info@auctorespublishing.com
+1-(302)-520-2644
+1-(302)-520-2644

Effect Of Puerarin on The Growth of Nasopharyngeal Carcinoma Cells and Its Impact on Angiogenesis

  1. Home
  2. Journals
  3. Cancer Research and Cellular Therapeutics
  4. Archives
Submit Guidelines

Research | DOI: https://doi.org/10.31579/2640-1053/114

Effect Of Puerarin on The Growth of Nasopharyngeal Carcinoma Cells and Its Impact on Angiogenesis

  • Jingjing Zhao 1
  • Bo Yang 2
  • Yepeng Li 2*

1 Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China.
2 Department of Oncology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China.

*Corresponding Author: Yepeng Li, Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, 18 Zhongshan Second Road, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China.

Citation: J Zhao, B Yang, Yepeng Li. (2022). Effect Of Puerarin on The Growth of Nasopharyngeal Carcinoma Cells and Its Impact on Angiogenesis. J. Cancer Research and Cellular Therapeutics. 6(2); DOI:10.31579/2640-1053/114

Copyright: © 2022 Yepeng Li, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 21 March 2022 | Accepted: 04 April 2022 | Published: 11 April 2022

Keywords: cne1 cells; puerarin; cell proliferation; rna sequencing

Abstract

Objective

Puerarin is a form of isoflavones obtained from Pueraria lobata. It stimulates hepatic metabolic function and lowers serum ALT, AST, and total-bilirubin level. The purpose of this study was to examine the effect of puerarin on nasopharyngeal carcinoma (NPC) CNE1 cells and preliminarily explore its possible mechanism.

Materials and Methods

CCK8 method was used to detect the proliferation activity of puerarin on NPC CNE1 cells and IC50 was calculated. CNE1 cells were treated with 0 μmol/L puerarin (containing equal volume of DMSO solution) as control group and 1000 μmol/L puerarin (IC50 concentration) as experimental group. Colony formation assay, Scratch-wound test and Transwell invasion assay were used to detect the clone formation ability, migration and invasion ability of puerarin on CNE1 cells. Then, RNA Sequencing was used to detect the changes of differentially expressed genes (DEGs) and signaling pathways after puerarin was applied to CNE1 cells.

Results

The inhibitory effect of puerarin on the proliferation activity of CNE1 cells was enhanced with the increase of concentration, and IC50 was calculated as 1000 μmol/L. Compared with the control group, the treatment of CNE1 cells with 1000 μmol/L puerarin could inhibit the clone formation, migration and invasion of CNE1 cells (P<0.05). A total of 379 DEGs were found by RNA sequencing, including 295 down-regulated genes and 84 up-regulated genes (padj<0.05). The significant differences in biological functions of differentially expressed genes were mainly distributed in “negative regulation of growth”, “angiogenesis”, “regulation of peptidase activity”, “positive regulation of vasculature development”, “digestion”, “positive regulation of angiogenesis”, “negative regulation of peptidase activity”, “extracellular matrix” and “Golgi lumen” (padj<0.05).

Conclusion

Puerarin could inhibit the proliferation, migration and invasion of NPC CNE1 cells, and its mechanism might be related to the inhibition of angiogenesis and cell growth.

Introduction

Nasopharyngeal Carcinoma (NPC) is an epithelial cancer that occurs in the nasopharyngeal mucosa. It is one of the common malignant tumors of head and neck. It has obvious geographical distribution characteristics and high incidence in Southeast Asia and southern China [1,2]. In southern China, the incidence rate is as high as 25/100,000-50/100,000 [3], and non-keratinizing NPC accounts for more than 95%, mainly related to Epstein-barr Virus (EBV) infection [4]. Due to the particularity of NPC anatomy and radiotherapy sensitivity, intensity-modulated radiotherapy (IMRT) has become an important treatment for NPC. NPC patients are difficult to be found in the early stage, and 75 % of the patients are diagnosed in the late stage [5]. Distant metastasis in locally advanced NPC patients is the main reason for treatment failure, and the 5-year survival rate is still only 50-60% in metastatic patients [6, 7].

