutr. Metab. (Lond.),  2012, 9(1), 88.
[http://dx.doi.org/10.1186/1743-7075-9-88] [PMID: 23009606] 
[79] 
Desvarieux, M.; Demmer, R.T.; Jacobs, D.R., Jr; Rundek, T.; Boden-Albala, B.; Sacco, R.L.; Papapanou, P.N. Periodontal bacteria and hypertension: the oral infections and vascular disease epidemiology study (INVEST). J. Hypertens.,  2010, 28(7), 1413-1421.
[http://dx.doi.org/10.1097/HJH.0b013e328338cd36] [PMID: 20453665] 
[80] 
Pazos, P.; Leira, Y.; Domínguez, C.; Pías-Peleteiro, J.M.; Blanco, J.; Aldrey, J.M. Association between periodontal disease and dementia: A literature review. Neurologia,  2018, 33(9), 602-613. English Edition].
[http://dx.doi.org/10.1016/j.nrl.2016.07.013] [PMID: 27780615] 
[81] 
Leira, Y.; Domínguez, C.; Seoane, J.; Seoane-Romero, J.; Pías-Peleteiro, J.M.; Takkouche, B.; Blanco, J.; Aldrey, J.M. Is periodontal disease associated with Alzheimer’s disease? A systematic review with meta-analysis. Neuroepidemiology,  2017, 48(1-2), 21-31.
[http://dx.doi.org/10.1159/000458411] [PMID: 28219071] 
[82] 
Tonsekar, P.P.; Jiang, S.S.; Yue, G. Periodontal disease, tooth loss and dementia: Is there a link? A systematic review. Gerodontology,  2017, 34(2), 151-163.
[http://dx.doi.org/10.1111/ger.12261] [PMID: 28168759] 
[83] 
Maldonado, A.; Laugisch, O.; Bürgin, W.; Sculean, A.; Eick, S. Clinical periodontal variables in patients with and without dementia-a systematic review and meta-analysis. Clin. Oral Investig.,  2018, 22(7), 2463-2474.
[http://dx.doi.org/10.1007/s00784-018-2523-x] [PMID: 29934798] 
[84] 
Takeuchi, K.; Ohara, T.; Furuta, M.; Takeshita, T.; Shibata, Y.; Hata, J.; Yoshida, D.; Yamashita, Y.; Ninomiya, T. Tooth loss and risk of dementia in the community: the Hisayama study. J. Am. Geriatr. Soc.,  2017, 65(5), e95-e100.
[http://dx.doi.org/10.1111/jgs.14791] [PMID: 28272750] 
[85] 
Lee, Y.L.; Hu, H.Y.; Huang, L.Y.; Chou, P.; Chu, D. Periodontal disease associated with higher risk of dementia: population-based cohort study in Taiwan. J. Am. Geriatr. Soc.,  2017, 65(9), 1975-1980.
[http://dx.doi.org/10.1111/jgs.14944] [PMID: 28598507] 
[86] 
Ide, M.; Harris, M.; Stevens, A.; Sussams, R.; Hopkins, V.; Culliford, D.; Fuller, J.; Ibbett, P.; Raybould, R.; Thomas, R.; Puenter, U.; Teeling, J.; Perry, V.H.; Holmes, C. Periodontitis and cognitive decline in alzheimer’s disease. PLoS One,  2016, 11(3), e0151081
[http://dx.doi.org/10.1371/journal.pone.0151081] [PMID: 26963387] 
[87] 
Kaushal, V.; Dye, R.; Pakavathkumar, P.; Foveau, B.; Flores, J.; Hyman, B.; Ghetti, B.; Koller, B.H.; LeBlanc, A.C. Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ.,  2015, 22(10), 1676-1686.
[http://dx.doi.org/10.1038/cdd.2015.16] [PMID: 25744023] 
[88] 
Wyss-Coray, T.; Rogers, J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med.,  2012, 2(1), a006346
[http://dx.doi.org/10.1101/cshperspect.a006346] [PMID: 22315714] 
[89] 
Spitzer, P.; Condic, M.; Herrmann, M.; Oberstein, T.J.; Scharin-Mehlmann, M.; Gilbert, D.F.; Friedrich, O.; Grömer, T.; Kornhuber, J.; Lang, R.; Maler, J.M. Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity. Sci. Rep.,  2016, 6, 32228.
[http://dx.doi.org/10.1038/srep32228] [PMID: 27624303] 
[90] 
Soscia, S.J.; Kirby, J.E.; Washicosky, K.J.; Tucker, S.M.; Ingelsson, M.; Hyman, B.; Burton, M.A.; Goldstein, L.E.; Duong, S.; Tanzi, R.E.; Moir, R.D. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One,  2010, 5(3), e9505
[http://dx.doi.org/10.1371/journal.pone.0009505] [PMID: 20209079] 
[91] 
Kumar, D.K.; Choi, S.H.; Washicosky, K.J.; Eimer, W.A.; Tucker, S.; Ghofrani, J.; Lefkowitz, A.; McColl, G.; Goldstein, L.E.; Tanzi, R.E.; Moir, R.D. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci. Transl. Med.,  2016, 8(340), 340ra72
[http://dx.doi.org/10.1126/scitranslmed.aaf1059] [PMID: 27225182] 
[92] 
Stein, P.S.; Desrosiers, M.; Donegan, S.J.; Yepes, J.F.; Kryscio, R.J. Tooth loss, dementia and neuropathology in the Nun study. J. Am. Dent. Assoc.,  2007, 138(10), 1314-1322.
[http://dx.doi.org/10.14219/jada.archive.2007.0046] [PMID: 17908844] 
[93] 
Kamer, A.R.; Pirraglia, E.; Tsui, W.; Rusinek, H.; Vallabhajosula, S.; Mosconi, L.; Yi, L.; McHugh, P.; Craig, R.G.; Svetcov, S.; Linker, R.; Shi, C.; Glodzik, L.; Williams, S.; Corby, P.; Saxena, D.; de Leon, M.J. Periodontal disease associates with higher brain amyloid load in normal elderly. Neurobiol. Aging,  2015, 36(2), 627-633.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.10.038] [PMID: 25491073] 
[94] 
Noble, J.M.; Borrell, L.N.; Papapanou, P.N.; Elkind, M.S.; Scarmeas, N.; Wright, C.B. Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III. J. Neurol. Neurosurg. Psychiatry,  2009, 80(11), 1206-1211.
[http://dx.doi.org/10.1136/jnnp.2009.174029] [PMID: 19419981] 
[95] 
Kaye, E.K.; Valencia, A.; Baba, N.; Spiro, A., III; Dietrich, T.; Garcia, R.I. Tooth loss and periodontal disease predict poor cognitive function in older men. J. Am. Geriatr. Soc.,  2010, 58(4), 713-718.
[http://dx.doi.org/10.1111/j.1532-5415.2010.02788.x] [PMID: 20398152] 
[96] 
Gatz, M.; Mortimer, J.A.; Fratiglioni, L.; Johansson, B.; Berg, S.; Reynolds, C.A.; Pedersen, N.L. Potentially modifiable risk factors for dementia in identical twins. Alzheimers Dement.,  2006, 2(2), 110-117.
[http://dx.doi.org/10.1016/j.jalz.2006.01.002] [PMID: 19595867] 
[97] 
Poole, S.; Singhrao, S.K.; Chukkapalli, S.; Rivera, M.; Velsko, I.; Kesavalu, L.; Crean, S. Active invasion of Porphyromonas gingivalis and infection-induced complement activation in ApoE-/- mice brains. J. Alzheimers Dis.,  2015, 43(1), 67-80.
[http://dx.doi.org/10.3233/JAD-140315] [PMID: 25061055] 
[98] 
Ishida, N.; Ishihara, Y.; Ishida, K.; Tada, H.; Funaki-Kato, Y.; Hagiwara, M.; Ferdous, T.; Abdullah, M.; Mitani, A.; Michikawa, M.; Matsushita, K. Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice. NPJ Aging Mech. Dis.,  2017, 3, 15.
[http://dx.doi.org/10.1038/s41514-017-0015-x] [PMID: 29134111] 
[99] 
Poole, S.; Singhrao, S.K.; Kesavalu, L.; Curtis, M.A.; Crean, S. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J. Alzheimers Dis.,  2013, 36(4), 665-677.
[http://dx.doi.org/10.3233/JAD-121918] [PMID: 23666172] 
[100] 
Singhrao, S.K.; Harding, A.; Poole, S.; Kesavalu, L.; Crean, S. Porphyromonas gingivalis periodontal infection and its putative links with alzheimer’s disease. Mediators Inflamm.,  2015, 2015, 137357
[http://dx.doi.org/10.1155/2015/137357] [PMID: 26063967] 
[101] 
Dominy, S.S.; Lynch, C.; Ermini, F.; Benedyk, M.; Marczyk, A.; Konradi, A.; Nguyen, M.; Haditsch, U.; Raha, D.; Griffin, C.; Holsinger, L.J.; Arastu-Kapur, S.; Kaba, S.; Lee, A.; Ryder, M.I.; Potempa, B.; Mydel, P.; Hellvard, A.; Adamowicz, K.; Hasturk, H.; Walker, G.D.; Reynolds, E.C.; Faull, R.L.M.; Curtis, M.A.; Dragunow, M.; Potempa, J. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv.,  2019, 5(1), eaau3333
[http://dx.doi.org/10.1126/sciadv.aau3333] [PMID: 30746447] 
[102] 
Chi, L.; Cheng, X.; He, X.; Sun, J.; Liang, F.; Pei, Z.; Teng, W. Increased cortical infarction and neuroinflammation in ischemic stroke mice with experimental periodontitis. Neuroreport,  2019, 30(6), 428-433.
[http://dx.doi.org/10.1097/WNR.0000000000001220] [PMID: 30829959] 
[103] 
Angelillo, I.F.; Nobile, C.G.; Pavia, M.; De Fazio, P.; Puca, M.; Amati, A. Dental health and treatment needs in institutionalized psychiatric patients in Italy. Community Dent. Oral Epidemiol.,  1995, 23(6), 360-364.
[http://dx.doi.org/10.1111/j.1600-0528.1995.tb00263.x] [PMID: 8681519] 
[104] 
Burchell, A.; Fernbacher, S.; Lewis, R.; Neil, A. “Dental as Anything” inner south community health service dental outreach to people with a mental illness. Aust. J. Prim. Health,  2006, 12(2), 75-82.
[http://dx.doi.org/10.1071/PY06025] 
[105] 
Rekha, R.; Hiremath, S.S. Oral health status and treatment requirments of confectionery workers in Bangalore city. A comparative study. Indian J. Dent. Res.,  2002, 13(3-4), 161-165.
[PMID: 12765096] 
[106] 
Tang, W.K.; Sun, F.C.; Ungvari, G.S.; O’Donnell, D. Oral health of psychiatric in-patients in Hong Kong. Int. J. Soc. Psychiatry,  2004, 50(2), 186-191.
[http://dx.doi.org/10.1177/0020764004043134] [PMID: 15293435] 
[107] 
Kisely, S.; Baghaie, H.; Lalloo, R.; Siskind, D.; Johnson, N.W. A systematic review and meta-analysis of the association between poor oral health and severe mental illness. Psychosom. Med.,  2015, 77(1), 83-92.
[http://dx.doi.org/10.1097/PSY.0000000000000135] [PMID: 25526527] 
[108] 
Singh, A.; Mittal, P.; Goel, P.; Purohit, B.M.; Thukral, R. Severity of illness and extra pyramidal symptoms as predictors for oral diseases among patients with schizophrenia. Acta Odontol. Scand.,  2017, 75(3), 220-226.
[http://dx.doi.org/10.1080/00016357.2017.1278789] [PMID: 28116993] 
[109] 
Shetty, S.; Bose, A. Schizophrenia and periodontal disease: An oro-neural connection? A cross-sectional epidemiological study. J. Indian Soc. Periodontol.,  2014, 18(1), 69-73.
[http://dx.doi.org/10.4103/0972-124X.128222] [PMID: 24744548] 
[110] 
Cunha, F.A.; Cota, L.O.M.; Cortelli, S.C.; Miranda, T.B.; Neves, F.S.; Cortelli, J.R.; Costa, F.O. Periodontal condition and levels of bacteria associated with periodontitis in individuals with bipolar affective disorders: A case-control study. J. Periodontal Res.,  2019, 54(1), 63-72.
[http://dx.doi.org/10.1111/jre.12605] [PMID: 30207388] 
[111] 
Gurbuz Oflezer, O.; Altinbas, K.; Delice, M.; Oflezer, C.; Kurt, E. Oral health among patients with bipolar disorder. Oral Health Prev. Dent.,  2018, 16(6), 509-516.
[PMID: 30574605] 
[112] 
Kopycka-Kedzierawski, D.T.; Li, D.; Xiao, J.; Billings, R.J.; Dye, T.D. Association of periodontal disease with depression and adverse birth outcomes: Results from the Perinatal database; Finger Lakes region, New York State. PLoS One,  2019, 14(4), e0215440
[http://dx.doi.org/10.1371/journal.pone.0215440] [PMID: 30998794] 
[113] 
Nascimento, G.G.; Gastal, M.T.; Leite, F.R.M.; Quevedo, L.A.; Peres, K.G.; Peres, M.A.; Horta, B.L.; Barros, F.C.; Demarco, F.F. Is there an association between depression and periodontitis? A birth cohort study. J. Clin. Periodontol.,  2019, 46(1), 31-39.
[PMID: 30499588] 
[114] 
Dagdag, A.; Reynolds, M.A.; Daue, M.; Wadhawan, A.; Nijjar, G.; Ryan, K.A.; Fuchs, D.; Mitchell, B.; Postolache, T.T. F156. Anhedonia and Hopelessness/Dysphoria Associated With Tooth Loss in the Old Order Amish: Gender Differences and Neopterin Levels-Mediator or Confounder? Biol. Psychiatry,  2018, 83(9), S298-S299.
[http://dx.doi.org/10.1016/j.biopsych.2018.02.770] 
[115] 
Warren, K.R.; Postolache, T.T.; Groer, M.E.; Pinjari, O.; Kelly, D.L.; Reynolds, M.A. Role of chronic stress and depression in periodontal diseases. Periodontol. 2000,  2014, 64(1), 127-138.
[http://dx.doi.org/10.1111/prd.12036] [PMID: 24320960] 
[116] 
Alkan, A.; Cakmak, O.; Yilmaz, S.; Cebi, T.; Gurgan, C. Relationship between psychological factors and oral health status and behaviours. Oral Health Prev. Dent.,  2015, 13(4), 331-339.
[PMID: 25197739] 
[117] 
Little, J.W. Dental implications of mood disorders. Gen. Dent.,  2004, 52(5), 442-450.
[PMID: 15544223] 
[118] 
Clark, D.B. Dental care for the patient with bipolar disorder. J. Can. Dent. Assoc.,  2003, 69(1), 20-24.
[PMID: 12556265] 
[119] 
Milosevic, A. Eating disorders and the dentist. Br. Dent. J.,  1999, 186(3), 109-113.
[http://dx.doi.org/10.1038/sj.bdj.4800036] [PMID: 10101906] 
[120] 
Bretz, W.A. Oral profiles of bulimic women: Diagnosis and management. What is the evidence? J. Evid. Based Dent. Pract.,  2002, 2(4), 267-272.
[http://dx.doi.org/10.1016/S1532-3382(02)70078-X] [PMID: 22287937] 
[121] 
Page, M.M. Psychotropic drugs and dentistry. Aust. Prescr.,  2007, 30(4), 98-101.
[http://dx.doi.org/10.18773/austprescr.2007.059] 
[122] 
Lalloo, R.; Kisely, S.; Amarasinghe, H.; Perera, R.; Johnson, N. Oral health of patients on psychotropic medications: a study of outpatients in Queensland. Australas. Psychiatry,  2013, 21(4), 338-342.
[http://dx.doi.org/10.1177/1039856213486308] [PMID: 23671224] 
[123] 
Cormac, I.; Jenkins, P. Understanding the importance of oral health in psychiatric patients. Adv. Psychiatr. Treat.,  1999, 5(1), 53-60.
[http://dx.doi.org/10.1192/apt.5.1.53] 
[124] 
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed; American Psychiatric Association: Washington, DC, 2013. 
[125] 
Beck, A.T. Cognitive therapy. A 30-year retrospective. Am. Psychol.,  1991, 46(4), 368-375.
[http://dx.doi.org/10.1037/0003-066X.46.4.368] [PMID: 2048795] 
[126] 
O’Dowd, L.K.; Durham, J.; McCracken, G.I.; Preshaw, P.M. Patients’ experiences of the impact of periodontal disease. J. Clin. Periodontol.,  2010, 37(4), 334-339.
[http://dx.doi.org/10.1111/j.1600-051X.2010.01545.x] [PMID: 20447256] 
[127] 
Bardow, A.; Nyvad, B.; Nauntofte, B. Relationships between medication intake, complaints of dry mouth, salivary flow rate and composition, and the rate of tooth demineralization in situ. Arch. Oral Biol.,  2001, 46(5), 413-423.
[http://dx.doi.org/10.1016/S0003-9969(01)00003-6] [PMID: 11286806] 
[128] 
Lewis, S.; Jagger, R.G.; Treasure, E. The oral health of psychiatric in-patients in South Wales. Spec. Care Dentist.,  2001, 21(5), 182-186.
[http://dx.doi.org/10.1111/j.1754-4505.2001.tb00252.x] [PMID: 11803642] 
[129] 
Ramon, T.; Grinshpoon, A.; Zusman, S.P.; Weizman, A. Oral health and treatment needs of institutionalized chronic psychiatric patients in Israel. Eur. Psychiatry,  2003, 18(3), 101-105.
[http://dx.doi.org/10.1016/S0924-9338(03)00023-3] [PMID: 12763294] 
[130] 
Wadhawan, A.; Daue, M.L.; Dagdag, A.; Makkar, H.; Ryan, K.A.; Gragnoli, C.; Postolache, T.T. S144. Obesity is associated with anhedonia only in the younger amish women. Biol. Psychiatry,  2019, 85(10), S352.
[http://dx.doi.org/10.1016/j.biopsych.2019.03.895] 
[131] 
Postolache, T.T.; Del Bosque-Plata, L.; Jabbour, S.; Vergare, M.; Wu, R.; Gragnoli, C. Co-shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome. Am. J. Med. Genet. B. Neuropsychiatr. Genet.,  2019, 180(3), 186-203.
[http://dx.doi.org/10.1002/ajmg.b.32712] [PMID: 30729689] 
[132] 
Marcotte, H.; Lavoie, M.C. Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol. Mol. Biol. Rev.,  1998, 62(1), 71-109.
[http://dx.doi.org/10.1128/MMBR.62.1.71-109.1998] [PMID: 9529888] 
[133] 
Pennisi, E. A mouthful of microbes. Science,  2005, 307(5717), 1899-1901.
[http://dx.doi.org/10.1126/science.307.5717.1899] [PMID: 15790840] 
[134] 
Aas, J.A.; Paster, B.J.; Stokes, L.N.; Olsen, I.; Dewhirst, F.E. Defining the normal bacterial flora of the oral cavity. J. Clin. Microbiol.,  2005, 43(11), 5721-5732.
[http://dx.doi.org/10.1128/JCM.43.11.5721-5732.2005] [PMID: 16272510] 
[135] 
Paster, B.J.; Olsen, I.; Aas, J.A.; Dewhirst, F.E. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol. 2000,  2006, 42, 80-87.
[http://dx.doi.org/10.1111/j.1600-0757.2006.00174.x] [PMID: 16930307] 
[136] 
Eloe-Fadrosh, E.A.; Rasko, D.A. The human microbiome: from symbiosis to pathogenesis. Annu. Rev. Med.,  2013, 64, 145-163.
[http://dx.doi.org/10.1146/annurev-med-010312-133513] [PMID: 23327521] 
[137] 
Socransky, S.S.; Haffajee, A.D.; Cugini, M.A.; Smith, C.; Kent, R.L., Jr Microbial complexes in subgingival plaque. J. Clin. Periodontol.,  1998, 25(2), 134-144.
[http://dx.doi.org/10.1111/j.1600-051X.1998.tb02419.x] [PMID: 9495612] 
[138] 
Socransky, S.S.; Haffajee, A.D. Dental biofilms: difficult therapeutic targets. Periodontol. 2000,  2002, 28, 12-55.
[http://dx.doi.org/10.1034/j.1600-0757.2002.280102.x] [PMID: 12013340] 
[139] 
Carrouel, F.; Viennot, S.; Santamaria, J.; Veber, P.; Bourgeois, D. Quantitative molecular detection of 19 major pathogens in the interdental biofilm of periodontally healthy young adults. Front. Microbiol.,  2016, 7, 840.
[http://dx.doi.org/10.3389/fmicb.2016.00840] [PMID: 27313576] 
[140] 
Socransky, S.S.; Haffajee, A.D. Periodontal microbial ecology. Periodontol. 2000,  2005, 38, 135-187.
[http://dx.doi.org/10.1111/j.1600-0757.2005.00107.x] [PMID: 15853940] 
[141] 
Yang, H.W.; Huang, Y.F.; Chou, M.Y. Occurrence of Porphyromonas gingivalis and Tannerella forsythensis in periodontally diseased and healthy subjects. J. Periodontol.,  2004, 75(8), 1077-1083.
[http://dx.doi.org/10.1902/jop.2004.75.8.1077] [PMID: 15455734] 
[142] 
Hwang, A.M.; Stoupel, J.; Celenti, R.; Demmer, R.T.; Papapanou, P.N. Serum antibody responses to periodontal microbiota in chronic and aggressive periodontitis: a postulate revisited. J. Periodontol.,  2014, 85(4), 592-600.
[http://dx.doi.org/10.1902/jop.2013.130172] [PMID: 23725029] 
[143] 
Shah, H.; Collins, M. Proposal for reclassification of bacteroides asaccharolyticus, bacteroides gingivalis, and bacteroides endodontalis in a new genus, porphyromonas. Int. J. Syst. Evol. Microbiol.,  1988, 38(1), 128-131.
[144] 
Bostanci, N.; Belibasakis, G.N. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol. Lett.,  2012, 333(1), 1-9.
[http://dx.doi.org/10.1111/j.1574-6968.2012.02579.x] [PMID: 22530835] 
[145] 
Bodet, C.; Chandad, F.; Grenier, D. [Pathogenic potential of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, the red bacterial complex associated with periodontitis]. Pathol. Biol. (Paris),  2007, 55(3-4), 154-162.
[http://dx.doi.org/10.1016/j.patbio.2006.07.045] [PMID: 17049750] 
[146] 
Casarin, R.C.; Ribeiro, Edel.P.; Mariano, F.S.; Nociti, F.H., Jr; Casati, M.Z.; Gonçalves, R.B. Levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, inflammatory cytokines and species-specific immunoglobulin G in generalized aggressive and chronic periodontitis. J. Periodontal Res.,  2010, 45(5), 635-642.
[http://dx.doi.org/10.1111/j.1600-0765.2010.01278.x] [PMID: 20546109] 
[147] 
Mahanonda, R.; Seymour, G.J.; Powell, L.W.; Good, M.F.; Halliday, J.W. Effect of initial treatment of chronic inflammatory periodontal disease on the frequency of peripheral blood T-lymphocytes specific to periodontopathic bacteria. Oral Microbiol. Immunol.,  1991, 6(4), 221-227.
[http://dx.doi.org/10.1111/j.1399-302X.1991.tb00481.x] [PMID: 1667435] 
[148] 
Moore, W.E.; Moore, L.H.; Ranney, R.R.; Smibert, R.M.; Burmeister, J.A.; Schenkein, H.A. The microflora of periodontal sites showing active destructive progression. J. Clin. Periodontol.,  1991, 18(10), 729-739.
[http://dx.doi.org/10.1111/j.1600-051X.1991.tb00064.x] [PMID: 1752997] 
[149] 
Schmidt, J.; Jentsch, H.; Stingu, C.S.; Sack, U. General immune status and oral microbiology in patients with different forms of periodontitis and healthy control subjects. PLoS One,  2014, 9(10), e109187
[http://dx.doi.org/10.1371/journal.pone.0109187] [PMID: 25299619] 
[150] 
Baek, K.J.; Ji, S.; Kim, Y.C.; Choi, Y. Association of the invasion ability of Porphyromonas gingivalis with the severity of periodontitis. Virulence,  2015, 6(3), 274-281.
