Tumor Necrosis Factor Superfamily 14 Regulates the Inflammatory Response of Human Dental Pulp Stem Cells

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript titled “Tumor Necrosis Factor Superfamily 14 Regulates the Inflammatory Response of Human Dental Pulp Stem Cells” presents a study of TNFSF14 effects on inflammatory responses in human pulp stem cells (hDPSCs). The topic is important given the implications for treating pulpal inflammation. The experimental design is robust, the data analyzed are well reported. However, to enhance the clarity, depth and overall impact of the study, there are several areas where the manuscript could be improved.

1.      The Abstract presents the aims of the study in a more detailed view, compared to the aims mentioned in the Introduction. The authors should rephrase this.

2.      Introduction well describes the background; however, it would benefit from a more detailed discussion on the role of TNFSF14 in modulating immune responses, especially in a oral/ dental context. Also, the aims should be emphasized in a more in-depth analysis.

3.      The Methods are generally well-described. However, the study design should be integrated clearly and systematically within the section to maintain coherence and flow. So separate sections, such as overview of the study design, samples/ groups, experimental setup, data measurement and analysis should be included, and the Methods should be re-organized accordingly.

4.      There should also be an indication of whether and where the raw data are available, and any supplementary information (authors should indicate whether supplementary methods or data are available).

5.      Results - for an in vitro experiment, the results section should clearly and systematically present the findings, starting with a summary of the key findings without interpreting the data.

6.      Results - present the data on cell viability quantitatively. Use graphs to illustrate changes over time or between groups. If there is extensive data, consider including supplementary material and reference it appropriately in this section.

7.      Discussion -explain the theoretical implications of the findings and discuss any potential practical applications. Highlight how this research contributes to the broader field and its relevance to clinical practice.

8.      Discussion - identify the limitations of this study and discuss any factors that could affect the validity of your results and how they might be addressed in future research.

9.       Discussion- suggest areas for future research based on the main findings. and highlight specific questions that were raised during your research or that remain unanswered.

10. Conclusion section does not exists – please conclude the findings, including the limitations and future search strategies, as well as possible implications in the clinical context.

Author Response

Review Report Form Reviewer 1

 

Dear Reviewer,

We would like to thank you for the constructive comments regarding our submitted manuscript (Reference number: cimb-3329941) which will make it a stronger piece of science.

 

Comments and Suggestions for Authors

The manuscript titled “Tumor Necrosis Factor Superfamily 14 Regulates the Inflammatory Response of Human Dental Pulp Stem Cells” presents a study of TNFSF14 effects on inflammatory responses in human pulp stem cells (hDPSCs). The topic is important given the implications for treating pulpal inflammation. The experimental design is robust, the data analyzed are well reported. However, to enhance the clarity, depth and overall impact of the study, there are several areas where the manuscript could be improved.

1. The Abstract presents the aims of the study in a more detailed view, compared to the aims mentioned in the Introduction. The authors should rephrase this.

Thank you for addressing this point. The Introduction and the Abstract have been rewritten to address your comment. (page1, line 15-17; page 3, paragraph 3, line 124-127)

2. Introduction well describes the background; however, it would benefit from a more detailed discussion on the role of TNFSF14 in modulating immune responses, especially in a oral/ dental context. Also, the aims should be emphasized in a more in-depth analysis.

We appreciate your constructive feedback. The role of TNFSF14 in modulating immune responses including oral context has been added in the Introduction (page 3, paragraph 2, line 104 – 123). However, there are limited studies that examined the role of TNFSF14 in the oral/dental context.

3. The Methods are generally well-described. However, the study design should be integrated clearly and systematically within the section to maintain coherence and flow. So separate sections, such as overview of the study design, samples/ groups, experimental setup, data measurement and analysis should be included, and the Methods should be re-organized accordingly.