The role of traditional Chinese medicine in tumor treatment has become increasingly prominent. Traditional Chinese medicine can alleviate adverse reactions such as nausea and vomiting caused by chemotherapy [8]. In addition, some traditional Chinese medicine components can play an anti-tumor role by improving the immunity of the body [9]. Flavonoids are one of the active components of traditional Chinese medicine, which can play a role in anti-tumor. Puerarin is an isoflavone compound extracted from Puerariae Lobatae Radix. Its molecular formula is C21H20O9 and its relative molecular mass is 416, which can be dissolved in organic solvents such as dimethyl sulfoxide (DMSO). It has been reported that puerarin has the effects of protecting myocardial cells, lowering blood pressure, anti-oxidation and reducing inflammatory response [10-12]. Studies have found that puerarin can lead to cancer cell death by regulating different mechanisms, including oxidative stress, cell cycle, Phosphatidylinositol 3-Kinase/ Pmtein Kinase B (PI3K / AKT) pathway, Mitogen- activated Protein Kinases/ Extracellular Signal-regulated Kinases (MAPK/ERK) pathway, Nuclear Factor κB (NF-κB) pathway, etc. [13]. The role of puerarin in non- small cell lung cancer showed that puerarin inhibited the proliferation of NCI-H441 and NCI-H460 cells, and induced autophagy through PI3K/Akt and MAPK/Erk signaling pathways [14]. Puerarin can inhibit the proliferation and promote apoptosis of bladder cancer T24 cells, and can inactivate NF-κB signaling pathway [15]. Puerarin can also act on liver cancer [16], ovarian cancer [17], cervical cancer [18], esophageal cancer [19], and gastric cancer [20] through different mechanisms. However, there are few studies on puerarin in NPC. In this study, the effects of puerarin on the proliferation, migration and invasion of NPC CNE1 cells were observed in vitro, and RNA sequencing (RNA-seq) was used to detect the changes of differentially expressed genes and possible pathways after puerarin was applied to CNE1 cells, providing a theoretical basis for the clinical application of puerarin in NPC.

Materials and methods

Cell Culture

Nasopharyngeal carcinoma CNE1 cells obtained from Cell Institute of Shanghai Academy of Life Sciences were cultured in RPMI Medium 1640 containing 10

Statistical analysis

Each experiment in this study was repeated three times independently, represented by mean±sd. Graph Pad Prism 9.0 software was used to count and draw pictures. The mean of the two samples (control vs treated) was compared by unpaired Student's test, P<0>

Results

Puerarin inhibits the proliferation of NPC CNE1 cells.

CCK8 assay showed that puerarin decreased the proliferation activity of CNE1 cells (Figure. 1A), and IC50 was calculated as 1000 μmol/L. The colony formation assay demonstrated that puerarin reduced(P<0>)

Figure 1: Puerarin inhibits migration and invasion of NPC CNE1 cells. (A and B) Transwell invasion assay to detect the number of invasive cells. (C and D) Scratch-wound test to detect cells healing rate. Unpaired Student'st‑test was used for statistical analysis. *P<0>.

Puerarin inhibits migration and invasion of NPC CNE1 cells 

Scratch-wound test results showed that compared with the control group, 1000μmol/L puerarin group had no significant difference in healing at 24h and 48h, but decreased (P<0>

Figure 2: Puerarin inhibits migration and invasion of NPC CNE1 cells. (A and B) Transwell invasion assay to detect the number of invasive cells. (C and D) Scratch-wound test to detect cells healing rate. Unpaired Student's t‑test was used forstatistical analysis. *P<0>

Analysis of the DEGs.

The hierarchical clustering heat map of DEGs is shown in Fig. 3A. Compared with the control group, a total of 379 DEGs, 295 downregulated and 84 upregulated were detected in CNE1 cells treated with puerarin(padj<0>

Figure 3: Analysis of the DEGs. (A) Heatmap of hierarchical clustering for DEGs. Red scale represented upregulated DEGs and green scale was for downregulated DEGs. (B) Volcano plot of DEGs. Red dots indicated upregulated DEGs and green dots indicated downregulated DEGs. (C) Statistical histogram of DEGs number.
Table I: Top 20 significantly DEGs between control and 1000μmol/L puerarin group.

