Targeting CD3-CD16+CD56+ NK Cells and NK Cell Activity by Intralipid in the Management of Reproductive Failure

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review topic is interesting and is necessary , please consider the following comments.

The review is too broad in scope. Although the title states 'Targeting CD3-CD16+CD56+ NK and NKT Cells by Intralipid,' it broadly discusses the use of Intralipid treatment for infertility. While there are numerous citations describing the benefits of Intralipid in improving IVF results, none specifically target NKT cells. The title should be changed to reflect this.

Considering that IVIg, Intralipid, and sHLA-G suppressed NK cell cytotoxicity (Allahbadia, G.N. J Obstet Gynecol India 65, 213–217 (2015). https://doi.org/10.1007/s13224-015-0732-7),what are the specific advantages of Intralipid therapy? especially in comparison to other forms of immune tolerance molecules.

It would be beneficial to include more illustrative figures explaining how Intralipid therapy can enhance fertility outcomes. 

Comments on the Quality of English Language

The English can be improved; please consider restructuring specific sentences to convey the meaning more easily.

Author Response

Comments and Suggestions for Authors

The review topic is interesting and is necessary , please consider the following comments.

• Thank you for your valuable feedback and for recognizing the importance of the topic. I appreciate your insightful comments, which will help refine and improve the clarity and focus of the manuscript. Below are our responses to your suggestions.

The review is too broad in scope. Although the title states 'Targeting CD3-CD16+CD56+ NK and NKT Cells by Intralipid,' it broadly discusses the use of Intralipid treatment for infertility. While there are numerous citations describing the benefits of Intralipid in improving IVF results, none specifically target NKT cells. The title should be changed to reflect this.

• We acknowledge your concern regarding the breadth of the review. While our intention was to provide a comprehensive overview of Intralipid therapy in the context of infertility via targeting CD3-CD16+CD56+ NK and NKT cells, we agree that in the literature, we have data only for targeting NK cells, but no data on NKT cells. We revised the title to more accurately reflect the content, emphasizing the broader context of Intralipid’s role in infertility treatment, and focusing on NK cells and NK cell activity.

Considering that IVIg, Intralipid, and sHLA-G suppressed NK cell cytotoxicity (Allahbadia, G.N. J Obstet Gynecol India 65, 213–217 (2015). https://doi.org/10.1007/s13224-015-0732-7),what are the specific advantages of Intralipid therapy? especially in comparison to other forms of immune tolerance molecules.

• Your suggestion to further elaborate on the specific advantages of Intralipid therapy in comparison to other immune tolerance molecules, such as IVIG and sHLA-G, is well taken. We expanded this section to provide a more detailed analysis, highlighting the unique aspects of Intralipid therapy, particularly its safety profile, cost-effectiveness, and mechanism of action. This comparison has been supported by the literature, including the reference you cited (Allahbadia, 2015).

It would be beneficial to include more illustrative figures explaining how Intralipid therapy can enhance fertility outcomes.

• We agree that incorporating more illustrative figures would enhance the manuscript and make the mechanisms and benefits of Intralipid therapy clearer to the reader. We added detailed diagrams that visually represent how Intralipid therapy interacts with NK and NKT cells and other components of the immune system to improve fertility outcomes. These figures will aim to simplify complex processes and provide a clearer understanding for a broader audience.

 

Comments on the Quality of English Language

The English can be improved; please consider restructuring specific sentences to convey the meaning more easily.

• We appreciate your suggestion regarding the language and clarity of the manuscript. We have carefully reviewed the text and made improvements to the English, particularly by restructuring specific sentences to convey the meaning more clearly and effectively. We are confident that these changes have enhanced the readability of the manuscript and better communicated the key points of our review. Thank you once again for your constructive comments.

 

Reviewer 2 Report

Comments and Suggestions for Authors

To: Targets MDPI

Dear EIC,

Dear AE,

This is my review report for the manuscript ID: targets-3064852

The manuscript reviewed immunological risk factors in recurrent pregnancy loss, with particular attention to the mechanisms of intralipid action and outcomes of clinical trials regarding the efficacy and safety of tralipid infusions in women with reproductive failure. This is qualitative study which I think couldn’t add some novel things to the field. Performing meta-analyses are highly suggested to expand the edges of the filed. However, I carefully read the manuscript and prepare my comments hope to level up the quality of that.  

 

Comments

·      The manuscript should supply several figures, illustrations, and pathway maps, especially for immunological pathways illustrations. It is highly recommended to design these figures by a professional graphist used by Adobe Illustrator or Adobe Photoshop software.

·      I saw some minor writing errors. The manuscript should be checked carefully. Line: 72 space between words.

·      Section 2 should be divided to several subsections, according to the manuscript flow.

·      Line 129: fit the title writing style.

·      Section 3 should be divided to several subsections, according to the manuscript flow.

·      The major error of writing is the exceeded use of paragraphs. Kindly recheck that.

Good luck

Comments on the Quality of English Language

·      I saw some minor writing errors. The manuscript should be checked carefully. Line: 72 space between words.

 

·      The major error of writing is the exceeded use of paragraphs. Kindly recheck that.

Author Response

To: Targets MDPI

Dear EIC,

Dear AE,

This is my review report for the manuscript ID: targets-3064852

The manuscript reviewed immunological risk factors in recurrent pregnancy loss, with particular attention to the mechanisms of intralipid action and outcomes of clinical trials regarding the efficacy and safety of tralipid infusions in women with reproductive failure. This is qualitative study which I think couldn’t add some novel things to the field. Performing meta-analyses are highly suggested to expand the edges of the filed. However, I carefully read the manuscript and prepare my comments hope to level up the quality of that.  

