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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
October-2016 Volume 12 Issue 4

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
October-2016 Volume 12 Issue 4

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

Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice

  • Authors:
    • Longfeng Luo
    • Tianlun Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
  • Pages: 2307-2313
    |
    Published online on: August 24, 2016
       https://doi.org/10.3892/etm.2016.3619
  • 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

Atherosclerosis, the major cause of cardiovascular disease, is accompanied by a chronic inflammatory response during the disease. Triptolide (TPL) is an active natural compound that has been demonstrated to possess anti‑inflammatory activities in various cell types. However, the effects of TPL on atherosclerosis have not yet been studied. The goal of the present study was to determine the effects of TPL on apolipoprotein E knock‑out (ApoE‑/‑) mice fed with a high‑fat diet and to analyze the changes in lipid metabolism and inflammatory cytokines to clarify the underlying molecular mechanisms. Firstly, the genotypes of ApoE‑/‑ mice and corresponding wild‑type mice were identified using polymerase chain reaction. The ApoE‑/‑ mice were randomly divided into four groups: ApoE‑/‑ model mice, and ApoE‑/‑ mice treated with 25, 50 or 100 µg/kg TPL every twice day. Wild‑type mice with the same genetic background constituted the fifth group. The mice in each group were given a high‑fat diet from week 8 after birth until week 20. Total cholesterol and total triglyceride levels were determined at 16 and 20 weeks. The results demonstrated that the levels of total cholesterol and total triglyceride in the plasma were highly increased in ApoE‑/‑ mice models, compared with those of wild‑­type mice, and the ApoE‑/‑ mice treated with TPL had decreased levels of total cholesterol and total triglyceride in plasma, which exhibited a dose‑dependent reduction as the dose of TPL increased. Moreover, the effects of TPL on the production of inflammatory cytokines in macrophages were determined by ELISA. The results demonstrated that the macrophages from ApoE‑/‑ mice produced high levels of the inflammatory cytokines tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑8. However, following treatment with TPL doses of 25, 50 and 100 µg/kg, the cytokine levels were significantly decreased in a dose‑dependent manner. Additionally, proteins associated with lipid metabolism were tested by western blotting. The results showed that the expression of anti‑ATP‑binding cassette transporter A1 in the macrophages of ApoE‑/‑ mice was increased following treatment with TPL. However, the expression levels of LXRα were not markedly changed following treatment of the mice with different doses of TPL. These results suggest that TPL inhibited the progression of atherosclerosis not only by inhibiting the chronic inflammatory response, but also by regulating lipid metabolism, which may provide new insights useful in the clinical therapy of atherosclerosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Watanabe T, Sato K, Itoh F, Iso Y, Nagashima M, Hirano T and Shichiri M: The roles of salusins in atherosclerosis and related cardiovascular diseases. J Am Soc Hypertens. 5:359–365. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Zeng Y, Song JX and Shen XC: Herbal remedies supply a novel prospect for the treatment of atherosclerosis: A review of current mechanism studies. Phytother Res. 26:159–167. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Suzuki M, Minami A, Nakanishi A, Kobayashi K, Matsuda S, Ogura Y and Kitagishi Y: Atherosclerosis and tumor suppressor molecules (review). Int J Mol Med. 34:934–940. 2014.PubMed/NCBI

4 

Hulthe J, Wikstrand J, Mattsson-Hulten L and Fagerberg B: Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58 year-old men: The atherosclerosis and insulin resistance (AIR) study. Clin Sci (Lond). 103:123–129. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Maranhão RC and Leite AC Jr: Development of anti-atherosclerosis therapy based on the inflammatory and proliferative aspects of the disease. Curr Pharm Des. 21:1196–1204. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Shing CM, Fassett RG, Peake JM and Coombes JS: Voluntary exercise decreases atherosclerosis in nephrectomised ApoE knockout mice. PloS One. 10:e01202872015. View Article : Google Scholar : PubMed/NCBI