Enrichment Analysis of DEGs.

GO enrichment analysis was performed on DEGs of control group and puerarin group (Figure. 4A). It indicates that DEGs are mainly enriched in BP, such as “negative regulation of growth”, “angiogenesis”, “regulation of peptidase activity”, “positive regulation of vasculature development”, “digestion”, “positive regulation of angiogenesis”, “negative regulation of peptidase activity”. The top 7 entries of BP were annotated (Table II).

About CC, DEGs enriched in “extracellular matrix” and “Golgi lumen”. KEGG analysis showed DEGs enriched in “Complement and coagulation cascades” (padj<0>

Figure 4: GO and KEGG Analysis of DEGs. (A) GO analysis and of the DEGs. (B)     KEGG pathway analysis of the DEGs. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Table 2: Top 7 entries of BP in GO enrichment analysis of DEGs.

and invasion of CNE1 cells. Studies have found that when puerarin acts on bladder cancer T24 and EJ cells, puerarin can block the G0/G1 phase cell cycle and reduce the proliferation activity of bladder cancer cells [21]. Puerarin can also inhibitthe proliferation of chronic myeloid leukemia K562 cells and promote apoptosis by inducing autophagy in K562 cells [22]. Uncontrolled cell proliferation is the basic feature of cancer. The main mechanism is that the disorder of cell cycle leads to excessive proliferation and less apoptosis. Whether puerarin can inhibit the proliferation of CNE1 cells by blocking cell cycle remains unknown.Migration and invasion of tumor cells play an important role in tumor metastasis [23]. Studies have shown that puerarin can inhibit the migration and invasion of lipopolysaccharide--stimulated breast cancer cells by acting on the NF-κB pathway and Erk phosphorylation [24]. Puerarin can also inhibit the invasion and migration of ovarian cancer HO-8910 cells [25]. The incidence of NPC lymph node metastasis is high, and the cervical lymph node metastasis is found to be 70%-80% or more. Distant metastasis remains the leading cause of death in NPC patients [26]. Therefore, effective inhibition of tumor metastasis is an important part of treatment. Can puerarin control NPC metastasis by inhibiting cell migration and invasion? And the mechanism by which puerarin inhibits the migration and invasion of CNE1 cells needs further verification.

It was found by RNA-seq that the effect of puerarin on NPC may be related to the inhibition of angiogenesis and the inhibition of proliferation. It is well known that the growth of tumors requires blood vessels to provide nutrition, and blood vessels provide pathways for tumor metastasis and invasion. Vascular dysplasia exists in various types of tumors [27]. Excessive angiogenesis promotes the rapid growth of tumors, which is one of the main causes of tumor death [28]. Hypoxia is the main driver of tumor angiogenesis [29]. Radiotherapy, chemotherapy and immunotherapy can reduce the efficacy of hypoxia [30-32]. Angiogenesis and the production of vascular endothelial growth factor (VEGF) can also promote tumor growth, leading to increased expression of oncogenes or loss of tumor suppressor genes [33]. VEGF induces the expression of matrix metalloproteinases (MMPs) in NPC, which not only participates in the formation of new blood vessels by degrading the extracellular matrix of endothelial cells, but also regulates the invasion and metastasis of cancer, leading to the progress of NPC [34]. In addition, VEGF was overexpressed in nearly 70% of EBV-positive NPC patients and was associated with lymph node metastasis, recurrence and overall survival [35]. Studies have shown that Chinese herbal medicine can reduce the expression level of VEGF by inhibiting the expression of Hypoxia-inducible factor-1α (HIF-1α), and ultimately inhibit tumor angiogenesis [36,37]. NPC01 is an ancient Chinese herbal medicine prescription modified by Liang Gesang. NPC01 has the effect of inhibiting the growth of NPC cells. By inhibiting the PI3K/Akt signaling pathway, NPC01 reduces the expression of angiogenesis-related factors, including HIF-1α and VEGF [38]. Puerarin is also a kind of Chinese herbal medicine. This study found that puerarin acting on CNE1 cells may be related to inhibiting angiogenesis. Therefore, whether puerarin can play a role in NPC by inhibiting angiogenesis deserves further study.

