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
Biomedical Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9434 Online ISSN: 2049-9442
Journal Cover
August-2021 Volume 15 Issue 2

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
August-2021 Volume 15 Issue 2

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

Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors

  • Authors:
    • Lucyna Piera
    • Jacek Szymański
    • Marlena Juszczak
    • Jacek Drobnik
  • View Affiliations / Copyright

    Affiliations: Laboratory of Connective Tissue Metabolism, Department of Pathophysiology, Medical University of Łódź, 90‑752 Łódź, Poland, Central Scientific Laboratory, Medical University of Łódź, 92‑215 Łódź, Poland, Department of Pathophysiology and Experimental Neuroendocrinology, Medical University of Łódź, 90‑752 Łódź, Poland
  • Article Number: 71
    |
    Published online on: July 5, 2021
       https://doi.org/10.3892/br.2021.1447
  • 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

Histamine is involved in the regulation of collagen metabolism during healing following a myocardial infarction; however, its effects on the intact heart tissue is unknown. The aim of the present study was to determine whether histamine may influence collagen content in cells isolated from intact heart, and to identify the histamine receptor involved in the regulation of collagen deposition. Cells were isolated from intact rat hearts and subjected to identification by flow cytometry. The effects of histamine and its receptor agonists and antagonists were investigated. The heart cells were found to be actin, desmin and vimentin positive. Histamine (used at a concentrations of 1x10‑10‑1x10‑5 M) increased collagen content within the culture and increased the expression of α1 chain of the procollagen type III gene. The H2, H3 and H4 receptor inhibitors ranitidine, ciproxifan and JNJ 7777120 blocked the effect of histamine on collagen content. All tested histamine receptor agonists, viz. 2‑pyridylethylamine dihydrochloride (H1 receptor agonist), amthamine dihydrobromide (H2 receptor agonist), imetit (H3 receptor agonist) and 4‑methylhistamine hydrochloride (H4 receptor agonist), elevated collagen content within the heart myofibroblast cultures. The cells isolated from the intact heart were identified as myofibroblasts. Thus, the results of the present study showed that histamine augmented collagen content in the heart myofibroblast culture by activation of three histamine receptors (H2, H3 and H4). The effect of the amine was also dependent on the activation of collagen type III gene expression.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Souders CA, Bowers SL and Baudino TA: Cardiac fibroblast: The renaissance cell. Circ Res. 105:1164–1176. 2009.PubMed/NCBI View Article : Google Scholar

2 

Gałdyszyńska M, Bobrowska E, Lekka M, Radwańska P, Piera L, Szymański J and Drobnik J: . The stiffness-controlled release of interleukin-6 by cardiac fibroblasts is dependent on integrin α2β1. J Cell Mol Med. 24:13853–13862. 2020.PubMed/NCBI View Article : Google Scholar

3 

Sandstedt J, Sandstedt M, Lundqvist A, Jansson M, Sopasakis VR, Jeppsson A and Hultén LM: Human cardiac fibroblasts isolated from patients with severe heart failure are immune-competent cells mediating an inflammatory response. Cytokine. 113:319–325. 2019.PubMed/NCBI View Article : Google Scholar

4 

Sandstedt M, Rotter Sopasakis V, Lundqvist A, Vukusic K, Oldfors A, Dellgren G, Sandstedt J and Hultén LM: Hypoxic cardiac fibroblasts from failing human hearts decrease cardiomyocyte beating frequency in an ALOX15 dependent manner. PLoS One. 13(e0202693)2018.PubMed/NCBI View Article : Google Scholar

5 

Bageghni SA, Hemmings KE, Zava N, Denton CP, Porter KE, Ainscough JFX, Drinkhill MJ and Turner NA: Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism. FASEB J. 32:4941–4954. 2018.PubMed/NCBI View Article : Google Scholar

6 

Cao F, Liu X, Cao X, Wang S, Fu K, Zhao Y, Shen F and Liu J: Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system. Biochem Biophys Res Commun. 491:578–586. 2017.PubMed/NCBI View Article : Google Scholar

7 

Mcgettrick HM, Ward LS, Rainger GE and Nash GB: Mesenchymal stromal cells as active regulators of lymphocyte recruitment to blood vascular endothelial cells. Methods Mol Biol. 1591:121–142. 2017.PubMed/NCBI View Article : Google Scholar

8 

Goh KY, He L, Song J, Jinno M, Rogers AJ, Sethu P, Halade GV, Rajasekaran NS, Liu X, Prabhu SD, et al: Mitoquinone ameliorates pressure overload-induced cardiac fibrosis and left ventricular dysfunction in mice. Redox Biol. 21(101100)2019.PubMed/NCBI View Article : Google Scholar

