Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
February-2016 Volume 11 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
February-2016 Volume 11 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 Open Access

Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats

  • Authors:
    • Xiaojuan Gao
    • Lei Fan
    • Hua Li
    • Juan Li
    • Xiaorui Liu
    • Ranran Sun
    • Zujiang Yu
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Pharmacy, Children's Hospital of Zhengzhou City, Zhengzhou, Henan 450053, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 427-434
    |
    Published online on: December 11, 2015
       https://doi.org/10.3892/etm.2015.2931
  • 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

Hyperammonemia is considered to be central to the pathophysiology of hepatic encephalopathy in patients exhibiting hepatic failure (HF). It has previously been determined that hyperammonemia is a serious metabolic disorder commonly observed in patients with HF. However, it is unclear whether hyperammonemia has a direct adverse effect on hepatic cells or serves as a cause and effect of HF. The present study investigated whether hepatic injury is caused by hyperammonemia, and aimed to provide an insight into the causes and mechanisms of HF. Hyperammonemic rats were established via intragastric administration of ammonium chloride solution. Hepatic tissues were assessed using biochemistry, histology, immunohistochemistry, flow cytometry (FCM), semi‑quantitative reverse transcription‑polymerase chain reaction and western blot analysis. Hyperammonemic rats exhibited significantly increased levels of liver function markers, including alanine transaminase (P<0.01), aspartate aminotransferase (P<0.01), blood ammonia (P<0.01) and direct bilirubin (P<0.05), which indicated hepatic injury. A pathological assessment revealed mild hydropic degeneration, but no necrosis or inflammatory cell infiltration. However, terminal deoxynucleotidyl transferase dUTP nick end‑labeling assays confirmed a significant increase in the rate of cellular apoptosis in hyperammonemic rat livers (P<0.01). FCM analysis revealed that there were significantly more cells in the S phase and fewer in the G2/M phase (P<0.01), and the expression levels of cyclin A and D1 mRNA and proteins were significantly increased (P<0.01). In summary, cell cycle arrest, apoptosis and an alteration of cyclin A and D1 levels were all markers of hyperammonemia‑induced hepatic injury. These findings provide an insight into the potential mechanisms underlying hyperammonemia‑induced hepatic injury, and may be used as potential targets for treating or preventing hepatic damage caused by hyperammonemia, including hepatic encephalopathy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Adeva MM, Souto G, Blanco N and Donapetry C: Ammonium metabolism in humans. Metabolism. 61:1495–1511. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Wright G and Noiret L: OldeD amink SW and Jalan R: Interorgan ammonia metabolism in liver failure: The basis of current and future therapies. Liver Int. 31:163–175. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Jones EA and Mullen KD: Theories of the pathogenesis of hepatic encephalopathy. Clin Liver Dis. 16:7–26. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Lee WM: Acute liver failure. N Engl J Med. 329:1862–1872. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Blackmore L and Bernal W: Acute liver failure. Clin Med. 15:468–472. 2015. View Article : Google Scholar

6 

Butterworth RF: Hepatic encephalopathy:. A central neuroinflammatory disorder? Hepatology. 53:1372–1376. 2011.PubMed/NCBI

7 

Trautwein C and Koch A: Mechanisms of acute liver failure. Liver Immunology. Gershwin MR, Vierling J and Manns MP: (2nd). (New York, NY). Springer International Publishing. 373–388. 2014. View Article : Google Scholar

8 

Mouli Pratap V, Benjamin J, Singh Bhushan M, Mani K, Garg SK, Saraya A and Joshi YK: Effect of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy, A non-inferiority randomized controlled trial. Hepatol Res. 45:880–889. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Jover-Cobos M, Khetan V and Jalan R: Treatment of hyperammonemia in liver failure. Curr Opin Clin Nutr Metab Care. 17:105–110. 2014.PubMed/NCBI

10 

Lange CM, Bojunga J, Hofmann WP, Wunder K, Mihm U, Zeuzem S and Sarrazin C: Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function. Hepatology. 50:2001–2006. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Fuhrmann V, Drolz A, Jaeger B, Wewalka M, Saxa R, Horvatits T, Perkmann T, Zauner C and Ferenci P: Prognostic relevance of arterial ammonia levels in different acute and acute-on-chronic liver diseases. Crit Care. 16(Suppl 1): P3902012. View Article : Google Scholar