Current cancer research efforts focus on epigenetic alterations that may be related to Sirtuin (SIRT) 1-7 [39]. In recent years, SIRT1 is considered to be the most characteristic sirtuin in seven members. And SIRT1 can be widely involved in cell processes, such as cell division, autophagy and senescence [40]. SIRT1 plays an important role in aging, metabolism and cancer [41]. SIRT1 is related to tumor cell proliferation, migration, invasion and angiogenesis [42,43]. A study found that after puerarin treatment of ovarian cancer cells, the expression of SIRT1 decreased and inhibited Wnt/β-catenin signaling pathway, thereby increasing the apoptosis of platinum-resistant ovarian cancer cells [44]. At present, many SIRT1 inhibitors have been reported, and whether puerarin can be used as a SIRT1 inhibitor related to the inhibition of NPC cells remains to be studied.

Conclusion

In summary, the results of this study showed that puerarin could inhibit the proliferation, migration and invasion of CNE1 cells in vitro, which might be related to the inhibition of angiogenesis and cell growth. The inhibitory mechanism of puerarin on NPC still needs further verification. In addition, in vivo investigation is highly recommended. This study provides a theoretical basis for the study of puerarin in nasopharyngeal carcinoma.

Acknowledgements

Not applicable.

Funding

The present work was supported by Doctorate Awarding Unit Funding of the Affiliated Hospital of Youjiang Medical University for Nationalities [grant no. (2021)29]. The funders had no role in the design of the study, the collection, analyses or interpretation of data, the writing of the manuscript or the decision to publish the results.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

