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
April-2018 Volume 17 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
April-2018 Volume 17 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 Open Access

HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy

  • Authors:
    • Yunbo Shi
    • Lingli Zhang
    • Junfang Teng
    • Wang Miao
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5125-5131
    |
    Published online on: January 25, 2018
       https://doi.org/10.3892/mmr.2018.8485
  • 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

Epilepsy is a chronic and recurrent disease of the central nervous system, with a complex pathology. Recent studies have demonstrated that the activation of glial cells serve an important role in the development of epilepsy. The objective of the present study was to investigate the role of high‑mobility group box‑1 (HMGB1) in mediating the activation of glial cells through the toll‑like receptor 4 (TLR4)/nuclear factor (NF)‑κB signaling pathway in seizure, and the underlying mechanism. The brain tissue of post‑surgery patients with intractable epilepsy after resection and the normal control brain tissue of patients with craniocerebral trauma induced intracranial hypertension were collected. The expression level and distribution pattern of HMGB1, OX42 and NF‑κB p65 were detected by immunohistochemistry. HMGB1, TLR4, receptor for advanced glycation end products (RAGE), NF‑κB p65 and inducible nitric oxide synthase (iNOS) expression levels were detected by western blotting, and serum cytokine levels of interleukin (IL)‑1, IL‑6, tumor necrosis factor (TNF)‑α, transforming growth factor (TGF)‑β and IL‑10 in patients with epilepsy and craniocerebral trauma were detected by ELISA. And cell model of epilepsy was established by coriaria lactone (CL)‑stimulated HM cell, and the same factors were measured. The potential toxic effect of HMGB1 on HM cells was evaluated by MTT and 5‑ethynyl‑2‑deoxyuridine assays. The results demonstrated that compared with the control group, levels of HMGB1, TLR4, RAGE, NF‑κB p65 and iNOS in the brain of the epilepsy group were significantly increased, and increased cytokine levels of IL‑1, IL‑6, TNF‑α, TGF‑β and IL‑10 in patients with epilepsy were also observed. At the same time, the above results were also observed in HM cells stimulated with CL. Overexpression of HMGB1 enhanced the results, while HMGB1 small interfering RNA blocked the function of CL. There was no significant toxic effect of HMGB1 on HM cells. In conclusion, overexpression of HMGB1 potentially promoted epileptogenesis. CL‑induced activation of glial cells may act via up‑regulation of HMGB1 and TLR4/RAGE receptors, and the downstream transcription factor NF‑κB.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Snoeijen-Schouwenaars FM, van Ool JS, Tan IY, Schelhaas HJ and Majoie MH: Evaluation of perampanel in patients with intellectual disability and epilepsy. Epilepsy Behav. 66:64–67. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Gavvala JR and Schuele SU: New-onset seizure in adults and adolescents: A review. JAMA. 316:2657–2668. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Pohlmann-Eden B, Aldenkamp A, Baker GA, Brandt C, Cendes F, Coras R, Crocker CE, Helmstaedter C, Jones-Gotman M, Kanner AM, et al: The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy-Current knowledge and understanding. Epilepsy Behav. 51:199–209. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Singh T and Goel RK: Managing epilepsy-associated depression: Serotonin enhancers or serotonin producers? Epilepsy Behav. 66:93–99. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Jehi LE, Palmini A, Aryal U, Coras R and Paglioli E: Cerebral cavernous malformations in the setting of focal epilepsies: Pathological findings, clinical characteristics and surgical treatment principles. Acta Neuropathol. 128:55–65. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Zubkov S and Friedman D: Epilepsy treatment and creativity. Epilepsy Behav. 57:230–233. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Prontera P, Sarchielli P, Caproni S, Bedetti C, Cupini LM, Calabresi P and Costa C: Epilepsy in hemiplegic migraine: Genetic mutations and clinical implications. Cephalalgia. 2017.(Epub ahead of print). PubMed/NCBI

8 

Wang C, Ding H, Tang X, Li Z and Gan L: Liuweibuqi capsules suppress inflammation by affecting T cell polarization and survival in chronic obstructive pulmonary disease. Med Chem Res. 26:2816–2823. 2017. View Article : Google Scholar

