Download PDF
Thromb Haemost 2022; 122(07): 1209-1220
DOI: 10.1055/s-0041-1740637
Stroke, Systemic or Venous Thromboembolism

Plasma Homocysteine in Behcet's Disease: A Systematic Review and Meta-Analysis

Mira Merashli
1   Department of Rheumatology, American University of Beirut, Bliss, Beirut, Lebanon
,
Tommaso Bucci
2   Department of General Surgery, Surgical Specialties and Organ Transplantation “Paride Stefanini,” Sapienza University of Rome, Rome, Italy
,
Daniele Pastori
3   Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Pasquale Pignatelli
3   Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Alessia Arcaro
4   Department of Medicine and Health Sciences ‘V. Tiberio’, Università del Molise, Campobasso, Italy
,
Fabrizio Gentile
4   Department of Medicine and Health Sciences ‘V. Tiberio’, Università del Molise, Campobasso, Italy
,
Vincenzo Marottoli
5   Multimedica SRL, Naples, Italy
,
Paul R. J. Ames 
6   Immune Response and Vascular Disease Unit, CEDOC, Nova University Lisbon, Rua Camara Pestana, Lisbon Portugal
7   Department of Haematology, Dumfries Royal Infirmary, Cargenbridge, Dumfries, United Kingdom
› Author Affiliations Funding This work was supported by Fondazione Anticorpi Antifosfolipidi ONLUS (www.fondazioneaps.org), an Italian registered charity organization that had no role in the systematic review.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Aim To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations.

Methods Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes.

Results The search strategy retrieved 48 case–control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p < 0.0001) with wide heterogeneity (I2  = 89.7%) that remained unchanged after sensitivity analysis according to year of article publication, age of BD participants, study size, study quality, method of HC determination, and male/female ratio >1.5; some pooled ethnicities explained a small part of the heterogeneity (I2  = 16.3%). Active BD participants had higher HC than inactive ones (p < 0.0001), with moderate heterogeneity (I2  = 49.2%) that disappeared after removal of an outlier study with very high disease activity. BD participants with any vascular involvement had higher HC than those without (p < 0.0001) with wide heterogeneity (I2  = 89.7%); subgroup analysis on venous thrombosis only changed neither effect size (p < 0.0001) nor heterogeneity (I2  = 72.7%). BD participants with ocular involvement had higher HC than those without (p < 0.0001) with moderate heterogeneity (I2  = 40.3%).

Conclusion Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.