12 

Liu CP and Yu ZJ: Study on L-Ornithine-L-Aspartate in the treatment of acute-on-chronic liver failure. Zhonghua Gan Zang Bing Za Zhi. 19:63–64. 2011.(In Chinese). PubMed/NCBI

13 

Schmid M, Peck-Radosavljevic M, König F, Mittermaier C, Gangl A and Ferenci P: A double-blind, randomized, placebo-controlled trial of intravenous L-ornithine-L-aspartate on postural control in patients with cirrhosis. Liver Int. 30:574–582. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Yu ZJ, Sun R, Liu XR, Yan JY, Gao XJ and Kan QC: Hyperammonemia-induced hepatic injury in rats, Characterization of a new animal model. Zhonghua Gan Zang Bing Za Zhi. 21:467–472. 2013.(In Chinese). PubMed/NCBI

15 

Li J, Yu Z, Wang Q, Li D, Jia B, Zhou Y, Ye Y, Shen S, Wang Y, Li S, et al: Hyperammonia induces specific liver injury through an intrinsic Ca2+-independent apoptosis pathway. BMC Gastroenterol. 14:1512014. View Article : Google Scholar : PubMed/NCBI

16 

Zhu Q, Gu L, Wang Y, Jia L, Zhao Z, Peng S and Lei L: The role of alpha-1 and alpha-2 adrenoceptors in restraint stress-induced liver injury in mice. PLoS One. 9:e921252014. View Article : Google Scholar : PubMed/NCBI

17 

Bartek J and Lukas J: Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr Opin Cell Biol. 13:738–747. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Myklebust MP, Li Z, Tran TH, Rui H, Knudsen ES, Elsaleh H, Fluge Ø, Vonen B, Myrvold HE, Leh S, et al: Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer. Br J Cancer. 107:1684–1691. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Esposti Degli D, Hamelin J, Bosselut N, Saffroy R, Sebagh M, Pommier A, Martel C and Lemoine A: Mitochondrial roles and cytoprotection in chronic liver injury. Biochem Res Int. 2012:3876262012.PubMed/NCBI

20 

Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, Arroyo V and Kamath PS: Acute-on chronic liver failure. J Hepatol. 57:1336–1348. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, Hamid SS, Jalan R, Komolmit P, et al: Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int. 3:269–282. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Aldridge DR, Tranah EJ and Shawcross DL: Pathogenesis of hepatic encephalopathy, Role of ammonia and systemic inflammation. J Clin Exp Hepatol. 5((Suppl 1)): S7–S20. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Bobermin LD, Quincozes-Santos A, Guerra MC, Leite MC, Souza DO, Gonçalves CA and Gottfried C: Resveratrol prevents ammonia toxicity in astroglial cells. PLoS One. 7:e521642012. View Article : Google Scholar : PubMed/NCBI

24 

Rose CF: Ammonia: M ore than a neurotoxin? Liver Int. 34:649–651. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Wang Q, Wang Y, Yu Z, Li D, Jia B, Li J, Guan K, Zhou Y, Chen Y and Kan Q: Ammonia-induced energy disorders interfere with bilirubin metabolism in hepatocytes. Arch Biochem Biophys 555-556. 16–22. 2014. View Article : Google Scholar

26 

Zhang LJ, Qi R, Zhong J, Xu Q, Zheng G and Lu GM: The effect of hepatic encephalopathy, hepatic failure, and portosystemic shunt on brain volume of cirrhotic patients, A voxel-based morphometry study. PLoS One. 7:e428242012. View Article : Google Scholar : PubMed/NCBI

27 

Jia B, Yu ZJ, Duan ZF, Lü XQ, Li JJ, Liu XR, Sun R, Gao XJ, Wang YF, Yan JY and Kan QC: Hyperammonaemia induces hepatic injury with alteration of gene expression profiles. Liver Int. 34:748–758. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Johnson DG and Walker CL: Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol. 39:295–312. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Hartwell LH and Kastan MB: Cell cycle control and cancer. Science. 266:1821–1828. 1994. View Article : Google Scholar : PubMed/NCBI

