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
December-2018 Volume 18 Issue 6

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
December-2018 Volume 18 Issue 6

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

Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo

  • Authors:
    • Hucheng Chen
    • Jiyu Xu
    • Yuan Lv
    • Ping He
    • Chunyan Liu
    • Jie Jiao
    • Shiwei Li
    • Xuhua Mao
    • Xue Xue
  • View Affiliations / Copyright

    Affiliations: Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China, Department of Clinical Laboratory, Yixing People Hospital, Affiliated Jiangsu University, Yixing, Jiangsu 214200, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4913-4921
    |
    Published online on: September 25, 2018
       https://doi.org/10.3892/mmr.2018.9509
  • 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 pathological alterations of Parkinson's disease (PD) predominantly manifest as a loss of dopaminergic neurons in the substantia nigra, which may be caused by oxidative stress damage. Proanthocyanidins (PCs) are a class of compounds found in various plants, which have significant antioxidant and free radical‑scavenging activity. The present study investigated the protective effects and underlying mechanisms of PCs in a 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑induced PD model in vitro and in vivo. MTT assays were used to detect cell viability, and flow cytometry and TUNEL assays were used to detect cell apoptosis. Mitochondrial membrane potential (MMP) alterations were investigated using a JC‑1 MMP Assay kit. The pole test was used to measure motor behavior in a mouse model of PD. Levels of reactive oxygen species (ROS) were measured using the fluorescent probe, 2',7'‑dichlorodihydrofluorescein diacetate. Immunohistochemistry and western blotting were performed to detect the expression levels of proteins associated with PD. In vitro, it was demonstrated that in MPTP‑treated PC12 cells, PCs increased cell viability and reduced cell apoptosis in a dose‑dependent manner. In vivo, it was revealed that PC treatment inhibited striatal dopamine depletion, which resulted in significant improvements in PD‑like movement impairment. Reactive oxygen species (ROS) production and MPTP‑induced apoptosis were also inhibited. Furthermore, the results demonstrated that the neuroprotective activity of PCs may be mediated via the inhibition of ROS generation, as well as modulation of c‑Jun N‑terminal kinase activation. Taken together, these data revealed that PCs may exert neuroprotective effects in in vivo and in vitro PD models, and may have potential in the prevention or treatment of PD.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Keeney PM, Xie J, Capaldi RA and Bennett JP Jr: Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 26:5256–5264. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Jenner P: Oxidative stress in Parkinson's disease. Ann Neurol. 53 Suppl 3:S26–S38. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Reynolds A, Laurie C, Mosley RL and Gendelman HE: Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol. 82:297–325. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Sharpe MA, Han J, Baskin AM and Baskin DS: Design and synthesis of a MAO-B-selectively activated prodrug based on MPTP: A mitochondria-targeting chemotherapeutic agent for treatment of human malignant gliomas. ChemMedChem. 10:621–628. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Chalimoniuk M, Snoek GT, Adamczyk A, Małecki A and Strosznajder JB: Phosphatidylinositol transfer protein expression altered by aging and Parkinson disease. Cell Mol Neurobiol. 26:1151–1164. 2006. View Article : Google Scholar

6 

Lee WS, Tsai WJ, Yeh PH, Wei BL and Chiou WF: Divergent role of calcium on Abeta- and MPTP-induced cell death in SK-N-SH neuroblastoma. Life Sci. 78:1268–1275. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Dalia A, Neff NH and Hadjiconstantinou M: Tyrosine hydroxylase and aromatic L-amino acid decarboxylase in mesencephalic cultures after MPP+: The consequences of treatment with GM1 ganglioside. Brain Res. 742:260–264. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Kim MJ, Kim DW, Jeong HJ, Sohn EJ, Shin MJ, Ahn EH, Kwon SW, Kim YN, Kim DS, Park J, et al: Tat-Frataxin protects dopaminergic neuronal cells against MPTP-induced toxicity in a mouse model of Parkinson's disease. Biochimie. 94:2448–2456. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Rocarodríguez MM, Lópeztinoco C, Murri M, Fernández-Deudero A, García-Palacios MV, García-Valero MA, Tinahones-Madueño FJ and Aguilar-Diosdado M: Postpartum development of endothelial dysfunction and oxidative stress markers in women with previous gestational diabetes mellitus. J Endocrinol Invest. 37:503–509. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Prasad R, Vaid M and Katiyar SK: Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway. PLoS One. 7:e430642012. View Article : Google Scholar : PubMed/NCBI

