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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
2014-January Volume 33 Issue 1

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
2014-January Volume 33 Issue 1

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

The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats

  • Authors:
    • Min-Chao Li
    • Gang Yang
    • Xiang-Dong Zhou
    • Sergey Tselluyko
    • Juliy M. Perelman
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China, Department of Neurosurgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China, Department of Histology, Amur State Medical Academy, Blagoveshchensk 675000, Russia, Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveshchensk 675000, Russia
  • Pages: 83-90
    |
    Published online on: October 23, 2013
       https://doi.org/10.3892/ijmm.2013.1535
  • 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

In a recent study, we demonstrated that transient receptor potential melastatin 8 (TRPM8), a calcium-permeable cation channel that is activated by cold temperatures, is localized in the bronchial epithelium and is upregulated in subjects with chronic obstructive pulmonary disease, which causes them to be more sensitive to cold air. In the present study, we found that exposure to cold temperatures induced ciliary ultrastructural anomalies and mucus accumulation on the epithelial surface. Male Sprague-Dawley rats were exposed to cold temperatures to determine the effects of cold air on ultrastructural changes in cilia and the airway epithelial surface. The rats were also exposed to cigarette smoke and/or cold temperatures to determine the effects of smoke and cold air on TRPM8 expression and the role of cold air in cigarette smoke-induced mucus hypersecretion. Following real-time RT-PCR and western blot analysis, we observed a high expression of TRPM8 mRNA and protein in the bronchial tissue following cigarette smoke inhalation. As shown by ELISA, concurrent cold air enhanced the levels of mucin 5AC (MUC5AC) protein, as well as those of inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-8] that were induced by cigarette smoke inhalation to a greater extent than stimulation with separate stimuli (cold air and cigarette smoke separately). The results suggest that cold air stimuli are responsible for the ultrastructural abnormalities of bronchial cilia, which contribute to abnormal mucus clearance. In addition, cold air synergistically amplifies cigarette smoke-induced mucus hypersecretion and the production of inflammatory factors through the elevated expression of the TRPM8 channel that is initiated by cigarette smoke inhalation.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Davis MS, Malayer JR, Vandeventer L, Royer CM, McKenzie EC and Williamson KK: Cold weather exercise and airway cytokine expression. J Appl Physiol. 98:2132–2136. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Koskela HO: Cold air-provoked respiratory symptoms: the mechanisms and management. Int J Circumpolar Health. 66:91–100. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Larsson K, Tornling G, Gavhed D, Muller-Suur C and Palmberg L: Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects. Eur Respir J. 12:825–830. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Giesbrecht GG: The respiratory system in a cold environment. Aviat Space Environ Med. 66:890–902. 1995.PubMed/NCBI

5 

Donaldson GC, Seemungal T, Jeffries DJ and Wedzicha JA: Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease. Eur Respir J. 13:844–849. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Sabnis AS, Shadid M, Yost GS and Reilly CA: Human lung epithelial cells express a functional cold-sensing TRPM8 variant. Am J Respir Cell Mol Biol. 39:466–474. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Montell C: The TRP superfamily of cation channels. Sci STKE. 2005:re32005.PubMed/NCBI

8 

Song MY and Yuan JX: Introduction to TRP channels: structure, function, and regulation. Adv Exp Med Biol. 661:99–108. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Peier AM, Moqrich A, Hergarden AC, et al: A TRP channel that senses cold stimuli and menthol. Cell. 108:705–715. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ and Corey DP: TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron. 50:277–289. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Karashima Y, Talavera K, Everaerts W, et al: TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci USA. 106:1273–1278. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Colburn RW, Lubin ML, Stone DJ Jr, et al: Attenuated cold sensitivity in TRPM8 null mice. Neuron. 54:379–386. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Huang J, Zhang X and McNaughton PA: Modulation of temperature-sensitive TRP channels. Semin Cell Dev Biol. 17:638–645. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Nealen ML, Gold MS, Thut PD and Caterina MJ: TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J Neurophysiol. 90:515–520. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Van Haute C, De Ridder D and Nilius B: TRP channels in human prostate. Scientific World Journal. 10:1597–1611. 2010.

16 

Li Q, Wang X, Yang Z, Wang B and Li S: Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24. Oncology. 77:335–341. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Yang XR, Lin MJ, McIntosh LS and Sham JS: Functional expression of transient receptor potential melastatin- (TRPM) and vanilloid-related (TRPV) channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol. 290:L1267–L1276. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Voets T, Owsianik G and Nilius B: TRPM8. Handb Exp Pharmacol. 179:329–344. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Mälkiä A, Madrid R, Meseguer V, de la Peña E, Valero M, Belmonte C and Viana F: Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors. J Physiol. 581:155–174. 2007.PubMed/NCBI

20 

Li M, Li Q, Yang G, Kolosov VP, Perelman JM and Zhou XD: Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism. J Allergy Clin Immunol. 128:626–634. 2011. View Article : Google Scholar

21 

Laniado-Laborín R: Smoking and chronic obstructive pulmonary disease (COPD). Parallel epidemics of the 21 century. Int J Environ Res Public Health. 6:209–224. 2009.PubMed/NCBI

22 

Taylor JD: COPD and the response of the lung to tobacco smoke exposure. Pulm Pharmacol Ther. 23:376–383. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Voynow JA, Gendler SJ and Rose MC: Regulation of mucin genes in chronic inflammatory airway diseases. Am J Respir Cell Mol Biol. 34:661–665. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Rogers DF: Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir Care. 52:1134–1146. 2007.PubMed/NCBI