7 

González-Gay MA, González-Juanatey C, Llorca J and Castañeda S: The influence of inflammation in the development of subclinical atherosclerosis in psoriatic arthritis: Comment on ‘Cardiovascular comorbidities in patients with psoriatic arthritis: A systematic review’ by Jamnistki etal. Ann Rheum Dis. 73:e272014. View Article : Google Scholar : PubMed/NCBI

8 

Hansson GK: Immune and inflammatory mechanisms in the development of atherosclerosis. Br Heart J. 69:(Suppl). S38–S41. 1993. View Article : Google Scholar : PubMed/NCBI

9 

Pizzi J, Silva LR, Moser D and Leite N: Relationship between subclinical atherosclerosis, blood pressure and lipid profile in obese children and adolescents: A systematic review. Arq Bras Endocrinol Metabol. 57:1–6. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Kreisberg RA and Oberman A: Clinical review 141: Lipids and atherosclerosis: Lessons learned from randomized controlled trials of lipid lowering and other relevant studies. J Clin Endocrinol Metab. 87:423–437. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Zhang L and Yang L: Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: A review of the literature. Molecules. 20:335–347. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Ross R: Atherosclerosis is an inflammatory disease. Am Heart J. 138:S419–S420. 1999. View Article : Google Scholar : PubMed/NCBI

13 

Ross R: Atherosclerosis - an inflammatory disease. N Engl J Med. 340:115–126. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Schlag B, Winkler L, Plonné D, Dürer U and Dargel R: Preparation of apoE-free rat low density lipoprotein for catabolic studies. J Lipid Res. 28:1521–1524. 1987.PubMed/NCBI

15 

Martinez-Oliván J, Arias-Moreno X, Velazquez-Campoy A, Millet O and Sancho J: LDL receptor/lipoprotein recognition: Endosomal weakening of ApoB and ApoE binding to the convex face of the LR5 repeat. FEBS J. 281:1534–1546. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Kostogrys RB, Franczyk-żarów M, Maślak E, Gajda M, Mateuszuk L, Jackson CL and Chłopicki S: Low carbohydrate, high protein diet promotes atherosclerosis in apolipoprotein E/low-density lipoprotein receptor double knockout mice (apoE/LDLR−/−). Atherosclerosis. 223:327–331. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Shimano H, Yamada N, Katsuki M, Yamamoto K, Gotoda T, Harada K, Shimada M and Yazaki Y: Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B. J Clin Invest. 90:2084–2091. 1992. View Article : Google Scholar : PubMed/NCBI

18 

Shimano H, Yamada N, Katsuki M, Shimada M, Gotoda T, Harada K, Murase T, Fukazawa C, Takaku F and Yazaki Y: Overexpression of apolipoprotein E in transgenic mice: Marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia. Proc Natl Acad Sci USA. 89:1750–1754. 1992. View Article : Google Scholar : PubMed/NCBI

19 

Dallongeville J, Lussier-Cacan S and Davignon J: Modulation of plasma triglyceride levels by apoE phenotype: A meta-analysis. J Lipid Res. 33:447–454. 1992.PubMed/NCBI

20 

Zhang SH, Reddick RL, Piedrahita JA and Maeda N: Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 258:468–471. 1992. View Article : Google Scholar : PubMed/NCBI

21 

Weingärtner O, Ulrich C, Lütjohann D, Ismail K, Schirmer SH, Vanmierlo T, Böhm M and Laufs U: Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE−/− mice. Cardiovasc Res. 90:484–492. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Sato M, Yamada Y, Matsuoka H, Nakashima S, Kamiya T, Ikeguchi M and Imaizumi K: Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level. Biosci Biotechnol Biochem. 73:1314–1317. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Gopal K, Kumar K, Nandini R, Jahan P and Kumar MJ: High fat diet containing cholesterol induce aortic aneurysm through recruitment and proliferation of circulating agranulocytes in apoE knock out mice model. J Thromb Thrombolysis. 30:154–163. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Zou Y, Du H, Yin M, Zhang L, Mao L, Xiao N, Ren G, Zhang C and Pan J: Effects of high dietary fat and cholesterol on expression of PPAR alpha, LXR alpha and their responsive genes in the liver of apoE and LDLR double deficient mice. Mol Cell Biochem. 323:195–205. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Wang X, Zhang L, Duan W, Liu B, Gong P, Ding Y and Wu X: Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model. Mol Med Rep. 10:447–452. 2014.PubMed/NCBI