[http://dx.doi.org/10.1080/21505594.2014.1000764] [PMID: 25616643] 
[151] 
Dorn, B.R.; Burks, J.N.; Seifert, K.N.; Progulske-Fox, A. Invasion of endothelial and epithelial cells by strains of Porphyromonas gingivalis. FEMS Microbiol. Lett.,  2000, 187(2), 139-144.
[http://dx.doi.org/10.1111/j.1574-6968.2000.tb09150.x] [PMID: 10856647] 
[152] 
Hajishengallis, G.; Darveau, R.P.; Curtis, M.A. The keystone-pathogen hypothesis. Nat. Rev. Microbiol.,  2012, 10(10), 717-725.
[http://dx.doi.org/10.1038/nrmicro2873] [PMID: 22941505] 
[153] 
Hajishengallis, G.; Lamont, R.J. Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur. J. Immunol.,  2014, 44(2), 328-338.
[http://dx.doi.org/10.1002/eji.201344202] [PMID: 24338806] 
[154] 
Holt, S.C.; Kesavalu, L.; Walker, S.; Genco, C.A. Virulence factors of Porphyromonas gingivalis. Periodontol. 2000,  1999, 20, 168-238.
[http://dx.doi.org/10.1111/j.1600-0757.1999.tb00162.x] [PMID: 10522227] 
[155] 
Lamont, R.J.; Jenkinson, H.F. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol. Mol. Biol. Rev.,  1998, 62(4), 1244-1263.
[http://dx.doi.org/10.1128/MMBR.62.4.1244-1263.1998] [PMID: 9841671] 
[156] 
Curtis, M.A.; Aduse-Opoku, J.; Rangarajan, M. Cysteine proteases of Porphyromonas gingivalis. Crit. Rev. Oral Biol. Med.,  2001, 12(3), 192-216.
[http://dx.doi.org/10.1177/10454411010120030101] [PMID: 11497373] 
[157] 
Travis, J.; Pike, R.; Imamura, T.; Potempa, J. Porphyromonas gingivalis proteinases as virulence factors in the development of periodontitis. J. Periodontal Res.,  1997, 32(1 Pt 2), 120-125.
[http://dx.doi.org/10.1111/j.1600-0765.1997.tb01392.x] [PMID: 9085221] 
[158] 
de Diego, I.; Veillard, F.; Sztukowska, M.N.; Guevara, T.; Potempa, B.; Pomowski, A.; Huntington, J.A.; Potempa, J.; Gomis-Rüth, F.X. Structure and mechanism of cysteine peptidase gingipain K (Kgp), a major virulence factor of Porphyromonas gingivalis in periodontitis. J. Biol. Chem.,  2014, 289(46), 32291-32302.
[http://dx.doi.org/10.1074/jbc.M114.602052] [PMID: 25266723] 
[159] 
Potempa, J.; Banbula, A.; Travis, J. Role of bacterial proteinases in matrix destruction and modulation of host responses. Periodontol. 2000,  2000, 24, 153-192.
[http://dx.doi.org/10.1034/j.1600-0757.2000.2240108.x] [PMID: 11276866] 
[160] 
Kristoffersen, A.K.; Solli, S.J.; Nguyen, T.D.; Enersen, M. Association of the rgpB gingipain genotype to the major fimbriae (fimA) genotype in clinical isolates of the periodontal pathogen Porphyromonas gingivalis. J. Oral Microbiol.,  2015, 7, 29124.
[http://dx.doi.org/10.3402/jom.v7.29124] [PMID: 26387644] 
[161] 
Dubin, G.; Koziel, J.; Pyrc, K.; Wladyka, B.; Potempa, J. Bacterial proteases in disease - role in intracellular survival, evasion of coagulation/ fibrinolysis innate defenses, toxicoses and viral infections. Curr. Pharm. Des.,  2013, 19(6), 1090-1113.
[http://dx.doi.org/10.2174/1381612811319060011] [PMID: 23016681] 
[162] 
Andrian, E.; Grenier, D.; Rouabhia, M. In vitro models of tissue penetration and destruction by Porphyromonas gingivalis. Infect. Immun.,  2004, 72(8), 4689-4698.
[http://dx.doi.org/10.1128/IAI.72.8.4689-4698.2004] [PMID: 15271930] 
[163] 
Imamura, T.; Travis, J.; Potempa, J. The biphasic virulence activities of gingipains: activation and inactivation of host proteins. Curr. Protein Pept. Sci.,  2003, 4(6), 443-450.
[http://dx.doi.org/10.2174/1389203033487027] [PMID: 14683429] 
[164] 
Haraguchi, A.; Miura, M.; Fujise, O.; Hamachi, T.; Nishimura, F. Porphyromonas gingivalis gingipain is involved in the detachment and aggregation of Aggregatibacter actinomycetemcomitans biofilm. Mol. Oral Microbiol.,  2014, 29(3), 131-143.
[http://dx.doi.org/10.1111/omi.12051] [PMID: 24661327] 
[165] 
Bao, K.; Belibasakis, G.N.; Thurnheer, T.; Aduse-Opoku, J.; Curtis, M.A.; Bostanci, N. Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation. BMC Microbiol.,  2014, 14, 258.
[http://dx.doi.org/10.1186/s12866-014-0258-7] [PMID: 25270662] 
[166] 
Sroka, A.; Sztukowska, M.; Potempa, J.; Travis, J.; Genco, C.A. Degradation of host heme proteins by lysine- and arginine-specific cysteine proteinases (gingipains) of Porphyromonas gingivalis. J. Bacteriol.,  2001, 183(19), 5609-5616.
[http://dx.doi.org/10.1128/JB.183.19.5609-5616.2001] [PMID: 11544223] 
[167] 
Hajishengallis, G.; Abe, T.; Maekawa, T.; Hajishengallis, E.; Lambris, J.D. Role of complement in host-microbe homeostasis of the periodontium. Semin. Immunol.,  2013, 25(1), 65-72.
[http://dx.doi.org/10.1016/j.smim.2013.04.004] [PMID: 23684627] 
[168] 
Maekawa, T.; Krauss, J.L.; Abe, T.; Jotwani, R.; Triantafilou, M.; Triantafilou, K.; Hashim, A.; Hoch, S.; Curtis, M.A.; Nussbaum, G.; Lambris, J.D.; Hajishengallis, G. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe,  2014, 15(6), 768-778.
[http://dx.doi.org/10.1016/j.chom.2014.05.012] [PMID: 24922578] 
[169] 
Bostanci, N.; Thurnheer, T.; Aduse-Opoku, J.; Curtis, M.A.; Zinkernagel, A.S.; Belibasakis, G.N. Porphyromonas gingivalis regulates TREM-1 in human polymorphonuclear neutrophils via its gingipains. PLoS One,  2013, 8(10), e75784
[http://dx.doi.org/10.1371/journal.pone.0075784] [PMID: 24124513] 
[170] 
Belibasakis, G.N.; Bostanci, N.; Reddi, D. Regulation of protease-activated receptor-2 expression in gingival fibroblasts and Jurkat T cells by Porphyromonas gingivalis. Cell Biol. Int.,  2010, 34(3), 287-292.
[http://dx.doi.org/10.1042/CBI20090290] [PMID: 19947912] 
[171] 
Hamedi, M.; Belibasakis, G.N.; Cruchley, A.T.; Rangarajan, M.; Curtis, M.A.; Bostanci, N. Porphyromonas gingivalis culture supernatants differentially regulate interleukin-1beta and interleukin-18 in human monocytic cells. Cytokine,  2009, 45(2), 99-104.
[http://dx.doi.org/10.1016/j.cyto.2008.11.005] [PMID: 19091595] 
[172] 
Sheets, S.M.; Potempa, J.; Travis, J.; Casiano, C.A.; Fletcher, H.M. Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule cleavage and apoptosis in endothelial cells. Infect. Immun.,  2005, 73(3), 1543-1552.
[http://dx.doi.org/10.1128/IAI.73.3.1543-1552.2005] [PMID: 15731052] 
[173] 
Kinane, J.A.; Benakanakere, M.R.; Zhao, J.; Hosur, K.B.; Kinane, D.F. Porphyromonas gingivalis influences actin degradation within epithelial cells during invasion and apoptosis. Cell. Microbiol.,  2012, 14(7), 1085-1096.
[http://dx.doi.org/10.1111/j.1462-5822.2012.01780.x] [PMID: 22381126] 
[174] 
Stathopoulou, P.G.; Galicia, J.C.; Benakanakere, M.R.; Garcia, C.A.; Potempa, J.; Kinane, D.F. Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism. BMC Microbiol.,  2009, 9, 107.
[http://dx.doi.org/10.1186/1471-2180-9-107] [PMID: 19473524] 
[175] 
Guo, Y.; Nguyen, K.A.; Potempa, J. Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon’s knife to a meat chopper-like brutal degradation of proteins. Periodontol. 2000,  2010, 54(1), 15-44.
[http://dx.doi.org/10.1111/j.1600-0757.2010.00377.x] [PMID: 20712631] 
[176] 
Travis, J.; Potempa, J. Bacterial proteinases as targets for the development of second-generation antibiotics. Biochim. Biophys. Acta,  2000, 1477(1-2), 35-50.
[http://dx.doi.org/10.1016/S0167-4838(99)00278-2] [PMID: 10708847] 
[177] 
Clatworthy, A.E.; Pierson, E.; Hung, D.T. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol.,  2007, 3(9), 541-548.
[http://dx.doi.org/10.1038/nchembio.2007.24] [PMID: 17710100] 
[178] 
Supuran, C.T.; Scozzafava, A.; Mastrolorenzo, A. Bacterial proteases: current therapeutic use and future prospects for the development of new antibiotics. Expert Opin. Ther. Pat.,  2001, 11(2), 221-259.
[http://dx.doi.org/10.1517/13543776.11.2.221] 
[179] 
Flemmig, T.F.; Milián, E.; Karch, H.; Klaiber, B. Differential clinical treatment outcome after systemic metronidazole and amoxicillin in patients harboring Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis. J. Clin. Periodontol.,  1998, 25(5), 380-387.
[http://dx.doi.org/10.1111/j.1600-051X.1998.tb02459.x] [PMID: 9650874] 
[180] 
Kadowaki, T.; Baba, A.; Abe, N.; Takii, R.; Hashimoto, M.; Tsukuba, T.; Okazaki, S.; Suda, Y.; Asao, T.; Yamamoto, K. Suppression of pathogenicity of Porphyromonas gingivalis by newly developed gingipain inhibitors. Mol. Pharmacol.,  2004, 66(6), 1599-1606.
[http://dx.doi.org/10.1124/mol.104.004366] [PMID: 15361547] 
[181] 
Raetz, C.R.H. Biochemistry of endotoxins. Annu. Rev. Biochem.,  1990, 59, 129-170.
[http://dx.doi.org/10.1146/annurev.bi.59.070190.001021] [PMID: 1695830] 
[182] 
Beutler, B.; Du, X.; Poltorak, A. Identification of Toll-like receptor 4 (Tlr4) as the sole conduit for LPS signal transduction: genetic and evolutionary studies. J. Endotoxin Res.,  2001, 7(4), 277-280.
[183] 
Raetz, C.R.H.; Whitfield, C. Lipopolysaccharide endotoxins. Annu. Rev. Biochem.,  2002, 71, 635-700.
[http://dx.doi.org/10.1146/annurev.biochem.71.110601.135414] [PMID: 12045108] 
[184] 
Jain, S.; Darveau, R.P. Contribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontol. 2000,  2010, 54(1), 53-70.
[http://dx.doi.org/10.1111/j.1600-0757.2009.00333.x] [PMID: 20712633] 
[185] 
Mühlradt, P.F.; Golecki, J.R. Asymmetrical distribution and artifactual reorientation of lipopolysaccharide in the outer membrane bilayer of Salmonella typhimurium. Eur. J. Biochem.,  1975, 51(2), 343-352.
[http://dx.doi.org/10.1111/j.1432-1033.1975.tb03934.x] [PMID: 807474] 
[186] 
Hajjar, A.M.; Ernst, R.K.; Tsai, J.H.; Wilson, C.B.; Miller, S.I. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat. Immunol.,  2002, 3(4), 354-359.
[http://dx.doi.org/10.1038/ni777] [PMID: 11912497] 
[187] 
Miller, S.I.; Ernst, R.K.; Bader, M.W. LPS, TLR4 and infectious disease diversity. Nat. Rev. Microbiol.,  2005, 3(1), 36-46.
[http://dx.doi.org/10.1038/nrmicro1068] [PMID: 15608698] 
[188] 
Scott, A.J.; Oyler, B.L.; Goodlett, D.R.; Ernst, R.K. Lipid A structural modifications in extreme conditions and identification of unique modifying enzymes to define the Toll-like receptor 4 structure-activity relationship. Biochim. Biophys. Acta Mol. Cell Biol. Lipids,  2017, 1862(11), 1439-1450.
[http://dx.doi.org/10.1016/j.bbalip.2017.01.004] [PMID: 28108356] 
[189] 
Kumada, H.; Haishima, Y.; Umemoto, T.; Tanamoto, K. Structural study on the free lipid A isolated from lipopolysaccharide of Porphyromonas gingivalis. J. Bacteriol.,  1995, 177(8), 2098-2106.
[http://dx.doi.org/10.1128/JB.177.8.2098-2106.1995] [PMID: 7721702] 
[190] 
Ogawa, T.; Asai, Y.; Hashimoto, M.; Takeuchi, O.; Kurita, T.; Yoshikai, Y.; Miyake, K.; Akira, S. Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4- and myeloid differentiation factor 88-dependent signaling pathway. Int. Immunol.,  2002, 14(11), 1325-1332.
[http://dx.doi.org/10.1093/intimm/dxf097] [PMID: 12407023] 
[191] 
Reife, R.A.; Coats, S.R.; Al-Qutub, M.; Dixon, D.M.; Braham, P.A.; Billharz, R.J.; Howald, W.N.; Darveau, R.P. Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition. Cell. Microbiol.,  2006, 8(5), 857-868.
[http://dx.doi.org/10.1111/j.1462-5822.2005.00672.x] [PMID: 16611234] 
[192] 
Herath, T.D.K.; Darveau, R.P.; Seneviratne, C.J.; Wang, C-Y.; Wang, Y.; Jin, L. Tetra- and penta-acylated lipid A structures of Porphyromonas gingivalis LPS differentially activate TLR4-mediated NF-κB signal transduction cascade and immuno-inflammatory response in human gingival fibroblasts. PLoS One,  2013, 8(3), e58496-e17.
[http://dx.doi.org/10.1371/journal.pone.0058496] [PMID: 23554896] 
[193] 
Nativel, B.; Couret, D.; Giraud, P.; Meilhac, O. Porphyromonas gingivalis lipopolysaccharides act exclusively through TLR4 with a resilience between mouse and human. Sci. Rep.,  2017, 7(1), 1-12.
[http://dx.doi.org/10.1038/s41598-017-16190-y] 
[194] 
Hirschfeld, M.; Ma, Y.; Weis, J.H.; Vogel, S.N.; Weis, J.J. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J. Immunol.,  2000, 165(2), 618-622.
[195] 
Hirschfeld, M.; Weis, J.J.; Toshchakov, V.; Salkowski, C.A.; Cody, M.J.; Ward, D.C.; Qureshi, N.; Michalek, S.M.; Vogel, S.N. Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect. Immun.,  2001, 69(3), 1477-1482.
[http://dx.doi.org/10.1128/IAI.69.3.1477-1482.2001] [PMID: 11179315] 
[196] 
Darveau, R.P.; Arbabi, S.; Garcia, I.; Bainbridge, B.; Maier, R.V. Porphyromonas gingivalis lipopolysaccharide is both agonist and antagonist for p38 mitogen-activated protein kinase activation. Infect. Immun.,  2002, 70(4), 1867-1873.
[http://dx.doi.org/10.1128/IAI.70.4.1867-1873.2002] [PMID: 11895949] 
[197] 
Hashimoto, M.; Asai, Y.; Ogawa, T. Separation and structural analysis of lipoprotein in a lipopolysaccharide preparation from Porphyromonas gingivalis. Int. Immunol.,  2004, 16(10), 1431-1437.
[http://dx.doi.org/10.1093/intimm/dxh146] [PMID: 15326096] 
[198] 
Darveau, R.P.; Pham, T.T.; Lemley, K.; Reife, R.A.; Bainbridge, B.W.; Coats, S.R.; Howald, W.N.; Way, S.S.; Hajjar, A.M. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infect. Immun.,  2004, 72(9), 5041-5051.
[http://dx.doi.org/10.1128/IAI.72.9.5041-5051.2004] [PMID: 15321997] 
[199] 
Lee, H-K.; Lee, J.; Tobias, P.S. Two lipoproteins extracted from Escherichia coli K-12 LCD25 lipopolysaccharide are the major components responsible for Toll-like receptor 2-mediated signaling. J. Immunol.,  2002, 168(8), 4012-4017.
[200] 
Asai, Y.; Hashimoto, M.; Fletcher, H.M.; Miyake, K.; Akira, S.; Ogawa, T. Lipopolysaccharide preparation extracted from Porphyromonas gingivalis lipoprotein-deficient mutant shows a marked decrease in toll-like receptor 2-mediated signaling. Infect. Immun.,  2005, 73(4), 2157-2163.
[http://dx.doi.org/10.1128/IAI.73.4.2157-2163.2005] [PMID: 15784558] 
[201] 
Sawada, N.; Ogawa, T.; Asai, Y.; Makimura, Y.; Sugiyama, A. Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis. Clin. Exp. Immunol.,  2007, 148(3), 529-536.
[http://dx.doi.org/10.1111/j.1365-2249.2007.03346.x] [PMID: 17335558] 
[202] 
Kumada, H.; Haishima, Y.; Watanabe, K.; Hasegawa, C.; Tsuchiya, T.; Tanamoto, K.; Umemoto, T. Biological properties of the native and synthetic lipid A of Porphyromonas gingivalis lipopolysaccharide. Oral Microbiol. Immunol.,  2008, 23(1), 60-69.
[http://dx.doi.org/10.1111/j.1399-302X.2007.00392.x] [PMID: 18173800] 
[203] 
Al-Qutub, M.N.; Braham, P.H.; Karimi-Naser, L.M.; Liu, X.; Genco, C.A.; Darveau, R.P. Hemin-dependent modulation of the lipid A structure of Porphyromonas gingivalis lipopolysaccharide. Infect. Immun.,  2006, 74(8), 4474-4485.
[http://dx.doi.org/10.1128/IAI.01924-05] [PMID: 16861633] 
[204] 
Olsen, I.; Singhrao, S.K. Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling. J. Oral Microbiol.,  2018, 10(1), 1440128
[http://dx.doi.org/10.1080/20002297.2018.1440128] [PMID: 29503705] 
[205] 
Zenobia, C.; Hasturk, H.; Nguyen, D.; Van Dyke, T.E.; Kantarci, A.; Darveau, R.P.; Bäumler, A.J. Porphyromonas gingivalis lipid A phosphatase activity is critical for colonization and increasing the commensal load in the rabbit ligature model. Infect. Immun.,  2014, 82(2), 650-659.
[http://dx.doi.org/10.1128/IAI.01136-13] [PMID: 24478080] 
[206] 
Darveau, R.P.; Belton, C.M.; Reife, R.A.; Lamont, R.J. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infect. Immun.,  1998, 66(4), 1660-1665.
[http://dx.doi.org/10.1128/IAI.66.4.1660-1665.1998] [PMID: 9529095] 
[207] 
Yoshimura, A.; Hara, Y.; Kaneko, T.; Kato, I. Secretion of IL-1 beta, TNF-alpha, IL-8 and IL-1ra by human polymorphonuclear leukocytes in response to lipopolysaccharides from periodontopathic bacteria. J. Periodontal Res.,  1997, 32(3), 279-286.
[http://dx.doi.org/10.1111/j.1600-0765.1997.tb00535.x] [PMID: 9138193] 
[208] 
Kato, H.; Taguchi, Y.; Tominaga, K.; Umeda, M.; Tanaka, A. Porphyromonas gingivalis LPS inhibits osteoblastic differentiation and promotes pro-inflammatory cytokine production in human periodontal ligament stem cells. Arch. Oral Biol.,  2014, 59(2), 167-175.
[http://dx.doi.org/10.1016/j.archoralbio.2013.11.008] [PMID: 24370188] 
[209] 
Deleon-Pennell, K.Y.; de Castro Brás, L.E.; Lindsey, M.L. Circulating Porphyromonas gingivalis lipopolysaccharide resets cardiac homeostasis in mice through a matrix metalloproteinase-9-dependent mechanism. Physiol. Rep.,  2013, 1(5), e00079
[http://dx.doi.org/10.1002/phy2.79] [PMID: 24159380] 
[210] 
Gokyu, M.; Kobayashi, H.; Nanbara, H.; Sudo, T.; Ikeda, Y.; Suda, T.; Izumi, Y. Thrombospondin-1 production is enhanced by Porphyromonas gingivalis lipopolysaccharide in THP-1 cells. PLoS One,  2014, 9(12), e115107
[http://dx.doi.org/10.1371/journal.pone.0115107] [PMID: 25501558] 
[211] 
Na, H.S.; Lim, E.J.; Jeong, S.Y.; Ryu, M.H.; Park, M.H.; Chung, J. Plasminogen activator inhibitor type 1 expression induced by lipopolysaccharide of Porphyromonas gingivalis in human gingival fibroblast. J. Microbiol.,  2014, 52(2), 154-160.
[http://dx.doi.org/10.1007/s12275-014-3022-7] [PMID: 24500480] 
[212] 
Frangogiannis, N.G.; Ren, G.; Dewald, O.; Zymek, P.; Haudek, S.; Koerting, A.; Winkelmann, K.; Michael, L.H.; Lawler, J.; Entman, M.L. Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation,  2005, 111(22), 2935-2942.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.510354] [PMID: 15927970] 
[213] 
Kohler, H.P.; Grant, P.J. Plasminogen-activator inhibitor type 1 and coronary artery disease. N. Engl. J. Med.,  2000, 342(24), 1792-1801.
[http://dx.doi.org/10.1056/NEJM200006153422406] [PMID: 10853003] 
[214] 
Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev.,  2003, 67(4), 593-656.
[http://dx.doi.org/10.1128/MMBR.67.4.593-656.2003] [PMID: 14665678] 
[215] 
Bos, M.P.; Robert, V.; Tommassen, J. Biogenesis of the gram-negative bacterial outer membrane. Annu. Rev. Microbiol.,  2007, 61, 191-214.
[http://dx.doi.org/10.1146/annurev.micro.61.080706.093245] [PMID: 17506684] 
[216] 
Gonzales, J.R.; Groeger, S.; Johansson, A.; Meyle, J. T helper cells from aggressive periodontitis patients produce higher levels of interleukin-1 beta and interleukin-6 in interaction with Porphyromonas gingivalis. Clin. Oral Investig.,  2014, 18(7), 1835-1843.
[http://dx.doi.org/10.1007/s00784-013-1162-5] [PMID: 24352581] 
[217] 
Watanabe, K.; Yamaji, Y.; Umemoto, T. Correlation between cell-adherent activity and surface structure in Porphyromonas gingivalis. Oral Microbiol. Immunol.,  1992, 7(6), 357-363.
[http://dx.doi.org/10.1111/j.1399-302X.1992.tb00636.x] [PMID: 1363734] 
[218] 
Saito, S.; Hiratsuka, K.; Hayakawa, M.; Takiguchi, H.; Abiko, Y. Inhibition of a Porphyromonas gingivalis colonizing factor between Actinomyces viscosus ATCC 19246 by monoclonal antibodies against recombinant 40-kDa outer-membrane protein. Gen. Pharmacol.,  1997, 28(5), 675-680.