30 

Stewart ZA, Mays D and Pietenpol JA: Defective G1-S cell cycle checkpoint function sensitizes cells to microtubule inhibitor-induced apoptosis. Cancer Res. 59:3831–3837. 1999.PubMed/NCBI

31 

Chibazakura T, Kamachi K, Ohara M, Tane S, Yoshikawa H and Roberts JM: Cyclin A promotes S-phase entry via interaction with the replication licensing factor Mcm7. Mol Cell Biol. 31:248–255. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Kang DS, Hong K-M, Park J and Bae CD: Cyclin A regulates a cell-cycle-dependent expression of CKAP2 through phosphorylation of Sp1. Biochem Biophys Res Commun. 420:822–827. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Pardo FS, Su M and Borek C: Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation. Somat Cell Mol Genet. 22:135–144. 1996. View Article : Google Scholar : PubMed/NCBI

34 

Ha SY, Kim HK, Im JS, Cho HY, Chung DH and An J: Expression of Cyclin A, B1, D1, D3, and E in non-small lung cancers. J Lung Cancer. 11:33–37. 2012. View Article : Google Scholar

35 

Meng FJ, Jiao SM and Yu B: Picroside II protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by activating the PI3K/Akt and CREB pathways. Int J Mol Med. 30:263–270. 2012.PubMed/NCBI

36 

Wu D, Jiang H, Chen S and Zhang H: Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes. Mol Med Rep. 11:3988–3994. 2015.PubMed/NCBI

37 

Hashimoto T, Yanaihara N, Okamoto A, Nikaido T, Saito M, Takakura S, Yasuda M, Sasaki H, Ochiai K and Tanaka T: Cyclin D1 predicts the prognosis of advanced serous ovarian cancer. Exp Ther Med. 2:213–219. 2011.PubMed/NCBI

38 

Pontano LL and Diehl JA: Speeding through cell cycle roadblocks: Nuclear cyclin D1-dependent kinase and neoplastic transformation. Cell Div. 3:122008. View Article : Google Scholar : PubMed/NCBI

39 

Peurala E, Koivunen P, Haapasaari KM, Bloigu R and Jukkola-Vuorinen A: The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer. Breast Cancer Res. 15:R52013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gao X, Fan L, Li H, Li J, Liu X, Sun R and Yu Z: Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats. Exp Ther Med 11: 427-434, 2016.
APA
Gao, X., Fan, L., Li, H., Li, J., Liu, X., Sun, R., & Yu, Z. (2016). Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats. Experimental and Therapeutic Medicine, 11, 427-434. https://doi.org/10.3892/etm.2015.2931
MLA
Gao, X., Fan, L., Li, H., Li, J., Liu, X., Sun, R., Yu, Z."Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats". Experimental and Therapeutic Medicine 11.2 (2016): 427-434.
Chicago
Gao, X., Fan, L., Li, H., Li, J., Liu, X., Sun, R., Yu, Z."Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats". Experimental and Therapeutic Medicine 11, no. 2 (2016): 427-434. https://doi.org/10.3892/etm.2015.2931
Copy and paste a formatted citation
x
Spandidos Publications style
Gao X, Fan L, Li H, Li J, Liu X, Sun R and Yu Z: Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats. Exp Ther Med 11: 427-434, 2016.
APA
Gao, X., Fan, L., Li, H., Li, J., Liu, X., Sun, R., & Yu, Z. (2016). Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats. Experimental and Therapeutic Medicine, 11, 427-434. https://doi.org/10.3892/etm.2015.2931
MLA
Gao, X., Fan, L., Li, H., Li, J., Liu, X., Sun, R., Yu, Z."Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats". Experimental and Therapeutic Medicine 11.2 (2016): 427-434.
Chicago
Gao, X., Fan, L., Li, H., Li, J., Liu, X., Sun, R., Yu, Z."Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride‑induced hyperammonemic rats". Experimental and Therapeutic Medicine 11, no. 2 (2016): 427-434. https://doi.org/10.3892/etm.2015.2931
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