Thank you for your helpful suggestion. We have restructured the Materials and Methods section to incorporate the recommended subsections. (page 3-6, paragraph 4, line 130-235)

4. There should also be an indication of whether and where the raw data are available, and any supplementary information (authors should indicate whether supplementary methods or data are available).

We appreciate your insightful recommendation. The manuscript included most of the data, however, during submission it was indicated that further details could be obtained by contacting the corresponding author.

5. Results - for an in vitro experiment, the results section should clearly and systematically present the findings, starting with a summary of the key findings without interpreting the data.

Thank you for your feedback. We carefully organized the Results section to thoroughly describe the findings of our in vitro experiment and we have added a brief summary of key findings at the beginning of this section. (page 6 , paragraph 5, line 238-240)

6. Results - present the data on cell viability quantitatively. Use graphs to illustrate changes over time or between groups. If there is extensive data, consider including supplementary material and reference it appropriately in this section.

Thank you for your insightful comment. We developed four different graphs, to demonstrate the difference of cell viability among groups at each time point. The graphs have been added into the Results section. (page 7, line 247)

7. Discussion -explain the theoretical implications of the findings and discuss any potential practical applications. Highlight how this research contributes to the broader field and its relevance to clinical practice.

Thank you for the great suggestion. The theoretical implications of the findings as well as practical applications have been added to the Discussion section (page 10 and 11, paragraph 8, line 321-327)

8. Discussion - identify the limitations of this study and discuss any factors that could affect the validity of your results and how they might be addressed in future research.

Thank you for your helpful comments. The discussion was modified to address this point (page 11, paragraph 2, line 328-333).

9. Discussion- suggest areas for future research based on the main findings. and highlight specific questions that were raised during your research or that remain unanswered.

Thank you for the feedback. The discussion was modified to address this point (page 11, paragraph 2, line 328-333).

10. Conclusion section does not exists – please conclude the findings, including the limitations and future search strategies, as well as possible implications in the clinical context.

We appreciate your useful recommendation. A Conclusion section heading has been added (page 11, paragraph 4, line 340). As far as including the limitations and future search strategies, as well as possible implications in the clinical context is concerned, this has been addressed in our response to points 8 and 9 above, however, if you feel it is necessary to add them to the conclusion section, we will be happy to do so.

Reviewer 2 Report

Comments and Suggestions for Authors

1- The role of different types of cytokines must be added in the introduction, not in the discussion

2- the scientific must be italic

3- please clear the groups in section 2.3

4-line 134 the experiments were conducted in duplicate, must be in triplicate  not duplicate 

5-  in all figures  (Tukey post-hoc test), must add alphabetical instead of stars

6- Please add how to calculate fold change in material and methods

Author Response

Review Report Form Reviewer 2

 

Dear Reviewer,

We would like to thank you for the constructive comments regarding our submitted manuscript (Reference number: cimb-3329941) which will make it a stronger piece of science.

 

Comments and Suggestions for Authors

1- The role of different types of cytokines must be added in the introduction, not in the discussion

Thank you for your valuable feedback. We agree with your suggestion, therefore, we transferred the relevant text from the Discussion to the Introduction and modified accordingly to blend smoothly in the manuscript. (page 2, paragraph 4, line 78-91)

2- the scientific must be italic

We went through the article and confirmed that all scientific terminologies are italicized in accordance with https://www.mdpi.com/authors/layout

3- please clear the groups in section 2.3

We appreciate your comment. Section 2.3 has been updated to provide a cleared description of the study groups. (page 3, paragraph 5, line 138-142).

4-line 134 the experiments were conducted in duplicate, must be in triplicate not duplicate 

Thank you for bringing our attention to this point. The experiments were conducted in two independent experiments with 9 samples in each experimental group leading to a total of n=18. The manuscript was modified accordingly (page 4, paragraph 2, line 169-170).