Keywords

Behcet's disease - homocysteine - disease activity

Supplementary Material



Publication History

Received: 25 September 2021

Accepted: 11 November 2021

Article published online:
07 January 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell 2010; 140 (06) 784-790
    CrossrefPubMedSearch in Google Scholar
  • 2 Seyahi E. Behçet's disease: How to diagnose and treat vascular involvement. Best Pract Res Clin Rheumatol 2016; 30 (02) 279-295
    CrossrefPubMedSearch in Google Scholar
  • 3 Chamorro AJ, Marcos M, Hernández-García I. et al. Association of allelic variants of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase with thrombosis or ocular involvement in Behçet's disease: a systematic review and meta-analysis. Autoimmun Rev 2013; 12 (05) 607-616
    CrossrefPubMedSearch in Google Scholar
  • 4 Nalçaci M, Pekçelen Y. Antithrombin III, protein C and protein S plasma levels in patients with Behçet's disease. J Int Med Res 1998; 26 (04) 206-208
    CrossrefPubMedSearch in Google Scholar
  • 5 Islam MA, Alam SS, Kundu S. et al. Prevalence of antiphospholipid antibodies in Behçet's disease: a systematic review and meta-analysis. PLoS One 2020; 15 (01) e0227836
    CrossrefPubMedSearch in Google Scholar
  • 6 Ricart JM, Vayá A, Todolí J. et al. Thrombophilic risk factors and homocysteine levels in Behçet's disease in eastern Spain and their association with thrombotic events. Thromb Haemost 2006; 95 (04) 618-624
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Blachier F, Andriamihaja M, Blais A. Sulfur-containing amino acids and lipid metabolism. J Nutr 2020; 150 (Suppl. 01) 2524S-2531S
    CrossrefPubMedSearch in Google Scholar
  • 8 Esse R, Barroso M, Tavares de Almeida I, Castro R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. Int J Mol Sci 2019; 20 (04) 867
    CrossrefPubMedSearch in Google Scholar
  • 9 La Regina M, Orlandini F, Prisco D, Dentali F. Homocysteine in vascular Behcet disease: a meta-analysis. Arterioscler Thromb Vasc Biol 2010; 30 (10) 2067-2074
    CrossrefPubMedSearch in Google Scholar
  • 10 Rethlefsen ML, Kirtley S, Waffenschmidt S. et al; PRISMA-S Group. PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews. Syst Rev 2021; 10 (01) 39
    CrossrefPubMedSearch in Google Scholar
  • 11 Wells GA, Shea B, O'Connell D. et al. Ottawa Hospital Research Institute. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Accessed December 2, 2021: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp#:~:text=The%20Newcastle%2DOttawa%20Scale%20(NOS,nonrandomised%20studies%20in%20meta%2Danalyses&text=It%20was%20developed%20to%20assess,interpretation%20of%20meta%2Danalytic%20results
    PubMed
  • 12 Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 2010; 1 (02) 97-111
    Search in Google Scholar
  • 13 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
    Search in Google Scholar
  • 14 Tang JL, Liu JL. Misleading funnel plot for detection of bias in meta-analysis. J Clin Epidemiol 2000; 53 (05) 477-484
    CrossrefPubMedSearch in Google Scholar
  • 15 Lau J, Ioannidis JPA, Terrin N, Schmid CH, Olkin I. The case of the misleading funnel plot. BMJ 2006; 333 (7568): 597-600
    CrossrefPubMedSearch in Google Scholar
  • 16 Aksu K, Turgan N, Oksel F. et al. Hyperhomocysteinaemia in Behçet's disease. Rheumatology (Oxford) 2001; 40 (06) 687-690
    CrossrefPubMedSearch in Google Scholar
  • 17 Calikoğlu E, Oztaş M, Sengül N, Adam B, Gürer MA. Serum homocysteine level in Behçet's disease. Haematologia (Budap) 2002; 32 (03) 219-224
    CrossrefPubMedSearch in Google Scholar
  • 18 Er H, Evereklioglu C, Cumurcu T. et al. Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behçet's disease. Br J Ophthalmol 2002; 86 (06) 653-657
    CrossrefPubMedSearch in Google Scholar
  • 19 Korkmaz C, Bozan B, Kosar M, Sahin F, Gülbas Z. Is there an association of plasma homocysteine levels with vascular involvement in patients with Behçet's syndrome?. Clin Exp Rheumatol 2002; 20 (04, Suppl 26): S30-S34
