Simvastatin Attenuates Areca Nut Extract-Induced Subdermal Fibrosis in Mice by Targeting TGF-β Signaling Pathways

Round 1

Reviewer 1 Report

Dear Authors, 

you made a great work! 

 

Comments for author File: Comments.pdf

Author Response

Here's my detailed response to the comments provided by the reviewer:

 

Discussion of the Figures: We sincerely value the reviewer's astute recommendation regarding our figures. Consequently, we've expanded upon the images in our Discussion, offering more in-depth commentary (refer to the second paragraph of the Discussion).

 

Deepening the Discussion: The reviewer's insights have proven pivotal in enhancing the depth and richness of our discourse. Drawing upon the suggested reference, we've further delineated the parallels between cell differentiation observed in other contexts and our current findings (please see the fourth paragraph of the Discussion for this integration).

 

Conclusion Section: Heeding the reviewer's advice, we've appended a comprehensive conclusion at the close of our discussion, summarizing the key takeaways and implications of our study.

 

In summary, I extend my heartfelt gratitude to the reviewer for their insightful suggestions, which I believe have significantly uplifted the caliber of my manuscript.

 

I eagerly await your response and hope for favorable consideration.

 

Reviewer 2 Report

Dear Authors,

I have had the opportunity to review the manuscript, and I must say that I find it exceptionally interesting. The manuscript is not only well-designed but also written with great clarity and precision. The research presented within is both thought-provoking and meticulously conducted.

The study discussed in this text investigates the potential of simvastatin, a commonly used statin drug, in treating Oral Submucous Fibrosis (OSMF), a chronic oral inflammatory condition with potential malignancy. OSMF is characterized by the fibrosis of oral mucosa, and it has been linked to the TGF-β signaling pathway, with areca nut extract (ANE) playing a role in its development.

The study used male BALB/c mice to assess the effects of simvastatin on OSMF. Mice were divided into different groups and treated with various drug formulations. After treatment, specimens were analyzed to evaluate skin thickness, fibrosis, and collagen deposition.

Results showed that ANE treatment alone significantly increased skin thickness and collagen deposition compared to the control group, especially at the 4-week time point. However, when simvastatin was administered alongside ANE, there was a notable reduction in skin thickness and collagen deposition. Additionally, Western blot analysis revealed that simvastatin effectively suppressed the expression of fibrosis-related proteins, such as CTGF and α-SMA, induced by ANE-induced subdermal fibrosis.

These findings suggest that simvastatin holds promise as a potential therapeutic agent for ANE-induced subdermal fibrosis associated with OSMF. While further research is needed to confirm these results and explore clinical applications, this study provides a solid foundation for future investigations into simvastatin's role in managing OSMF.

The study's findings regarding the potential therapeutic effects of simvastatin on ANE-induced subdermal fibrosis in the context of Oral Submucous Fibrosis (OSMF) are of significant scientific value. The use of the BALB/c mouse model and the comprehensive analysis of skin thickness, fibrosis, and collagen deposition provide robust support for the study's conclusions.

Given the importance of OSMF as a chronic oral disorder with potential malignancy and the lack of established treatments, the results presented in this manuscript have the potential to make a substantial impact in the field. I believe that this manuscript will be of great interest to a wide range of readers, including researchers, clinicians, and healthcare professionals.

I strongly recommend the publication of this manuscript as it not only advances our understanding of OSMF but also suggests a promising avenue for future research and clinical applications. The well-structured study and clear presentation make it a valuable contribution to the scientific literature.

Kind regards,

 

 

Author Response

Here is my point-by-point response to the reviewer's comments:

 

On the overall quality and contribution of the paper:

 

Reviewer’s comment: The paper is not only well-designed but also very clearly written. The research is thought-provoking and has been meticulously carried out.

 

Response: Thank you very much for recognizing the quality of our work. We have endeavored to ensure that the design and presentation of our research meet the highest scientific standards.

 

On the study of simvastatin in OSMF treatment:

 

Reviewer’s comment: The study holds significant scientific value concerning the therapeutic potential of simvastatin against ANE-induced subdermal fibrosis.

 

Response: We do believe that simvastatin may have immense potential in the treatment of OSMF and hope that our findings will serve as compelling evidence for further research and treatment.

 

On the experimental methods and conclusions:

 

Reviewer’s comment: The use of the BALB/c mouse model, along with a comprehensive analysis of skin thickness, fibrosis, and collagen deposition, provides robust support for the research conclusions.

 

Response: Thank you for recognizing the precision and efficacy of our methods. We believe these analyses form a solid foundation for our conclusions.

 

In conclusion:

 

I once again thank the reviewer for their positive feedback and suggestions. We are confident that our work offers a fresh perspective on the treatment of OSMF and hope that it will resonate with a broader readership.

 

Looking forward to your positive response. Thank you!