[http://dx.doi.org/10.1016/S0306-3623(96)00366-7] [PMID: 9184801] 
[219] 
Chen, Y.Y.; Peng, B.; Yang, Q.; Glew, M.D.; Veith, P.D.; Cross, K.J.; Goldie, K.N.; Chen, D.; O’Brien-Simpson, N.; Dashper, S.G.; Reynolds, E.C. The outer membrane protein LptO is essential for the O-deacylation of LPS and the co-ordinated secretion and attachment of A-LPS and CTD proteins in Porphyromonas gingivalis. Mol. Microbiol.,  2011, 79(5), 1380-1401.
[http://dx.doi.org/10.1111/j.1365-2958.2010.07530.x] [PMID: 21244528] 
[220] 
Saiki, K.; Konishi, K. Identification of a novel Porphyromonas gingivalis outer membrane protein, PG534, required for the production of active gingipains. FEMS Microbiol. Lett.,  2010, 310(2), 168-174.
[http://dx.doi.org/10.1111/j.1574-6968.2010.02059.x] [PMID: 20695897] 
[221] 
Handley, P.S.; Tipler, L.S. An electron microscope survey of the surface structures and hydrophobicity of oral and non-oral species of the bacterial genus Bacteroides. Arch. Oral Biol.,  1986, 31(5), 325-335.
[http://dx.doi.org/10.1016/0003-9969(86)90047-6] [PMID: 2875705] 
[222] 
Nagano, K.; Hasegawa, Y.; Abiko, Y.; Yoshida, Y.; Murakami, Y.; Yoshimura, F. Porphyromonas gingivalis FimA fimbriae: fimbrial assembly by fimA alone in the fim gene cluster and differential antigenicity among fimA genotypes. PLoS One,  2012, 7(9), e43722
[http://dx.doi.org/10.1371/journal.pone.0043722] [PMID: 22970139] 
[223] 
Amano, A. Bacterial adhesins to host components in periodontitis. Periodontol. 2000,  2010, 52(1), 12-37.
[http://dx.doi.org/10.1111/j.1600-0757.2009.00307.x] [PMID: 20017793] 
[224] 
Amano, A.; Nakagawa, I.; Okahashi, N.; Hamada, N. Variations of Porphyromonas gingivalis fimbriae in relation to microbial pathogenesis. J. Periodontal Res.,  2004, 39(2), 136-142.
[http://dx.doi.org/10.1111/j.1600-0765.2004.00719.x] [PMID: 15009522] 
[225] 
Lee, J.Y.; Sojar, H.T.; Bedi, G.S.; Genco, R.J. Synthetic peptides analogous to the fimbrillin sequence inhibit adherence of Porphyromonas gingivalis. Infect. Immun.,  1992, 60(4), 1662-1670.
[http://dx.doi.org/10.1128/IAI.60.4.1662-1670.1992] [PMID: 1347762] 
[226] 
Amano, A. Disruption of epithelial barrier and impairment of cellular function by Porphyromonas gingivalis. Front. Biosci.,  2007, 12, 3965-3974.
[http://dx.doi.org/10.2741/2363] [PMID: 17485350] 
[227] 
Sharma, A.; Sojar, H.T.; Lee, J.Y.; Genco, R.J. Expression of a functional Porphyromonas gingivalis fimbrillin polypeptide in Escherichia coli: purification, physicochemical and immunochemical characterization, and binding characteristics. Infect. Immun.,  1993, 61(8), 3570-3573.
[http://dx.doi.org/10.1128/IAI.61.8.3570-3573.1993] [PMID: 8392975] 
[228] 
Zenobia, C.; Hajishengallis, G. Porphyromonas gingivalis virulence factors involved in subversion of leukocytes and microbial dysbiosis. Virulence,  2015, 6(3), 236-243.
[http://dx.doi.org/10.1080/21505594.2014.999567] [PMID: 25654623] 
[229] 
Yang, J.; Wu, J.; Liu, Y.; Huang, J.; Lu, Z.; Xie, L.; Sun, W.; Ji, Y. Porphyromonas gingivalis infection reduces regulatory T cells in infected atherosclerosis patients. PLoS One,  2014, 9(1), e86599-e86599.
[http://dx.doi.org/10.1371/journal.pone.0086599] [PMID: 24466164] 
[230] 
Maiden, M.F.; Cohee, P.; Tanner, A.C. Proposal to conserve the adjectival form of the specific epithet in the reclassification of Bacteroides forsythus Tanner et al. 1986 to the genus Tannerella Sakamoto et al. 2002 as Tannerella forsythia corrig., gen. nov., comb. nov. Request for an Opinion. Int. J. Syst. Evol. Microbiol.,  2003, 53(Pt 6), 2111-2112.
[http://dx.doi.org/10.1099/ijs.0.02641-0] [PMID: 14657155] 
[231] 
Hajishengallis, G.; Lamont, R.J. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol. Oral Microbiol.,  2012, 27(6), 409-419.
[http://dx.doi.org/10.1111/j.2041-1014.2012.00663.x] [PMID: 23134607] 
[232] 
Dashper, S.G.; Seers, C.A.; Tan, K.H.; Reynolds, E.C. Virulence factors of the oral spirochete Treponema denticola. J. Dent. Res.,  2011, 90(6), 691-703.
[http://dx.doi.org/10.1177/0022034510385242] [PMID: 20940357] 
[233] 
Polak, D.; Wilensky, A.; Shapira, L.; Halabi, A.; Goldstein, D.; Weiss, E.I.; Houri-Haddad, Y. Mouse model of experimental periodontitis induced by Porphyromonas gingivalis/Fusobacterium nucleatum infection: bone loss and host response. J. Clin. Periodontol.,  2009, 36(5), 406-410.
[http://dx.doi.org/10.1111/j.1600-051X.2009.01393.x] [PMID: 19419440] 
[234] 
Kesavalu, L.; Sathishkumar, S.; Bakthavatchalu, V.; Matthews, C.; Dawson, D.; Steffen, M.; Ebersole, J.L. Rat model of polymicrobial infection, immunity, and alveolar bone resorption in periodontal disease. Infect. Immun.,  2007, 75(4), 1704-1712.
[http://dx.doi.org/10.1128/IAI.00733-06] [PMID: 17210663] 
[235] 
Deng, Z-L.; Sztajer, H.; Jarek, M.; Bhuju, S.; Wagner-Döbler, I. Worlds apart - transcriptome profiles of key oral microbes in the periodontal pocket compared to single laboratory culture reflect synergistic interactions. Front. Microbiol.,  2018, 9, 124-124.
[http://dx.doi.org/10.3389/fmicb.2018.00124] [PMID: 29467738] 
[236] 
Lee, S.H.; Kim, K.K.; Choi, B.K. Upregulation of intercellular adhesion molecule 1 and proinflammatory cytokines by the major surface proteins of Treponema maltophilum and Treponema lecithinolyticum, the phylogenetic group IV oral spirochetes associated with periodontitis and endodontic infections. Infect. Immun.,  2005, 73(1), 268-276.
[http://dx.doi.org/10.1128/IAI.73.1.268-276.2005] [PMID: 15618163] 
[237] 
Bolstad, A.I.; Jensen, H.B.; Bakken, V. Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum. Clin. Microbiol. Rev.,  1996, 9(1), 55-71.
[http://dx.doi.org/10.1128/CMR.9.1.55-71.1996] [PMID: 8665477] 
[238] 
Skaar, E.P. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog.,  2010, 6(8), e1000949
[http://dx.doi.org/10.1371/journal.ppat.1000949] [PMID: 20711357] 
[239] 
Ebersole, J.L.; Cappelli, D. Acute-phase reactants in infections and inflammatory diseases. Periodontol. 2000,  2000, 23, 19-49.
[http://dx.doi.org/10.1034/j.1600-0757.2000.2230103.x] [PMID: 11276764] 
[240] 
Loos, B.G. Systemic markers of inflammation in periodontitis. J. Periodontol.,  2005, 76(11)(Suppl.), 2106-2115.
[http://dx.doi.org/10.1902/jop.2005.76.11-S.2106] 
[241] 
Khader, Y.S.; Albashaireh, Z.S.; Alomari, M.A. Periodontal diseases and the risk of coronary heart and cerebrovascular diseases: a meta-analysis. J. Periodontol.,  2004, 75(8), 1046-1053.
[http://dx.doi.org/10.1902/jop.2004.75.8.1046] [PMID: 15455730] 
[242] 
Lafon, A.; Pereira, B.; Dufour, T.; Rigouby, V.; Giroud, M.; Béjot, Y.; Tubert-Jeannin, S. Periodontal disease and stroke: a meta-analysis of cohort studies. Eur. J. Neurol.,  2014, 21(9), 1155-1161, e66-e67.
[http://dx.doi.org/10.1111/ene.12415] 
[243] 
Mustapha, I.Z.; Debrey, S.; Oladubu, M.; Ugarte, R. Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis. J. Periodontol.,  2007, 78(12), 2289-2302.
[http://dx.doi.org/10.1902/jop.2007.070140] [PMID: 18052701] 
[244] 
Kweider, M.; Lowe, G.D.; Murray, G.D.; Kinane, D.F.; McGowan, D.A. Dental disease, fibrinogen and white cell count; links with myocardial infarction? Scott. Med. J.,  1993, 38(3), 73-74.
[http://dx.doi.org/10.1177/003693309303800304] [PMID: 8356427] 
[245] 
Slade, G.D.; Offenbacher, S.; Beck, J.D.; Heiss, G.; Pankow, J.S. Acute-phase inflammatory response to periodontal disease in the US population. J. Dent. Res.,  2000, 79(1), 49-57.
[http://dx.doi.org/10.1177/00220345000790010701] [PMID: 10690660] 
[246] 
Wu, T.; Trevisan, M.; Genco, R.J.; Falkner, K.L.; Dorn, J.P.; Sempos, C.T. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am. J. Epidemiol.,  2000, 151(3), 273-282.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a010203] [PMID: 10670552] 
[247] 
Liljestrand, J.M.; Paju, S.; Pietiäinen, M.; Buhlin, K.; Persson, G.R.; Nieminen, M.S.; Sinisalo, J.; Mäntylä, P.; Pussinen, P.J. Immunologic burden links periodontitis to acute coronary syndrome. Atherosclerosis,  2018, 268, 177-184.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.12.007] [PMID: 29232563] 
[248] 
Hajishengallis, G.; Liang, S.; Payne, M.A.; Hashim, A.; Jotwani, R.; Eskan, M.A.; McIntosh, M.L.; Alsam, A.; Kirkwood, K.L.; Lambris, J.D.; Darveau, R.P.; Curtis, M.A. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe,  2011, 10(5), 497-506.
[http://dx.doi.org/10.1016/j.chom.2011.10.006] [PMID: 22036469] 
[249] 
Walsh, M.C.; Lee, J.; Choi, Y. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system. Immunol. Rev.,  2015, 266(1), 72-92.
[http://dx.doi.org/10.1111/imr.12302] [PMID: 26085208] 
[250] 
Tang, L.; Zhou, X.D.; Wang, Q.; Zhang, L.; Wang, Y.; Li, X.Y.; Huang, D.M. Expression of TRAF6 and pro-inflammatory cytokines through activation of TLR2, TLR4, NOD1, and NOD2 in human periodontal ligament fibroblasts. Arch. Oral Biol.,  2011, 56(10), 1064-1072.
[http://dx.doi.org/10.1016/j.archoralbio.2011.02.020] [PMID: 21457942] 
[251] 
Tang, L.; Zhou, X.D.; Wang, Q.; Zhang, L.; Wang, Y.; Huang, D.M. TNF receptor-associated factor 6 suppression inhibits inflammatory response to Porphyromonas gingivialis in human periodontal ligament cells. Quintessence Int.,  2011, 42(9), 787-796.
[PMID: 21909504] 
[252] 
Ikeda, U.; Ito, T.; Shimada, K. Interleukin-6 and acute coronary syndrome. Clin. Cardiol.,  2001, 24(11), 701-704.
[http://dx.doi.org/10.1002/clc.4960241103] [PMID: 11714126] 
[253] 
Bagavad Gita, J.; George, A.V.; Pavithra, N.; Chandrasekaran, S.C.; Latchumanadhas, K.; Gnanamani, A. Dysregulation of miR-146a by periodontal pathogens: A risk for acute coronary syndrome. J. Periodontol.,  2019, 90(7), 756-765.
[http://dx.doi.org/10.1002/JPER.18-0466] [PMID: 30618100] 
[254] 
Shimada, Y.; Komatsu, Y.; Ikezawa-Suzuki, I.; Tai, H.; Sugita, N.; Yoshie, H. The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. J. Periodontol.,  2010, 81(8), 1118-1123.
[http://dx.doi.org/10.1902/jop.2010.090741] [PMID: 20370420] 
[255] 
Sabatine, M.S.; Morrow, D.A.; Cannon, C.P.; Murphy, S.A.; Demopoulos, L.A.; DiBattiste, P.M.; McCabe, C.H.; Braunwald, E.; Gibson, C.M. Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy- Thrombolysis in Myocardial Infarction 18 trial)substudy. J. Am. Coll. Cardiol.,  2002, 40(10), 1761-1768.
[http://dx.doi.org/10.1016/S0735-1097(02)02484-1] [PMID: 12446059] 
[256] 
Takeda, Y.; Suzuki, S.; Fukutomi, T.; Kondo, H.; Sugiura, M.; Suzumura, H.; Murasaki, G.; Okutani, H.; Itoh, M. Elevated white blood cell count as a risk factor of coronary artery disease: inconsistency between forms of the disease. Jpn. Heart J.,  2003, 44(2), 201-211.
[http://dx.doi.org/10.1536/jhj.44.201] [PMID: 12718482] 
[257] 
Pitsavos, C.; Kourlaba, G.; Panagiotakos, D.B.; Tsamis, E.; Kogias, Y.; Stravopodis, P.; Stefanadis, C. Does smoking status affect the association between baseline white blood cell count and in-hospital mortality of patients presented with acute coronary syndrome? The Greek study of acute coronary syndromes (GREECS). Int. J. Cardiol.,  2008, 125(1), 94-100.
[http://dx.doi.org/10.1016/j.ijcard.2007.05.030] [PMID: 17655949] 
[258] 
Johannsen, A.; Susin, C.; Gustafsson, A. Smoking and inflammation: evidence for a synergistic role in chronic disease. Periodontol. 2000,  2014, 64(1), 111-126.
[http://dx.doi.org/10.1111/j.1600-0757.2012.00456.x] [PMID: 24320959] 
[259] 
Srivastava, P. Roles of heat-shock proteins in innate and adaptive immunity. Nat. Rev. Immunol.,  2002, 2(3), 185-194.
[http://dx.doi.org/10.1038/nri749] [PMID: 11913069] 
[260] 
Lamb, D.J.; El-Sankary, W.; Ferns, G.A. Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Atherosclerosis,  2003, 167(2), 177-185.
[http://dx.doi.org/10.1016/S0021-9150(02)00301-5] [PMID: 12818399] 
[261] 
Rizzo, M.; Cappello, F.; Marfil, R.; Nibali, L.; Marino Gammazza, A.; Rappa, F.; Bonaventura, G.; Galindo-Moreno, P.; O’Valle, F.; Zummo, G.; Conway de Macario, E.; Macario, A.J.; Mesa, F. Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study. Cell Stress Chaperones,  2012, 17(3), 399-407.
[http://dx.doi.org/10.1007/s12192-011-0315-1] [PMID: 22215516] 
[262] 
Maeda, H.; Miyamoto, M.; Hongyo, H.; Nagai, A.; Kurihara, H.; Murayama, Y. Heat shock protein 60 (GroEL) from Porphyromonas gingivalis: molecular cloning and sequence analysis of its gene and purification of the recombinant protein. FEMS Microbiol. Lett.,  1994, 119(1-2), 129-135.
[http://dx.doi.org/10.1111/j.1574-6968.1994.tb06879.x] [PMID: 7913687] 
[263] 
Vayssier, C.; Mayrand, D.; Grenier, D. Detection of stress proteins in Porphyromonas gingivalis and other oral bacteria by western immunoblotting analysis. FEMS Microbiol. Lett.,  1994, 121(3), 303-307.
[http://dx.doi.org/10.1111/j.1574-6968.1994.tb07117.x] [PMID: 7926686] 
[264] 
Lu, B.; McBride, B.C. Stress response of Porphyromonas gingivalis. Oral Microbiol. Immunol.,  1994, 9(3), 166-173.
[http://dx.doi.org/10.1111/j.1399-302X.1994.tb00054.x] [PMID: 7936723] 
[265] 
Choi, J-I.; Chung, S-W.; Kang, H-S.; Rhim, B.Y.; Park, Y-M.; Kim, U-S.; Kim, S-J. Epitope mapping of Porphyromonas gingivalis heat-shock protein and human heat-shock protein in human atherosclerosis. J. Dent. Res.,  2004, 83(12), 936-940.
[http://dx.doi.org/10.1177/154405910408301209] [PMID: 15557401] 
[266] 
Hinode, D.; Nakamura, R.; Grenier, D.; Mayrand, D. Cross-reactivity of specific antibodies directed to heat shock proteins from periodontopathogenic bacteria and of human origin [corrected]. Oral Microbiol. Immunol.,  1998, 13(1), 55-58.
[http://dx.doi.org/10.1111/j.1399-302X.1998.tb00752.x] [PMID: 9573824] 
[267] 
Yamazaki, K.; Ohsawa, Y.; Itoh, H.; Ueki, K.; Tabeta, K.; Oda, T.; Nakajima, T.; Yoshie, H.; Saito, S.; Oguma, F.; Kodama, M.; Aizawa, Y.; Seymour, G.J. T-cell clonality to Porphyromonas gingivalis and human heat shock protein 60s in patients with atherosclerosis and periodontitis. Oral Microbiol. Immunol.,  2004, 19(3), 160-167.
[http://dx.doi.org/10.1111/j.0902-0055.2004.00134.x] [PMID: 15107067] 
[268] 
Ford, P.; Gemmell, E.; Walker, P.; West, M.; Cullinan, M.; Seymour, G. Characterization of heat shock protein-specific T cells in atherosclerosis. Clin. Diagn. Lab. Immunol.,  2005, 12(2), 259-267.
[PMID: 15699420] 
[269] 
Fuchs, D.; Hausen, A.; Reibnegger, G.; Werner, E.R.; Dierich, M.P.; Wachter, H. Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunol. Today,  1988, 9(5), 150-155.
[http://dx.doi.org/10.1016/0167-5699(88)91203-0] [PMID: 3076770] 
[270] 
Huber, C.; Batchelor, J.R.; Fuchs, D.; Hausen, A.; Lang, A.; Niederwieser, D.; Reibnegger, G.; Swetly, P.; Troppmair, J.; Wachter, H. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J. Exp. Med.,  1984, 160(1), 310-316.
[http://dx.doi.org/10.1084/jem.160.1.310] [PMID: 6429267] 
[271] 
Wirleitner, B.; Reider, D.; Ebner, S.; Böck, G.; Widner, B.; Jaeger, M.; Schennach, H.; Romani, N.; Fuchs, D. Monocyte-derived dendritic cells release neopterin. J. Leukoc. Biol.,  2002, 72(6), 1148-1153.
[PMID: 12488496] 
[272] 
Werner-Felmayer, G.; Werner, E.R.; Fuchs, D.; Hausen, A.; Reibnegger, G.; Wachter, H. Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells. Biol. Chem. Hoppe Seyler,  1989, 370(9), 1063-1069.
[http://dx.doi.org/10.1515/bchm3.1989.370.2.1063] [PMID: 2482041] 
[273] 
Murr, C.; Widner, B.; Wirleitner, B.; Fuchs, D. Neopterin as a marker for immune system activation. Curr. Drug Metab.,  2002, 3(2), 175-187.
[http://dx.doi.org/10.2174/1389200024605082] [PMID: 12003349] 
[274] 
Nathan, C.F. Peroxide and pteridine: a hypothesis on the regulation of macrophage antimicrobial activity by interferon gamma. Interferon,  1986, 7, 125-143.
[PMID: 3102389] 
[275] 
Ozmeriç, N.; Baydar, T.; Bodur, A.; Engin, A.B.; Uraz, A.; Eren, K.; Sahin, G. Level of neopterin, a marker of immune cell activation in gingival crevicular fluid, saliva, and urine in patients with aggressive periodontitis. J. Periodontol.,  2002, 73(7), 720-725.
[http://dx.doi.org/10.1902/jop.2002.73.7.720] [PMID: 12146530] 
[276] 
Vrecko, K.; Staedtler, P.; Mischak, I.; Maresch, L.; Reibnegger, G. Periodontitis and concentrations of the cellular immune activation marker neopterin in saliva and urine. Clin. Chim. Acta,  1997, 268(1-2), 31-40.
[http://dx.doi.org/10.1016/S0009-8981(97)00154-X] [PMID: 9495569] 
[277] 
Pradeep, A.R.; Kumar, M.S.; Ramachandraprasad, M.V.; Shikha, C. Gingival crevicular fluid levels of neopterin in healthy subjects and in patients with different periodontal diseases. J. Periodontol.,  2007, 78(10), 1962-1967.
[http://dx.doi.org/10.1902/jop.2007.070096] [PMID: 18062118] 
[278] 
Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell,  2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438] 
[279] 
Ebert, M.S.; Sharp, P.A. Roles for microRNAs in conferring robustness to biological processes. Cell,  2012, 149(3), 515-524.
[http://dx.doi.org/10.1016/j.cell.2012.04.005] [PMID: 22541426] 
[280] 
Lee, R.C.; Feinbaum, R.L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell,  1993, 75(5), 843-854.
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621] 
[281] 
Hamar, P. Role of regulatory micro RNAs in type 2 diabetes mellitus-related inflammation. Nucleic Acid Ther.,  2012, 22(5), 289-294.
[http://dx.doi.org/10.1089/nat.2012.0381] [PMID: 22950794] 
[282] 
Kloosterman, W.P.; Plasterk, R.H. The diverse functions of microRNAs in animal development and disease. Dev. Cell,  2006, 11(4), 441-450.
[http://dx.doi.org/10.1016/j.devcel.2006.09.009] [PMID: 17011485] 
[283] 
Kantharidis, P.; Wang, B.; Carew, R.M.; Lan, H.Y. Diabetes complications: the microRNA perspective. Diabetes,  2011, 60(7), 1832-1837.
[http://dx.doi.org/10.2337/db11-0082] [PMID: 21709278] 
[284] 
Baulina, N.M.; Kulakova, O.G.; Favorova, O.O. MicroRNAs: The Role in Autoimmune Inflammation. Acta Naturae,  2016, 8(1), 21-33.
[http://dx.doi.org/10.32607/20758251-2016-8-1-21-33] [PMID: 27099782] 
[285] 
Raisch, J.; Darfeuille-Michaud, A.; Nguyen, H.T.T. Role of microRNAs in the immune system, inflammation and cancer. World J. Gastroenterol.,  2013, 19(20), 2985-2996.
[http://dx.doi.org/10.3748/wjg.v19.i20.2985] [PMID: 23716978] 
[286] 
Dai, R.; Ahmed, S.A.; Micro, R.N.A. MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl. Res.,  2011, 157(4), 163-179.
[http://dx.doi.org/10.1016/j.trsl.2011.01.007] [PMID: 21420027] 
[287] 
Lu, L.F.; Liston, A. MicroRNA in the immune system, microRNA as an immune system. Immunology,  2009, 127(3), 291-298.
[http://dx.doi.org/10.1111/j.1365-2567.2009.03092.x] [PMID: 19538248] 
[288] 
Roy, B.; Dunbar, M.; Shelton, R.C.; Dwivedi, Y. Identification of MicroRNA-124-3p as a putative epigenetic signature of major depressive disorder. Neuropsychopharmacology,  2017, 42(4), 864-875.
[289] 
Roy, B.; Dwivedi, Y. Understanding the neuroepigenetic constituents of suicide brain. Prog. Mol. Biol. Transl. Sci.,  2018, 157, 233-262.
[http://dx.doi.org/10.1016/bs.pmbts.2018.01.007] [PMID: 29933952] 
[290] 
Roy, B.; Shelton, R.C.; Dwivedi, Y. DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideation. J. Psychiatr. Res.,  2017, 89, 115-124.