    PubMedSearch in Google Scholar
  • 20 Lee YJ, Kang SW, Yang JI. et al. Coagulation parameters and plasma total homocysteine levels in Behcet's disease. Thromb Res 2002; 106 (01) 19-24
    CrossrefPubMedSearch in Google Scholar
  • 21 Okka M, Oztürk M, Kockar MC, Bavbek N, Rasier Y, Gunduz K. Plasma homocysteine level and uveitis in Behçet's disease. Isr Med Assoc J 2002; 4 (11, Suppl): 931-934
    PubMedSearch in Google Scholar
  • 22 Bekpinar S, Koçak H, Unlüçerçi Y, Genç S, Akdağ-Köse A, Göğüş F. The evaluation of C-reactive protein, homocysteine and vitamin B6 concentrations in Behçet and rheumatoid arthritis disease. Clin Chim Acta 2003; 329 (1-2): 143-145
    CrossrefPubMedSearch in Google Scholar
  • 23 Canataroglu A, Tanriverdi K, Inal T. et al. Methylenetetrahydrofolate reductase gene C677T mutation and plasma homocysteine level in Behçet's disease. Rheumatol Int 2003; 23 (05) 236-240
    CrossrefPubMedSearch in Google Scholar
  • 24 Nalbant S, Aktay D, Cingozbay Y. et al. Homocysteine and Behçet disease. J Clin Rheumatol 2003; 9 (01) 65-66
    CrossrefPubMedSearch in Google Scholar
  • 25 Feki M, Houman H, Ghannouchi M. et al. Hyperhomocysteinaemia is associated with uveitis but not with deep venous thrombosis in Behcet's disease. Clin Chem Lab Med 2004; 42 (12) 1417-1423
    CrossrefPubMedSearch in Google Scholar
  • 26 Ozdemir R, Barutcu I, Sezgin AT. et al. Vascular endothelial function and plasma homocysteine levels in Behcet's disease. Am J Cardiol 2004; 94 (04) 522-525
    CrossrefPubMedSearch in Google Scholar
  • 27 Ateş A, Aydintuğ O, Olmez U, Düzgün N, Duman M. Serum homocysteine level is higher in Behçet's disease with vascular involvement. Rheumatol Int 2005; 25 (01) 42-44
    CrossrefPubMedSearch in Google Scholar
  • 28 Keser G, Aksu K, Tamsel S. et al. Increased thickness of the carotid artery intima-media assessed by ultrasonography in Behçet's disease. Clin Exp Rheumatol 2005; 23 (04, Suppl 38): S71-S76
    PubMedSearch in Google Scholar
  • 29 Topal E, Ozdemir R, Aksoy Y. et al. Tissue Doppler velocities of the right and left ventricles and their association with C-reactive protein and homocysteine levels in Behcet's disease. Am J Cardiol 2005; 96 (12) 1739-1742
    CrossrefPubMedSearch in Google Scholar
  • 30 Yesilova Z, Pay S, Oktenli C. et al. Hyperhomocysteinemia in patients with Behçet's disease: is it due to inflammation or therapy?. Rheumatol Int 2005; 25 (06) 423-428
    CrossrefPubMedSearch in Google Scholar
  • 31 Gullu H, Caliskan M, Erdogan D. et al. Impaired coronary microvascular functions in patients with Behçet disease. J Am Coll Cardiol 2006; 48 (03) 586-587
    CrossrefPubMedSearch in Google Scholar
  • 32 Kayikçioğlu M, Aksu K, Hasdemir C. et al. Endothelial functions in Behçet's disease. Rheumatol Int 2006; 26 (04) 304-308
    CrossrefPubMedSearch in Google Scholar
  • 33 Mungan AG, Can M, Açikgöz S, Eştürk E, Altinyazar C. Lipid peroxidation and homocysteine levels in Behçet's disease. Clin Chem Lab Med 2006; 44 (09) 1115-1118
    CrossrefPubMedSearch in Google Scholar
  • 34 Sentürk O, Ozgür O, Hülagü OS, Cantürk NZ, Celebi A, Karakaya AT. Effect of Helicobacter pylori infection on deep vein thrombosis seen in patients with Behçet's disease. East Afr Med J 2006; 83 (01) 49-51
    CrossrefPubMedSearch in Google Scholar
  • 35 Ozkan Y, Yardim-Akaydin S, Sepici A, Engin B, Sepici V, Simşek B. Assessment of homocysteine, neopterin and nitric oxide levels in Behçet's disease. Clin Chem Lab Med 2007; 45 (01) 73-77
    CrossrefPubMedSearch in Google Scholar
  • 36 Sarican T, Ayabakan H, Turkmen S, Kalaslioglu V, Baran F, Yenice N. Homocysteine: an activity marker in Behçet's disease?. J Dermatol Sci 2007; 45 (02) 121-126
    CrossrefPubMedSearch in Google Scholar
  • 37 Hong SN, Park JC, Yoon NS. et al. Carotid artery intima-media thickness in Behcet's disease patients without significant cardiovascular involvement. Korean J Intern Med (Korean Assoc Intern Med) 2008; 23 (02) 87-93
