Allicin Could Potentially Alleviate Oral Cancer Pain by Inhibiting “Pain Mediators” TNF-alpha, IL-8, and Endothelin

Round 1

Reviewer 1 Report

This is a very interesting article with regard to the alleviation of oral cancer pain by Allicin by inhibiting pain mediator's TNF-alpha, IL-8, and endothelin. Nevertheless, major revisions could improve the article's quality.

1. Title - TNF-alpha, IL-8, and endothelin are inflammatory mediators and may be considered as pain mediators, but the term should be placed in quotation marks.
2. Citations - should be in the form of numbers, sequentially appearing in the text. This citation format appears only in the discussion. 
3. The α in TNF- α is missing in subsection 2.5
4. The discussion is too short
5. What are the limitations of the study? What are the further perspectives of this research?
6) What are the inclusion and exclusion criteria of the study?
7) How was the material for the study obtained?

Author Response

Reviewer 1:

This is a very interesting article with regard to the alleviation of oral cancer pain by Allicin by inhibiting pain mediator's TNF-alpha, IL-8, and endothelin. Nevertheless, major revisions could improve the article's quality.

1. Title - TNF-alpha, IL-8, and endothelin are inflammatory mediators and may be considered as pain mediators, but the term should be placed in quotation marks.

Answer: Placed pain mediators in quotation marks in the title.

2. 
   Citations - should be in the form of numbers, sequentially appearing in the text. This citation format appears only in the discussion. 

Answer: Implemented corrections in the manuscript.

3. 
   The α in TNF- α is missing in subsection 2.5

Answer: Corrected the TNF-alpha word in subsection 2.5.

4. 
   The discussion is too short

Answer: Extended the discussion related to our results.

5. 
   What are the limitations of the study? What are the further perspectives of this research?

Answer: Discussed limitations and further perspectives of this research in the discussion section.

6) What are the inclusion and exclusion criteria of the study?

Answer: Biopsy samples were obtained from histopathologically normal oral mucosa during the surgical extraction of third molars of the subjects and primary oral tumors from oral squamous cell carcinoma (OSCC) patients were collected. The details are mentioned in the materials and methods section.

7) How was the material for the study obtained?

Answer: Mentioned the details of biological materials obtained for the study in materials and methods section.

Reviewer 2 Report

In the study, entitled "Allicin could potentially alleviate oral cancer pain by inhibiting pain mediator's TNF-alpha, IL-8 , and endothelin," the authors examine the effects of allicin on the release of pain sensitizing factors from primary oral tumor cells and also the effect on tumor stem cells (CSCs). In addition, the work provides evidence that CSCs are the subpopulation within the primary tumor that is primarily responsible for the release of pain mediators. The study is clinically relevant. Severe pain is a common symptom in patients with advanced oral cancer and limits quality of life. A better understanding of the pathogenesis of pain may contribute to the development of new therapeutic approaches. I therefore propose to accept this manuscript for publication in the journal current issues in molecular biology. As a suggestion for improvement, the authors should better explain allicin therapy of cells in the materials and methods section.

Author Response

Reviewer 2:

In the study, entitled "Allicin could potentially alleviate oral cancer pain by inhibiting pain mediator's TNF-alpha, IL-8 , and endothelin," the authors examine the effects of allicin on the release of pain sensitizing factors from primary oral tumor cells and also the effect on tumor stem cells (CSCs). In addition, the work provides evidence that CSCs are the subpopulation within the primary tumor that is primarily responsible for the release of pain mediators. The study is clinically relevant. Severe pain is a common symptom in patients with advanced oral cancer and limits quality of life. A better understanding of the pathogenesis of pain may contribute to the development of new therapeutic approaches. I therefore propose to accept this manuscript for publication in the journal current issues in molecular biology. As a suggestion for improvement, the authors should better explain allicin therapy of cells in the materials and methods section.

Answer: Explained treatment of cells with allicin in the materials and methods section.

Round 2

Reviewer 1 Report

Thank you very much for the opportunity to review your manuscript. After taking into account my remarks and making corrections in my opinion, it can be published in the MDPI CIMB.