5-  in all figures  (Tukey post-hoc test), must add alphabetical instead of stars

All figures have been updated using alphabetical labels rather than stars to indicate statistically significant differences as shown by Tukey’s post-hoc test. (page 7, line 247; page 8, line 257; page 9, line 270)

6- Please add how to calculate fold change in material and methods

We appreciate your feedback. In the Materials and Methods section, we have included a concise explanation of the fold change calculation. Fold change was determined by normalizing the LTA-only group to a value of 1 and calculating the other groups compared to it. (page 6, paragraph 3, line 222-224).

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for giving me an opportunity to review the manuscript titled “Tumor Necrosis Factor Superfamily 14 Regulates the Inflammatory Response of Human Dental Pulp Stem Cells”

I have few comments which I believe can help in improving the overall quality of the manuscript

1.       The similarity iThenticate report reveals 38 % similarity which is very high. Please make necessary changes and try to bring it below 20% (or as per journals acceptable limits).

2.       Please state null hypothesis and later in discussion write whether null hypothesis is rejected or accepted

3.       Sections 2.1., 2.4.1, 2.5.1. of methodology has very high similarity. Please rewrite it in own words.

4.       Please write who performed all procedures? Was the operator trained enough? How test was standardized?  How operator bias was controlled? How blinding was done?

5.       Quality of Figure 2 & 3 should be improved.

6.       Add study limitations

7.       Make separate sub heading for conclusion.

Author Response

Review Report Form Reviewer 3

 

Dear Reviewer,

We would like to thank you for the constructive comments regarding our submitted manuscript (Reference number: cimb-3329941) which will make it a stronger piece of science.

 

Comments and Suggestions for Authors

Thank you for giving me an opportunity to review the manuscript titled “Tumor Necrosis Factor Superfamily 14 Regulates the Inflammatory Response of Human Dental Pulp Stem Cells”

I have few comments which I believe can help in improving the overall quality of the manuscript

1. The similarity iThenticate report reveals 38 % similarity which is very high. Please make necessary changes and try to bring it below 20% (or as per journals acceptable limits).

Thank you for bringing our attention to this point. The similarity index has been reduced to within the journal's acceptable limits by rephrasing overlapping content. The PlagScan plagiarism analysis program showed a score of less than 20%. We are pleased to provide you with the similarity report upon request.

2. Please state null hypothesis and later in discussion write whether null hypothesis is rejected or accepted

Thank you for your comment. The null hypothesis was stated in the introduction section of the manuscript, and we explained why it was rejected in the Discussion section based on our findings. (page 3, paragraph 3, line 127-128) and (page 10, paragraph 3, line 289-290)

3. Sections 2.1., 2.4.1, 2.5.1. of methodology has very high similarity. Please rewrite it in own words.

We appreciate your useful recommendation. The Materials and Methods section has been re-organized and rewritten to enhance originality and minimize similarity. (page 3, paragraph 4, line 130)

4. Please write who performed all procedures? Was the operator trained enough? How test was standardized? How operator bias was controlled? How blinding was done?

 Thank you for your comment. Each testing procedures was conducted by a single blinded operator with extensive training and experience that particular area. The tests were standardized in accordance with laboratory protocols that are aligned with companies’ guidelines. The operator was blinded by handling samples that were coded. The following sentence was added “Each testing procedures was conducted blindly by a single trained operator” (page 3, paragraph 4, line 135-136)

5. Quality of Figure 2 & 3 should be improved.

We appreciate your suggestions. We have enhanced the quality of Figures 2 and 3 to guarantee that they are clear and adhere to the journal's standards. (page 8, line 257; page 9, line 270)

6. Add study limitations

Thank you for your recommendation. We included study limitations in the Discussion section (page 11, paragraph 2, line 328-333).

7. Make separate sub heading for conclusion.

Thank you for the comments. We have added a conclusion section (page 11, paragraph 4, line 340).

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

the authors have improved the manuscript

Reviewer 2 Report

Comments and Suggestions for Authors

Accept in present form

Reviewer 3 Report

Comments and Suggestions for Authors

Changes made were satisfactory.
Manuscript can be accepted in the current form