9 

Krenning G, Zeisberg EM and Kalluri R: The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol. 225:631–637. 2010.PubMed/NCBI View Article : Google Scholar

10 

Hiram R, Naud P, Xiong F, Al-U'datt D, Algalarrondo V, Sirois MG, Tanguay JF, Tardif JC and Nattel S: Right atrial mechanisms of atrial fibrillation in a rat model of right heart disease. J Am Coll Cardiol. 74:1332–1347. 2019.PubMed/NCBI View Article : Google Scholar

11 

Philip JL, Xu X, Han M, Akhter SA and Razzaque MA: Regulation of cardiac fibroblast-mediated maladaptive ventricular remodeling by β-arrestins. PLoS One. 14(e0219011)2019.PubMed/NCBI View Article : Google Scholar

12 

Porter KE and Turner NA: Cardiac fibroblasts: At the heart of myocardial remodeling. Pharmacol Ther. 123:255–278. 2009.PubMed/NCBI View Article : Google Scholar

13 

Varricchi G, Loffredo S, Borriello F, Pecoraro A, Rivellese F, Genovese A, Spadaro G and Marone G: Superantigenic activation of human cardiac mast cells. Int J Mol Sci. 20(E1828)2019.PubMed/NCBI View Article : Google Scholar

14 

Drobnik J, Karbownik-Lewińska M, Szczepanowska A, Słotwińska D, Olczak S, Jakubowski L and Dabrowski R: Regulatory influence of melatonin on collagen accumulation in the infarcted heart scar. J Pineal Res. 45:285–290. 2008.PubMed/NCBI View Article : Google Scholar

15 

Gergs U, Bernhardt G, Buchwalow IB, Edler H, Fröba J, Keller M, Kirchhefer U, Köhler F, Mißlinger N, Wache H, et al: Initial characterization of transgenic mice overexpressing human histamine H2 receptors. J Pharmacol Exp Ther. 369:129–141. 2019.PubMed/NCBI View Article : Google Scholar

16 

Kwon JS, Kim YS, Cho AS, Cho HH, Kim JS, Hong MH, Jeong HY, Kang WS, Hwang KK, Bae JW, et al: Regulation of MMP/TIMP by HUVEC transplantation attenuates ventricular remodeling in response to myocardial infarction. Life Sci. 101:15–26. 2014.PubMed/NCBI View Article : Google Scholar

17 

Chen J, Hong T, Ding S, Deng L, Abudupataer M, Zhang W, Tong M, Jia J, Gong H, Zou Y, et al: Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice. Sci Rep. 7(44007)2017.PubMed/NCBI View Article : Google Scholar

18 

Wolak M, Bojanowska E, Staszewska T, Ciosek J, Juszczak M and Drobnik J: The role of histamine in the regulation of the viability, proliferation and transforming growth factor β1 secretion of rat wound fibroblasts. Pharmacol Rep. 69:314–321. 2017.PubMed/NCBI View Article : Google Scholar

19 

Piera L, Olczak S, Kun T, Ciosek J and Drobnik J: Histamine augments collagen deposition in isolated from the myocardial infarction scar myofibroblasts culture, via H3 receptor stimulation. J Physiol Pharmacol. 70:239–247. 2019.

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

21 

Drobnik J, Słotwińska D, Olczak S, Tosik D, Pieniążek A, Matczak K, Koceva-Chyła A and Szczepanowska A: Pharmacological doses of melatonin reduce the glycosaminoglycan level within the infarcted heart scar. J Physiol Pharmacol. 62:29–35. 2011.PubMed/NCBI

22 

Drobnik J, Owczarek K, Piera L, Tosik D, Olczak S, Ciosek J and Hrabec E: Melatonin-induced augmentation of collagen deposition in cultures of fibroblasts and myofibroblasts is blocked by luzindole - a melatonin membrane receptors inhibitor. Pharmacol Rep. 65:642–649. 2013.PubMed/NCBI View Article : Google Scholar

23 

Kawasaki H, Ohama T, Hori M and Sato K: Establishment of mouse intestinal myofibroblast cell lines. World J Gastroenterol. 19:2629–2637. 2013.PubMed/NCBI View Article : Google Scholar

24 

van den Borne SW, Isobe S, Verjans JW, Petrov A, Lovhaug D, Li P, Zandbergen HR, Ni Y, Frederik P, Zhou J, et al: Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction. J Am Coll Cardiol. 52:2017–2028. 2008.PubMed/NCBI View Article : Google Scholar

25 

Olsen AL, Bloomer SA, Chan EP, Gaça MD, Georges PC, Sackey B, Uemura M, Janmey PA and Wells RG: Hepatic stellate cells require a stiff environment for myofibroblastic differentiation. Am J Physiol Gastrointest Liver Physiol. 301:G110–G118. 2011.PubMed/NCBI View Article : Google Scholar