11 

Gao X, Cassidy A, Schwarzschild MA, Rimm EB and Ascherio A: Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology. 78:1138–1145. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Strathearn KE, Yousef GG, Grace MH, Roy SL, Tambe MA, Ferruzzi MG, Wu QL, Simon JE, Lila MA and Rochet JC: Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson's disease. Brain Res. 1555:60–77. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Saad AA, Youssef MI and Elshennawy LK: Cisplatin induced damage in kidney genomic DNA and nephrotoxicity in male rats: The protective effect of grape seed proanthocyanidin extract. Food Chem Toxicol. 47:14992009. View Article : Google Scholar : PubMed/NCBI

14 

Basli A, Soulet S, Chaher N, Mérillon JM, Chibane M, Monti JP and Richard T: Wine polyphenols: Potential agents in neuroprotection. Oxid Med Cell Longev. 2012:8057622012. View Article : Google Scholar : PubMed/NCBI

15 

Park G, Park YJ, Yang HO and Oh MS: Ropinirole protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice via anti-apoptotic mechanism. Pharmacol Biochem Behav. 104:163–168. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Kim HG, Ju MS, Shim JS, Kim MC, Lee SH, Huh Y, Kim SY and Oh MS: Mulberry fruit protects dopaminergic neurons in toxin-induced Parkinson's disease models. Br J Nutr. 104:8–16. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Lamine A, Létourneau M, Doan ND, Maucotel J, Couvineau A, Vaudry H, Chatenet D, Vaudry D and Fournier A: Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson's disease model. Neuropharmacology. 108:440–450. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Ariga T and Asao Y: Isolation, identification and organoleptic astringency of dimeric proanthocyanidins occurring in Azuki Beans. J Agric Chem Soc Japan. 45:2709–2712. 2014.

19 

Celardo I, Martins LM and Gandhi S: Unravelling mitochondrial pathways to Parkinson's disease. Br J Pharmacol. 171:1943–1957. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Leppä S and Bohmann D: Diverse functions of JNK signaling and c-Jun in stress response and apoptosis. Oncogene. 18:6158–6162. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Freund TF, Bolam JP, Björklund A, Stenevi U, Dunnett SB, Powell JF and Smith AD: Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: A tyrosine hydroxylase immunocytochemical study. J Neurosci. 5:603–16. 1985. View Article : Google Scholar : PubMed/NCBI

22 

Dragicevic N, Smith A, Lin X, Yuan F, Copes N, Delic V, Tan J, Cao C, Shytle RD and Bradshaw PC: Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer's amyloid-induced mitochondrial dysfunction. J Alzheimers Dis. 26:507–521. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Laschober GT, Ruli D, Hofer E, Muck C, Carmona-Gutierrez D, Ring J, Hutter E, Ruckenstuhl C, Micutkova L, Brunauer R, et al: Identification of evolutionarily conserved genetic regulators of cellular aging. Aging Cell. 9:1084–1097. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Hartley A, Stone JM, Heron C, Cooper JM and Schapira AH: Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: Relevance to Parkinson's disease. J Neurochem. 63:1987–1990. 1994. View Article : Google Scholar : PubMed/NCBI

25 

Kuchta K, Qiao HX, Huang HB, Fang L, Chen Y and Wang RW: The neuroprotective activity of a proanthocyanidin enriched Ginkgo biloba L. leaves extract in vitro and in vivo. Planta Medica. 81 Suppl 1:S1–S381. 2016.

