Ginkgolic acid attenuates e chinococcus granulosus  infection-induced hepatic fibrosis by inhibiting Smad4 SUMOylation

PLOS Neglected Tropical Diseases

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Kind regards,

Robert Adamu SHEY, Ph.D.

Guest Editor

PLOS Neglected Tropical Diseases

Jong-Yil Chai

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

Additional Editor Comments:

Dear Authors,

Kindly revise the manuscript, taking consideration all comments from the reviewers.

Kind regards

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1) Please ensure that the CRediT author contributions listed for every co-author are completed accurately and in full.

At this stage, the following Authors/Authors require contributions: Qiuyue Chen, Dan Dong, Xueting Yu, Xinyu Jiang, Huijiao Jiang, Jun Hou, Lianghai Wang, Junying Xu, Xiangwei Wu, and xueling chen. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

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Reviewers' Comments:

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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Conclusions

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-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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Editorial and Data Presentation Modifications?

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Reviewer #1: (No Response)

Reviewer #2: Please enhance the clarity of the bar charts in Figures 1 and 2�Please improve the resolution of all result figures in the manuscript�.

Please display the sample size for each group in the article's figures.

The SUMO1 Western blot band in Figure 4a appears blurred.

Some figures like e.g., immunofluorescence images lack scale bars .

Some references lack DOI or PMID numbers (e.g., Ref 3).

The inconsistent use of "Ginkgo acid"(Line 89) and "Ginkgolic acid"(Title) should be unified to "Ginkgolic acid (GA)".

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: This manuscript investigates the therapeutic potential of GA in alleviating liver fibrosis induced by Echinococcus granulosus infection, focusing on its inhibition of Smad4 SUMOylation and modulation of macrophage–hepatic stellate cell crosstalk. The study is well-structured, combining clinical samples, animal models, and in vitro experiments to comprehensively explore the molecular mechanism.

While the findings are promising and suggest GA as a potential anti-fibrotic agent, the manuscript requires revisions to enhance clarity, statistical rigor, and methodological detail.

For the Introduction Section

While the introduction touches upon multiple concepts—CE, GA, SUMOylation, macrophage polarization, and TGF-β/Smad signaling—the connections between these ideas are not seamlessly established. Although the research gap is mentioned, it should be more explicitly stated what specific unanswered question the study aims to address.

For the Methods Section

The authors please provide missing critical details regarding experimental procedures, statistical reporting, and cell culture conditions.

For the Results Section

The language often implies a direct and proven causal relationship where the data primarily show correlation. The narrative flow between some paragraphs is abrupt.

the Results section must be substantially revised to include essential statistical details, employ more precise and cautious language regarding mechanistic claims, and improve overall clarity and language quality.

For the Discussion Sections

While a limitations paragraph is included, it remains superficial. The authors should delve deeper: Pharmacokinetics/Pharmacodynamics�Specificity of GA�In vivo validation.

Reviewer #2: In the animal experiment, the purpose of the "GA safety group" is unclear; it is recommended to clarify its role as a drug toxicity control group.Additionally, detailed justification for initiating GA administration at the 8th week is lacking.

The mechanism by which GA inhibits Smad4 SUMOylation in Figure 4 lacks direct evidence (e.g., SENP1 overexpression/knockdown experiments).

Control experiments demonstrating GA's specificity in inhibiting SUMOylation are absent (e.g., comparison with other SUMO inhibitors).

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Reviewer #2: No

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Dear Dr. chen,

We are pleased to inform you that your manuscript 'Ginkgolic acid attenuates e chinococcus granulosus  infection-induced hepatic fibrosis by inhibiting Smad4 SUMOylation' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Robert Adamu SHEY, Ph.D.

Guest Editor

PLOS Neglected Tropical Diseases

Jong-Yil Chai

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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