[http://dx.doi.org/10.1016/j.jpsychires.2017.02.005] [PMID: 28246044] 
[291] 
Smalheiser, N.R.; Lugli, G.; Rizavi, H.S.; Torvik, V.I.; Turecki, G.; Dwivedi, Y. MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. PLoS One,  2012, 7(3), e33201
[http://dx.doi.org/10.1371/journal.pone.0033201] [PMID: 22427989] 
[292] 
Smalheiser, N.R.; Lugli, G.; Zhang, H.; Rizavi, H.; Cook, E.H.; Dwivedi, Y. Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects. PLoS One,  2014, 9(1), e86469
[http://dx.doi.org/10.1371/journal.pone.0086469] [PMID: 24475125] 
[293] 
Wang, Q.; Roy, B.; Turecki, G.; Shelton, R.C.; Dwivedi, Y. Role of complex epigenetic switching in tumor necrosis factor-α upregulation in the prefrontal cortex of suicide subjects. Am. J. Psychiatry,  2018, 175(3), 262-274.
[http://dx.doi.org/10.1176/appi.ajp.2017.16070759] [PMID: 29361849] 
[294] 
Xiao, C.; Rajewsky, K. MicroRNA control in the immune system: basic principles. Cell,  2009, 136(1), 26-36.
[http://dx.doi.org/10.1016/j.cell.2008.12.027] [PMID: 19135886] 
[295] 
Sochocka, M.; Diniz, B.S.; Leszek, J. Inflammatory response in the CNS: friend or foe? Mol. Neurobiol.,  2017, 54(10), 8071-8089.
[http://dx.doi.org/10.1007/s12035-016-0297-1] [PMID: 27889895] 
[296] 
Soreq, H.; Wolf, Y. NeurimmiRs: microRNAs in the neuroimmune interface. Trends Mol. Med.,  2011, 17(10), 548-555.
[http://dx.doi.org/10.1016/j.molmed.2011.06.009] [PMID: 21813326] 
[297] 
Ksiazek-Winiarek, D.J.; Kacperska, M.J.; Glabinski, A. MicroRNAs as novel regulators of neuroinflammation. Mediators Inflamm.,  2013, 2013, 172351
[http://dx.doi.org/10.1155/2013/172351] [PMID: 23983402] 
[298] 
Slota, J.A.; Booth, S.A. MicroRNAs in neuroinflammation: implications in disease pathogenesis, biomarker discovery and therapeutic applications. Noncoding RNA,  2019, 5(2), E35
[http://dx.doi.org/10.3390/ncrna5020035] [PMID: 31022830] 
[299] 
Su, W.; Aloi, M.S.; Garden, G.A. MicroRNAs mediating CNS inflammation: Small regulators with powerful potential. Brain Behav. Immun.,  2016, 52, 1-8.
[http://dx.doi.org/10.1016/j.bbi.2015.07.003] [PMID: 26148445] 
[300] 
Thounaojam, M.C.; Kaushik, D.K.; Basu, A. MicroRNAs in the brain: it’s regulatory role in neuroinflammation. Mol. Neurobiol.,  2013, 47(3), 1034-1044.
[http://dx.doi.org/10.1007/s12035-013-8400-3] [PMID: 23315269] 
[301] 
Guo, Y.; Hong, W.; Wang, X.; Zhang, P.; Körner, H.; Tu, J.; Wei, W. MicroRNAs in microglia: how do microRNAs affect activation, inflammation, polarization of microglia and mediate the interaction between microglia and glioma? Front. Mol. Neurosci.,  2019, 12, 125.
[http://dx.doi.org/10.3389/fnmol.2019.00125] [PMID: 31133802] 
[302] 
Gaudet, A.D.; Fonken, L.K.; Watkins, L.R.; Nelson, R.J.; Popovich, P.G. MicroRNAs: Roles in regulating neuroinflammation. Neuroscientist,  2018, 24(3), 221-245.
[http://dx.doi.org/10.1177/1073858417721150] [PMID: 28737113] 
[303] 
Taganov, K.D.; Boldin, M.P.; Chang, K.J.; Baltimore, D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA,  2006, 103(33), 12481-12486.
[http://dx.doi.org/10.1073/pnas.0605298103] [PMID: 16885212] 
[304] 
Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol.,  2009, 1(6), a001651
[http://dx.doi.org/10.1101/cshperspect.a001651] [PMID: 20457564] 
[305] 
Meisgen, F.; Xu Landén, N.; Wang, A.; Réthi, B.; Bouez, C.; Zuccolo, M.; Gueniche, A.; Ståhle, M.; Sonkoly, E.; Breton, L.; Pivarcsi, A. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J. Invest. Dermatol.,  2014, 134(7), 1931-1940.
[http://dx.doi.org/10.1038/jid.2014.89] [PMID: 24670381] 
[306] 
Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell,  2009, 136(2), 215-233.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326] 
[307] 
Qin, Z.; Wang, P.Y.; Su, D.F.; Liu, X. miRNA-124 in Immune System and Immune Disorders. Front. Immunol.,  2016, 7, 406.
[http://dx.doi.org/10.3389/fimmu.2016.00406] [PMID: 27757114] 
[308] 
Hutchison, E.R.; Kawamoto, E.M.; Taub, D.D.; Lal, A.; Abdelmohsen, K.; Zhang, Y.; Wood, W.H., III; Lehrmann, E.; Camandola, S.; Becker, K.G.; Gorospe, M.; Mattson, M.P. Evidence for miR-181 involvement in neuroinflammatory responses of astrocytes. Glia,  2013, 61(7), 1018-1028.
[http://dx.doi.org/10.1002/glia.22483] [PMID: 23650073] 
[309] 
Sebastiani, G.; Grieco, F.A.; Spagnuolo, I.; Galleri, L.; Cataldo, D.; Dotta, F. Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab. Res. Rev.,  2011, 27(8), 862-866.
[http://dx.doi.org/10.1002/dmrr.1262] [PMID: 22069274] 
[310] 
Shi, C.; Zhu, L.; Chen, X.; Gu, N.; Chen, L.; Zhu, L.; Yang, L.; Pang, L.; Guo, X.; Ji, C.; Zhang, C. IL-6 and TNF-α induced obesity-related inflammatory response through transcriptional regulation of miR-146b. J. Interferon Cytokine Res.,  2014, 34(5), 342-348.
[http://dx.doi.org/10.1089/jir.2013.0078] [PMID: 24428800] 
[311] 
Li, J.J.; Wang, B.; Kodali, M.C.; Chen, C.; Kim, E.; Patters, B.J.; Lan, L.; Kumar, S.; Wang, X.; Yue, J.; Liao, F.F. In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J. Neuroinflammation,  2018, 15(1), 8.
[http://dx.doi.org/10.1186/s12974-017-1038-8] [PMID: 29310666] 
[312] 
Honda, T.; Takahashi, N.; Miyauchi, S.; Yamazaki, K. Porphyromonas gingivalis lipopolysaccharide induces miR-146a without altering the production of inflammatory cytokines. Biochem. Biophys. Res. Commun.,  2012, 420(4), 918-925.
[http://dx.doi.org/10.1016/j.bbrc.2012.03.102] [PMID: 22480686] 
[313] 
Xie, Y.F.; Shu, R.; Jiang, S.Y.; Liu, D.L.; Zhang, X.L. Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues. Int. J. Oral Sci.,  2011, 3(3), 125-134.
[http://dx.doi.org/10.4248/IJOS11046] [PMID: 21789961] 
[314] 
Stoecklin-Wasmer, C.; Guarnieri, P.; Celenti, R.; Demmer, R.T.; Kebschull, M.; Papapanou, P.N. MicroRNAs and their target genes in gingival tissues. J. Dent. Res.,  2012, 91(10), 934-940.
[http://dx.doi.org/10.1177/0022034512456551] [PMID: 22879578] 
[315] 
Tang, L.; Li, X.; Bai, Y.; Wang, P.; Zhao, Y. MicroRNA-146a negatively regulates the inflammatory response to Porphyromonas gingivalis in human periodontal ligament fibroblasts via TRAF6/p38 pathway. J. Periodontol.,  2019, 90(4), 391-399.
[http://dx.doi.org/10.1002/JPER.18-0190] [PMID: 30378773] 
[316] 
An, F.; Gong, B.; Wang, H.; Yu, D.; Zhao, G.; Lin, L.; Tang, W.; Yu, H.; Bao, S.; Xie, Q. miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure. Apoptosis,  2012, 17(7), 702-716.
[http://dx.doi.org/10.1007/s10495-012-0704-7] [PMID: 22374434] 
[317] 
Lezina, L.; Purmessur, N.; Antonov, A.V.; Ivanova, T.; Karpova, E.; Krishan, K.; Ivan, M.; Aksenova, V.; Tentler, D.; Garabadgiu, A.V.; Melino, G.; Barlev, N.A. miR-16 and miR-26a target checkpoint kinases Wee1 and Chk1 in response to p53 activation by genotoxic stress. Cell Death Dis.,  2013, 4, e953
[http://dx.doi.org/10.1038/cddis.2013.483] [PMID: 24336073] 
[318] 
Zhang, X.; Wan, G.; Mlotshwa, S.; Vance, V.; Berger, F.G.; Chen, H.; Lu, X. Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res.,  2010, 70(18), 7176-7186.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0697] [PMID: 20668064] 
[319] 
Zhan, X-H.; Xu, Q-Y.; Tian, R.; Yan, H.; Zhang, M.; Wu, J.; Wang, W.; He, J. MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1-ATM-p53 feedback loop. Oncotarget,  2017, 8(33), 54788-54798.
[http://dx.doi.org/10.18632/oncotarget.18510] [PMID: 28903382] 
[320] 
Besnier, M.; Shantikumar, S.; Anwar, M.; Dixit, P.; Chamorro-Jorganes, A.; Sweaad, W.; Sala-Newby, G.; Madeddu, P.; Thomas, A.C.; Howard, L.; Mushtaq, S.; Petretto, E.; Caporali, A.; Emanueli, C. miR-15a/-16 inhibit angiogenesis by targeting the Tie2 coding sequence: therapeutic potential of a miR-15a/16 decoy system in limb ischemia. Mol. Ther. Nucleic Acids,  2019, 17, 49-62.
[http://dx.doi.org/10.1016/j.omtn.2019.05.002] [PMID: 31220779] 
[321] 
Song, M.F.; Dong, J.Z.; Wang, Y.W.; He, J.; Ju, X.; Zhang, L.; Zhang, Y.H.; Shi, J.F.; Lv, Y.Y. CSF miR-16 is decreased in major depression patients and its neutralization in rats induces depression-like behaviors via a serotonin transmitter system. J. Affect. Disord.,  2015, 178, 25-31.
[http://dx.doi.org/10.1016/j.jad.2015.02.022] [PMID: 25779937] 
[322] 
Gheysarzadeh, A.; Sadeghifard, N.; Afraidooni, L.; Pooyan, F.; Mofid, M.R.; Valadbeigi, H.; Bakhtiari, H.; Keikhavani, S. Serum-based microRNA biomarkers for major depression: MiR-16, miR-135a, and miR-1202. J. Res. Med. Sci.,  2018, 23, 69.
[http://dx.doi.org/10.4103/jrms.JRMS_879_17] [PMID: 30181751] 
[323] 
Zhong, J.; He, Y.; Chen, W.; Shui, X.; Chen, C.; Lei, W. Circulating microRNA-19a as a potential novel biomarker for diagnosis of acute myocardial infarction. Int. J. Mol. Sci.,  2014, 15(11), 20355-20364.
[http://dx.doi.org/10.3390/ijms151120355] [PMID: 25383678] 
[324] 
Chen, H.; Li, X.; Liu, S.; Gu, L.; Zhou, X. MircroRNA-19a promotes vascular inflammation and foam cell formation by targeting HBP-1 in atherogenesis. Sci. Rep.,  2017, 7(1), 12089.
[http://dx.doi.org/10.1038/s41598-017-12167-z] [PMID: 28935967] 
[325] 
Marques, F.Z.; Eikelis, N.; Bayles, R.G.; Lambert, E.A.; Straznicky, N.E.; Hering, D.; Esler, M.D.; Head, G.A.; Barton, D.A.; Schlaich, M.P.; Lambert, G.W. A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism. Mol. Psychiatry,  2017, 22(1), 134-141.
[http://dx.doi.org/10.1038/mp.2016.40] [PMID: 27046647] 
[326] 
Li, X.; Teng, C.; Ma, J.; Fu, N.; Wang, L.; Wen, J.; Wang, T.Y. miR-19 family: A promising biomarker and therapeutic target in heart, vessels and neurons. Life Sci.,  2019, 232, 116651
[http://dx.doi.org/10.1016/j.lfs.2019.116651] [PMID: 31302195] 
[327] 
Canfrán-Duque, A.; Rotllan, N.; Zhang, X.; Fernández-Fuertes, M.; Ramírez-Hidalgo, C.; Araldi, E.; Daimiel, L.; Busto, R.; Fernández-Hernando, C.; Suárez, Y. Macrophage deficiency of miR-21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis. EMBO Mol. Med.,  2017, 9(9), 1244-1262.
[http://dx.doi.org/10.15252/emmm.201607492] [PMID: 28674080] 
[328] 
Yuan, J.; Chen, H.; Ge, D.; Xu, Y.; Xu, H.; Yang, Y.; Gu, M.; Zhou, Y.; Zhu, J.; Ge, T.; Chen, Q.; Gao, Y.; Wang, Y.; Li, X.; Zhao, Y. Mir-21 promotes cardiac fibrosis after myocardial infarction via targeting smad7. Cell. Physiol. Biochem.,  2017, 42(6), 2207-2219.
[http://dx.doi.org/10.1159/000479995] [PMID: 28817807] 
[329] 
Wang, Z.H.; Sun, X.Y.; Li, C.L.; Sun, Y.M.; Li, J.; Wang, L.F.; Li, Z.Q. miRNA-21 expression in the serum of elderly patients with acute myocardial infarction. Med. Sci. Monit.,  2017, 23, 5728-5734.
[http://dx.doi.org/10.12659/MSM.904933] [PMID: 29197221] 
[330] 
Du, A.; Zhao, S.; Wan, L.; Liu, T.; Peng, Z.; Zhou, Z.; Liao, Z.; Fang, H. MicroRNA expression profile of human periodontal ligament cells under the influence of Porphyromonas gingivalis LPS. J. Cell. Mol. Med.,  2016, 20(7), 1329-1338.
[http://dx.doi.org/10.1111/jcmm.12819] [PMID: 26987780] 
[331] 
Yao, Q.; Xu, H.; Zhang, Q.Q.; Zhou, H.; Qu, L.H. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem. Biophys. Res. Commun.,  2009, 388(3), 539-542.
[http://dx.doi.org/10.1016/j.bbrc.2009.08.044] [PMID: 19682430] 
[332] 
Venugopal, P.; Koshy, T.; Lavu, V.; Ranga Rao, S.; Ramasamy, S.; Hariharan, S.; Venkatesan, V. Differential expression of microRNAs let-7a, miR-125b, miR-100, and miR-21 and interaction with NF-kB pathway genes in periodontitis pathogenesis. J. Cell. Physiol.,  2018, 233(8), 5877-5884.
[http://dx.doi.org/10.1002/jcp.26391] [PMID: 29226952] 
[333] 
Zhou, W.; Su, L.; Duan, X.; Chen, X.; Hays, A.; Upadhyayula, S.; Shivde, J.; Wang, H.; Li, Y.; Huang, D.; Liang, S. MicroRNA-21 down-regulates inflammation and inhibits periodontitis. Mol. Immunol.,  2018, 101, 608-614.
[http://dx.doi.org/10.1016/j.molimm.2018.05.008] [PMID: 29884447] 
[334] 
Miguel-Hidalgo, J. J.; Hall, K. O.; Bonner, H.; Roller, A. M.; Syed, M.; Park, C. J.; Ball, J. P.; Rothenberg, M. E.; Stockmeier, C. A.; Romero, D. G. MicroRNA-21: Expression in oligodendrocytes and
 correlation with low myelin mRNAs in depression and alcoholism
 Prog. Neuropsychopharmacol. Biol. Psychiatry,  2017, 79(Pt B), 503-514.
[335] 
Ouyang, Y.B.; Xu, L.; Lu, Y.; Sun, X.; Yue, S.; Xiong, X.X.; Giffard, R.G. Astrocyte-enriched miR-29a targets PUMA and reduces neuronal vulnerability to forebrain ischemia. Glia,  2013, 61(11), 1784-1794.
[http://dx.doi.org/10.1002/glia.22556] [PMID: 24038396] 
[336] 
Yang, Z.; Wu, L.; Zhu, X.; Xu, J.; Jin, R.; Li, G.; Wu, F. MiR-29a modulates the angiogenic properties of human endothelial cells. Biochem. Biophys. Res. Commun.,  2013, 434(1), 143-149.
[http://dx.doi.org/10.1016/j.bbrc.2013.03.054] [PMID: 23541945] 
[337] 
Kebschull, M.; Papapanou, P.N. Mini but mighty: microRNAs in the pathobiology of periodontal disease. Periodontol. 2000,  2015, 69(1), 201-220.
[http://dx.doi.org/10.1111/prd.12095] [PMID: 26252410] 
[338] 
Roncarati, R.; Viviani Anselmi, C.; Losi, M.A.; Papa, L.; Cavarretta, E.; Da Costa Martins, P.; Contaldi, C.; Saccani Jotti, G.; Franzone, A.; Galastri, L.; Latronico, M.V.; Imbriaco, M.; Esposito, G.; De Windt, L.; Betocchi, S.; Condorelli, G. Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. J. Am. Coll. Cardiol.,  2014, 63(9), 920-927.
[http://dx.doi.org/10.1016/j.jacc.2013.09.041] [PMID: 24161319] 
[339] 
Wang, P.; Gu, Y.; Zhang, Q.; Han, Y.; Hou, J.; Lin, L.; Wu, C.; Bao, Y.; Su, X.; Jiang, M.; Wang, Q.; Li, N.; Cao, X. Identification of resting and type I IFN-activated human NK cell miRNomes reveals microRNA-378 and microRNA-30e as negative regulators of NK cell cytotoxicity. J. Immunol.,  2012, 189(1), 211-221.
[http://dx.doi.org/10.4049/jimmunol.1200609] [PMID: 22649192] 
[340] 
Perri, R.; Nares, S.; Zhang, S.; Barros, S.P.; Offenbacher, S. MicroRNA modulation in obesity and periodontitis. J. Dent. Res.,  2012, 91(1), 33-38.
[http://dx.doi.org/10.1177/0022034511425045] [PMID: 22043006] 
[341] 
Wang, X.T.; Wu, X.D.; Lu, Y.X.; Sun, Y.H.; Zhu, H.H.; Liang, J.B.; He, W.K.; Zeng, Z.Y.; Li, L. Potential involvement of MiR-30e-3p in myocardial injury induced by coronary microembolization via autophagy activation. Cell. Physiol. Biochem.,  2017, 44(5), 1995-2004.
[http://dx.doi.org/10.1159/000485905] [PMID: 29237156] 
[342] 
Gorinski, N.; Bijata, M.; Prasad, S.; Wirth, A.; Abdel Galil, D.; Zeug, A.; Bazovkina, D.; Kondaurova, E.; Kulikova, E.; Ilchibaeva, T.; Zareba-Koziol, M.; Papaleo, F.; Scheggia, D.; Kochlamazashvili, G.; Dityatev, A.; Smyth, I.; Krzystyniak, A.; Wlodarczyk, J.; Richter, D.W.; Strekalova, T.; Sigrist, S.; Bang, C.; Hobuß, L.; Fiedler, J.; Thum, T.; Naumenko, V.S.; Pandey, G.; Ponimaskin, E. Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors. Nat. Commun.,  2019, 10(1), 3924.
[http://dx.doi.org/10.1038/s41467-019-11876-5] [PMID: 31477731] 
[343] 
Raitoharju, E.; Lyytikäinen, L.P.; Levula, M.; Oksala, N.; Mennander, A.; Tarkka, M.; Klopp, N.; Illig, T.; Kähönen, M.; Karhunen, P.J.; Laaksonen, R.; Lehtimäki, T. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study. Atherosclerosis,  2011, 219(1), 211-217.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.07.020] [PMID: 21820659] 
[344] 
Radović, N.; Nikolić Jakoba, N.; Petrović, N.; Milosavljević, A.; Brković, B.; Roganović, J. MicroRNA-146a and microRNA-155 as novel crevicular fluid biomarkers for periodontitis in non-diabetic and type 2 diabetic patients. J. Clin. Periodontol.,  2018, 45(6), 663-671.
[http://dx.doi.org/10.1111/jcpe.12888] [PMID: 29517812] 
[345] 
Chen, Y.; Li, L.; Lu, Y.; Su, Q.; Sun, Y.; Liu, Y.; Yang, D. Upregulation of miR-155 in CD4(+) t cells promoted th1 bias in patients with unstable angina. J. Cell. Physiol.,  2015, 230(10), 2498-2509.
[http://dx.doi.org/10.1002/jcp.24987] [PMID: 25760478] 
[346] 
Corsten, M.F.; Papageorgiou, A.; Verhesen, W.; Carai, P.; Lindow, M.; Obad, S.; Summer, G.; Coort, S.L.; Hazebroek, M.; van Leeuwen, R.; Gijbels, M.J.; Wijnands, E.; Biessen, E.A.; De Winther, M.P.; Stassen, F.R.; Carmeliet, P.; Kauppinen, S.; Schroen, B.; Heymans, S. MicroRNA profiling identifies microRNA-155 as an adverse mediator of cardiac injury and dysfunction during acute viral myocarditis. Circ. Res.,  2012, 111(4), 415-425.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.267443] [PMID: 22715471] 
[347] 
Wang, X.; Wang, B.; Zhao, J.; Liu, C.; Qu, X.; Li, Y. MiR-155 is involved in major depression disorder and antidepressant treatment via targeting SIRT1. Biosci. Rep.,  2018, 38(6), BSR20181139
[http://dx.doi.org/10.1042/BSR20181139] [PMID: 30482883] 
[348] 
Li, T.; Cao, H.; Zhuang, J.; Wan, J.; Guan, M.; Yu, B.; Li, X.; Zhang, W. Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans. Clin. Chim. Acta,  2011, 412(1-2), 66-70.
[http://dx.doi.org/10.1016/j.cca.2010.09.029] [PMID: 20888330] 
[349] 
Schulte, C.; Molz, S.; Appelbaum, S.; Karakas, M.; Ojeda, F.; Lau, D.M.; Hartmann, T.; Lackner, K.J.; Westermann, D.; Schnabel, R.B.; Blankenberg, S.; Zeller, T. miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease. PLoS One,  2015, 10(12), e0145930
[http://dx.doi.org/10.1371/journal.pone.0145930] [PMID: 26720041] 
[350] 
Li, C.; Fang, Z.; Jiang, T.; Zhang, Q.; Liu, C.; Zhang, C.; Xiang, Y. Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris. BMC Med. Genomics,  2013, 6, 16.
[http://dx.doi.org/10.1186/1755-8794-6-16] [PMID: 23641832] 
[351] 
Yuan, X.; Berg, N.; Lee, J.W.; Le, T.T.; Neudecker, V.; Jing, N.; Eltzschig, H. MicroRNA miR-223 as regulator of innate immunity. J. Leukoc. Biol.,  2018, 104(3), 515-524.
[http://dx.doi.org/10.1002/JLB.3MR0218-079R] [PMID: 29969525] 
[352] 
Camkurt, M.A.; Acar, Ş.; Coşkun, S.; Güneş, M.; Güneş, S.; Yılmaz, M.F.; Görür, A.; Tamer, L. Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls. J. Psychiatr. Res.,  2015, 69, 67-71.