  1. Chen Y P, Chan A, Le QT, et al. (2019). Nasopharyngeal carcinoma(J). Lancet. 394(10192):64-80.
    View at Publisher | View at Google Scholar
  2. Bray F, Ferlay J, Soerjomataram I, et al. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries(J). CA Cancer J Clin. 68(6):394-424.
    View at Publisher | View at Google Scholar
  3. Chen Y P, Chan A, Le QT, et al. (2019). Nasopharyngeal carcinoma(J). Lancet. 394(10192):64-80.
    View at Publisher | View at Google Scholar
  4. Wang H Y, Chang Y L, To K F, et al. (2016). A new prognostic histopathologic classification of nasopharyngeal carcinoma(J). Chin J Cancer. 35:41.
    View at Publisher | View at Google Scholar
  5. Yang Q, Cao S, Guo L, et al. (2019). Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradio-therapy alone in locoregionally advanced nasopharyngealcarcinoma long-term results of a phase III multicentre rand(J). Eur J Cancer. 119-187.
    View at Publisher | View at Google Scholar
  6. Bao L, You B, Shi S, et al. (2018). Metastasis-associated miR-23a from nasopharyngeal carcinoma- derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10(J). Oncogene. 37(21):2873-2889.
    View at Publisher | View at Google Scholar
  7. Hong X, Liu N, Liang Y, et al. (2020). Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1(J). Mol Cancer. 19(1):33.
    View at Publisher | View at Google Scholar
  8. Taixiang W, Munro A J, Guanjian L. (2005). Chinese medical herbs for chemotherapy side effects in colorectal cancer patients(J). Cochrane Database Syst Rev. (1):4540.
    View at Publisher | View at Google Scholar
  9. Cho W C, Leung K N. (2007). In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus(J). J Ethnopharmacol. 113(1):132-141.
    View at Publisher | View at Google Scholar
  10. Xu B, Wang H, Chen Z. (2021). Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells(J). Front Pediatr. 9:706327.
    View at Publisher | View at Google Scholar
  11. Ahmad B, Khan S, Liu Y, et al. (2020). Molecular Mechanisms of Anticancer Activities of Puerarin(J). Cancer Manag Res. 12:79-90.
    View at Publisher | View at Google Scholar
  12. Bui T T, Nguyen T H. (2017). Natural product for the treatment of Alzheimer's disease(J). J Basic Clin Physiol Pharmacol. 28(5):413-423.
    View at Publisher | View at Google Scholar
  13. Ahmad B, Khan S, Liu Y, et al. (2020). Molecular Mechanisms of Anticancer Activities of Puerarin(J). Cancer Manag Res. 12:79-90.
    View at Publisher | View at Google Scholar
  14. Hu Y, Li X, Lin L, et al. (2018). Puerarin inhibits non-small cell lung cancer cell growth via the induction of apoptosis(J). Oncol Rep. 39(4):1731-1738.
    View at Publisher | View at Google Scholar
  15. Liu X, Li S, Li Y, et al. (2018). Puerarin Inhibits Proliferation and Induces Apoptosis by Upregulation of miR-16 in Bladder Cancer Cell Line T24(J). Oncol Res. 26(8):1227-1234.
    View at Publisher | View at Google Scholar
  16. Zhang W G, Yin X C, Liu X F, et al. (2017). Puerarin Induces Hepatocellular Carcinoma Cell Apoptosis Modulated by MAPK Signaling Pathways in a Dose-dependent Manner(J). Anticancer Res. 37(8):4425-4431.
    View at Publisher | View at Google Scholar
  17. Duan J, Yin M, Shao Y, et al. (2021). Puerarin induces platinum-resistant epithelial ovarian cancer cell apoptosis by targeting SIRT1(J). J Int Med Res. 49(9):675865606.
    View at Publisher | View at Google Scholar
  18. Jia L, Hu Y, Yang G, et al. (2019). Puerarin suppresses cell growth and migration in HPV-positive cervical cancer cells by inhibiting the PI3K/mTOR signaling pathway(J). Exp Ther Med. 18(1):543-549.
    View at Publisher | View at Google Scholar
  19. Wang J, Yang Z R, Guo X F, et al. (2014). Synergistic effects of puerarin combined with 5-fluorouracil on esophageal cancer(J). Mol Med Rep. 10(5):2535-2541.
    View at Publisher | View at Google Scholar
  20. Guo X F, Yang Z R, Wang J, et al. (2015). Synergistic antitumor effect of puerarin combined with 5- fluorouracil on gastric carcinoma(J). Mol Med Rep. 11(4):2562-2568.
    View at Publisher | View at Google Scholar
  21. Jiang K, Chen H, Tang K, et al. (2018). Puerarin inhibits bladder cancer cell proliferation through the mTOR/p70S6K signaling pathway(J). Oncol Lett. 15(1):167-174.
    View at Publisher | View at Google Scholar
  22. Gao D, Xiao Z, Li H P. (2017). Puerarin leads to K562 cell apoptosis of chronic myelogenous leukemia via induction of autophagy(J). J BUON. 22(6):1554-1562.
    View at Publisher | View at Google Scholar
  23. Gupta G P, Massague J. (2006). Cancer metastasis: building a framework(J). Cell. 127(4):679-695.
    View at Publisher | View at Google Scholar
  24. Liu X, Zhao W, Wang W, et al. (2017). Puerarin suppresses LPS-induced breast cancer cell migration, invasion and adhesion by blockage NF-kappaB and Erk pathway(J). Biomed Pharmacother. 92:429-436.