9 

Okuneva O, Li Z, Körber I, Tegelberg S, Joensuu T, Tian L and Lehesjoki AE: Brain inflammation is accompanied by peripheral inflammation in Cstb-/-mice, a model for progressive myoclonus epilepsy. J Neuroinflammation. 13:2982016. View Article : Google Scholar : PubMed/NCBI

10 

Benson MJ, Thomas NK, Talwar S, Hodson MP, Lynch JW, Woodruff TM and Borges K: A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models. Neurobiol Dis. 76:87–97. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Alyu F and Dikmen M: Inflammatory aspects of epileptogenesis: Contribution of molecular inflammatory mechanisms. Acta Neuropsychiatr. 29:1–16. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Dambach H, Hinkerohe D, Prochnow N, Stienen MN, Moinfar Z, Haase CG, Hufnagel A and Faustmann PM: Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co-culture model of inflammation. Epilepsia. 55:184–192. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Patterson KP, Brennan GP, Curran M, Kinney-Lang E, Dubé C, Rashid F, Ly C, Obenaus A and Baram TZ: Rapid, coordinate inflammatory responses after experimental febrile status epilepticus: Implications for epileptogenesis. eNeuro. 2:2015. View Article : Google Scholar : PubMed/NCBI

14 

von Bernhardi R, Eugenín-von Bernhardi J, Flores B and Eugenín León J: Glial cells and integrity of the nervous system. Adv Exp Med Biol. 949:1–24. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Papageorgiou IE, Fetani AF, Lewen A, Heinemann U and Kann O: Widespread activation of microglial cells in the hippocampus of chronic epileptic rats correlates only partially with neurodegeneration. Brain Struct Funct. 220:2423–2439. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Luo C, Ikegaya Y and Koyama R: Microglia and neurogenesis in the epileptic dentate gyrus. Neurogenesis (Austin). 3:e12355252016. View Article : Google Scholar : PubMed/NCBI

17 

Najjar S, Pearlman D, Miller DC and Devinsky O: Refractory epilepsy associated with microglial activation. Neurologist. 17:249–254. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Mazarati A, Maroso M, Iori V, Vezzani A and Carli M: High-mobility group box-1 impairs memory in mice through both toll-like receptor 4 and receptor for advanced glycation end products. Exp Neurol. 232:143–148. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Zhang J, Xia J, Zhang Y, Xiao F, Wang J, Gao H, Liu Y, Rong S, Yao Y, Xu G and Li J: HMGB1-TLR4 signaling participates in renal ischemia reperfusion injury and could be attenuated by dexamethasone-mediated inhibition of the ERK/NF-κB pathway. Am J Transl Res. 8:4054–4067. 2016.PubMed/NCBI

20 

Li X, Jin Q, Yao Q, Xu B, Li Z and Tu C: Quercetin attenuates the activation of hepatic stellate cells and liver fibrosis in mice through modulation of HMGB1-TLR2/4-NF-κB signaling pathways. Toxicol Lett. 261:1–12. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Zurolo E, Iyer A, Maroso M, Carbonell C, Anink JJ, Ravizza T, Fluiter K, Spliet WG, van Rijen PC, Vezzani A and Aronica E: Activation of Toll-like receptor, RAGE and HMGB1 signalling in malformations of cortical development. Brain. 134:1015–1032. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Maroso M, Balosso S, Ravizza T, Liu J, Bianchi ME and Vezzani A: Interleukin-1 type 1 receptor/Toll-like receptor signalling in epilepsy: The importance of IL-1beta and high-mobility group box 1. J Intern Med. 270:319–326. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Chen Y, Huang XJ, Yu N, Xie Y, Zhang K, Wen F, Liu H and Di Q: HMGB1 contributes to the expression of P-glycoprotein in mouse epileptic brain through toll-like receptor 4 and receptor for advanced glycation end products. PLoS One. 10:e01409182015. View Article : Google Scholar : PubMed/NCBI