    PubMedSearch in Google Scholar
  • 38 Kartal Durmazlar SP, Akgul A, Eskioglu F. Homocysteine may involve in the pathogenesis of Behcet's disease by inducing inflammation. Mediators Inflamm 2008; 2008: 407972
    CrossrefPubMedSearch in Google Scholar
  • 39 Koubaa N, Hammami S, Nakbi A. et al. Relationship between thiolactonase activity and hyperhomocysteinemia according to MTHFR gene polymorphism in Tunisian Behçet's disease patients. Clin Chem Lab Med 2008; 46 (02) 187-192
    CrossrefPubMedSearch in Google Scholar
  • 40 Pathare A, AlKaabi J, Al Haddabi H, Alkindi S. Vascular thrombosis and relation to hemostatic parameters in omani patients with Behcet's disease. Blood 2008; 112 (11) 4090
    CrossrefPubMedSearch in Google Scholar
  • 41 Taysi S, Sari RA, Dursun H. et al. Evaluation of nitric oxide synthase activity, nitric oxide, and homocysteine levels in patients with active Behcet's disease. Clin Rheumatol 2008; 27 (12) 1529-1534
    CrossrefPubMedSearch in Google Scholar
  • 42 Gönül M, Gül U, Kilinç C, Cakmak SK, Soylu S, Kiliç A. Homocysteine levels in patients with Behçet's disease and patients with recurrent aphthous stomatitis. Clin Rheumatol 2009; 28 (10) 1153-1156
    CrossrefPubMedSearch in Google Scholar
  • 43 Hamzaoui A, Harzallah O, Klii R, Mahjoub S. Hyperhomocysteinaemia in Behçet's Disease. Biochem Res Int 2010; 2010: 361387
    CrossrefPubMedSearch in Google Scholar
  • 44 Hodeib AA, Elsharawy TA, Fawzi HA. Assessment of serum homocysteine, endothelin-1, and nitric oxide levels in behçet's disease. Indian J Dermatol 2010; 55 (03) 215-220
    CrossrefPubMedSearch in Google Scholar
  • 45 Shahram F, Faridar A, Hamedani MG. et al. Plasma homocysteine level in patients with Behcet's disease with or without thrombosis. Arch Iran Med 2010; 13 (06) 476-481
    PubMedSearch in Google Scholar
  • 46 Messedi M, Jamoussi K, Frigui M. et al. Atherogenic lipid profile in Behçet's disease: evidence of alteration of HDL subclasses. Arch Med Res 2011; 42 (03) 211-218
    CrossrefPubMedSearch in Google Scholar
  • 47 Messedi M, Frigui M, Ben Mahfoudh K. et al. Intima-media thickness of carotid artery in patients with Behçet's disease. Arch Med Res 2011; 42 (05) 398-404
    CrossrefPubMedSearch in Google Scholar
  • 48 Aydin M, Koca C, Uysal S. et al. Serum nitric oxide, asymmetric dimethylarginine, and plasma homocysteine levels in active Behçet's disease. Turk J Med Sci 2012; 42 (Suppl. 01) 1194-1199
    PubMedSearch in Google Scholar
  • 49 Messedi M, Frigui M, Chaabouni Kh. et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and variations of homocysteine concentrations in patients with Behcet's disease. Gene 2013; 527 (01) 306-310
    CrossrefPubMedSearch in Google Scholar
  • 50 Allam A, Ammar H, Radwan A. Serum homocysteine level and eye involvement in Egyptian patients with Behcet's disease. Egypt Rheumatol 2014; 36: 29-34
    CrossrefPubMedSearch in Google Scholar
  • 51 Ozuguz P, Karabulut AA, Tulmac M, Kisa U, Kocak M, Gunduz O. Markers of endothelial dysfunction and evaluation of vascular reactivity tests in Behçet disease. Angiology 2014; 65 (10) 937-943
    CrossrefPubMedSearch in Google Scholar
  • 52 Shadmanfar S, Shahram F, Nadji A. et al. The relationship between plasma homocysteine level and HLA-B51 in patients with Behcet's disease: a case-control study. Int J Rheum Dis 2014; 17 (04) 466-470
    CrossrefPubMedSearch in Google Scholar
  • 53 Vayá A, Rivera L, Todolí J, Hernandez JL, Laiz B, Ricart JM. Haematological, biochemical and inflammatory parameters in inactive Behçet's disease. Its association with red blood cell distribution width. Clin Hemorheol Microcirc 2014; 56 (04) 319-324
    CrossrefPubMedSearch in Google Scholar
  • 54 Elbay AE, Topalkara A, Elbay A, Erdoğan H, Vural A, Bahadır Çetin A. Evaluation of serum homocysteine and leptin levels in patients with uveitis. Turk J Ophthalmol 2015; 45 (04) 146-151
