-->PONE-D-24-56554-->-->Green synthesized Polyscias fulva silver nanoparticles ameliorate Uterine Fibroids in Female Wistar Albino Rats-->-->PLOS ONE

Dear Dr. Ahmed,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.-->-->

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Rajesh Kumar Singh, Ph.D.

Academic Editor

PLOS ONE

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 [This study was funded by COMSTECH-NAPRECCA Consortium Through a  PhD Fellowship (award number: 3(250)/23-COMSTECH) awarded to KK at the International center for Chemical and Biological Sciences (ICCBS), University of Karachi.]. 

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Additional Editor Comments:

The manuscript entitled "Green synthesized Polyscias fulva silver nanoparticles ameliorate Uterine Fibroids in Female Wistar Albino Rats" needs revision as per the suggestions of the reviewers.

[Note: HTML markup is below. Please do not edit.]

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: Yes

Reviewer #2: No

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

Reviewer #1: Yes

Reviewer #2: No

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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: No

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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: No

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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: A good and comprehensive study addressing non surgical treatment for a common gynaecological problem affecting many women with different presentations however, i give the following minor comments:

-Abrrevations: i suggest to be included in a seperate section at the begining of the manuscript.

-Design of the study: should be stated in the methodology section as well as linked to the title.

Reviewer #2: Some of the suggestions that could improve the quality of this work include:

1. Polyscias fulva silver nanoparticles (PFAgNPs) reported the synthesis method without sufficient characterization of essential reaction conditions including temperature, reaction time and reducing agent that are key for reproducibility.

2. UV-visible spectroscopy shows maximum absorbance at 425 nm, but there is no comparison of this value with other silver nanoparticles formulations to confirm this observation.

3. Characterization of nanoparticle size by DLS (107.4 nm), XRD (25 nm) and SEM (35 nm) show discrepancies and lack of clarification about aggregation state or size variation under biological conditions.

4. The toxicity assessment does not mechanistically explain the lethargy, hyperventilation, and mortality at higher dosages, and does not explore markers of oxidative stress or inflammatory response.

5. The absence of a dose-response curve for the therapeutic effects hampers the identification of the relevant effective dose unaccompanied by adverse histological effects.

6. Sex hormone (estrogen and progesterone) and serum parameters (cholesterol, proteins) transduction effects need to be further described in terms of their biochemical mechanisms and possible connections to uterine fibroid regression.

7. The histological finding supported by morphometric determination or uterine tissue score in grade is not enough.

8. Discuss the few WaveFlex Biosensors in the literature survey to get interest in the readers. Advanced modalities like PFAgNPs may yet represent potential therapeutics, but studies need to consider long-term stability under physiological conditions.

9. The investigator has stated that without a control AgNP group (no Polyscias fulva present), it cannot be determined whether the observed effects are because of the plant extract or induced by the silver nanoparticles.

10. The limitations of extrapolation of Wistar rats to humans are discussed, but possible strategies, such as performing in vitro human cell studies to bridge this knowledge gap prior to a clinical trial, are not suggested.

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

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Reviewer #1: Yes:  Mohsen M A Abdelhafez

Reviewer #2: No

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Green synthesized Polyscias fulva silver nanoparticles ameliorate Uterine Fibroids in Female Wistar Albino Rats

PONE-D-24-56554R1

Dear Dr. Ahmed,

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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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Rajesh Kumar Singh, Ph.D.

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: All comments have been addressed

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

-->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: Yes

Reviewer #2: Yes

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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: Yes

Reviewer #2: Yes

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-->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: Thank you for the prompt response and appreciate addressing all the comments and wish you to continue research in same topic.

Reviewer #2: Authors have revised the manuscript properly. They have addressed the comments. Now, it is suitable 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: Yes:  Mohsen M A Abdelhafez

Reviewer #2: No

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