26 

Nguyen DT, Nagarajan N and Zorlutuna P: Effect of substrate stiffness on mechanical coupling and force propagation at the infarct boundary. Biophys J. 115:1966–1980. 2018.PubMed/NCBI View Article : Google Scholar

27 

Murota H, Bae S, Hamasaki Y, Maruyama R and Katayama I: Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts. J Investig Allergol Clin Immunol. 18:245–252. 2008.PubMed/NCBI

28 

Takeda T, Goto H, Arisawa T, Hase S, Hayakawa T and Asai J: Effect of histamine on human fibroblast in vitro. Arzneimittelforschung. 47:1152–1155. 1997.PubMed/NCBI

29 

McCaffrey SL, Lim G, Bullock M, Kasparian AO, Clifton-Bligh R, Campbell WB, Widiapradja A and Levick SP: The histamine 3 receptor is expressed in the heart and its activation opposes adverse cardiac remodeling in the angiotensin II mouse model. Int J Mol Sci. 21(9757)2020.PubMed/NCBI View Article : Google Scholar

30 

Gergs U, Kirchhefer U, Bergmann F, Künstler B, Mißlinger N, Au B, Mahnkopf M, Wache H and Neumann J: Characterization of stressed transgenic mice overexpressing H2-histamine receptors in the heart. J Pharmacol Exp Ther. 374:479–488. 2020.PubMed/NCBI View Article : Google Scholar

31 

Shahid M, Tripathi T, Sobia F, Moin S, Siddiqui M and Khan RA: Histamine, histamine receptors and their role in immunomodulation: An updated systematic review. Open Immunol J. 2:9–41. 2009.PubMed/NCBI View Article : Google Scholar

32 

Wolak M, Bojanowska E, Staszewska T, Piera L, Szymański J and Drobnik J: Histamine augments collagen content via H1 receptor stimulation in cultures of myofibroblasts taken from wound granulation tissue. Mol Cell Biochem. 476:1083–1092. 2021.PubMed/NCBI View Article : Google Scholar

33 

Dabrowski R and Maśliński C: The role of histamine in wound healing. II. The effect of antagonists and agonists of histamine receptors (H1 and H2) on collagen levels in granulation tissue. Agents Actions. 11:122–124. 1981.PubMed/NCBI View Article : Google Scholar

34 

Hatamochi A, Fujiwara K and Ueki H: Effects of histamine on collagen synthesis by cultured fibroblasts derived from guinea pig skin. Arch Dermatol Res. 277:60–64. 1985.PubMed/NCBI View Article : Google Scholar

35 

Chen B and Frangogiannis NG: Chemokines in myocardial infarction. J Cardiovasc Transl Res. 14:35–52. 2021.PubMed/NCBI View Article : Google Scholar

36 

Pinheiro AR, Paramos-de-Carvalho D, Certal M, Costa MA, Costa C, Magalhães-Cardoso MT, Ferreirinha F, Sévigny J and Correia-de-Sá P: Histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to Ca2+ mobilization and cell proliferation. J Biol Chem. 288:27571–27583. 2013.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Piera L, Szymański J, Juszczak M and Drobnik J: Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors. Biomed Rep 15: 71, 2021.
APA
Piera, L., Szymański, J., Juszczak, M., & Drobnik, J. (2021). Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors. Biomedical Reports, 15, 71. https://doi.org/10.3892/br.2021.1447
MLA
Piera, L., Szymański, J., Juszczak, M., Drobnik, J."Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors". Biomedical Reports 15.2 (2021): 71.
Chicago
Piera, L., Szymański, J., Juszczak, M., Drobnik, J."Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors". Biomedical Reports 15, no. 2 (2021): 71. https://doi.org/10.3892/br.2021.1447
Copy and paste a formatted citation
x
Spandidos Publications style
Piera L, Szymański J, Juszczak M and Drobnik J: Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors. Biomed Rep 15: 71, 2021.
APA
Piera, L., Szymański, J., Juszczak, M., & Drobnik, J. (2021). Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors. Biomedical Reports, 15, 71. https://doi.org/10.3892/br.2021.1447
MLA
Piera, L., Szymański, J., Juszczak, M., Drobnik, J."Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors". Biomedical Reports 15.2 (2021): 71.
Chicago
Piera, L., Szymański, J., Juszczak, M., Drobnik, J."Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H<sub>2</sub>, H<sub>3</sub> and H<sub>4</sub> histamine receptors". Biomedical Reports 15, no. 2 (2021): 71. https://doi.org/10.3892/br.2021.1447
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