PONE-D-20-33956

Combination treatment of dendrosomal nanocurcumin and low-level laser therapy develops proliferation and migration of mouse embryonic fibroblasts and alter TGF-β, VEGF , TNF-α and IL-6 expressions involved in wound healing process

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The concept of this work is interesting, however, the manuscript suffers from significant grammatical and syntax errors, and i strongly suggest editing whole of the manuscript by a native-English speaker before proceed for the publication. Anyway, the major revision needed and the below points should be addressed before any publication:

1. The introduction needs major revision; please add more up-to-date prestigious papers related to the background of your work

2. Regarding the UV absorbance (Fig S1); i guess your sample tube or quartz cell is not clean, or there is problem with your DNC sample. Please re-investigate the UV experiment, and please add x- and y-axis labels to the graphs. Also, i see negative phase absorption in your UV, please have a complete and in-depth discussion regarding this.

3. Regarding the PL (Fig S2); why you state in the x-axis the time? this is the wavelength!!! what is the role of time here? also what is the intensity unit? a.u.?

4. The same question and concerns regarding the UV of Fig s3. arises, please be careful and address them.

5. Regarding the Fig. S4; why you are not trying to remove the lines inside the figure? is odd for me; please clear the graphs and set a clean white background for all of them

6. Regarding Fig. S5; please mark the states with significant changes, i cannot follow your text with the figure changes

7. Why there is no TEM, DLS and FESEM of the used DNC? how can i be sure that your used DNC is in the nano-dimension. You should provide all of the TEM, FESEM and DLS results to prove the nano-sized curcumin.

8. The quality of all of the images are really poor; please replace all of the images with high-quality one.

9. Please compare your results with the literature; it would be better to add a table regarding this

10. Also, i suggest to provide the raw data including the flowcytometry raw datas as well as the raw MTT results in the supplementary information; i need to be sure about the validity of your results

11. Please be careful about the syntax errors: 450nm is wrong!! 450 nm is in the appropriate form.

Major revision

Reviewer #2: This is an interesting study that looks at the proliferation, motility of embryonic fibroblasts and the expression profiles TGF-β,VEGF , TNF-α and IL-6 following application of nanocurcumin and 450 nm light.

Before publication, please consider the following comments.

P 4 line 5: what culture medium was used?

P4 4. Line 6: Although citations were included, some brief details of this optimized protocol should be included.

P4 Line 8: please add the exact model used and/or emission spectrum

P4 line 34: please defined DMEM when first used.

P5. Line 7: paint? Do you mean the pigment?

P5 Line 10: indeed, the MTT assay is a measure of metabolic activity. Metabolism is highly dynamic so I am unsure one could claim that it is strictly associated with viability?

P5 Line 12: what were the doses of nanocurcumin and/or light?

P5. Line 20: which experimental groups? please be specific.

P6. Line 4: were the proteins not extracted? Or was it just the supernatant? I would think it would be difficult to get enough protein concentration this way.

P6 Line 18: the authors need to provide the exact concentrations/doses used.

P 7: Line 13. Were the experiments performed on 3 different days?

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Reviewer #1: No

Reviewer #2: No

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Combination treatment of dendrosomal nanocurcumin and low-level laser therapy develops proliferation and migration of mouse embryonic fibroblasts and alter TGF-β, VEGF , TNF-α and IL-6 expressions involved in wound healing process

PONE-D-20-33956R1

Dear Dr. sadeghizadeh,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Michael R Hamblin

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: No

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The authors have appropriately responded to my concerns and I recommend acceptance of the manuscript for publication.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No