26 

Chen BJ: Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk Lymphoma. 42:253–265. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Calabresi L, Gomaraschi M, Simonelli S, Bernini F and Franceschini G: HDL and atherosclerosis: Insights from inherited HDL disorders. Biochim Biophys Acta. 1851:13–18. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Rao X, Zhong J, Maiseyeu A, Gopalakrishnan B, Villamena FA, Chen LC, Harkema JR, Sun Q and Rajagopalan S: CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure. Circulation Res. 115:770–780. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Woollard KJ: Immunological aspects of atherosclerosis. Clinical Sci. 125:221–235. 2013. View Article : Google Scholar

30 

Chen JH, Wang CJ, Wang CP, Sheu JY, Lin CL and Lin HH: Hibiscus sabdariffa leaf polyphenolic extract inhibits LDL oxidation and foam cell formation involving up-regulation of LXRalpha/ABCA1 pathway. Food Chem. 141:397–406. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Wang W, Lee Y and Lee CH: Review: The physiological and computational approaches for atherosclerosis treatment. Int J Cardiol. 167:1664–1676. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Rodondi N, Auer R, de Bosset Sulzer V, Ghali WA and Cornuz J: Atherosclerosis screening by noninvasive imaging for cardiovascular prevention: A systematic review. J Gen Intern Med. 27:220–231. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Hartman J and Frishman WH: Inflammation and atherosclerosis: A review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 22:147–151. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Ziaei S and Halaby R: Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review. Avicenna J Phytomed. 6:149–164. 2016.PubMed/NCBI

35 

Hoeke G, Kooijman S, Boon MR, Rensen PC and Berbee JF: Role of brown fat in lipoprotein metabolism and atherosclerosis. Circ Res. 118:173–182. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Smith BW, Miller RJ, Wilund KR, O'Brien WD Jr and Erdman JW Jr: Effects of tomato and soy germ on lipid bioaccumulation and atherosclerosis in ApoE-/- mice. J Food Sci. 80:H1918–1925. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Lee HF, Lee TS and Kou YR: Anti-inflammatory and neuroprotective effects of triptolide on traumatic brain injury in rats. Respir Physiol Neurobiol. 182:1–8. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Han R, Rostami-Yazdi M, Gerdes S and Mrowietz U: Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases. Br J Clin Pharmacol. 74:424–436. 2012. View Article : Google Scholar : PubMed/NCBI

39 

Matta R, Wang X, Ge H, Ray W, Nelin LD and Liu Y: Triptolide induces anti-inflammatory cellular responses. Am J Transl Res. 1:267–282. 2009.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Luo L and Yang T: Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice. Exp Ther Med 12: 2307-2313, 2016.
APA
Luo, L., & Yang, T. (2016). Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice. Experimental and Therapeutic Medicine, 12, 2307-2313. https://doi.org/10.3892/etm.2016.3619
MLA
Luo, L., Yang, T."Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice". Experimental and Therapeutic Medicine 12.4 (2016): 2307-2313.
Chicago
Luo, L., Yang, T."Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice". Experimental and Therapeutic Medicine 12, no. 4 (2016): 2307-2313. https://doi.org/10.3892/etm.2016.3619
Copy and paste a formatted citation
x
Spandidos Publications style
Luo L and Yang T: Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice. Exp Ther Med 12: 2307-2313, 2016.
APA
Luo, L., & Yang, T. (2016). Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice. Experimental and Therapeutic Medicine, 12, 2307-2313. https://doi.org/10.3892/etm.2016.3619
MLA
Luo, L., Yang, T."Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice". Experimental and Therapeutic Medicine 12.4 (2016): 2307-2313.
Chicago
Luo, L., Yang, T."Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice". Experimental and Therapeutic Medicine 12, no. 4 (2016): 2307-2313. https://doi.org/10.3892/etm.2016.3619
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