[http://dx.doi.org/10.1016/j.jpsychires.2015.07.023] [PMID: 26343596] 
[353] 
Niculescu, L.S.; Simionescu, N.; Sanda, G.M.; Carnuta, M.G.; Stancu, C.S.; Popescu, A.C.; Popescu, M.R.; Vlad, A.; Dimulescu, D.R.; Simionescu, M.; Sima, A.V. MiR-486 and miR-92a identified in circulating HDL discriminate between stable and vulnerable coronary artery disease patients. PLoS One,  2015, 10(10), e0140958
[http://dx.doi.org/10.1371/journal.pone.0140958] [PMID: 26485305] 
[354] 
Song, L.; Lin, C.; Gong, H.; Wang, C.; Liu, L.; Wu, J.; Tao, S.; Hu, B.; Cheng, S.Y.; Li, M.; Li, J. miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. Cell Res.,  2013, 23(2), 274-289.
[http://dx.doi.org/10.1038/cr.2012.174] [PMID: 23247627] 
[355] 
Mailhot, J.M.; Schuster, G.S.; Garnick, J.J.; Hanes, P.J.; Lapp, C.A.; Lewis, J.B. Human periodontal ligament and gingival fibroblast response to TGF-beta 1 stimulation. J. Clin. Periodontol.,  1995, 22(9), 679-685.
[http://dx.doi.org/10.1111/j.1600-051X.1995.tb00826.x] [PMID: 7593697] 
[356] 
Liu, Z.; Lu, C.L.; Cui, L.P.; Hu, Y.L.; Yu, Q.; Jiang, Y.; Ma, T.; Jiao, D.K.; Wang, D.; Jia, C.Y. MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4. Arch. Dermatol. Res.,  2012, 304(3), 195-202.
[http://dx.doi.org/10.1007/s00403-011-1178-0] [PMID: 21968601] 
[357] 
Xu, B.; Wang, N.; Wang, X.; Tong, N.; Shao, N.; Tao, J.; Li, P.; Niu, X.; Feng, N.; Zhang, L.; Hua, L.; Wang, Z.; Chen, M. MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate,  2012, 72(11), 1171-1178.
[http://dx.doi.org/10.1002/pros.22466] [PMID: 22161865] 
[358] 
O’Neill, L.A. When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. Immunity,  2008, 29(1), 12-20.
[http://dx.doi.org/10.1016/j.immuni.2008.06.004] [PMID: 18631453] 
[359] 
Kondo, T.; Kawai, T.; Akira, S. Dissecting negative regulation of Toll-like receptor signaling. Trends Immunol.,  2012, 33(9), 449-458.
[http://dx.doi.org/10.1016/j.it.2012.05.002] [PMID: 22721918] 
[360] 
Lopez, J.P.; Fiori, L.M.; Cruceanu, C.; Lin, R.; Labonte, B.; Cates, H.M.; Heller, E.A.; Vialou, V.; Ku, S.M.; Gerald, C.; Han, M.H.; Foster, J.; Frey, B.N.; Soares, C.N.; Müller, D.J.; Farzan, F.; Leri, F.; MacQueen, G.M.; Feilotter, H.; Tyryshkin, K.; Evans, K.R.; Giacobbe, P.; Blier, P.; Lam, R.W.; Milev, R.; Parikh, S.V.; Rotzinger, S.; Strother, S.C.; Lewis, C.M.; Aitchison, K.J.; Wittenberg, G.M.; Mechawar, N.; Nestler, E.J.; Uher, R.; Kennedy, S.H.; Turecki, G. MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat. Commun.,  2017, 8, 15497.
[http://dx.doi.org/10.1038/ncomms15497] [PMID: 28530238] 
[361] 
Kim, H.K.; Tyryshkin, K.; Elmi, N.; Dharsee, M.; Evans, K.R.; Good, J.; Javadi, M.; McCormack, S.; Vaccarino, A.L.; Zhang, X.; Andreazza, A.C.; Feilotter, H. Plasma microRNA expression levels and their targeted pathways in patients with major depressive disorder who are responsive to duloxetine treatment. J. Psychiatr. Res.,  2019, 110, 38-44.
[http://dx.doi.org/10.1016/j.jpsychires.2018.12.007] [PMID: 30580082] 
[362] 
Lagos-Quintana, M.; Rauhut, R.; Yalcin, A.; Meyer, J.; Lendeckel, W.; Tuschl, T. Identification of tissue-specific microRNAs from mouse. Curr. Biol.,  2002, 12(9), 735-739.
[http://dx.doi.org/10.1016/S0960-9822(02)00809-6] [PMID: 12007417] 
[363] 
Zhang, C. MicroRNomics: a newly emerging approach for disease biology. Physiol. Genomics,  2008, 33(2), 139-147.
[http://dx.doi.org/10.1152/physiolgenomics.00034.2008] [PMID: 18303086] 
[364] 
Roy, S.; Khanna, S.; Hussain, S.R.; Biswas, S.; Azad, A.; Rink, C.; Gnyawali, S.; Shilo, S.; Nuovo, G.J.; Sen, C.K. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc. Res.,  2009, 82(1), 21-29.
[http://dx.doi.org/10.1093/cvr/cvp015] [PMID: 19147652] 
[365] 
Ji, R.; Cheng, Y.; Yue, J.; Yang, J.; Liu, X.; Chen, H.; Dean, D.B.; Zhang, C. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ. Res.,  2007, 100(11), 1579-1588.
[http://dx.doi.org/10.1161/CIRCRESAHA.106.141986] [PMID: 17478730] 
[366] 
Suárez, Y.; Fernández-Hernando, C.; Pober, J.S.; Sessa, W.C. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ. Res.,  2007, 100(8), 1164-1173.
[http://dx.doi.org/10.1161/01.RES.0000265065.26744.17] [PMID: 17379831] 
[367] 
Cheng, Y.; Ji, R.; Yue, J.; Yang, J.; Liu, X.; Chen, H.; Dean, D.B.; Zhang, C. MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am. J. Pathol.,  2007, 170(6), 1831-1840.
[http://dx.doi.org/10.2353/ajpath.2007.061170] [PMID: 17525252] 
[368] 
Al-Hayali, M.A.; Sozer, V.; Durmus, S.; Erdenen, F.; Altunoglu, E.; Gelisgen, R.; Atukeren, P.; Atak, P.G.; Uzun, H. Clinical value of circulating microribonucleic acids miR-1 and miR-21 in evaluating the diagnosis of acute heart failure in asymptomatic type 2 diabetic patients. Biomolecules,  2019, 9(5), E193
[http://dx.doi.org/10.3390/biom9050193] [PMID: 31109008] 
[369] 
Thum, T.; Gross, C.; Fiedler, J.; Fischer, T.; Kissler, S.; Bussen, M.; Galuppo, P.; Just, S.; Rottbauer, W.; Frantz, S.; Castoldi, M.; Soutschek, J.; Koteliansky, V.; Rosenwald, A.; Basson, M.A.; Licht, J.D.; Pena, J.T.; Rouhanifard, S.H.; Muckenthaler, M.U.; Tuschl, T.; Martin, G.R.; Bauersachs, J.; Engelhardt, S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature,  2008, 456(7224), 980-984.
[http://dx.doi.org/10.1038/nature07511] [PMID: 19043405] 
[370] 
Thum, T.; Galuppo, P.; Wolf, C.; Fiedler, J.; Kneitz, S.; van Laake, L.W.; Doevendans, P.A.; Mummery, C.L.; Borlak, J.; Haverich, A.; Gross, C.; Engelhardt, S.; Ertl, G.; Bauersachs, J. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation,  2007, 116(3), 258-267.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.687947] [PMID: 17606841] 
[371] 
Wei, F.; Liu, D.; Feng, C.; Zhang, F.; Yang, S.; Hu, Y.; Ding, G.; Wang, S. microRNA-21 mediates stretch-induced osteogenic differentiation in human periodontal ligament stem cells. Stem Cells Dev.,  2015, 24(3), 312-319.
[http://dx.doi.org/10.1089/scd.2014.0191] [PMID: 25203845] 
[372] 
Li, C.; Li, C.; Yue, J.; Huang, X.; Chen, M.; Gao, J.; Wu, B. miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells. Mol. Med. Rep.,  2012, 5(5), 1340-1346.
[PMID: 22367347] 
[373] 
Wei, F.; Yang, S.; Guo, Q.; Zhang, X.; Ren, D.; Lv, T.; Xu, X. MicroRNA-21 regulates osteogenic differentiation of periodontal ligament stem cells by targeting smad5. Sci. Rep.,  2017, 7(1), 16608.
[http://dx.doi.org/10.1038/s41598-017-16720-8] [PMID: 29192241] 
[374] 
Li, X.; Guo, L.; Liu, Y.; Su, Y.; Xie, Y.; Du, J.; Wang, S.; Wang, H.; Liu, Y. MicroRNA-21 promotes wound healing via the Smad7-Smad2/3-Elastin pathway. Exp. Cell Res.,  2018, 362(2), 245-251.
[http://dx.doi.org/10.1016/j.yexcr.2017.11.019] [PMID: 29154818] 
[375] 
Niu, J.; Shi, Y.; Tan, G.; Yang, C.H.; Fan, M.; Pfeffer, L.M.; Wu, Z.H. DNA damage induces NF-κB-dependent microRNA-21 up-regulation and promotes breast cancer cell invasion. J. Biol. Chem.,  2012, 287(26), 21783-21795.
[http://dx.doi.org/10.1074/jbc.M112.355495] [PMID: 22547075] 
[376] 
Kocerha, J.; Dwivedi, Y.; Brennand, K.J. Noncoding RNAs and neurobehavioral mechanisms in psychiatric disease. Mol. Psychiatry,  2015, 20(6), 677-684.
[http://dx.doi.org/10.1038/mp.2015.30] [PMID: 25824307] 
[377] 
Dwivedi, Y. Emerging role of microRNAs in major depressive disorder: diagnosis and therapeutic implications. Dialogues Clin. Neurosci.,  2014, 16(1), 43-61.
[PMID: 24733970] 
[378] 
Miranda, R.C.; Pietrzykowski, A.Z.; Tang, Y.; Sathyan, P.; Mayfield, D.; Keshavarzian, A.; Sampson, W.; Hereld, D. MicroRNAs: master regulators of ethanol abuse and toxicity? Alcohol. Clin. Exp. Res.,  2010, 34(4), 575-587.
[http://dx.doi.org/10.1111/j.1530-0277.2009.01126.x] [PMID: 20102566] 
[379] 
Issler, O.; Haramati, S.; Paul, E.D.; Maeno, H.; Navon, I.; Zwang, R.; Gil, S.; Mayberg, H.S.; Dunlop, B.W.; Menke, A.; Awatramani, R.; Binder, E.B.; Deneris, E.S.; Lowry, C.A.; Chen, A. MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron,  2014, 83(2), 344-360.
[http://dx.doi.org/10.1016/j.neuron.2014.05.042] [PMID: 24952960] 
[380] 
Dwivedi, Y. MicroRNAs in depression and suicide: Recent insights and future perspectives. J. Affect. Disord.,  2018, 240, 146-154.
[http://dx.doi.org/10.1016/j.jad.2018.07.075] [PMID: 30071418] 
[381] 
Chen, S.D.; Sun, X.Y.; Niu, W.; Kong, L.M.; He, M.J.; Fan, H.M.; Li, W.S.; Zhong, A.F.; Zhang, L.Y.; Lu, J. A preliminary analysis of microRNA-21 expression alteration after antipsychotic treatment in patients with schizophrenia. Psychiatry Res.,  2016, 244, 324-332.
[http://dx.doi.org/10.1016/j.psychres.2016.04.087] [PMID: 27512922] 
[382] 
Beech, R.D.; Leffert, J.J.; Lin, A.; Hong, K.A.; Hansen, J.; Umlauf, S.; Mane, S.; Zhao, H.; Sinha, R. Stress-related alcohol consumption in heavy drinkers correlates with expression of miR-10a, miR-21, and components of the TAR-RNA-binding protein-associated complex. Alcohol. Clin. Exp. Res.,  2014, 38(11), 2743-2753.
[http://dx.doi.org/10.1111/acer.12549] [PMID: 25421511] 
[383] 
Friedman, M.; Levin, C.E. Nutritional and medicinal aspects of D-amino acids. Amino Acids,  2012, 42(5), 1553-1582.
[http://dx.doi.org/10.1007/s00726-011-0915-1] [PMID: 21519915] 
[384] 
Richard, D.M.; Dawes, M.A.; Mathias, C.W.; Acheson, A.; Hill-Kapturczak, N.; Dougherty, D.M. L-tryptophan: basic metabolic functions, behavioral research and therapeutic indications. Int. J. Tryptophan Res.,  2009, 2, 45-60.
[http://dx.doi.org/10.4137/IJTR.S2129] [PMID: 20651948] 
[385] 
Ruddick, J.P.; Evans, A.K.; Nutt, D.J.; Lightman, S.L.; Rook, G.A.; Lowry, C.A. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev. Mol. Med.,  2006, 8(20), 1-27.
[http://dx.doi.org/10.1017/S1462399406000068] [PMID: 16942634] 
[386] 
Stone, T.W.; Darlington, L.G. Endogenous kynurenines as targets for drug discovery and development. Nat. Rev. Drug Discov.,  2002, 1(8), 609-620.
[http://dx.doi.org/10.1038/nrd870] [PMID: 12402501] 
[387] 
Vécsei, L.; Szalárdy, L.; Fülöp, F.; Toldi, J. Kynurenines in the CNS: recent advances and new questions. Nat. Rev. Drug Discov.,  2013, 12(1), 64-82.
[http://dx.doi.org/10.1038/nrd3793] [PMID: 23237916] 
[388] 
Chen, Y.; Guillemin, G.J. Kynurenine pathway metabolites in humans: disease and healthy States. Int. J. Tryptophan Res.,  2009, 2, 1-19.
[http://dx.doi.org/10.4137/IJTR.S2097] 
[389] 
Grant, R.S.; Coggan, S.E.; Smythe, G.A. The physiological action of picolinic Acid in the human brain. Int. J. Tryptophan Res.,  2009, 2, 71-79.
[http://dx.doi.org/10.4137/IJTR.S2469] [PMID: 22084583] 
[390] 
Sublette, M.E.; Postolache, T.T. Neuroinflammation and depression: the role of indoleamine 2,3-dioxygenase (IDO) as a molecular pathway. Psychosom. Med.,  2012, 74(7), 668-672.
[http://dx.doi.org/10.1097/PSY.0b013e318268de9f] [PMID: 22923699] 
[391] 
Serafini, G.; Adavastro, G.; Canepa, G.; Capobianco, L.; Conigliaro, C.; Pittaluga, F.; Murri, M.B.; Valchera, A.; De Berardis, D.; Pompili, M.; Lindqvist, D.; Brundin, L.; Amore, M. Abnormalities in kynurenine pathway metabolism in treatment-resistant depression and suicidality: a systematic review. CNS Neurol. Disord. Drug Targets,  2017, 16(4), 440-453.
[http://dx.doi.org/10.2174/1871527316666170413110605] [PMID: 28412922] 
[392] 
Skolnick, P.; Layer, R.T.; Popik, P.; Nowak, G.; Paul, I.A.; Trullas, R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry,  1996, 29(1), 23-26.
[http://dx.doi.org/10.1055/s-2007-979537] [PMID: 8852530] 
[393] 
Trullas, R.; Skolnick, P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur. J. Pharmacol.,  1990, 185(1), 1-10.
[http://dx.doi.org/10.1016/0014-2999(90)90204-J] [PMID: 2171955] 
[394] 
Nowak, G.; Ordway, G.A.; Paul, I.A. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res.,  1995, 675(1-2), 157-164.
[http://dx.doi.org/10.1016/0006-8993(95)00057-W] [PMID: 7796124] 
[395] 
Krystal, J.H.; Sanacora, G.; Blumberg, H.; Anand, A.; Charney, D.S.; Marek, G.; Epperson, C.N.; Goddard, A.; Mason, G.F. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol. Psychiatry,  2002, 7(Suppl. 1), S71-S80.
[http://dx.doi.org/10.1038/sj.mp.4001021] [PMID: 11986998] 
[396] 
Zarate, C.A.; Quiroz, J.; Payne, J.; Manji, H.K. Modulators of the glutamatergic system: implications for the development of improved therapeutics in mood disorders. Psychopharmacol. Bull.,  2002, 36(4), 35-83.
[PMID: 12858143] 
[397] 
Erhardt, S.; Lim, C.K.; Linderholm, K.R.; Janelidze, S.; Lindqvist, D.; Samuelsson, M.; Lundberg, K.; Postolache, T.T.; Träskman-Bendz, L.; Guillemin, G.J.; Brundin, L. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology,  2013, 38(5), 743-752.
[http://dx.doi.org/10.1038/npp.2012.248] [PMID: 23299933] 
[398] 
Bryleva, E. Y.; Brundin, L. Kynurenine pathway metabolites and suicidality. Neuropharmacology,  2017, 112(Pt B), 324-330.
[http://dx.doi.org/10.1016/j.neuropharm.2016.01.034] 
[399] 
Sublette, M.E.; Galfalvy, H.C.; Fuchs, D.; Lapidus, M.; Grunebaum, M.F.; Oquendo, M.A.; Mann, J.J.; Postolache, T.T. Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav. Immun.,  2011, 25(6), 1272-1278.
[http://dx.doi.org/10.1016/j.bbi.2011.05.002] [PMID: 21605657] 
[400] 
Brundin, L.; Sellgren, C.M.; Lim, C.K.; Grit, J.; Pålsson, E.; Landén, M.; Samuelsson, M.; Lundgren, K.; Brundin, P.; Fuchs, D.; Postolache, T.T.; Traskman-Bendz, L.; Guillemin, G.J.; Erhardt, S. An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation. Transl. Psychiatry,  2016, 6(8), e865
[http://dx.doi.org/10.1038/tp.2016.133] [PMID: 27483383] 
[401] 
Reininghaus, E.Z.; McIntyre, R.S.; Reininghaus, B.; Geisler, S.; Bengesser, S.A.; Lackner, N.; Hecht, K.; Birner, A.; Kattnig, F.; Unterweger, R.; Kapfhammer, H.P.; Zelzer, S.; Fuchs, D.; Mangge, H. Tryptophan breakdown is increased in euthymic overweight individuals with bipolar disorder: a preliminary report. Bipolar Disord.,  2014, 16(4), 432-440.
[http://dx.doi.org/10.1111/bdi.12166] [PMID: 24330408] 
[402] 
Birner, A.; Platzer, M.; Bengesser, S.A.; Dalkner, N.; Fellendorf, F.T.; Queissner, R.; Pilz, R.; Rauch, P.; Maget, A.; Hamm, C.; Herzog-Eberhard, S.; Mangge, H.; Fuchs, D.; Moll, N.; Zelzer, S.; Schütze, G.; Schwarz, M.; Reininghaus, B.; Kapfhammer, H.P.; Reininghaus, E.Z. Increased breakdown of kynurenine towards its neurotoxic branch in bipolar disorder. PLoS One,  2017, 12(2), e0172699
[http://dx.doi.org/10.1371/journal.pone.0172699] [PMID: 28241062] 
[403] 
Maget, A.; Platzer, M.; Bengesser, S.A.; Fellendorf, F.T.; Birner, A.; Queissner, R.; Hamm, C.; Reininghaus, B.; Hecker, A.; Tomberger, L.; Pilz, R.; Dalkner, N.; Moll, N.; Schutze, G.; Schwarz, M.; Kapfhammer, H.P.; Reininghaus, E.Z. Differences in kynurenine metabolism during depressive, manic, and euthymic phases of bipolar affective disorder. Curr. Top. Med. Chem., 2019. Epub ahead of print
[http://dx.doi.org/10.2174/1568026619666190802145128] 
[404] 
Platzer, M.; Dalkner, N.; Fellendorf, F.T.; Birner, A.; Bengesser, S.A.; Queissner, R.; Kainzbauer, N.; Pilz, R.; Herzog-Eberhard, S.; Hamm, C.; Hörmanseder, C.; Maget, A.; Rauch, P.; Mangge, H.; Fuchs, D.; Zelzer, S.; Schütze, G.; Moll, N.; Schwarz, M.J.; Mansur, R.B.; McIntyre, R.S.; Reininghaus, E.Z. Tryptophan breakdown and cognition in bipolar disorder. Psychoneuroendocrinology,  2017, 81, 144-150.
[http://dx.doi.org/10.1016/j.psyneuen.2017.04.015] [PMID: 28482311] 
[405] 
Erhardt, S.; Schwieler, L.; Imbeault, S.; Engberg, G. The kynurenine pathway in schizophrenia and bipolar disorder. Neuropharmacology,  2017, 112(Pt B), 297-306.
[http://dx.doi.org/10.1016/j.neuropharm.2016.05.020] 
[406] 
Stone, T.W. Neuropharmacology of quinolinic and kynurenic acids. Pharmacol. Rev.,  1993, 45(3), 309-379.
[PMID: 8248282] 
[407] 
Hilmas, C.; Pereira, E.F.; Alkondon, M.; Rassoulpour, A.; Schwarcz, R.; Albuquerque, E.X. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J. Neurosci.,  2001, 21(19), 7463-7473.
[http://dx.doi.org/10.1523/JNEUROSCI.21-19-07463.2001] [PMID: 11567036] 
[408] 
Schwarcz, R.; Rassoulpour, A.; Wu, H.Q.; Medoff, D.; Tamminga, C.A.; Roberts, R.C. Increased cortical kynurenate content in schizophrenia. Biol. Psychiatry,  2001, 50(7), 521-530.
[http://dx.doi.org/10.1016/S0006-3223(01)01078-2] [PMID: 11600105] 
[409] 
Erhardt, S.; Blennow, K.; Nordin, C.; Skogh, E.; Lindström, L.H.; Engberg, G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci. Lett.,  2001, 313(1-2), 96-98.
[http://dx.doi.org/10.1016/S0304-3940(01)02242-X] [PMID: 11684348] 
[410] 
Nilsson, L.K.; Linderholm, K.R.; Engberg, G.; Paulson, L.; Blennow, K.; Lindström, L.H.; Nordin, C.; Karanti, A.; Persson, P.; Erhardt, S. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr. Res.,  2005, 80(2-3), 315-322.
[http://dx.doi.org/10.1016/j.schres.2005.07.013] [PMID: 16125901] 
[411] 
Linderholm, K.R.; Alm, M.T.; Larsson, M.K.; Olsson, S.K.; Goiny, M.; Hajos, M.; Erhardt, S.; Engberg, G. Inhibition of kynurenine aminotransferase II reduces activity of midbrain dopamine neurons. Neuropharmacology,  2016, 102, 42-47.
[http://dx.doi.org/10.1016/j.neuropharm.2015.10.028] [PMID: 26514401] 
[412] 
Sathyasaikumar, K.V.; Stachowski, E.K.; Wonodi, I.; Roberts, R.C.; Rassoulpour, A.; McMahon, R.P.; Schwarcz, R. Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr. Bull.,  2011, 37(6), 1147-1156.
[http://dx.doi.org/10.1093/schbul/sbq112] [PMID: 21036897] 
[413] 
Plitman, E.; Iwata, Y.; Caravaggio, F.; Nakajima, S.; Chung, J.K.; Gerretsen, P.; Kim, J.; Takeuchi, H.; Chakravarty, M.M.; Remington, G.; Graff-Guerrero, A. Kynurenic acid in schizophrenia: a systematic review and meta-analysis. Schizophr. Bull.,  2017, 43(4), 764-777.
[http://dx.doi.org/10.1093/schbul/sbw221] [PMID: 28187219] 
[414] 
Giil, L.M.; Midttun, Ø.; Refsum, H.; Ulvik, A.; Advani, R.; Smith, A.D.; Ueland, P.M. Kynurenine pathway metabolites in alzheimer’s disease. J. Alzheimers Dis.,  2017, 60(2), 495-504.
[http://dx.doi.org/10.3233/JAD-170485] [PMID: 28869479] 
[415] 
Busse, M.; Hettler, V.; Fischer, V.; Mawrin, C.; Hartig, R.; Dobrowolny, H.; Bogerts, B.; Frodl, T.; Busse, S. Increased quinolinic acid in peripheral mononuclear cells in Alzheimer’s dementia. Eur. Arch. Psychiatry Clin. Neurosci.,  2018, 268(5), 493-500.