25 

Wang IJ, Wu CY and Hu FR: Effect of proinflammatory cytokines on the human MUC5AC promoter activity in vitro and in vivo. Clin Ophthalmol. 1:71–77. 2007.PubMed/NCBI

26 

Bautista MV, Chen Y, Ivanova VS, Rahimi MK, Watson AM and Rose MC: IL-8 regulates mucin gene expression at the posttranscriptional level in lung epithelial cells. J Immunol. 183:2159–2166. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Davis MS, Lockard AJ, Marlin DJ and Freed AN: Airway cooling and mucosal injury during cold weather exercise. Equine Vet J Suppl. 34:413–416. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Houtmeyers E, Gosselink R, Gayan-Ramirez G and Decramer M: Regulation of mucociliary clearance in health and disease. Eur Respir J. 13:1177–1188. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Armengot M, Milara J, Mata M, Carda C and Cortijo J: Cilia motility and structure in primary and secondary ciliary dyskinesia. Am J Rhinol Allergy. 24:175–180. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Smith CM, Hirst RA, Bankart MJ, Jones DW, Easton AJ, Andrew PW and O’Callaghan C: Cooling of cilia allows functional analysis of the beat pattern for diagnostic testing. Chest. 140:186–190. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Calderón-Garcidueñas L, Valencia-Salazar G, Rodríguez-Alcaraz A, et al: Ultrastructural nasal pathology in children chronically and sequentially exposed to air pollutants. Am J Respir Cell Mol Biol. 24:132–138. 2001.PubMed/NCBI

32 

Abe J, Hosokawa H, Sawada Y, Matsumura K and Kobayashi S: Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8. Neurosci Lett. 397:140–144. 2006.

33 

Daniels RL, Takashima Y and McKemy DD: Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate. J Biol Chem. 284:1570–1582. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Baroody FM: Mucociliary transport in chronic rhinosinusitis. Clin Allergy Immunol. 20:103–119. 2007.

35 

Kim YM, Lee CH, Won TB, Kim SW, Kim JW, Rhee CS and Min YG: Functional recovery of rabbit maxillary sinus mucosa in two different experimental injury models. Laryngoscope. 118:541–545. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Sabnis AS, Reilly CA, Veranth JM and Yost GS: Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures. Am J Physiol Lung Cell Mol Physiol. 295:L194–L200. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Arnson Y, Shoenfeld Y and Amital H: Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun. 34:J258–J265. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Adcock IM, Caramori G and Barnes PJ: Chronic obstructive pulmonary disease and lung cancer: new molecular insights. Respiration. 81:265–284. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Mulligan RM, Atkinson C, Vertegel AA, Reukov V and Schlosser RJ: Cigarette smoke extract stimulates interleukin-8 production in human airway epithelium and is attenuated by superoxide dismutase in vitro. Am J Rhinol Allergy. 23:e1–e4. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Li YT, He B and Wang YZ: Exposure to cigarette smoke upregulates AP-1 activity and induces TNF-alpha overexpression in mouse lungs. Inhal Toxicol. 21:641–647. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Takeyama K, Jung B, Shim JJ, et al: Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol. 280:L165–L172. 2001.PubMed/NCBI

42 

Baginski TK, Dabbagh K, Satjawatcharaphong C and Swinney DC: Cigarette smoke synergistically enhances respiratory mucin induction by proinflammatory stimuli. Am J Respir Cell Mol Biol. 35:165–174. 2006. View Article : Google Scholar : PubMed/NCBI

43 

Innes AL, Woodruff PG, Ferrando RE, Donnelly S, Dolganov GM, Lazarus SC and Fahy JV: Epithelial mucin stores are increased in the large airways of smokers with airflow obstruction. Chest. 130:1102–1108. 2006. View Article : Google Scholar : PubMed/NCBI

44 

Haswell LE, Hewitt K, Thorne D, Richter A and Gaça MD: Cigarette smoke total particulate matter increases mucous secreting cell numbers in vitro: a potential model of goblet cell hyperplasia. Toxicol In Vitro. 24:981–987. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li M, Yang G, Zhou X, Tselluyko S and Perelman JM: The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats. Int J Mol Med 33: 83-90, 2014.
APA
Li, M., Yang, G., Zhou, X., Tselluyko, S., & Perelman, J.M. (2014). The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats. International Journal of Molecular Medicine, 33, 83-90. https://doi.org/10.3892/ijmm.2013.1535
MLA
Li, M., Yang, G., Zhou, X., Tselluyko, S., Perelman, J. M."The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats". International Journal of Molecular Medicine 33.1 (2014): 83-90.
Chicago
Li, M., Yang, G., Zhou, X., Tselluyko, S., Perelman, J. M."The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats". International Journal of Molecular Medicine 33, no. 1 (2014): 83-90. https://doi.org/10.3892/ijmm.2013.1535
Copy and paste a formatted citation
x
Spandidos Publications style
Li M, Yang G, Zhou X, Tselluyko S and Perelman JM: The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats. Int J Mol Med 33: 83-90, 2014.
APA
Li, M., Yang, G., Zhou, X., Tselluyko, S., & Perelman, J.M. (2014). The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats. International Journal of Molecular Medicine, 33, 83-90. https://doi.org/10.3892/ijmm.2013.1535
MLA
Li, M., Yang, G., Zhou, X., Tselluyko, S., Perelman, J. M."The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats". International Journal of Molecular Medicine 33.1 (2014): 83-90.
Chicago
Li, M., Yang, G., Zhou, X., Tselluyko, S., Perelman, J. M."The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats". International Journal of Molecular Medicine 33, no. 1 (2014): 83-90. https://doi.org/10.3892/ijmm.2013.1535
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