24 

Ratovitski T, Chaerkady R, Kammers K, Stewart JC, Zavala A, Pletnikova O, Troncoso JC, Rudnicki DD, Margolis RL, Cole RN and Ross CA: Quantitative proteomic analysis reveals similarities between huntington's disease (HD) and huntington's disease-like 2 (HDL2) human brains. J Proteome Res. 15:3266–3283. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Smith AM, Gibbons HM, Oldfield RL, Bergin PM, Mee EW, Curtis MA, Faull RL and Dragunow M: M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia. J Neuroinflammation. 10:852013. View Article : Google Scholar : PubMed/NCBI

26 

Delahaye-Duriez A, Srivastava P, Shkura K, Langley SR, Laaniste L, Moreno-Moral A, Danis B, Mazzuferi M, Foerch P, Gazina EV, et al: Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery. Genome Biol. 17:2452016. View Article : Google Scholar : PubMed/NCBI

27 

Mameniskiene R and Wolf P: Epilepsia partialis continua: A review. Seizure. 44:74–80. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Ertürk Çetin Ö, İşler C, Uzan M and Özkara Ç: Epilepsy-related brain tumors. Seizure. 44:93–97. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Falco-Walter J, Owen C, Sharma M, Reggi C, Yu M, Stoub TR and Stein MA: Magnetoencephalography and new imaging modalities in epilepsy. Neurotherapeutics. 14:4–10. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Loscher W, Hirsch LJ and Schmidt D: The enigma of the latent period in the development of symptomatic acquired epilepsy-Traditional view versus new concepts. Epilepsy Behav. 52:78–92. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Zhang I, Alizadeh D, Liang J, Zhang L, Gao H, Song Y, Ren H, Ouyang M, Wu X, D'Apuzzo M and Badie B: Characterization of arginase expression in glioma-associated microglia and macrophages. PLoS One. 11:e01651182016. View Article : Google Scholar : PubMed/NCBI

32 

Eyo UB, Murugan M and Wu LJ: Microglia-neuron communication in epilepsy. Glia. 65:5–18. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Luan G, Gao Q, Zhai F, Chen Y and Li T: Upregulation of HMGB1, toll-like receptor and RAGE in human Rasmussen's encephalitis. Epilepsy Res. 123:36–49. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Iori V, Maroso M, Rizzi M, Iyer AM, Vertemara R, Carli M, Agresti A, Antonelli A, Bianchi ME, Aronica E, et al: Receptor for advanced glycation endproducts is upregulated in temporal lobe epilepsy and contributes to experimental seizures. Neurobiol Dis. 58:102–114. 2013. View Article : Google Scholar : PubMed/NCBI

35 

van Beijnum JR, Buurman WA and Griffioen AW: Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis. 11:91–99. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Huang Z, Zhong Z, Zhang L, Wang X, Xu R, Zhu L, Wang Z, Hu S and Zhao X: Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway. Sci Rep. 5:128072015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shi Y, Zhang L, Teng J and Miao W: HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy. Mol Med Rep 17: 5125-5131, 2018.
APA
Shi, Y., Zhang, L., Teng, J., & Miao, W. (2018). HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy. Molecular Medicine Reports, 17, 5125-5131. https://doi.org/10.3892/mmr.2018.8485
MLA
Shi, Y., Zhang, L., Teng, J., Miao, W."HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy". Molecular Medicine Reports 17.4 (2018): 5125-5131.
Chicago
Shi, Y., Zhang, L., Teng, J., Miao, W."HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy". Molecular Medicine Reports 17, no. 4 (2018): 5125-5131. https://doi.org/10.3892/mmr.2018.8485
Copy and paste a formatted citation
x
Spandidos Publications style
Shi Y, Zhang L, Teng J and Miao W: HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy. Mol Med Rep 17: 5125-5131, 2018.
APA
Shi, Y., Zhang, L., Teng, J., & Miao, W. (2018). HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy. Molecular Medicine Reports, 17, 5125-5131. https://doi.org/10.3892/mmr.2018.8485
MLA
Shi, Y., Zhang, L., Teng, J., Miao, W."HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy". Molecular Medicine Reports 17.4 (2018): 5125-5131.
Chicago
Shi, Y., Zhang, L., Teng, J., Miao, W."HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy". Molecular Medicine Reports 17, no. 4 (2018): 5125-5131. https://doi.org/10.3892/mmr.2018.8485
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