[http://dx.doi.org/10.1007/s00406-017-0785-y] [PMID: 28386767] 
[416] 
Buczko, P.; Stokowska, W.; Górska, M.; Kucharewicz, I.; Pawlak, D.; Buczko, W. Tryptophan metabolites via kynurenine pathway in saliva of diabetic patients. Dent. Med. Probl,  2006, 43(1), 21-25.
[417] 
Buczko, W.; Cylwik, D.; Stokowska, W. [Metabolism of tryptophan via the kynurenine pathway in saliva]. Postepy Hig. Med. Dosw.,  2005, 59, 283-289.
[PMID: 15995595] 
[418] 
Nisapakultorn, K.; Makrudthong, J.; Sa-Ard-Iam, N.; Rerkyen, P.; Mahanonda, R.; Takikawa, O. Indoleamine 2,3-dioxygenase expression and regulation in chronic periodontitis. J. Periodontol.,  2009, 80(1), 114-121.
[http://dx.doi.org/10.1902/jop.2009.080315] [PMID: 19228097] 
[419] 
Moon, J.S.; Cheong, N.R.; Yang, S.Y.; Kim, I.S.; Chung, H.J.; Jeong, Y.W.; Park, J.C.; Kim, M.S.; Kim, S.H.; Ko, H.M. Lipopolysaccharide-induced indoleamine 2,3-dioxygenase expression in the periodontal ligament. J. Periodontal Res.,  2013, 48(6), 733-739.
[http://dx.doi.org/10.1111/jre.12063] [PMID: 23488665] 
[420] 
Wolowczuk, I.; Hennart, B.; Leloire, A.; Bessede, A.; Soichot, M.; Taront, S.; Caiazzo, R.; Raverdy, V.; Pigeyre, M.; Guillemin, G.J.; Allorge, D.; Pattou, F.; Froguel, P.; Poulain-Godefroy, O. ABOS Consortium. Tryptophan metabolism activation by indoleamine 2,3-dioxygenase in adipose tissue of obese women: an attempt to maintain immune homeostasis and vascular tone. Am. J. Physiol. Regul. Integr. Comp. Physiol.,  2012, 303(2), R135-R143.
[http://dx.doi.org/10.1152/ajpregu.00373.2011] [PMID: 22592557] 
[421] 
Favennec, M.; Hennart, B.; Caiazzo, R.; Leloire, A.; Yengo, L.; Verbanck, M.; Arredouani, A.; Marre, M.; Pigeyre, M.; Bessede, A.; Guillemin, G.J.; Chinetti, G.; Staels, B.; Pattou, F.; Balkau, B.; Allorge, D.; Froguel, P.; Poulain-Godefroy, O. The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. Obesity (Silver Spring),  2015, 23(10), 2066-2074.
[http://dx.doi.org/10.1002/oby.21199] [PMID: 26347385] 
[422] 
Dalkner, N.; Platzer, M.; Bengesser, S.A.; Birner, A.; Fellendorf, F.T.; Queissner, R.; Painold, A.; Mangge, H.; Fuchs, D.; Reininghaus, B.; Kapfhammer, H.P.; Holasek, S.J.; Reininghaus, E.Z. The role of tryptophan metabolism and food craving in the relationship between obesity and bipolar disorder. Clin. Nutr.,  2018, 37(5), 1744-1751.
[http://dx.doi.org/10.1016/j.clnu.2017.06.024] [PMID: 28712531] 
[423] 
Mangge, H.; Stelzer, I.; Reininghaus, E.Z.; Weghuber, D.; Postolache, T.T.; Fuchs, D. Disturbed tryptophan metabolism in cardiovascular disease. Curr. Med. Chem.,  2014, 21(17), 1931-1937.
[http://dx.doi.org/10.2174/0929867321666140304105526] [PMID: 24606499] 
[424] 
Zuo, H.; Ueland, P.M.; Ulvik, A.; Eussen, S.J.; Vollset, S.E.; Nygård, O.; Midttun, Ø.; Theofylaktopoulou, D.; Meyer, K.; Tell, G.S. Plasma biomarkers of inflammation, the kynurenine pathway, and risks of all-cause, cancer, and cardiovascular disease mortality: the hordaland health study. Am. J. Epidemiol.,  2016, 183(4), 249-258.
[http://dx.doi.org/10.1093/aje/kwv242] [PMID: 26823439] 
[425] 
Niinisalo, P.; Oksala, N.; Levula, M.; Pelto-Huikko, M.; Järvinen, O.; Salenius, J.P.; Kytömäki, L.; Soini, J.T.; Kähönen, M.; Laaksonen, R.; Hurme, M.; Lehtimäki, T. Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere vascular study. Ann. Med.,  2010, 42(1), 55-63.
[http://dx.doi.org/10.3109/07853890903321559] [PMID: 19941414] 
[426] 
Niinisalo, P.; Raitala, A.; Pertovaara, M.; Oja, S.S.; Lehtimäki, T.; Kähönen, M.; Reunanen, A.; Jula, A.; Moilanen, L.; Kesäniemi, Y.A.; Nieminen, M.S.; Hurme, M. Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors: the Health 2000 study. Scand. J. Clin. Lab. Invest.,  2008, 68(8), 767-770.
[http://dx.doi.org/10.1080/00365510802245685] [PMID: 18622801] 
[427] 
Pedersen, E.R.; Tuseth, N.; Eussen, S.J.; Ueland, P.M.; Strand, E.; Svingen, G.F.; Midttun, Ø.; Meyer, K.; Mellgren, G.; Ulvik, A.; Nordrehaug, J.E.; Nilsen, D.W.; Nygård, O. Associations of plasma kynurenines with risk of acute myocardial infarction in patients with stable angina pectoris. Arterioscler. Thromb. Vasc. Biol.,  2015, 35(2), 455-462.
[http://dx.doi.org/10.1161/ATVBAHA.114.304674] [PMID: 25524770] 
[428] 
Ormstad, H.; Verkerk, R.; Amthor, K.F.; Sandvik, L. Activation of the kynurenine pathway in the acute phase of stroke and its role in fatigue and depression following stroke. J. Mol. Neurosci.,  2014, 54(2), 181-187.
[http://dx.doi.org/10.1007/s12031-014-0272-0] [PMID: 24664436] 
[429] 
Gold, A.B.; Herrmann, N.; Swardfager, W.; Black, S.E.; Aviv, R.I.; Tennen, G.; Kiss, A.; Lanctôt, K.L. The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment. J. Neuroinflammation,  2011, 8, 17.
[http://dx.doi.org/10.1186/1742-2094-8-17] [PMID: 21324164] 
[430] 
Singhrao, S.K.; Olsen, I. Assessing the role of Porphyromonas gingivalis in periodontitis to determine a causative relationship with Alzheimer’s disease. J. Oral Microbiol.,  2019, 11(1), 1563405
[http://dx.doi.org/10.1080/20002297.2018.1563405] [PMID: 30728914] 
[431] 
Sochocka, M.; Zwolińska, K.; Leszek, J. The Infectious Etiology of Alzheimer’s Disease. Curr. Neuropharmacol.,  2017, 15(7), 996-1009.
[http://dx.doi.org/10.2174/1570159X15666170313122937] [PMID: 28294067] 
[432] 
Hashioka, S.; Inoue, K.; Hayashida, M.; Wake, R.; Oh-Nishi, A.; Miyaoka, T. Implications of systemic inflammation and periodontitis for major depression. Front. Neurosci.,  2018, 12, 483.
[http://dx.doi.org/10.3389/fnins.2018.00483] [PMID: 30072865] 
[433] 
McGeer, P.L.; McGeer, E.G. History of innate immunity in neurodegenerative disorders. Front. Pharmacol.,  2011, 2, 77.
[http://dx.doi.org/10.3389/fphar.2011.00077] [PMID: 22144960] 
[434] 
McGeer, P.L.; McGeer, E.; Rogers, J.; Sibley, J. Anti-inflammatory drugs and Alzheimer disease. Lancet,  1990, 335(8696), 1037.
[http://dx.doi.org/10.1016/0140-6736(90)91101-F] [PMID: 1970087] 
[435] 
McGeer, P.L.; Itagaki, S.; Tago, H.; McGeer, E.G. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci. Lett.,  1987, 79(1-2), 195-200.
[http://dx.doi.org/10.1016/0304-3940(87)90696-3] [PMID: 3670729] 
[436] 
Torres-Platas, S.G.; Cruceanu, C.; Chen, G.G.; Turecki, G.; Mechawar, N. Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav. Immun.,  2014, 42, 50-59.
[http://dx.doi.org/10.1016/j.bbi.2014.05.007] [PMID: 24858659] 
[437] 
Su, L.; Faluyi, Y.O.; Hong, Y.T.; Fryer, T.D.; Mak, E.; Gabel, S.; Hayes, L.; Soteriades, S.; Williams, G.B.; Arnold, R.; Passamonti, L.; Rodríguez, P.V.; Surendranathan, A.; Bevan-Jones, R.W.; Coles, J.; Aigbirhio, F.; Rowe, J.B.; O’Brien, J.T. Neuroinflammatory and morphological changes in late-life depression: the NIMROD study. Br. J. Psychiatry,  2016, 209(6), 525-526.
[http://dx.doi.org/10.1192/bjp.bp.116.190165] [PMID: 27758838] 
[438] 
van Berckel, B.N.; Bossong, M.G.; Boellaard, R.; Kloet, R.; Schuitemaker, A.; Caspers, E.; Luurtsema, G.; Windhorst, A.D.; Cahn, W.; Lammertsma, A.A.; Kahn, R.S. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol. Psychiatry,  2008, 64(9), 820-822.
[http://dx.doi.org/10.1016/j.biopsych.2008.04.025] [PMID: 18534557] 
[439] 
Fillman, S.G.; Cloonan, N.; Catts, V.S.; Miller, L.C.; Wong, J.; McCrossin, T.; Cairns, M.; Weickert, C.S. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol. Psychiatry,  2013, 18(2), 206-214.
[http://dx.doi.org/10.1038/mp.2012.110] [PMID: 22869038] 
[440] 
Doorduin, J.; de Vries, E.F.; Willemsen, A.T.; de Groot, J.C.; Dierckx, R.A.; Klein, H.C. Neuroinflammation in schizophrenia-related psychosis: a PET study. J. Nucl. Med.,  2009, 50(11), 1801-1807.
[http://dx.doi.org/10.2967/jnumed.109.066647] [PMID: 19837763] 
[441] 
Kessler, R.C. The effects of stressful life events on depression. Annu. Rev. Psychol.,  1997, 48, 191-214.
[http://dx.doi.org/10.1146/annurev.psych.48.1.191] [PMID: 9046559] 
[442] 
Hammen, C. Stress and depression. Annu. Rev. Clin. Psychol.,  2005, 1, 293-319.
[http://dx.doi.org/10.1146/annurev.clinpsy.1.102803.143938] [PMID: 17716090] 
[443] 
Krishnan, V.; Nestler, E.J. The molecular neurobiology of depression. Nature,  2008, 455(7215), 894-902.
[http://dx.doi.org/10.1038/nature07455] [PMID: 18923511] 
[444] 
Cohen, S.; Tyrrell, D.A.; Smith, A.P. Psychological stress and susceptibility to the common cold. N. Engl. J. Med.,  1991, 325(9), 606-612.
[http://dx.doi.org/10.1056/NEJM199108293250903] [PMID: 1713648] 
[445] 
Genco, R.J.; Ho, A.W.; Grossi, S.G.; Dunford, R.G.; Tedesco, L.A. Relationship of stress, distress and inadequate coping behaviors to periodontal disease. J. Periodontol.,  1999, 70(7), 711-723.
[http://dx.doi.org/10.1902/jop.1999.70.7.711] [PMID: 10440631] 
[446] 
Vedhara, K.; Bennett, P.D.; Clark, S.; Lightman, S.L.; Shaw, S.; Perks, P.; Hunt, M.A.; Philip, J.M.; Tallon, D.; Murphy, P.J.; Jones, R.W.; Wilcock, G.K.; Shanks, N.M. Enhancement of antibody responses to influenza vaccination in the elderly following a cognitive-behavioural stress management intervention. Psychother. Psychosom.,  2003, 72(5), 245-252.
[http://dx.doi.org/10.1159/000071895] [PMID: 12920328] 
[447] 
Nadkarni, R.B.; Fristad, M.A. Stress and support for parents of youth with bipolar disorder. Isr. J. Psychiatry Relat. Sci.,  2012, 49(2), 104-110.
[PMID: 22801289] 
[448] 
Caserta, M.T.; O’Connor, T.G.; Wyman, P.A.; Wang, H.; Moynihan, J.; Cross, W.; Tu, X.; Jin, X. The associations between psychosocial stress and the frequency of illness, and innate and adaptive immune function in children. Brain Behav. Immun.,  2008, 22(6), 933-940.
[http://dx.doi.org/10.1016/j.bbi.2008.01.007] [PMID: 18308510] 
[449] 
Kiecolt-Glaser, J.K.; Page, G.G.; Marucha, P.T.; MacCallum, R.C.; Glaser, R. Psychological influences on surgical recovery. Perspectives from psychoneuroimmunology. Am. Psychol.,  1998, 53(11), 1209-1218.
[http://dx.doi.org/10.1037/0003-066X.53.11.1209] [PMID: 9830373] 
[450] 
Kiecolt-Glaser, J.K.; Marucha, P.T.; Malarkey, W.B.; Mercado, A.M.; Glaser, R. Slowing of wound healing by psychological stress. Lancet,  1995, 346(8984), 1194-1196.
[http://dx.doi.org/10.1016/S0140-6736(95)92899-5] [PMID: 7475659] 
[451] 
Kiecolt-Glaser, J.K.; Loving, T.J.; Stowell, J.R.; Malarkey, W.B.; Lemeshow, S.; Dickinson, S.L.; Glaser, R. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch. Gen. Psychiatry,  2005, 62(12), 1377-1384.
[http://dx.doi.org/10.1001/archpsyc.62.12.1377] [PMID: 16330726] 
[452] 
Marucha, P.T.; Kiecolt-Glaser, J.K.; Favagehi, M. Mucosal wound healing is impaired by examination stress. Psychosom. Med.,  1998, 60(3), 362-365.
[http://dx.doi.org/10.1097/00006842-199805000-00025] [PMID: 9625226] 
[453] 
Pariante, C.M.; Miller, A.H. Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol. Psychiatry,  2001, 49(5), 391-404.
[http://dx.doi.org/10.1016/S0006-3223(00)01088-X] [PMID: 11274650] 
[454] 
Raison, C.L.; Capuron, L.; Miller, A.H. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol.,  2006, 27(1), 24-31.
[http://dx.doi.org/10.1016/j.it.2005.11.006] [PMID: 16316783] 
[455] 
Pollak, Y.; Yirmiya, R. Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int. J. Neuropsychopharmacol.,  2002, 5(4), 389-399.
[http://dx.doi.org/10.1017/S1461145702003152] [PMID: 12466037] 
[456] 
Leonard, B.E. Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr.,  2018, 30(1), 1-16.
[http://dx.doi.org/10.1017/neu.2016.69] [PMID: 28112061] 
[457] 
Sugama, S.; Fujita, M.; Hashimoto, M.; Conti, B. Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18. Neuroscience,  2007, 146(3), 1388-1399.
[http://dx.doi.org/10.1016/j.neuroscience.2007.02.043] [PMID: 17433555] 
[458] 
Steiner, J.; Bielau, H.; Brisch, R.; Danos, P.; Ullrich, O.; Mawrin, C.; Bernstein, H.G.; Bogerts, B. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J. Psychiatr. Res.,  2008, 42(2), 151-157.
[http://dx.doi.org/10.1016/j.jpsychires.2006.10.013] [PMID: 17174336] 
[459] 
Glaser, R.; Robles, T.F.; Sheridan, J.; Malarkey, W.B.; Kiecolt-Glaser, J.K. Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults. Arch. Gen. Psychiatry,  2003, 60(10), 1009-1014.
[http://dx.doi.org/10.1001/archpsyc.60.10.1009] [PMID: 14557146] 
[460] 
Ongür, D.; Drevets, W.C.; Price, J.L. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc. Natl. Acad. Sci. USA,  1998, 95(22), 13290-13295.
[http://dx.doi.org/10.1073/pnas.95.22.13290] [PMID: 9789081] 
[461] 
Myint, A.M. Inflammation, neurotoxins and psychiatric disorders. Mod. Trends Pharmacopsychiatry,  2013, 28, 61-74.
[http://dx.doi.org/10.1159/000343968] [PMID: 25224891] 
[462] 
Duman, R.S.; Heninger, G.R.; Nestler, E.J. A molecular and cellular theory of depression. Arch. Gen. Psychiatry,  1997, 54(7), 597-606.
[http://dx.doi.org/10.1001/archpsyc.1997.01830190015002] [PMID: 9236543] 
[463] 
Yeager, M.P.; Pioli, P.A.; Guyre, P.M. Cortisol exerts bi-phasic regulation of inflammation in humans. Dose Response,  2011, 9(3), 332-347.
[http://dx.doi.org/10.2203/dose-response.10-013.Yeager] [PMID: 22013396] 
[464] 
Smyth, G.P.; Stapleton, P.P.; Freeman, T.A.; Concannon, E.M.; Mestre, J.R.; Duff, M.; Maddali, S.; Daly, J.M. Glucocorticoid pretreatment induces cytokine overexpression and nuclear factor-kappaB activation in macrophages. J. Surg. Res.,  2004, 116(2), 253-261.
[http://dx.doi.org/10.1016/S0022-4804(03)00300-7] [PMID: 15013364] 
[465] 
Sheline, Y.I.; Mittler, B.L.; Mintun, M.A. The hippocampus and depression. Eur. Psychiatry,  2002, 17(Suppl. 3), 300-305.
[http://dx.doi.org/10.1016/S0924-9338(02)00655-7] [PMID: 15177085] 
[466] 
Maes, M.; Yirmyia, R.; Noraberg, J.; Brene, S.; Hibbeln, J.; Perini, G.; Kubera, M.; Bob, P.; Lerer, B.; Maj, M. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab. Brain Dis.,  2009, 24(1), 27-53.
[http://dx.doi.org/10.1007/s11011-008-9118-1] [PMID: 19085093] 
[467] 
Myint, A.M.; Kim, Y.K. Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med. Hypotheses,  2003, 61(5-6), 519-525.
[http://dx.doi.org/10.1016/S0306-9877(03)00207-X] [PMID: 14592780] 
[468] 
Khabazghazvini, B.; Groer, M.; Fuchs, D.; Strassle, P.; Lapidus, M.; Sleemi, A.; Cabassa, J.B.; Postolache, T.T. Psychiatric manifestations of latent toxoplasmosis. Potential mediation by indoleamine 2, 3-dioxygenase. Int. J. Disabil. Hum. Dev.,  2010, 9(1), 3-10.
[http://dx.doi.org/10.1515/IJDHD.2010.002] 
[469] 
Wadhawan, A.; Daue, M.L.; Brenner, L.A.; Lowry, C.A.; Dagdag, A.; Stiller, J.W.; Benros, M.E.; Erlangsen, A.; Baca-Garcia, E.; Hoisington, A.J. F158. Toxoplasma Gondii-Oocyst Seropositivity and Depression in the Old Order Amish. Biol. Psychiatry,  2018, 83(9), S299-S300.
[http://dx.doi.org/10.1016/j.biopsych.2018.02.772] 
[470] 
Wadhawan, A.; Dagdag, A.; Duffy, A.; Daue, M.L.; Ryan, K.A.; Brenner, L.A.; Stiller, J.W.; Pollin, T.I.; Groer, M.W.; Huang, X.; Lowry, C.A.; Mitchell, B.D.; Postolache, T.T. Positive association between Toxoplasma gondii IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study. Pteridines,  2017, 28(3-4), 185-194.
[http://dx.doi.org/10.1515/pterid-2017-0019] [PMID: 29657363] 
[471] 
Postolache, T.; Constantine, N.; Daue, M.; Dagdag, A.; Wadhawan, A.; Brenner, L.A.; Lowry, C.A.; Makkar, H.; Reynolds, M.A. S91. P. Gingivalis and Cardinal Symptoms of Depression. Biol. Psychiatry,  2019, 85(10), S332.
[http://dx.doi.org/10.1016/j.biopsych.2019.03.842] 
[472] 
Myint, A-M.; Leonard, B.E.; Steinbusch, H.W.; Kim, Y-K. Th1, Th2, and Th3 cytokine alterations in major depression. J. Affect. Disord.,  2005, 88(2), 167-173.
[http://dx.doi.org/10.1016/j.jad.2005.07.008] [PMID: 16126278] 
[473] 
Kaestner, F.; Hettich, M.; Peters, M.; Sibrowski, W.; Hetzel, G.; Ponath, G.; Arolt, V.; Cassens, U.; Rothermundt, M. Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity. J. Affect. Disord.,  2005, 87(2-3), 305-311.
[http://dx.doi.org/10.1016/j.jad.2005.03.012] [PMID: 15951024] 
[474] 
Schiepers, O.J.; Wichers, M.C.; Maes, M. Cytokines and major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2005, 9(2), 201-217.
[http://dx.doi.org/10.1016/j.pnpbp.2004.11.003] 
[475] 
Maes, M. Cytokines and major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2005, 29(2), 201-217.
[http://dx.doi.org/10.1016/0006-3223(94)90652-1] 
[476] 
Kim, Y-K.; Myint, A-M.; Lee, B-H.; Han, C-S.; Lee, H-J.; Kim, D-J.; Leonard, B.E. Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2004, 28(7), 1129-1134.
[http://dx.doi.org/10.1016/j.pnpbp.2004.05.047] [PMID: 15610925] 
[477] 
Rapaport, M.H.; McAllister, C.G.; Pickar, D.; Nelson, D.L.; Paul, S.M. Elevated levels of soluble interleukin 2 receptors in schizophrenia. Arch. Gen. Psychiatry,  1989, 46(3), 291-292.
[http://dx.doi.org/10.1001/archpsyc.1989.01810030097017] [PMID: 2784047] 
[478] 
Cazzullo, C.L.; Sacchetti, E.; Galluzzo, A.; Panariello, A.; Colombo, F.; Zagliani, A.; Clerici, M. Cytokine profiles in drug-naive schizophrenic patients. Schizophr. Res.,  2001, 47(2-3), 293-298.
[http://dx.doi.org/10.1016/S0920-9964(00)00046-3] [PMID: 11278147] 
[479] 
Moises, H.W.; Schindler, L.; Leroux, M.; Kirchner, H. Decreased production of interferon alpha and interferon gamma in leucocyte cultures of schizophrenic patients. Acta Psychiatr. Scand.,  1985, 72(1), 45-50.
[http://dx.doi.org/10.1111/j.1600-0447.1985.tb02569.x] [PMID: 3929565] 
[480] 
Stertz, L.; Magalhães, P.V.; Kapczinski, F. Is bipolar disorder an inflammatory condition? The relevance of microglial activation. Curr. Opin. Psychiatry,  2013, 26(1), 19-26.
[http://dx.doi.org/10.1097/YCO.0b013e32835aa4b4] [PMID: 23196997] 
[481] 
Goldstein, B.I.; Kemp, D.E.; Soczynska, J.K.; McIntyre, R.S. Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J. Clin. Psychiatry,  2009, 70(8), 1078-1090.
[http://dx.doi.org/10.4088/JCP.08r04505] [PMID: 19497250] 
[482] 
Berk, M.; Kapczinski, F.; Andreazza, A.C.; Dean, O.M.; Giorlando, F.; Maes, M.; Yücel, M.; Gama, C.S.; Dodd, S.; Dean, B.; Magalhães, P.V.; Amminger, P.; McGorry, P.; Malhi, G.S. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci. Biobehav. Rev.,  2011, 35(3), 804-817.
[http://dx.doi.org/10.1016/j.neubiorev.2010.10.001] [PMID: 20934453] 
[483] 
Brietzke, E.; Stertz, L.; Fernandes, B.S.; Kauer-Sant’anna, M.; Mascarenhas, M.; Escosteguy Vargas, A.; Chies, J.A.; Kapczinski, F. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J. Affect. Disord.,  2009, 116(3), 214-217.