    CrossrefPubMedSearch in Google Scholar
  • 55 Bahsi M, Ilhan N, Cicek D. Homocysteine metabolism and haemostatic factor in Behcet's disease. Pharm Chem J 2017; 4: 72-79
    PubMedSearch in Google Scholar
  • 56 Bitik B, Tufan A, Elbeg Ş. et al. Serum vitamin B12, homocysteine and methylmalonic acid levels in patients with parenchymal neuro-Behçet's syndrome. Arch Rheumatol 2017; 32 (02) 118-122
    CrossrefPubMedSearch in Google Scholar
  • 57 Kuo YS, Chang JY, Wang YP, Wu YC, Wu YH, Sun A. Significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in patients with Behcet's disease. J Formos Med Assoc 2018; 117 (10) 932-938
    CrossrefPubMedSearch in Google Scholar
  • 58 Mostafa HA, Ahmed AR, Elsammak AA. et al. Role of serum homocysteine and venous doppler ultrasonography in venous insufficiency in Behcet's disease at Zagazig University Hospitals. Zagazig Univ Med J 2019; 25: 54-70
    PubMedSearch in Google Scholar
  • 59 Ozdemir R, Yagmur J, Acikgoz N. et al. Relationship between serum homocysteine levels and structural-functional carotid arterial abnormalities in inactive Behçet's disease. Kardiol Pol 2018; 76 (02) 413-417
    CrossrefPubMedSearch in Google Scholar
  • 60 Çalık AN, Özcan KS, Mesci B. et al. The association of inflammatory markers and echocardiographic parameters in Behçet's disease. Acta Cardiol 2020; 75 (02) 130-137
    CrossrefPubMedSearch in Google Scholar
  • 61 El-Najjar AR, Elsammak AA. Association between serum homocysteine and arterial stiffness in patients with Behçet's disease. Egypt Rheumatol 2020; 42: 129-133
    CrossrefPubMedSearch in Google Scholar
  • 62 Yücel Ç, Omma A, Sertoğlu E, Sezer S, Turhan T, Özgürtaş T. Evaluation of atherogenic laboratory markers in Behçet's disease patients with vascular involvement. Arch Med Sci 2019; 16 (03) 531-537
    CrossrefPubMedSearch in Google Scholar
  • 63 Leiba M, Seligsohn U, Sidi Y. et al. Thrombophilic factors are not the leading cause of thrombosis in Behçet's disease. Ann Rheum Dis 2004; 63 (11) 1445-1449
    CrossrefPubMedSearch in Google Scholar
  • 64 Nazarinia MA, Aflaki E, Habibaghahl Z. et al. Serum homocysteine level and vascular thrombosis in patients with Behcet's disease. J Rheumatol 2007; 10: 178-181
    PubMedSearch in Google Scholar
  • 65 Aflaki E, Mehryar M, Nazarinia MA, Habibagahi Z, Rajaee A, Ranjbar-Omrani G. The relation between serum homocysteine level and eye involvement in Behçet's disease. Arch Iran Med 2008; 11 (06) 625-628
    PubMedSearch in Google Scholar
  • 66 Düzgün N, Duman T, Morris Y. et al. Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behçet's disease. Clin Rheumatol 2008; 27 (10) 1221-1225
    CrossrefPubMedSearch in Google Scholar
  • 67 Shao Z, Lu q, Zhao D. et al. Vascular involvements in Behçet's disease: a retrospective clinical study of 41 cases. Chinese J Rheum 2018
    PubMedSearch in Google Scholar
  • 68 Jin H, Cheng H, Chen W. et al. An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis. Am J Clin Nutr 2018; 107 (05) 817-825
    CrossrefPubMedSearch in Google Scholar
  • 69 Lv B, Chen S, Tang C, Jin H, Du J, Huang Y. Hydrogen sulfide and vascular regulation - An update. J Adv Res 2020; 27: 85-97
    CrossrefPubMedSearch in Google Scholar
  • 70 Niu W, Wang J, Qian J. et al. Allosteric control of human cystathionine β-synthase activity by a redox active disulfide bond. J Biol Chem 2018; 293 (07) 2523-2533
    CrossrefPubMedSearch in Google Scholar
  • 71 Wang H, Sun Q, Zhou Y. et al. Nitration-mediated deficiency of cystathionine β-synthase activity accelerates the progression of hyperhomocysteinemia. Free Radic Biol Med 2017; 113: 519-529
    CrossrefPubMedSearch in Google Scholar
  • 72 Rius-Pérez S, Pérez S, Torres-Cuevas I. et al. Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase. Redox Biol 2020; 28: 101324
    CrossrefPubMedSearch in Google Scholar
  • 73 Moreno ML, Escobar J, Izquierdo-Álvarez A. et al. Disulfide stress: a novel type of oxidative stress in acute pancreatitis. Free Radic Biol Med 2014; 70: 265-277