    View at Publisher | View at Google Scholar
  25. Han J, Yu C Q, Shen W. (2009). (Inhibitory effects of puerarin on invasion and metastasis of oophoroma cells HO-8910) (J). Zhongguo Zhong Xi Yi Jie He Za Zhi. 29(7):632-635.
    View at Publisher | View at Google Scholar
  26. Li A C, Xiao W W, Shen G Z, et al. (2015). Distant metastasis risk and patterns of nasopharyngeal carcinoma in the era of IMRT: long-term results and benefits of chemotherapy(J). Oncotarget. 6(27):24511-24521.
    View at Publisher | View at Google Scholar
  27. Carmeliet P, Jain RK. (2000). Angiogenesis in cancer and other diseases. [J].Nature. 407(6801):249-57
    View at Publisher | View at Google Scholar
  28. Weis S M, Cheresh D A. (2011). Tumor angiogenesis: molecular pathways and therapeutic targets(J). Nat Med. 17(11):1359-1370.
    View at Publisher | View at Google Scholar
  29. Jain R K, Martin J D, Stylianopoulos T. (2014). The role of mechanical forces in tumor growth and therapy(J). Annu Rev Biomed Eng. 16:321-346.
    View at Publisher | View at Google Scholar
  30. Busk M, Horsman M R. (2013). Relevance of hypoxia in radiation oncology: pathophysiology, tumor biology and implications for treatment(J). Q J Nucl Med Mol Imaging. 57(3):219-234.
    View at Publisher | View at Google Scholar
  31. Huang Y, Goel S, Duda D G, et al. (2013). Vascular normalization as an emerging strategy to enhance cancer immunotherapy(J). Cancer Res. 73(10):2943-2948.
    View at Publisher | View at Google Scholar
  32. Cosse J P, Michiels C. (2008). Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression(J). Anticancer Agents Med Chem. 8(7):790- 797.
    View at Publisher | View at Google Scholar
  33. Larcher F, Franco M, Bolontrade M, et al. (2003). Modulation of the angiogenesis response through Ha- ras control, placenta growth factor, and angiopoietin expression in mouse skin carcinogenesis(J). Mol Carcinog. 37(2):83-90.
    View at Publisher | View at Google Scholar
  34. Li X Y, Lin Y C, Huang W L, et al. (2012). Zoledronic acid inhibits proliferation and impairs migration and invasion through downregulating VEGF and MMPs expression in human nasopharyngeal carcinoma cells (J). Med Oncol. 29(2):714-720.
    View at Publisher | View at Google Scholar
  35. Krishna S M, James S, Balaram P. (2006). Expression of VEGF as prognosticator in primary nasopharyngeal cancer and its relation to EBV status(J). Virus Res. 115(1):85-90.
    View at Publisher | View at Google Scholar
  36. Kim K M, Heo D R, Lee J, et al. (2015). 5,3'-Dihydroxy-6,7,4'-trimethoxyflavanone exerts its anticancer and antiangiogenesis effects through regulation of the Akt/mTOR signaling pathway in human lung cancer cells(J). Chem Biol Interact. 225:32-39.
    View at Publisher | View at Google Scholar
  37. Liu Z, Xi R, Zhang Z, et al. (2014). 4-hydroxyphenylacetic acid attenuated inflammation and edema via suppressing HIF-1alpha in seawater aspiration-induced lung injury in rats(J). Int J Mol Sci. 15(7):12861-12884.
    View at Publisher | View at Google Scholar
  38. Yanwei L, Yinli Y, Pan Z. (2018). Traditional Herbal Formula NPC01 Exerts Antiangiogenic Effects through Inhibiting the PI3K/Akt/mTOR Signaling Pathway in Nasopharyngeal Carcinoma Cells(J). Evid Based Complement Alternat Med. 2018:5291517.
    View at Publisher | View at Google Scholar
  39. Beyer S, Chen F, Meister S, et al. (2020). Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer. [J]. Histochem Cell Biol. 154(2):189-195
    View at Publisher | View at Google Scholar
  40. Bartosch C, Monteiro-Reis S, Almeida-Rios D, et al. (2016). Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium. [J]. Oncotarget. 7(2):1144-54
    View at Publisher | View at Google Scholar
  41. Herranz D, Mu?oz-Martin M, Ca?amero M, et al. (2010). Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. [J].Nat Commun. 1:3
    View at Publisher | View at Google Scholar
  42. Jiang W, Jiang P, Yang R, et al. (2018). Functional role of SIRT1-induced HMGB1 expression and acetylation in migration, invasion and angiogenesis of ovarian cancer. [J].Eur Rev Med Pharmacol Sci. 22(14):4431-4439
    View at Publisher | View at Google Scholar
  43. Huang S, Li Y, Sheng G, et al. (2021). Sirtuin 1 promotes autophagy and proliferation of endometrial cancer cells by reducing acetylation level of LC3. [J].Cell Biol Int. 45(5):1050-1059
    View at Publisher | View at Google Scholar
  44. Duan J, Yin M, Shao Y, et al. (2021). Puerarin induces platinum-resistant epithelial ovarian cancer cell apoptosis by targeting SIRT1. [J]. J Int Med Res. 49(9):3000605211040762
    View at Publisher | View at Google Scholar

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad