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
November-2021 Volume 24 Issue 5

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
November-2021 Volume 24 Issue 5

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

  • Authors:
    • Weidang Xie
    • Wei Huang
    • Shumin Cai
    • Hui Chen
    • Weijun Fu
    • Zhongqing Chen
    • Yanan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
    Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 814
    |
    Published online on: September 22, 2021
       https://doi.org/10.3892/mmr.2021.12454
  • 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 results of a previous study demonstrated that heat stress (HS) triggered oxidative stress, which in turn induced the apoptosis of epithelial cells. These results uncovered a novel mechanism underlying the activation of NF‑κB in primary human umbilical vein endothelial cells. The present study aimed to further investigate the role of NF‑κB/IκBα signaling pathways in the inhibition of HS‑induced reactive oxygen species (ROS) generation and cytotoxicity in endothelial cells. The results of the present study demonstrated that HS triggered a significant amount of NF‑κB and IκBα nuclear translocation without IκBα degradation in a time‑dependent manner. Mutant constructs of IκBα phosphorylation sites (Ser32, Ser36) were employed in rat pulmonary microvascular endothelial cells (PMVECs). Cell Counting Kit‑8 assays demonstrated that both the small interfering (si)RNA‑mediated knockdown of p65 and IκBα mutant constructs significantly decreased cell viability and aggravated ROS accumulation in HS‑induced rat PMVECs compared with the control. Additionally, western blot analysis revealed that p65 siRNA attenuated the protein expression of IκBα. However, IκBα mutant constructs failed to attenuate NF‑κB activation and nuclear translocation, indicating that IκBα‑independent pathways contributed to NF‑κB activity and nucleus translocation in a time‑dependent manner following HS. Collectively, the results of the present study suggested that the NF‑κB/IκBα pathway was essential for resistance to HS‑induced ROS production and cytotoxicity in rat PMVECs, and that it could be a potential therapeutic target to reduce the mortality and morbidity of heat stroke.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Bouchama A and Knochel JP: Heat stroke. N Engl J Med. 346:1978–1988. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Lin C-H, Tsai C-C, Chen T-H, Chang C-P and Yang H-H: Oxytocin maintains lung histological and functional integrity to confer protection in heat stroke. Sci Rep. 9:183902019. View Article : Google Scholar : PubMed/NCBI

3 

Yang Y, Li C, Liu N, Wang M, Zhou X, Kim IH and Wu Z: Ursolic acid alleviates heat stress-induced lung injury by regulating endoplasmic reticulum stress signaling in mice. J Nutr Biochem. 89:1085572021. View Article : Google Scholar : PubMed/NCBI

4 

Li L, Tan H, Gu Z, Liu Z, Geng Y, Liu Y, Tong H, Tang Y, Qiu J and Su L: Heat stress induces apoptosis through a Ca2+-mediated mitochondrial apoptotic pathway in human umbilical vein endothelial cells. PLoS One. 9:e1110832014. View Article : Google Scholar : PubMed/NCBI

5 

Rodriguez-Fernandez M, Grosman B, Yuraszeck TM, Helwig BG, Leon LR and Doyle FJ III: Modeling the intra- and extracellular cytokine signaling pathway under heat stroke in the liver. PLoS One. 8:e733932013. View Article : Google Scholar : PubMed/NCBI

6 

Zhang L, Li Y, Xing D and Gao C: Characterization of mitochondrial dynamics and subcellular localization of ROS reveal that HsfA2 alleviates oxidative damage caused by heat stress in Arabidopsis. J Exp Bot. 60:2073–2091. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Das M, Solanki A, Ganesh A and Thakore S: Emerging hybrid biomaterials for oxidative stress induced photodynamic therapy. Photodiagnosis Photodyn Ther. 34:1022592021. View Article : Google Scholar : PubMed/NCBI

8 

Sharma A, Tewari D, Nabavi SF, Nabavi SM and Habtemariam S: Reactive oxygen species modulators in pulmonary medicine. Curr Opin Pharmacol. 57:157–164. 2021. View Article : Google Scholar : PubMed/NCBI

9 

Liu Y, Zhou G, Wang Z, Guo X, Xu Q, Huang Q and Su L: NF-κB signaling is essential for resistance to heat stress-induced early stage apoptosis in human umbilical vein endothelial cells. Sci Rep. 5:135472015. View Article : Google Scholar : PubMed/NCBI

10 

Kostyuk SV, Porokhovnik LN, Ershova ES, Malinovskaya EM, Konkova MS, Kameneva LV, Dolgikh OA, Veiko VP, Pisarev VM, Martynov AV, et al: Changes of KEAP1/NRF2 and IKB/NF-κB Expression Levels Induced by Cell-Free DNA in Different Cell Types. Oxid Med Cell Longev. 2018:10524132018. View Article : Google Scholar : PubMed/NCBI

11 

Lalle G, Twardowski J and Grinberg-Bleyer Y: NF-κB in Cancer Immunity: Friend or Foe? Cells. 10:3552021. View Article : Google Scholar : PubMed/NCBI

12 

Zhao H, Wang Y, Liu Y, Yin K, Wang D, Li B, Yu H and Xing M: ROS-Induced Hepatotoxicity under Cypermethrin: Involvement of the Crosstalk between Nrf2/Keap1 and NF-κB/iκB-α Pathways Regulated by Proteasome. Environ Sci Technol. 55:6171–6183. 2021. View Article : Google Scholar : PubMed/NCBI

13 

Shen H, Ji Y, Xiong Y, Kim H, Zhong X, Jin MG, Shah YM, Omary MB, Liu Y, Qi L, et al: Medullary thymic epithelial NF-κB-inducing kinase (NIK)/IKKα pathway shapes autoimmunity and liver and lung homeostasis in mice. Proc Natl Acad Sci USA. 116:19090–19097. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Shen J, Cheng J, Zhu S, Zhao J, Ye Q, Xu Y, Dong H and Zheng X: Regulating effect of baicalin on IKK/IKB/NF-κB signaling pathway and apoptosis-related proteins in rats with ulcerative colitis. Int Immunopharmacol. 73:193–200. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Liang W-J, Yang H-W, Liu H-N, Qian W and Chen X-L: HMGB1 upregulates NF-κB by inhibiting IKB-α and associates with diabetic retinopathy. Life Sci. 241:1171462020. View Article : Google Scholar : PubMed/NCBI

16 

Nelson DE, Ihekwaba AE, Elliott M, Johnson JR, Gibney CA, Foreman BE, Nelson G, See V, Horton CA, Spiller DG, et al: Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science. 306:704–708. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Amaro-Leal Â, Shvachiy L, Pinto R, Geraldes V, Rocha I and Mota-Filipe H: Therapeutic effects of IkB kinase inhibitor during systemic inflammation. Int Immunopharmacol. 84:1065092020. View Article : Google Scholar : PubMed/NCBI

18 

Fordjour FA, Asiedu E, Larbi A and Kwarteng A: The role of nuclear factor kappa B (NF-κB) in filarial pathology. J Cell Commun Signal. 15:185–193. 2021. View Article : Google Scholar : PubMed/NCBI

19 

Huang W, Xie W, Gong J, Wang W, Cai S, Huang Q, Chen Z and Liu Y: Heat stress induces RIP1/RIP3-dependent necroptosis through the MAPK, NF-κB, and c-Jun signaling pathways in pulmonary vascular endothelial cells. Biochem Biophys Res Commun. 528:206–212. 2020. View Article : Google Scholar : PubMed/NCBI

20 

Zhang H, Ji J, Liu Q and Xu S: MUC1 downregulation promotes TNF-α-induced necroptosis in human bronchial epithelial cells via regulation of the RIPK1/RIPK3 pathway. J Cell Physiol. 234:15080–15088. 2019. View Article : Google Scholar : PubMed/NCBI

21 

Li L, Tan H, Zou Z, Gong J, Zhou J, Peng N, Su L, Maegele M, Cai D and Gu Z: Preventing necroptosis by scavenging ROS production alleviates heat stress-induced intestinal injury. Int J Hyperthermia. 37:517–530. 2020. View Article : Google Scholar : PubMed/NCBI

22 

Huang Z, Wu SQ, Liang Y, Zhou X, Chen W, Li L, Wu J, Zhuang Q, Chen C, Li J, et al: RIP1/RIP3 binding to HSV-1 ICP6 initiates necroptosis to restrict virus propagation in mice. Cell Host Microbe. 17:229–242. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Peng D, Li J, Deng Y, Zhu X, Zhao L, Zhang Y, Li Z, Ou S, Li S and Jiang Y: Sodium para-aminosalicylic acid inhibits manganese-induced NLRP3 inflammasome-dependent pyroptosis by inhibiting NF-κB pathway activation and oxidative stress. J Neuroinflammation. 17:3432020. View Article : Google Scholar : PubMed/NCBI