[http://dx.doi.org/10.1016/j.jad.2008.12.001] [PMID: 19251324] 
[484] 
Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G.M.; Cooper, N.R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B.L.; Finch, C.E.; Frautschy, S.; Griffin, W.S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I.R.; McGeer, P.L.; O’Banion, M.K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; Van Muiswinkel, F.L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T. Inflammation and Alzheimer’s disease. Neurobiol. Aging,  2000, 21(3), 383-421.
[http://dx.doi.org/10.1016/S0197-4580(00)00124-X] [PMID: 10858586] 
[485] 
Wyss-Coray, T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med.,  2006, 12(9), 1005-1015.
[PMID: 16960575] 
[486] 
McGeer, P.L.; Rogers, J.; McGeer, E.G. Inflammation, Antiinflammatory Agents, and Alzheimer’s Disease: The Last 22 Years. J. Alzheimers Dis.,  2016, 54(3), 853-857.
[http://dx.doi.org/10.3233/JAD-160488] [PMID: 27716676] 
[487] 
McGeer, P.L.; Schulzer, M.; McGeer, E.G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology,  1996, 47(2), 425-432.
[http://dx.doi.org/10.1212/WNL.47.2.425] [PMID: 8757015] 
[488] 
Dregan, A.; Chowienczyk, P.; Gulliford, M.C. Are inflammation and related therapy associated with all-cause dementia in a primary care population? J. Alzheimers Dis.,  2015, 46(4), 1039-1047.
[http://dx.doi.org/10.3233/JAD-150171] [PMID: 26402631] 
[489] 
Brundin, L.; Erhardt, S.; Bryleva, E.Y.; Achtyes, E.D.; Postolache, T.T. The role of inflammation in suicidal behaviour. Acta Psychiatr. Scand.,  2015, 132(3), 192-203.
[http://dx.doi.org/10.1111/acps.12458] [PMID: 26256862] 
[490] 
Black, C.; Miller, B.J. Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol. Psychiatry,  2015, 78(1), 28-37.
[http://dx.doi.org/10.1016/j.biopsych.2014.10.014] [PMID: 25541493] 
[491] 
Ducasse, D.; Olié, E.; Guillaume, S.; Artéro, S.; Courtet, P. A meta-analysis of cytokines in suicidal behavior. Brain Behav. Immun.,  2015, 46, 203-211.
[http://dx.doi.org/10.1016/j.bbi.2015.02.004] [PMID: 25678163] 
[492] 
Serafini, G.; Pompili, M.; Elena Seretti, M.; Stefani, H.; Palermo, M.; Coryell, W.; Girardi, P. The role of inflammatory cytokines in suicidal behavior: a systematic review. Eur. Neuropsychopharmacol.,  2013, 23(12), 1672-1686.
[http://dx.doi.org/10.1016/j.euroneuro.2013.06.002] [PMID: 23896009] 
[493] 
Tonelli, L.H.; Stiller, J.; Rujescu, D.; Giegling, I.; Schneider, B.; Maurer, K.; Schnabel, A.; Möller, H.J.; Chen, H-H.; Postolache, T.T. Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Acta Psychiatr. Scand.,  2008, 117(3), 198-206.
[http://dx.doi.org/10.1111/j.1600-0447.2007.01128.x] [PMID: 18081924] 
[494] 
Mann, J.J.; Arango, V.A.; Avenevoli, S.; Brent, D.A.; Champagne, F.A.; Clayton, P.; Currier, D.; Dougherty, D.M.; Haghighi, F.; Hodge, S.E.; Kleinman, J.; Lehner, T.; McMahon, F.; Mościcki, E.K.; Oquendo, M.A.; Pandey, G.N.; Pearson, J.; Stanley, B.; Terwilliger, J.; Wenzel, A. Candidate endophenotypes for genetic studies of suicidal behavior. Biol. Psychiatry,  2009, 65(7), 556-563.
[http://dx.doi.org/10.1016/j.biopsych.2008.11.021] [PMID: 19201395] 
[495] 
Hassanain, M.; Bhatt, S.; Zalcman, S.; Siegel, A. Potentiating role of interleukin-1beta (IL-1beta) and IL-1beta type 1 receptors in the medial hypothalamus in defensive rage behavior in the cat. Brain Res.,  2005, 1048(1-2), 1-11.
[http://dx.doi.org/10.1016/j.brainres.2005.04.086] [PMID: 15919060] 
[496] 
Bhatt, S.; Bhatt, R.; Zalcman, S.S.; Siegel, A. Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat. Brain Behav. Immun.,  2008, 22(2), 224-233.
[http://dx.doi.org/10.1016/j.bbi.2007.07.011] [PMID: 17890051] 
[497] 
Dunn, A.J. Effects of cytokines and infections on brain neurochemistry. Clin. Neurosci. Res.,  2006, 6(1-2), 52-68.
[http://dx.doi.org/10.1016/j.cnr.2006.04.002] [PMID: 18079991] 
[498] 
Pandey, G.N.; Rizavi, H.S.; Ren, X.; Fareed, J.; Hoppensteadt, D.A.; Roberts, R.C.; Conley, R.R.; Dwivedi, Y. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J. Psychiatr. Res.,  2012, 46(1), 57-63.
[http://dx.doi.org/10.1016/j.jpsychires.2011.08.006] [PMID: 21906753] 
[499] 
Lindqvist, D.; Janelidze, S.; Hagell, P.; Erhardt, S.; Samuelsson, M.; Minthon, L.; Hansson, O.; Björkqvist, M.; Träskman-Bendz, L.; Brundin, L. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol. Psychiatry,  2009, 66(3), 287-292.
[http://dx.doi.org/10.1016/j.biopsych.2009.01.030] [PMID: 19268915] 
[500] 
Wadhawan, A.; Stiller, J.W.; Potocki, E.; Okusaga, O.; Dagdag, A.; Lowry, C.A.; Benros, M.E.; Postolache, T.T. Traumatic brain injury and suicidal behavior: a review. J. Alzheimers Dis.,  2019, 68(4), 1339-1370.
[http://dx.doi.org/10.3233/JAD-181055] [PMID: 30909230] 
[501] 
Valkanova, V.; Ebmeier, K.P.; Allan, C.L. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J. Affect. Disord.,  2013, 150(3), 736-744.
[http://dx.doi.org/10.1016/j.jad.2013.06.004] [PMID: 23870425] 
[502] 
Howren, M.B.; Lamkin, D.M.; Suls, J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom. Med.,  2009, 71(2), 171-186.
[http://dx.doi.org/10.1097/PSY.0b013e3181907c1b] [PMID: 19188531] 
[503] 
Liu, Y.; Ho, R.C-M.; Mak, A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J. Affect. Disord.,  2012, 139(3), 230-239.
[http://dx.doi.org/10.1016/j.jad.2011.08.003] [PMID: 21872339] 
[504] 
Dowlati, Y.; Herrmann, N.; Swardfager, W.; Liu, H.; Sham, L.; Reim, E.K.; Lanctôt, K.L. A meta-analysis of cytokines in major depression. Biol. Psychiatry,  2010, 67(5), 446-457.
[http://dx.doi.org/10.1016/j.biopsych.2009.09.033] [PMID: 20015486] 
[505] 
Fleshner, M.; Frank, M.; Maier, S.F. Danger signals and inflammasomes: stress-evoked sterile inflammation in mood disorders. Neuropsychopharmacology,  2017, 42(1), 36-45.
[http://dx.doi.org/10.1038/npp.2016.125] [PMID: 27412959] 
[506] 
O’Donovan, A.; Rush, G.; Hoatam, G.; Hughes, B.M.; McCrohan, A.; Kelleher, C.; O’Farrelly, C.; Malone, K.M. Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress. Anxiety,  2013, 30(4), 307-314.
[http://dx.doi.org/10.1002/da.22087] [PMID: 23504697] 
[507] 
Janelidze, S.; Mattei, D.; Westrin, Å.; Träskman-Bendz, L.; Brundin, L. Cytokine levels in the blood may distinguish suicide attempters from depressed patients. Brain Behav. Immun.,  2011, 25(2), 335-339.
[http://dx.doi.org/10.1016/j.bbi.2010.10.010] [PMID: 20951793] 
[508] 
Yang, C.; Tiemessen, K.M.; Bosker, F.J.; Wardenaar, K.J.; Lie, J.; Schoevers, R.A. Interleukin, tumor necrosis factor-α and C-reactive protein profiles in melancholic and non-melancholic depression: A systematic review. J. Psychosom. Res.,  2018, 111, 58-68.
[http://dx.doi.org/10.1016/j.jpsychores.2018.05.008] [PMID: 29935756] 
[509] 
Adhikari, A.; Dikshit, R.; Karia, S.; Sonavane, S.; Shah, N.; De Sousa, A. Neutrophil-lymphocyte ratio and c-reactive protein level in patients with major depressive disorder before and after pharmacotherapy. East Asian Arch. Psychiatry,  2018, 28(2), 53-58.
[PMID: 29921741] 
[510] 
Hoekstra, R.; Fekkes, D.; Pepplinkhuizen, L.; Loonen, A.J.; Tuinier, S.; Verhoeven, W.M. Nitric oxide and neopterin in bipolar affective disorder. Neuropsychobiology,  2006, 54(1), 75-81.
[http://dx.doi.org/10.1159/000096042] [PMID: 17028447] 
[511] 
Korte, S.; Arolt, V.; Peters, M.; Weitzsch, C.; Rothermundt, M.; Kirchner, H. Increased serum neopterin levels in acutely ill and recovered schizophrenic patients. Schizophr. Res.,  1998, 32(1), 63-67.
[http://dx.doi.org/10.1016/S0920-9964(98)00037-1] [PMID: 9690336] 
[512] 
Sperner-Unterweger, B.; Barnas, C.; Fleischhacker, W.W.; Fuchs, D.; Meise, U.; Reibnegger, G.; Wachter, H. Is schizophrenia linked to alteration in cellular immunity? Schizophr. Res.,  1989, 2(4-5), 417-421.
[http://dx.doi.org/10.1016/0920-9964(89)90035-2] [PMID: 2487182] 
[513] 
Celik, C.; Erdem, M.; Cayci, T.; Ozdemir, B.; Ozgur Akgul, E.; Kurt, Y.G.; Yaman, H.; Isintas, M.; Ozgen, F.; Ozsahin, A. The association between serum levels of neopterin and number of depressive episodes of major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2010, 34(2), 372-375.
[http://dx.doi.org/10.1016/j.pnpbp.2010.01.002] [PMID: 20074610] 
[514] 
Dunbar, P.R.; Hill, J.; Neale, T.J.; Mellsop, G.W. Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychol. Med.,  1992, 22(4), 1051-1057.
[http://dx.doi.org/10.1017/S0033291700038629] [PMID: 1488478] 
[515] 
Taymur, I.; Özdel, K.; Özen, N.E.; Güngör, B.B.; Atmaca, M. Urinary neopterine levels in patients with major depressive disorder: alterations after treatment with paroxetine and comparison with healthy controls. Psychiatr. Danub.,  2015, 27(1), 25-30.
[PMID: 25751446] 
[516] 
Abou-Saleh, M.T.; Anderson, D.N.; Collins, J.; Hughes, K.; Cattell, R.J.; Hamon, C.G.; Blair, J.A. The role of pterins in depression and the effects of antidepressive therapy. Biol. Psychiatry,  1995, 38(7), 458-463.
[http://dx.doi.org/10.1016/0006-3223(94)00323-U] [PMID: 8672606] 
[517] 
Tang, C.Z.; Zhang, Y.L.; Wang, W.S.; Li, W.G.; Shi, J.P. Elevated serum levels of neopterin at admission predicts depression after acute ischemic stroke: a 6-month follow-up study. Mol. Neurobiol.,  2016, 53(5), 3194-3204.
[http://dx.doi.org/10.1007/s12035-015-9220-4] [PMID: 26041659] 
[518] 
Chittiprol, S.; Venkatasubramanian, G.; Neelakantachar, N.; Babu, S.V.; Reddy, N.A.; Shetty, K.T.; Gangadhar, B.N. Oxidative stress and neopterin abnormalities in schizophrenia: a longitudinal study. J. Psychiatr. Res.,  2010, 44(5), 310-313.
[http://dx.doi.org/10.1016/j.jpsychires.2009.09.002] [PMID: 19850302] 
[519] 
Park, R.J.; Kim, Y.H. Association between high sensitivity CRP and suicidal ideation in the Korean general population. Eur. Neuropsychopharmacol.,  2017, 27(9), 885-891.
[http://dx.doi.org/10.1016/j.euroneuro.2017.06.010] [PMID: 28663123] 
[520] 
Barnes, J.; Mondelli, V.; Pariante, C.M. Genetic contributions of inflammation to depression. Neuropsychopharmacology,  2017, 42(1), 81-98.
[http://dx.doi.org/10.1038/npp.2016.169] [PMID: 27555379] 
[521] 
De Berardis, D.; Fornaro, M.; Orsolini, L.; Iasevoli, F.; Tomasetti, C.; de Bartolomeis, A.; Serroni, N.; De Lauretis, I.; Girinelli, G.; Mazza, M.; Valchera, A.; Carano, A.; Vellante, F.; Matarazzo, I.; Perna, G.; Martinotti, G.; Di Giannantonio, M. Effect of agomelatine treatment on C-reactive protein levels in patients with major depressive disorder: an exploratory study in “real-world,” everyday clinical practice. CNS Spectr.,  2017, 22(4), 342-347.
[http://dx.doi.org/10.1017/S1092852916000572] [PMID: 27702411] 
[522] 
De Berardis, D.; Campanella, D.; Gambi, F.; La Rovere, R.; Carano, A.; Conti, C.M.; Sivestrini, C.; Serroni, N.; Piersanti, D.; Di Giuseppe, B.; Moschetta, F.S.; Cotellessa, C.; Fulcheri, M.; Salerno, R.M.; Ferro, F.M. The role of C-reactive protein in mood disorders. Int. J. Immunopathol. Pharmacol.,  2006, 19(4), 721-725.
[http://dx.doi.org/10.1177/039463200601900402] [PMID: 17166394] 
[523] 
Endres, D.; Perlov, E.; Dersch, R.; Baumgartner, A.; Hottenrott, T.; Berger, B.; Stich, O.; Tebartz van Elst, L. Evidence of cerebrospinal fluid abnormalities in patients with depressive syndromes. J. Affect. Disord.,  2016, 198, 178-184.
[http://dx.doi.org/10.1016/j.jad.2016.03.030] [PMID: 27017374] 
[524] 
Sutin, A.R.; Milaneschi, Y.; Cannas, A.; Ferrucci, L.; Uda, M.; Schlessinger, D.; Zonderman, A.B.; Terracciano, A. Impulsivity-related traits are associated with higher white blood cell counts. J. Behav. Med.,  2012, 35(6), 616-623.
[http://dx.doi.org/10.1007/s10865-011-9390-0] [PMID: 22190235] 
[525] 
Mann, J.J.; Waternaux, C.; Haas, G.L.; Malone, K.M. Toward a clinical model of suicidal behavior in psychiatric patients. Am. J. Psychiatry,  1999, 156(2), 181-189.
[PMID: 9989552] 
[526] 
Batty, G.D.; Jung, K.J.; Lee, S.; Back, J.H.; Jee, S.H. Systemic inflammation and suicide risk: cohort study of 419 527 Korean men and women. J. Epidemiol. Community Health,  2018, 72(7), 572-574.
[http://dx.doi.org/10.1136/jech-2017-210086] [PMID: 29572361] 
[527] 
Keaton, S.A.; Madaj, Z.B.; Heilman, P.; Smart, L.; Grit, J.; Gibbons, R.; Postolache, T.T.; Roaten, K.; Achtyes, E.D.; Brundin, L. An inflammatory profile linked to increased suicide risk. J. Affect. Disord.,  2019, 247, 57-65.
[http://dx.doi.org/10.1016/j.jad.2018.12.100] [PMID: 30654266] 
[528] 
Miná, V.A.; Lacerda-Pinheiro, S.F.; Maia, L.C.; Pinheiro, R.F., Jr; Meireles, C.B.; de Souza, S.I.; Reis, A.O.; Bianco, B.; Rolim, M.L. The influence of inflammatory cytokines in physiopathology of suicidal behavior. J. Affect. Disord.,  2015, 172, 219-230.
[http://dx.doi.org/10.1016/j.jad.2014.09.057] [PMID: 25451421] 
[529] 
Isung, J.; Aeinehband, S.; Mobarrez, F.; Nordström, P.; Runeson, B.; Asberg, M.; Piehl, F.; Jokinen, J. High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide. Transl. Psychiatry,  2014, 4, e470
[http://dx.doi.org/10.1038/tp.2014.113] [PMID: 25335166] 
[530] 
Zimmermann, M.; Arruda-Silva, F.; Bianchetto-Aguilera, F.; Finotti, G.; Calzetti, F.; Scapini, P.; Lunardi, C.; Cassatella, M.A.; Tamassia, N. IFNα enhances the production of IL-6 by human neutrophils activated via TLR8. Sci. Rep.,  2016, 6, 19674.
[http://dx.doi.org/10.1038/srep19674] [PMID: 26790609] 
[531] 
Ericson, S.G.; Zhao, Y.; Gao, H.; Miller, K.L.; Gibson, L.F.; Lynch, J.P.; Landreth, K.S. Interleukin-6 production by human neutrophils after Fc-receptor cross-linking or exposure to granulocyte colony-stimulating factor. Blood,  1998, 91(6), 2099-2107.
[http://dx.doi.org/10.1182/blood.V91.6.2099] [PMID: 9490696] 
[532] 
Oishi, K.; Machida, K. Some plasma component is essential for IL-6 secretion by Neutrophils. Environ. Health Prev. Med.,  1997, 2(2), 89-92.
[http://dx.doi.org/10.1007/BF02931972] [PMID: 21432460] 
[533] 
Lyngsø, D.; Simonsen, L.; Bülow, J. Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise. J. Physiol.,  2002, 543(Pt 1), 373-378.
[http://dx.doi.org/10.1113/jphysiol.2002.019380] [PMID: 12181307] 
[534] 
Makki, K.; Froguel, P.; Wolowczuk, I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm.,  2013, 2013, 139239
[http://dx.doi.org/10.1155/2013/139239] [PMID: 24455420] 
[535] 
Hallberg, L.; Janelidze, S.; Engstrom, G.; Wisén, A.G.; Westrin, A.; Brundin, L. Exercise-induced release of cytokines in patients with major depressive disorder. J. Affect. Disord.,  2010, 126(1-2), 262-267.
[http://dx.doi.org/10.1016/j.jad.2010.02.133] [PMID: 20347489] 
[536] 
Kern, P.A.; Ranganathan, S.; Li, C.; Wood, L.; Ranganathan, G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab.,  2001, 280(5), E745-E751.
[http://dx.doi.org/10.1152/ajpendo.2001.280.5.E745] [PMID: 11287357] 
[537] 
Broz, P.; Monack, D.M. Newly described pattern recognition receptors team up against intracellular pathogens. Nat. Rev. Immunol.,  2013, 13(8), 551-565.
[http://dx.doi.org/10.1038/nri3479] [PMID: 23846113] 
[538] 
Pandey, G.N.; Rizavi, H.S.; Bhaumik, R.; Ren, X. Innate immunity in the postmortem brain of depressed and suicide subjects: Role of Toll-like receptors. Brain Behav. Immun.,  2019, 75, 101-111.
[http://dx.doi.org/10.1016/j.bbi.2018.09.024] [PMID: 30266463] 
[539] 
Hung, Y.Y.; Kang, H.Y.; Huang, K.W.; Huang, T.L. Association between toll-like receptors expression and major depressive disorder. Psychiatry Res.,  2014, 220(1-2), 283-286.
[http://dx.doi.org/10.1016/j.psychres.2014.07.074] [PMID: 25155940] 
[540] 
Griffen, A.L.; Becker, M.R.; Lyons, S.R.; Moeschberger, M.L.; Leys, E.J. Prevalence of Porphyromonas gingivalis and periodontal health status. J. Clin. Microbiol.,  1998, 36(11), 3239-3242.
[http://dx.doi.org/10.1128/JCM.36.11.3239-3242.1998] [PMID: 9774572] 
[541] 
Ishikawa, M.; Yoshida, K.; Okamura, H.; Ochiai, K.; Takamura, H.; Fujiwara, N.; Ozaki, K. Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway. Biochim. Biophys. Acta,  2013, 1832(12), 2035-2043.
[http://dx.doi.org/10.1016/j.bbadis.2013.07.012] [PMID: 23899607] 
[542] 
Mahendra, J.; Mahendra, L.; Kurian, V.M.; Jaishankar, K.; Mythilli, R. Prevalence of periodontal pathogens in coronary atherosclerotic plaque of patients undergoing coronary artery bypass graft surgery. J. Maxillofac. Oral Surg.,  2009, 8(2), 108-113.
[http://dx.doi.org/10.1007/s12663-009-0028-5] [PMID: 23139486] 
[543] 
Katz, J.; Chegini, N.; Shiverick, K.T.; Lamont, R.J. Localization of P. gingivalis in preterm delivery placenta. J. Dent. Res.,  2009, 88(6), 575-578.
[http://dx.doi.org/10.1177/0022034509338032] [PMID: 19587165] 
[544] 
Mougeot, J.C.; Stevens, C.B.; Paster, B.J.; Brennan, M.T.; Lockhart, P.B.; Mougeot, F.K. Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries. J. Oral Microbiol.,  2017, 9(1), 1281562
[http://dx.doi.org/10.1080/20002297.2017.1281562] [PMID: 28326156] 
[545] 
Hayashi, C.; Gudino, C.V.; Gibson, F.C., III; Genco, C.A. Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol. Oral Microbiol.,  2010, 25(5), 305-316.
[http://dx.doi.org/10.1111/j.2041-1014.2010.00582.x] [PMID: 20883220] 
[546] 
Gibson, F.C., III; Yumoto, H.; Takahashi, Y.; Chou, H.H.; Genco, C.A. Innate immune signaling and Porphyromonas gingivalis-accelerated atherosclerosis. J. Dent. Res.,  2006, 85(2), 106-121.
[http://dx.doi.org/10.1177/154405910608500202] [PMID: 16434728] 
[547] 
Gibson, F.C., III; Genco, C.A. Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs. Curr. Pharm. Des.,  2007, 13(36), 3665-3675.
[http://dx.doi.org/10.2174/138161207783018554] [PMID: 18220804] 
[548] 
Chiu, B. Multiple infections in carotid atherosclerotic plaques. Am. Heart J.,  1999, 138(5 Pt 2), S534-S536.
[http://dx.doi.org/10.1016/S0002-8703(99)70294-2] [PMID: 10539867] 
[549] 
Kozarov, E.V.; Dorn, B.R.; Shelburne, C.E.; Dunn, W.A., Jr; Progulske-Fox, A. Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Arterioscler. Thromb. Vasc. Biol.,  2005, 25(3), e17-e18.
[http://dx.doi.org/10.1161/01.ATV.0000155018.67835.1a] [PMID: 15662025] 
[550] 
Tomás, I.; Diz, P.; Tobías, A.; Scully, C.; Donos, N. Periodontal health status and bacteraemia from daily oral activities: systematic review/meta-analysis. J. Clin. Periodontol.,  2012, 39(3), 213-228.
[http://dx.doi.org/10.1111/j.1600-051X.2011.01784.x] [PMID: 22092606] 
[551] 
Nakano, K.; Inaba, H.; Nomura, R.; Nemoto, H.; Takeda, M.; Yoshioka, H.; Matsue, H.; Takahashi, T.; Taniguchi, K.; Amano, A.; Ooshima, T. Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens. J. Clin. Microbiol.,  2006, 44(9), 3313-3317.