26 

Li L, Zhang Y, Sun B, Zhang H, Tao W, Tian J, Ye X and Chen S: The neuroprotective effects of Chinese bayberry leaves proanthocyanidins. J Funct Foods. 40:554–563. 2018. View Article : Google Scholar

27 

Agrawal S, Singh A, Tripathi P, Mishra M, Singh PK and Singh MP: Cypermethrin-induced nigrostriatal dopaminergic neurodegeneration alters the mitochondrial function: A proteomics study. Mol Neurobiol. 51:448–465. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Huang QR, Li Q, Chen YH, Li L, Liu LL, Lei SH, Chen HP, Peng WJ and He M: Involvement of anion exchanger-2 in apoptosis of endothelial cells induced by high glucose through an mPTP-ROS-Caspase-3 dependent pathway. Apoptosis. 15:693–704. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Lu M, Su C, Qiao C, Bian Y, Ding J and Hu G: Metformin prevents dopaminergic neuron death in MPTP/P-induced mouse model of Parkinson's disease via autophagy and mitochondrial ROS clearance. Int J Neuropsychopharmacol. 19:pyw0472016. View Article : Google Scholar : PubMed/NCBI

30 

Stefanis L, Burke RE and Greene LA: Apoptosis in neurodegenerative disorders. Curr Opin Neurol. 10:299–305. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Hoehn MM and Yahr MD: Parkinsonism: Onset, progression, and mortality. Neurology. 17:427–442. 1967. View Article : Google Scholar : PubMed/NCBI

32 

Kim SY, Kim MY, Mo JS, Park JW and Park HS: SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling. Neurosci Lett. 413:132–136. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Voss T and Ravina B: Neuroprotection in Parkinson's disease: Myth or reality? Curr Neurol Neurosci Rep. 8:304–309. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Zhang L, Xing Y, Ye CF, Ai HX, Wei HF and Li L: Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease and intervention by using tetrahydroxystilbene glucoside. Behav Brain Res. 173:246–254. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen H, Xu J, Lv Y, He P, Liu C, Jiao J, Li S, Mao X and Xue X: Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo. Mol Med Rep 18: 4913-4921, 2018.
APA
Chen, H., Xu, J., Lv, Y., He, P., Liu, C., Jiao, J. ... Xue, X. (2018). Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo. Molecular Medicine Reports, 18, 4913-4921. https://doi.org/10.3892/mmr.2018.9509
MLA
Chen, H., Xu, J., Lv, Y., He, P., Liu, C., Jiao, J., Li, S., Mao, X., Xue, X."Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo". Molecular Medicine Reports 18.6 (2018): 4913-4921.
Chicago
Chen, H., Xu, J., Lv, Y., He, P., Liu, C., Jiao, J., Li, S., Mao, X., Xue, X."Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo". Molecular Medicine Reports 18, no. 6 (2018): 4913-4921. https://doi.org/10.3892/mmr.2018.9509
Copy and paste a formatted citation
x
Spandidos Publications style
Chen H, Xu J, Lv Y, He P, Liu C, Jiao J, Li S, Mao X and Xue X: Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo. Mol Med Rep 18: 4913-4921, 2018.
APA
Chen, H., Xu, J., Lv, Y., He, P., Liu, C., Jiao, J. ... Xue, X. (2018). Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo. Molecular Medicine Reports, 18, 4913-4921. https://doi.org/10.3892/mmr.2018.9509
MLA
Chen, H., Xu, J., Lv, Y., He, P., Liu, C., Jiao, J., Li, S., Mao, X., Xue, X."Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo". Molecular Medicine Reports 18.6 (2018): 4913-4921.
Chicago
Chen, H., Xu, J., Lv, Y., He, P., Liu, C., Jiao, J., Li, S., Mao, X., Xue, X."Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP‑induced Parkinson's disease models in vitro and in vivo". Molecular Medicine Reports 18, no. 6 (2018): 4913-4921. https://doi.org/10.3892/mmr.2018.9509
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