24 

Epstein Y and Yanovich R: Heatstroke. N Engl J Med. 380:2449–2459. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Dokladny K, Myers OB and Moseley PL: Heat shock response and autophagy - cooperation and control. Autophagy. 11:200–213. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Li L, Su Z, Zou Z, Tan H, Cai D, Su L and Gu Z: Ser46 phosphorylation of p53 is an essential event in prolyl-isomerase Pin1-mediated p53-independent apoptosis in response to heat stress. Cell Death Dis. 10:962019. View Article : Google Scholar : PubMed/NCBI

27 

Liu ZF, Zheng D, Fan GC, Peng T and Su L: Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling. Apoptosis. 21:896–904. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Gu ZT, Wang H, Li L, Liu YS, Deng XB, Huo SF, Yuan FF, Liu ZF, Tong HS and Su L: Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell. Sci Rep. 4:44692014. View Article : Google Scholar : PubMed/NCBI

29 

Yu J, Liu F, Yin P, Zhao H, Luan W, Hou X, Zhong Y, Jia D, Zan J, Ma W, et al: Involvement of oxidative stress and mitogen-activated protein kinase signaling pathways in heat stress-induced injury in the rat small intestine. Stress. 16:99–113. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Hop HT, Arayan LT, Reyes AWB, Huy TXN, Min WG, Lee HJ, Rhee MH, Chang HH and Kim S: Heat-stress-modulated induction of NF-κB leads to brucellacidal pro-inflammatory defense against Brucella abortus infection in murine macrophages and in a mouse model. BMC Microbiol. 18:442018. View Article : Google Scholar : PubMed/NCBI

31 

Rasmi RR, Sakthivel KM and Guruvayoorappan C: NF-κB inhibitors in treatment and prevention of lung cancer. Biomed Pharmacother. 1105692020. View Article : Google Scholar : PubMed/NCBI

32 

Hellweg CE: The Nuclear Factor κB pathway: A link to the immune system in the radiation response. Cancer Lett. 368:275–289. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Kawai T and Akira S: Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med. 13:460–469. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Alharbi KS, Fuloria NK, Fuloria S, Rahman SB, Al-Malki WH, Javed Shaikh MA, Thangavelu L, Singh SK, Rama Raju Allam VS, Jha NK, et al: Nuclear factor-kappa B and its role in inflammatory lung disease. Chem Biol Interact. 345:1095682021. View Article : Google Scholar : PubMed/NCBI

35 

Cai J, Guan H, Jiao X, Yang J, Chen X, Zhang H, Zheng Y, Zhu Y, Liu Q and Zhang Z: NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1β/IkB-α-NF-κB-NLRP3 feedback loop in swine. Toxicology. 453:1527202021. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xie W, Huang W, Cai S, Chen H, Fu W, Chen Z and Liu Y: NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells. Mol Med Rep 24: 814, 2021.
APA
Xie, W., Huang, W., Cai, S., Chen, H., Fu, W., Chen, Z., & Liu, Y. (2021). NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells. Molecular Medicine Reports, 24, 814. https://doi.org/10.3892/mmr.2021.12454
MLA
Xie, W., Huang, W., Cai, S., Chen, H., Fu, W., Chen, Z., Liu, Y."NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells". Molecular Medicine Reports 24.5 (2021): 814.
Chicago
Xie, W., Huang, W., Cai, S., Chen, H., Fu, W., Chen, Z., Liu, Y."NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells". Molecular Medicine Reports 24, no. 5 (2021): 814. https://doi.org/10.3892/mmr.2021.12454
Copy and paste a formatted citation
x
Spandidos Publications style
Xie W, Huang W, Cai S, Chen H, Fu W, Chen Z and Liu Y: NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells. Mol Med Rep 24: 814, 2021.
APA
Xie, W., Huang, W., Cai, S., Chen, H., Fu, W., Chen, Z., & Liu, Y. (2021). NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells. Molecular Medicine Reports, 24, 814. https://doi.org/10.3892/mmr.2021.12454
MLA
Xie, W., Huang, W., Cai, S., Chen, H., Fu, W., Chen, Z., Liu, Y."NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells". Molecular Medicine Reports 24.5 (2021): 814.
Chicago
Xie, W., Huang, W., Cai, S., Chen, H., Fu, W., Chen, Z., Liu, Y."NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells". Molecular Medicine Reports 24, no. 5 (2021): 814. https://doi.org/10.3892/mmr.2021.12454
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