[http://dx.doi.org/10.1128/JCM.00377-06] [PMID: 16954266] 
[552] 
Oliveira, F.A.F.; Forte, C.P.F.; Silva, P.G.; Lopes, C.B.; Montenegro, R.C.; Santos, Â.K.; Sobrinho, C.R.M.R.; Mota, M.R.L.; Sousa, F.B.; Alves, A.P.N.N. Molecular analysis of oral bacteria in heart valve of patients with cardiovascular disease by real-time polymerase chain reaction. Medicine (Baltimore),  2015, 94(47), e2067
[http://dx.doi.org/10.1097/MD.0000000000002067] [PMID: 26632711] 
[553] 
Teles, R.; Wang, C.Y. Mechanisms involved in the association between periodontal diseases and cardiovascular disease. Oral Dis.,  2011, 17(5), 450-461.
[http://dx.doi.org/10.1111/j.1601-0825.2010.01784.x] [PMID: 21223455] 
[554] 
Kuramitsu, H.K.; Qi, M.; Kang, I.C.; Chen, W. Role for periodontal bacteria in cardiovascular diseases. Ann. Periodontol.,  2001, 6(1), 41-47.
[http://dx.doi.org/10.1902/annals.2001.6.1.41] [PMID: 11887470] 
[555] 
Herzberg, M.C.; Meyer, M.W. Effects of oral flora on platelets: possible consequences in cardiovascular disease. J. Periodontol.,  1996, 67(10)(Suppl.), 1138-1142.
[http://dx.doi.org/10.1902/jop.1996.67.10s.1138] 
[556] 
D’Aiuto, F.; Parkar, M.; Tonetti, M.S. Periodontal therapy: a novel acute inflammatory model. Inflamm. Res.,  2005, 54(10), 412-414.
[http://dx.doi.org/10.1007/s00011-005-1375-4] [PMID: 16283108] 
[557] 
Tonetti, M.S.; D’Aiuto, F.; Nibali, L.; Donald, A.; Storry, C.; Parkar, M.; Suvan, J.; Hingorani, A.D.; Vallance, P.; Deanfield, J. Treatment of periodontitis and endothelial function. N. Engl. J. Med.,  2007, 356(9), 911-920.
[http://dx.doi.org/10.1056/NEJMoa063186] [PMID: 17329698] 
[558] 
Tonetti, M.S.; Van Dyke, T.E. Working group 1 of the joint EFP/AAP workshop. Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J. Clin. Periodontol.,  2013, 40(Suppl. 14), S24-S29.
[http://dx.doi.org/10.1111/jcpe.12089] [PMID: 23627332] 
[559] 
Minassian, C.; D’Aiuto, F.; Hingorani, A.D.; Smeeth, L. Invasive dental treatment and risk for vascular events: a self-controlled case series. Ann. Intern. Med.,  2010, 153(8), 499-506.
[http://dx.doi.org/10.7326/0003-4819-153-8-201010190-00006] [PMID: 20956706] 
[560] 
Hotamisligil, G.S. Inflammation and metabolic disorders. Nature,  2006, 444(7121), 860-867.
[http://dx.doi.org/10.1038/nature05485] [PMID: 17167474] 
[561] 
Burcelin, R.; Garidou, L.; Pomié, C. Immuno-microbiota cross and talk: the new paradigm of metabolic diseases. Semin. Immunol.,  2012, 24(1), 67-74.
[http://dx.doi.org/10.1016/j.smim.2011.11.011] [PMID: 22265028] 
[562] 
Nicholson, J.K.; Holmes, E.; Kinross, J.; Burcelin, R.; Gibson, G.; Jia, W.; Pettersson, S. Host-gut microbiota metabolic interactions. Science,  2012, 336(6086), 1262-1267.
[http://dx.doi.org/10.1126/science.1223813] [PMID: 22674330] 
[563] 
Kolb, H.; Eizirik, D.L. Resistance to type 2 diabetes mellitus: a matter of hormesis? Nat. Rev. Endocrinol.,  2011, 8(3), 183-192.
[http://dx.doi.org/10.1038/nrendo.2011.158] [PMID: 22024974] 
[564] 
Clemente, J.C.; Ursell, L.K.; Parfrey, L.W.; Knight, R. The impact of the gut microbiota on human health: an integrative view. Cell,  2012, 148(6), 1258-1270.
[http://dx.doi.org/10.1016/j.cell.2012.01.035] [PMID: 22424233] 
[565] 
Furusho, H.; Miyauchi, M.; Hyogo, H.; Inubushi, T.; Ao, M.; Ouhara, K.; Hisatune, J.; Kurihara, H.; Sugai, M.; Hayes, C.N.; Nakahara, T.; Aikata, H.; Takahashi, S.; Chayama, K.; Takata, T. Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice. J. Gastroenterol.,  2013, 48(11), 1259-1270.
[http://dx.doi.org/10.1007/s00535-012-0738-1] [PMID: 23307045] 
[566] 
Qin, N.; Yang, F.; Li, A.; Prifti, E.; Chen, Y.; Shao, L.; Guo, J.; Le Chatelier, E.; Yao, J.; Wu, L.; Zhou, J.; Ni, S.; Liu, L.; Pons, N.; Batto, J.M.; Kennedy, S.P.; Leonard, P.; Yuan, C.; Ding, W.; Chen, Y.; Hu, X.; Zheng, B.; Qian, G.; Xu, W.; Ehrlich, S.D.; Zheng, S.; Li, L. Alterations of the human gut microbiome in liver cirrhosis. Nature,  2014, 513(7516), 59-64.
[http://dx.doi.org/10.1038/nature13568] [PMID: 25079328] 
[567] 
Hotamisligil, G.S.; Budavari, A.; Murray, D.; Spiegelman, B.M. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J. Clin. Invest.,  1994, 94(4), 1543-1549.
[http://dx.doi.org/10.1172/JCI117495] [PMID: 7523453] 
[568] 
Arimatsu, K.; Yamada, H.; Miyazawa, H.; Minagawa, T.; Nakajima, M.; Ryder, M.I.; Gotoh, K.; Motooka, D.; Nakamura, S.; Iida, T.; Yamazaki, K. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci. Rep.,  2014, 4, 4828.
[http://dx.doi.org/10.1038/srep04828] [PMID: 24797416] 
[569] 
Nakajima, M.; Arimatsu, K.; Kato, T.; Matsuda, Y.; Minagawa, T.; Takahashi, N.; Ohno, H.; Yamazaki, K. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver. PLoS One,  2015, 10(7), e0134234
[http://dx.doi.org/10.1371/journal.pone.0134234] [PMID: 26218067] 
[570] 
Darveau, R.P. Periodontitis: a polymicrobial disruption of host homeostasis. Nat. Rev. Microbiol.,  2010, 8(7), 481-490.
[http://dx.doi.org/10.1038/nrmicro2337] [PMID: 20514045] 
[571] 
Ritchie, C.S.; Kinane, D.F. Nutrition, inflammation, and periodontal disease. Nutrition,  2003, 19(5), 475-476.
[http://dx.doi.org/10.1016/S0899-9007(02)01043-2] [PMID: 12714106] 
[572] 
Kau, A.L.; Ahern, P.P.; Griffin, N.W.; Goodman, A.L.; Gordon, J.I. Human nutrition, the gut microbiome and the immune system. Nature,  2011, 474(7351), 327-336.
[http://dx.doi.org/10.1038/nature10213] [PMID: 21677749] 
[573] 
Kelly, J.R.; Kennedy, P.J.; Cryan, J.F.; Dinan, T.G.; Clarke, G.; Hyland, N.P. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci.,  2015, 9, 392.
[http://dx.doi.org/10.3389/fncel.2015.00392] [PMID: 26528128] 
[574] 
Messaoudi, M.; Lalonde, R.; Violle, N.; Javelot, H.; Desor, D.; Nejdi, A.; Bisson, J-F.; Rougeot, C.; Pichelin, M.; Cazaubiel, M.; Cazaubiel, J.M. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr.,  2011, 105(5), 755-764.
[http://dx.doi.org/10.1017/S0007114510004319] [PMID: 20974015] 
[575] 
Ong, I.M.; Gonzalez, J.G.; McIlwain, S.J.; Sawin, E.A.; Schoen, A.J.; Adluru, N.; Alexander, A.L.; Yu, J.J. Gut microbiome populations are associated with structure-specific changes in white matter architecture. Transl. Psychiatry,  2018, 8(1), 6.
[http://dx.doi.org/10.1038/s41398-017-0022-5] [PMID: 29317592] 
[576] 
Bercik, P.; Park, A.J.; Sinclair, D.; Khoshdel, A.; Lu, J.; Huang, X.; Deng, Y.; Blennerhassett, P.A.; Fahnestock, M.; Moine, D.; Berger, B.; Huizinga, J.D.; Kunze, W.; McLean, P.G.; Bergonzelli, G.E.; Collins, S.M.; Verdu, E.F. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol. Motil.,  2011, 23(12), 1132-1139.
[http://dx.doi.org/10.1111/j.1365-2982.2011.01796.x] [PMID: 21988661] 
[577] 
Lyte, M.; Li, W.; Opitz, N.; Gaykema, R.P.; Goehler, L.E. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiol. Behav.,  2006, 89(3), 350-357.
[http://dx.doi.org/10.1016/j.physbeh.2006.06.019] [PMID: 16887154] 
[578] 
Zheng, P.; Zeng, B.; Zhou, C.; Liu, M.; Fang, Z.; Xu, X.; Zeng, L.; Chen, J.; Fan, S.; Du, X.; Zhang, X.; Yang, D.; Yang, Y.; Meng, H.; Li, W.; Melgiri, N.D.; Licinio, J.; Wei, H.; Xie, P. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol. Psychiatry,  2016, 21(6), 786-796.
[http://dx.doi.org/10.1038/mp.2016.44] [PMID: 27067014] 
[579] 
Burokas, A.; Arboleya, S.; Moloney, R.D.; Peterson, V.L.; Murphy, K.; Clarke, G.; Stanton, C.; Dinan, T.G.; Cryan, J.F. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol. Psychiatry,  2017, 82(7), 472-487.
[http://dx.doi.org/10.1016/j.biopsych.2016.12.031] [PMID: 28242013] 
[580] 
Desbonnet, L.; Clarke, G.; Traplin, A.; O’Sullivan, O.; Crispie, F.; Moloney, R.D.; Cotter, P.D.; Dinan, T.G.; Cryan, J.F. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behav. Immun.,  2015, 48, 165-173.
[http://dx.doi.org/10.1016/j.bbi.2015.04.004] [PMID: 25866195] 
[581] 
Diaz Heijtz, R.; Wang, S.; Anuar, F.; Qian, Y.; Björkholm, B.; Samuelsson, A.; Hibberd, M.L.; Forssberg, H.; Pettersson, S. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA,  2011, 108(7), 3047-3052.
[http://dx.doi.org/10.1073/pnas.1010529108] [PMID: 21282636] 
[582] 
Ait-Belgnaoui, A.; Colom, A.; Braniste, V.; Ramalho, L.; Marrot, A.; Cartier, C.; Houdeau, E.; Theodorou, V.; Tompkins, T. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol. Motil.,  2014, 26(4), 510-520.
[http://dx.doi.org/10.1111/nmo.12295] [PMID: 24372793] 
[583] 
Hemarajata, P.; Versalovic, J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap. Adv. Gastroenterol.,  2013, 6(1), 39-51.
[http://dx.doi.org/10.1177/1756283X12459294] [PMID: 23320049] 
[584] 
Cryan, J.F.; Dinan, T.G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci.,  2012, 13(10), 701-712.
[http://dx.doi.org/10.1038/nrn3346] [PMID: 22968153] 
[585] 
Galland, L. The gut microbiome and the brain. J. Med. Food,  2014, 17(12), 1261-1272.
[http://dx.doi.org/10.1089/jmf.2014.7000] [PMID: 25402818] 
[586] 
Painold, A.; Mörkl, S.; Kashofer, K.; Halwachs, B.; Dalkner, N.; Bengesser, S.; Birner, A.; Fellendorf, F.; Platzer, M.; Queissner, R.; Schütze, G.; Schwarz, M.J.; Moll, N.; Holzer, P.; Holl, A.K.; Kapfhammer, H.P.; Gorkiewicz, G.; Reininghaus, E.Z. A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode. Bipolar Disord.,  2019, 21(1), 40-49.
[http://dx.doi.org/10.1111/bdi.12682] [PMID: 30051546] 
[587] 
Talamo, B.R.; Feng, W.H.; Perez-Cruet, M.; Adelman, L.; Kosik, K.; Lee, M.Y.; Cork, L.C.; Kauer, J.S. Pathologic changes in olfactory neurons in Alzheimer’s disease. Ann. N. Y. Acad. Sci.,  1991, 640(1), 1-7.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb00182.x] [PMID: 1776726] 
[588] 
Coureuil, M.; Lécuyer, H.; Bourdoulous, S.; Nassif, X. A journey into the brain: insight into how bacterial pathogens cross blood-brain barriers. Nat. Rev. Microbiol.,  2017, 15(3), 149-159.
[http://dx.doi.org/10.1038/nrmicro.2016.178] [PMID: 28090076] 
[589] 
Giacona, M.B.; Papapanou, P.N.; Lamster, I.B.; Rong, L.L.; D’Agati, V.D.; Schmidt, A.M.; Lalla, E. Porphyromonas gingivalis induces its uptake by human macrophages and promotes foam cell formation in vitro. FEMS Microbiol. Lett.,  2004, 241(1), 95-101.
[http://dx.doi.org/10.1016/j.femsle.2004.10.009] [PMID: 15556715] 
[590] 
Li, L.; Michel, R.; Cohen, J.; Decarlo, A.; Kozarov, E. Intracellular survival and vascular cell-to-cell transmission of Porphyromonas gingivalis. BMC Microbiol.,  2008, 8, 26.
[http://dx.doi.org/10.1186/1471-2180-8-26] [PMID: 18254977] 
[591] 
Cope, T.E.; Rittman, T.; Borchert, R.J.; Jones, P.S.; Vatansever, D.; Allinson, K.; Passamonti, L.; Vazquez Rodriguez, P.; Bevan-Jones, W.R.; O’Brien, J.T.; Rowe, J.B. Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy. Brain,  2018, 141(2), 550-567.
[http://dx.doi.org/10.1093/brain/awx347] [PMID: 29293892] 
[592] 
Frister, A.; Schmidt, C.; Schneble, N.; Brodhun, M.; Gonnert, F.A.; Bauer, M.; Hirsch, E.; Müller, J.P.; Wetzker, R.; Bauer, R. Phosphoinositide 3-kinase γ affects LPS-induced disturbance of blood-brain barrier via lipid kinase-independent control of cAMP in microglial cells. Neuromolecular Med.,  2014, 16(4), 704-713.
[http://dx.doi.org/10.1007/s12017-014-8320-z] [PMID: 25033932] 
[593] 
Wu, Z.; Ni, J.; Liu, Y.; Teeling, J.L.; Takayama, F.; Collcutt, A.; Ibbett, P.; Nakanishi, H. Cathepsin B plays a critical role in inducing Alzheimer’s disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice. Brain Behav. Immun.,  2017, 65, 350-361.
[http://dx.doi.org/10.1016/j.bbi.2017.06.002] [PMID: 28610747] 
[594] 
Liu, Y.; Wu, Z.; Nakanishi, Y.; Ni, J.; Hayashi, Y.; Takayama, F.; Zhou, Y.; Kadowaki, T.; Nakanishi, H. Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice. Sci. Rep.,  2017, 7(1), 11759.
[http://dx.doi.org/10.1038/s41598-017-12173-1] [PMID: 28924232] 
[595] 
Wu, Z.; Zhang, J.; Nakanishi, H. Leptomeningeal cells activate microglia and astrocytes to induce IL-10 production by releasing pro-inflammatory cytokines during systemic inflammation. J. Neuroimmunol.,  2005, 167(1-2), 90-98.
[http://dx.doi.org/10.1016/j.jneuroim.2005.06.025] [PMID: 16095726] 
[596] 
Liu, Y.; Wu, Z.; Zhang, X.; Ni, J.; Yu, W.; Zhou, Y.; Nakanishi, H. Leptomeningeal cells transduce peripheral macrophages inflammatory signal to microglia in reponse to Porphyromonas gingivalis LPS. Mediators Inflamm.,  2013, 2013, 407562
[http://dx.doi.org/10.1155/2013/407562] [PMID: 24363500] 
[597] 
D’Mello, C.; Swain, M.G. Immune-to-brain communication pathways in inflammation-associated sickness and depression.  In Inflammation-Associated Depression: Evidence, Mechanisms and Implications; Springer: Berlin, 2016, pp. 73-94.
[http://dx.doi.org/10.1007/7854_2016_37] 
[598] 
Perry, V.H. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav. Immun.,  2004, 18(5), 407-413.
[http://dx.doi.org/10.1016/j.bbi.2004.01.004] [PMID: 15265532] 
[599] 
D’Mello, C.; Le, T.; Swain, M.G. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J. Neurosci.,  2009, 29(7), 2089-2102.
[http://dx.doi.org/10.1523/JNEUROSCI.3567-08.2009] [PMID: 19228962] 
[600] 
Capuron, L.; Miller, A.H. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol. Ther.,  2011, 130(2), 226-238.
[http://dx.doi.org/10.1016/j.pharmthera.2011.01.014] [PMID: 21334376] 
[601] 
Bluthé, R-M.; Walter, V.; Parnet, P.; Layé, S.; Lestage, J.; Verrier, D.; Poole, S.; Stenning, B.E.; Kelley, K.W.; Dantzer, R. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C. R. Acad. Sci. III,  1994, 317(6), 499-503.
[PMID: 7987701] 
[602] 
 GAIN Trial: Phase 2/3 Study of COR388 in Subjects With
  Alzheimer's Disease.. https://clinicaltrials.gov/ct2/show/NCT03823404 (Accessed September 26, 2019).
[603] 
Fornicola, W.; Pelcovits, A.; Li, B.X.; Heath, J.; Perry, G.; Castellani, R.J. Alzheimer disease pathology in middle age reveals a spatial-temporal disconnect between amyloid-β and Phosphorylated Tau. Open Neurol. J.,  2014, 8, 22-26.
[http://dx.doi.org/10.2174/1874205X01408010022] [PMID: 25628768] 
[604] 
Yamasaki, Y.; Nomura, R.; Nakano, K.; Naka, S.; Matsumoto-Nakano, M.; Asai, F.; Ooshima, T. Distribution of periodontopathic bacterial species in dogs and their owners. Arch. Oral Biol.,  2012, 57(9), 1183-1188.
[http://dx.doi.org/10.1016/j.archoralbio.2012.02.015] [PMID: 22417880] 
[605] 
Murakami, Y.; Kawata, A.; Ito, S.; Katayama, T.; Fujisawa, S. The radical scavenging activity and cytotoxicity of resveratrol, orcinol and 4-allylphenol and their inhibitory effects on cox-2 gene expression and nf-κb activation in raw264.7 cells stimulated with porphyromonas gingivalis-fimbriae. In Vivo,  2015, 29(3), 341-349.
[PMID: 25977379] 
[606] 
Murakami, Y.; Kawata, A.; Ito, S.; Katayama, T.; Fujisawa, S. Radical-scavenging and anti-inflammatory activity of quercetin and related compounds and their combinations against raw264.7 cells stimulated with porphyromonas gingivalis fimbriae. relationships between anti-inflammatory activity and quantum chemical parameters. In Vivo,  2015, 29(6), 701-710.
[PMID: 26546527] 
[607] 
Yiemwattana, I.; Kaomongkolgit, R. Alpha-mangostin suppresses IL-6 and IL-8 expression in P. gingivalis LPS-stimulated human gingival fibroblasts. Odontology,  2015, 103(3), 348-355.
[http://dx.doi.org/10.1007/s10266-014-0160-7] [PMID: 24888491] 
[608] 
Derradjia, A.; Alanazi, H.; Park, H.J.; Djeribi, R.; Semlali, A.; Rouabhia, M. α-tocopherol decreases interleukin-1β and -6 and increases human β-defensin-1 and -2 secretion in human gingival fibroblasts stimulated with Porphyromonas gingivalis lipopolysaccharide. J. Periodontal Res.,  2016, 51(3), 295-303.
[http://dx.doi.org/10.1111/jre.12308] [PMID: 26214284] 
[609] 
Jian, C.X.; Li, M.Z.; Zheng, W.Y.; He, Y.; Ren, Y.; Wu, Z.M.; Fan, Q.S.; Hu, Y.H.; Li, C.J. Tormentic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts via inhibition of TLR4-mediated NF-κB and MAPK signalling pathway. Arch. Oral Biol.,  2015, 60(9), 1327-1332.
[http://dx.doi.org/10.1016/j.archoralbio.2015.05.005] [PMID: 26123747] 
[610] 
Ci, X.; Chen, L.; Ou, X. [Grape seed proanthocyanidin extracts inhibit lipopolysaccharide of Porphyromonas gingivalis.]. Shanghai kou qiang yi xue,  2015, 24(4), 433-436.
[611] 
Azelmat, J.; Larente, J.F.; Grenier, D. The anthraquinone rhein exhibits synergistic antibacterial activity in association with metronidazole or natural compounds and attenuates virulence gene expression in Porphyromonas gingivalis. Arch. Oral Biol.,  2015, 60(2), 342-346.
[http://dx.doi.org/10.1016/j.archoralbio.2014.11.006] [PMID: 25463909] 
[612] 
Kong, L.; Qi, X.; Huang, S.; Chen, S.; Wu, Y.; Zhao, L. Theaflavins inhibit pathogenic properties of P. gingivalis and MMPs production in P. gingivalis-stimulated human gingival fibroblasts. Arch. Oral Biol.,  2015, 60(1), 12-22.
[http://dx.doi.org/10.1016/j.archoralbio.2014.08.019] [PMID: 25244614] 
[613] 
Kataoka, S.; Baba, A.; Suda, Y.; Takii, R.; Hashimoto, M.; Kawakubo, T.; Asao, T.; Kadowaki, T.; Yamamoto, K. A novel, potent dual inhibitor of Arg-gingipains and Lys-gingipain as a promising agent for periodontal disease therapy. FASEB J.,  2014, 28(8), 3564-3578.
[http://dx.doi.org/10.1096/fj.14-252130] [PMID: 24776743] 
[614] 
Löhr, G.; Beikler, T.; Podbielski, A.; Standar, K.; Redanz, S.; Hensel, A. Polyphenols from Myrothamnus flabellifolia Welw. inhibit in vitro adhesion of Porphyromonas gingivalis and exert anti-inflammatory cytoprotective effects in KB cells. J. Clin. Periodontol.,  2011, 38(5), 457-469.
[http://dx.doi.org/10.1111/j.1600-051X.2010.01654.x] [PMID: 21158896] 
[615] 
Medawar, P.B. In Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol.,  1953, 320-337.
[616] 
Scrandis, D.A.; Langenberg, P.; Tonelli, L.H.; Sheikh, T.M.; Manogura, A.C.; Alberico, L.A.; Hermanstyne, T.; Fuchs, D.; Mighty, H.; Hasday, J.D.; Boteva, K.; Postolache, T.T. Prepartum depressive symptoms correlate positively with c-reactive protein levels and negatively with tryptophan levels: a preliminary report. Int. J. Child Health Hum. Dev.,  2008, 1(2), 167-174.
[PMID: 18924606] 
[617] 
Groer, M.; Fuchs, D.; Duffy, A.; Louis-Jacques, A.; D’Agata, A.; Postolache, T.T. Associations among obesity, inflammation, and tryptophan catabolism in pregnancy. associations among obesity, inflammation, and tryptophan catabolism in pregnancy. Biol. Res. Nurs.,  2018, 20(3), 284-291.
[http://dx.doi.org/10.1177/1099800417738363] [PMID: 29141444] 
Rights & Permissions Print Export Cite as
Article Details
VOLUME: 20
ISSUE: 15
Year: 2020
Published on: 01 June, 2020
Page: [1353 - 1397]
Pages: 45
DOI: 10.2174/1568026620666200110161105
Price: $65
Article Metrics
PDF: 20
HTML: 1
DOI https://doi.org/10.2174/1568026620666200110161105	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Periodontal Pathogens and Neuropsychiatric Health

Graphical Abstract:

Abstract:

Related Article(s)

Most Downloaded Article(s)