    CrossrefPubMedSearch in Google Scholar
  • 74 Sagun G, Oguz A, Mesci B. et al. Levels of F2 isoprostane in Behcet's disease: correlation with cardiometabolic risk factors. Redox Rep 2015; 20 (05) 223-227
    CrossrefPubMedSearch in Google Scholar
  • 75 Emmi G, Becatti M, Bettiol A, Hatemi G, Prisco D, Fiorillo C. Behçet's syndrome as a model of thrombo-inflammation: the role of neutrophils. Front Immunol 2019; 10: 1085
    CrossrefPubMedSearch in Google Scholar
  • 76 Bekpinar S, Kiliç N, Unlüçerçi Y, Akdag-Köse A, Azizlerli G, Ozbek-Kir Z. Evaluation of nitrosative and oxidative stress in Behçet disease. J Eur Acad Dermatol Venereol 2005; 19 (02) 167-171
    CrossrefPubMedSearch in Google Scholar
  • 77 Sharda A, Furie B. Regulatory role of thiol isomerases in thrombus formation. Expert Rev Hematol 2018; 11 (05) 437-448
    CrossrefPubMedSearch in Google Scholar
  • 78 Zucker M, Seligsohn U, Yeheskel A, Mor-Cohen R. An allosteric disulfide bond is involved in enhanced activation of factor XI by protein disulfide isomerase. J Thromb Haemost 2016; 14 (11) 2202-2211
    CrossrefPubMedSearch in Google Scholar
  • 79 Lai WK, Kan MY. Homocysteine-induced endothelial dysfunction. Ann Nutr Metab 2015; 67 (01) 1-12
    CrossrefPubMedSearch in Google Scholar
  • 80 Genoud V, Quintana PG, Gionco S, Baldessari A, Quintana I. Structural changes of fibrinogen molecule mediated by the N-homocysteinylation reaction. J Thromb Thrombolysis 2018; 45 (01) 66-76
    CrossrefPubMedSearch in Google Scholar
  • 81 Chan CYT, Cheuk BLY, Cheng SWK. Abdominal aortic aneurysm-associated MicroRNA-516a-5p regulates expressions of methylenetetrahydrofolate reductase, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1 in human abdominal aortic vascular smooth muscle cells. Ann Vasc Surg 2017; 42: 263-273
    CrossrefPubMedSearch in Google Scholar
  • 82 Ma SC, Zhang HP, Jiao Y. et al. Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol. Mol Med Rep 2018; 17 (04) 5312-5319
    PubMedSearch in Google Scholar
  • 83 Xu M, Hua Y, Qi Y, Meng G, Yang S. Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement. Exp Dermatol 2019; 28 (07) 776-785
    CrossrefPubMedSearch in Google Scholar
  • 84 Alibaz-Oner F, Ergelen R, Yıldız Y. et al. Femoral vein wall thickness measurement: a new diagnostic tool for Behçet's disease. Rheumatology (Oxford) 2021; 60 (01) 288-296
    CrossrefPubMedSearch in Google Scholar
  • 85 Merashli M, Ster IC, Ames PRJ. Subclinical atherosclerosis in Behcet's disease: a systematic review and meta-analysis. Semin Arthritis Rheum 2016; 45 (04) 502-510
    CrossrefPubMedSearch in Google Scholar
  • 86 Takır S, Semiz AT, Uydeş Doğan BS. Hydrogen sulfide is synthesized endogenously in both retinal artery and retina mostly via CSE. Exp Eye Res 2021; 204: 108443
    CrossrefPubMedSearch in Google Scholar
  • 87 Bedoui Y, Guillot X, Sélambarom J. et al. Methotrexate an old drug with new tricks. Int J Mol Sci 2019; 20 (20) 5023
    CrossrefPubMedSearch in Google Scholar
  • 88 Stroup DF, Berlin JA, Morton SC. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15) 2008-2012
    Search in Google Scholar
  • 89 Mueller M, D'Addario M, Egger M. et al. Methods to systematically review and meta-analyse observational studies: a systematic scoping review of recommendations. BMC Med Res Methodol 2018; 18 (01) 44
    CrossrefPubMedSearch in Google Scholar
  • 90 Gutierrez-Mariscal FM, Arenas-de Larriva AP, Limia-Perez L, Romero-Cabrera JL, Yubero-Serrano EM, López-Miranda J. Coenzyme Q10 supplementation for the reduction of oxidative stress: clinical implications in the treatment of chronic diseases. Int J Mol Sci 2020; 21 (21) 7870
    CrossrefPubMedSearch in Google Scholar
  • 91 Emmi G, Bettiol A, Niccolai E. et al. Butyrate-rich diets improve redox status and fibrin lysis in Behçet's syndrome. Circ Res 2021; 128 (02) 278-280
    CrossrefPubMedSearch in Google Scholar