Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2017 Volume 15 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 15 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling

  • Authors:
    • Jingmiao Liu
    • Da Chen
    • Xiaowei Liu
    • Zhi Liu
  • View Affiliations / Copyright

    Affiliations: Department of Emergency Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 3739-3746
    |
    Published online on: March 31, 2017
       https://doi.org/10.3892/mmr.2017.6421
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to investigate whether cyclosporine A (CSA) improved cardiac dysfunction at an early stage of sepsis. Male Wistar rats were randomly divided into the following three groups: the sham‑operated control group, the cecal ligation puncture (CLP) procedure‑induced sepsis group and the CSA intervention group. Cecal ligation was performed to generate a sepsis model. At different time points (2, 6, 12, 24 and 72 h) following sepsis induction, blood pressure, cardiac function, and non‑esterified free fatty acid (NEFA) levels in the plasma and myocardia were measured, and the expression levels of components associated with the AMP‑activated protein kinase (AMPK)‑acetyl CoA carboxylase (ACC)‑carnitine palmitoyl transferase 1 (CPT1) signaling pathway were compared among the three groups. Sepsis induced a decrease in blood pressure and cardiac function at 24 h following sepsis induction in the CLP group, and CSA treatment ameliorated these pathophysiological alterations. In addition, rats in the CLP group exhibited significant increases in calcineurin activity and NEFA accumulation in the heart when compared with those in the sham group. These effects were attenuated by CSA treatment. Mechanistically, the activity of the AMPK‑ACC‑CPT1 pathway was enhanced by CSA treatment. The present study revealed that CSA treatment increases cardiac function at an early stage of sepsis in rats. This treatment partially suppresses calcineurin activity while activating the AMPK‑TCC‑CPT1 pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C and Remick DG: Sepsis: Multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 93:1247–1288. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al: The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 315:801–810. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Park HG, Yi H, Kim SH, Yu HS, Ahn YM, Lee YH, Roh MS and Kim YS: The effect of cyclosporine A on the phosphorylation of the AMPK pathway in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 35:1933–1937. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Parrillo JE: The cardiovascular pathophysiology of sepsis. Annu Rev Med. 40:469–485. 1989. View Article : Google Scholar : PubMed/NCBI

5 

dos Santos CC, Gattas DJ, Tsoporis JN, Smeding L, Kabir G, Masoom H, Akram A, Plotz F, Slutsky AS, Husain M, et al: Sepsis-induced myocardial depression is associated with transcriptional changes in energy metabolism and contractile related genes: A physiological and gene expression-based approach. Crit Care Med. 38:894–902. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Remick DG: Pathophysiology of sepsis. Am J Pathol. 170:1435–1444. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Bueno OF, Van Rooij E, Molkentin JD, Doevendans PA and De Windt LJ: Calcineurin and hypertrophic heart disease: Novel insights and remaining questions. Cardiovasc Res. 53:806–821. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR and Olson EN: A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 93:215–228. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Berry JM, Le V, Rotter D, Battiprolu PK, Grinsfelder B, Tannous P, Burchfield JS, Czubryt M, Backs J, Olson EN, et al: Reversibility of adverse, calcineurin-dependent cardiac remodeling. Circ Res. 109:407–417. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Sussman MA, Lim HW, Gude N, Taigen T, Olson EN, Robbins J, Colbert MC, Gualberto A, Wieczorek DF and Molkentin JD: Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science. 281:1690–1693. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Suzuki J, Bayna E, Li HL, Molle ED and Lew WY: Lipopolysaccharide activates calcineurin in ventricular myocytes. J Am Coll Cardiol. 49:491–499. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Larche J, Lancel S, Hassoun SM, Favory R, Decoster B, Marchetti P, Chopin C and Neviere R: Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality. J Am Coll Cardiol. 48:377–385. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Rudiger A and Singer M: Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med. 35:1599–1608. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Iwamura H, Sato M and Wakitani K: Comparative study of glucocorticoids, cyclosporine A, and JTE-607 [(−)-Ethyl-N[3,5-dichloro-2-hydroxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl]-L-phenylalaninate dihydrochloride] in a mouse septic shock model. J Pharmacol Exp Ther. 311:1256–1263. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Joshi MS, Julian MW, Huff JE, Bauer JA, Xia Y and Crouser ED: Calcineurin regulates myocardial function during acute endotoxemia. Am J Respir Crit Care Med. 173:999–1007. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Fauvel H, Marchetti P, Obert G, Joulain O, Chopin C, Formstecher P and Nevière R: Protective effects of cyclosporin A from endotoxin-induced myocardial dysfunction and apoptosis in rats. Am J Respir Crit Care Med. 165:449–455. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Zu L, He J, Jiang H, Xu C, Pu S and Xu G: Bacterial endotoxin stimulates adipose lipolysis via toll-like receptor 4 and extracellular signal-regulated kinase pathway. J Biol Chem. 284:5915–5926. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Heidrich F, Schotola H, Popov AF, Sohns C, Schuenemann J, Friedrich M, Coskun KO, von Lewinski D, Hinz J, Bauer M, et al: AMPK-activated protein kinase and its role in energy metabolism of the heart. Curr Cardiol Rev. 6:337–342. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Fillmore N and Lopaschuk GD: Targeting mitochondrial oxidative metabolism as an approach to treat heart failure. Biochim Biophys Acta. 1833:857–865. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Kiuchi S, Matsuo N, Takeyama N and Tanaka T: Accelerated hepatic lipid synthesis in fasted septic rats. Eur Surg Res. 25:146–154. 1993. View Article : Google Scholar : PubMed/NCBI

21 

Borradaile NM, Han X, Harp JD, Gale SE, Ory DS and Schaffer JE: Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res. 47:2726–2737. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Son NH, Park TS, Yamashita H, Yokoyama M, Huggins LA, Okajima K, Homma S, Szabolcs MJ, Huang LS and Goldberg IJ: Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice. J Clin Invest. 117:2791–2801. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Torac E, Gaman L and Atanasiu V: The regulator of calcineurin (RCAN1. an important factor involved in atherosclerosis and cardiovascular diseases development. J Med Life. 7:481–487. 2014.PubMed/NCBI

24 

Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Otsu K, et al: MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway. Circ Res. 116:279–288. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Ahrens T: Hemodynamics in sepsis. AACN Adv Crit Care. 17:435–445. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Merx MW and Weber C: Sepsis and the heart. Circulation. 116:793–802. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Zaky A, Deem S, Bendjelid K and Treggiari MM: Characterization of cardiac dysfunction in sepsis: An ongoing challenge. Shock. 41:12–24. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Molnar AO, Fergusson D, Tsampalieros AK, Bennett A, Fergusson N, Ramsay T and Knoll GA: Generic immunosuppression in solid organ transplantation: Systematic review and meta-analysis. BMJ. 350:h31632015. View Article : Google Scholar : PubMed/NCBI

29 

Kakihana Y, Ito T, Nakahara M, Yamaguchi K and Yasuda T: Sepsis-induced myocardial dysfunction: Pathophysiology and management. J Intensive Care. 4:222016. View Article : Google Scholar : PubMed/NCBI

30 

Stanley WC, Lopaschuk GD, Hall JL and McCormack JG: Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions. Cardiovasc Res. 33:243–257. 1997. View Article : Google Scholar : PubMed/NCBI

31 

van der Vusse GJ, Glatz JF, Stam HC and Reneman RS: Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev. 72:881–940. 1992.PubMed/NCBI

32 

Ebong IA, Goff DC Jr, Rodriguez CJ, Chen H and Bertoni AG: Mechanisms of heart failure in obesity. Obes Res Clin Pract. 8:e540–e548. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Haffar T, Bérubé-Simard FA and Bousette N: Cardiomyocyte lipotoxicity is mediated by Il-6 and causes down-regulation of PPARs. Biochem Biophys Res Commun. 459:54–59. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Srivastava RA, Pinkosky SL, Filippov S, Hanselman JC, Cramer CT and Newton RS: AMP-activated protein kinase: An emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J Lipid Res. 53:2490–2514. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Viollet B and Andreelli F: AMP-activated protein kinase and metabolic control. Handb Exp Pharmacol. 303–330. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Park TS, Hu Y, Noh HL, Drosatos K, Okajima K, Buchanan J, Tuinei J, Homma S, Jiang XC, Abel ED and Goldberg IJ: Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res. 49:2101–2112. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Borradaile NM, Buhman KK, Listenberger LL, Magee CJ, Morimoto ET, Ory DS and Schaffer JE: A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. Mol Biol Cell. 17:770–778. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Song XJ, Yang CY, Liu B, Wei Q, Korkor MT, Liu JY and Yang P: Atorvastatin inhibits myocardial cell apoptosis in a rat model with post-myocardial infarction heart failure by downregulating ER stress response. Int J Med Sci. 8:564–572. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Turner MD: Fatty acyl CoA-mediated inhibition of endoplasmic reticulum assembly. Biochim Biophys Acta. 1693:1–4. 2004. View Article : Google Scholar : PubMed/NCBI

40 

He H, Liu X, Lv L, Liang H, Leng B, Zhao D, Zhang Y, Du Z, Chen X, Li S, et al: Calcineurin suppresses AMPK-dependent cytoprotective autophagy in cardiomyocytes under oxidative stress. Cell Death Dis. 5:e9972014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu J, Chen D, Liu X and Liu Z: Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling. Mol Med Rep 15: 3739-3746, 2017.
APA
Liu, J., Chen, D., Liu, X., & Liu, Z. (2017). Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling. Molecular Medicine Reports, 15, 3739-3746. https://doi.org/10.3892/mmr.2017.6421
MLA
Liu, J., Chen, D., Liu, X., Liu, Z."Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling". Molecular Medicine Reports 15.6 (2017): 3739-3746.
Chicago
Liu, J., Chen, D., Liu, X., Liu, Z."Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling". Molecular Medicine Reports 15, no. 6 (2017): 3739-3746. https://doi.org/10.3892/mmr.2017.6421
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Chen D, Liu X and Liu Z: Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling. Mol Med Rep 15: 3739-3746, 2017.
APA
Liu, J., Chen, D., Liu, X., & Liu, Z. (2017). Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling. Molecular Medicine Reports, 15, 3739-3746. https://doi.org/10.3892/mmr.2017.6421
MLA
Liu, J., Chen, D., Liu, X., Liu, Z."Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling". Molecular Medicine Reports 15.6 (2017): 3739-3746.
Chicago
Liu, J., Chen, D., Liu, X., Liu, Z."Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling". Molecular Medicine Reports 15, no. 6 (2017): 3739-3746. https://doi.org/10.3892/mmr.2017.6421
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team