• Authors` responses: Thank you for your thorough review of our manuscript and for providing valuable feedback. We appreciate the time and effort you invested in reading and commenting on our work. Below, we have addressed each of your suggestions.

Comments

• The manuscript should supply several figures, illustrations, and pathway maps, especially for immunological pathways illustrations. It is highly recommended to design these figures by a professional graphist used by Adobe Illustrator or Adobe Photoshop software.

• Authors` responses: As scientists dedicated to effectively communicating our research, we understand the importance of clear and accurate visual representation of complex ideas. We have created 2 new figures on implantation and immunomodulatory therapy for reproductive failure. These visuals have been carefully crafted using tools to ensure they meet high standards of clarity and precision. We believe these figures will significantly contribute to the reader's understanding of our findings.

• I saw some minor writing errors. The manuscript should be checked carefully. Line: 72 space between words.

• Authors` responses: We conducted a thorough review of the manuscript and corrected all minor writing errors. Regarding the spacing issue on line 72, we corrected it by making it superscript as it should be.

• Section 2 should be divided to several subsections, according to the manuscript flow.

• Authors` responses: We have restructured Sections 2 and 3 by dividing them into several subsections, which better align with the manuscript's flow. This reorganization has improved the logical progression and readability of the content.

• Line 129: fit the title writing style.

• Authors` responses: Thank you for the helpful suggestion. We have formatted the title on line 129 to ensure consistency with the writing style throughout the manuscript. The changes have been made to align with the manuscript's overall format.

• Section 3 should be divided to several subsections, according to the manuscript flow.

• Authors` responses: We have restructured Sections 3 as suggested to improve the logical progression and readability of the content.

• The major error of writing is the exceeded use of paragraphs. Kindly recheck that.

• Authors` responses: We recognized the excessive use of paragraphs in the original manuscript. We have streamlined the text by merging and reorganizing paragraphs where appropriate, resulting in a more concise and cohesive narrative.

Good luck

 

Comments on the Quality of English Language

• I saw some minor writing errors. The manuscript should be checked carefully. Line: 72 space between words.
• The major error of writing is the exceeded use of paragraphs. Kindly recheck that.

• Authors` responses: We believe these revisions have significantly enhanced the quality of the manuscript, both in content and presentation. Thank you again for your constructive feedback and for helping us improve our work.

Reviewer 3 Report

Comments and Suggestions for Authors

The review manuscript “Targeting CD3-CD16+CD56+ NK and NKT Cells by Intralipid 2 in the Management of Reproduction Failure” describes the importance of intralipid infusions for preventing reproductive failure in women. The article is interesting, but it needs a major edition.

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Author Response

Comments and Suggestions for Authors

The review manuscript “Targeting CD3-CD16+CD56+ NK and NKT Cells by Intralipid 2 in the Management of Reproduction Failure” describes the importance of intralipid infusions for preventing reproductive failure in women. The article is interesting, but it needs a major edition.

• Authors` responses: Thank you for your review of our manuscript. We appreciate your recognition of the manuscript’s significance and your comments on its need for a major revision.
• Authors` responses: In the revised manuscript, we focused on refining the content to enhance its readability, ensuring that our discussion is both comprehensive and well-organized. Additionally, we carefully edited the text to address any issues that might detract from the manuscript’s quality. We believe that with these revisions, the manuscript will be significantly strengthened, and we look forward to presenting a more polished version.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Satisfied with the response and corrections. 

Author Response

Satisfied with the response and corrections. 

• Authors` response: Thank you for your positive feedback and for taking the time to review our revisions. We appreciate your acknowledgment of our efforts to address your comments and suggestions.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear EIC,

Dear AE,

I convinced by responses to my comments.

 

Author Response

I convinced by responses to my comments.

• Authors` response: Thank you for your review and for considering our responses. We appreciate your time and effort in evaluating our work.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have not corrected most of the suggestions. Please submit it again with change control and a response letter explaining how they made the changes and why not when they didn't.

Comments on the Quality of English Language

No major concerns

Author Response

The authors have not corrected most of the suggestions. Please submit it again with change control and a response letter explaining how they made the changes and why not when they didn't.

• Authors` response: Thank you for your valuable feedback. We would like to clarify that we have made substantial revisions to the manuscript based on the suggestions provided by all three reviewers. These changes are clearly highlighted in the revised version. Although we did not receive specific suggestions from the third reviewer, we made improvements based on the detailed comments from the other reviewers. Additionally, we have outlined the changes made and provided explanations for any suggestions that were not fully implemented. Thank you for your consideration.
• Here are all the specific changes:
• We changed the title - While our intention was to provide a comprehensive overview of Intralipid therapy in the context of infertility via targeting CD3-CD16+CD56+ NK and NKT cells, we agree that in the literature, we have data only for targeting NK cells, but no data on NKT cells. We revised the title to more accurately reflect the content, emphasizing the broader context of Intralipid’s role in infertility treatment, and focusing on NK cells and NK cell activity.
• We further elaborated on the specific advantages of Intralipid therapy in comparison to other immune tolerance molecules, such as IVIG and sHLA-G. We expanded this section to provide a more detailed analysis, highlighting the unique aspects of Intralipid therapy, particularly its safety profile, cost-effectiveness, and mechanism of action. This comparison has been supported by the literature, including the reference you cited (Allahbadia, 2015).
• We agree that incorporating more illustrative figures would enhance the manuscript and make the mechanisms and benefits of Intralipid therapy clearer to the reader. We added detailed diagrams that visually represent how Intralipid therapy interacts with NK and NKT cells and other components of the immune system to improve fertility outcomes. These figures will aim to simplify complex processes and provide a clearer understanding for a broader audience.
• We have carefully reviewed the text and made improvements to the English, particularly by restructuring specific sentences to convey the meaning more clearly and effectively. We are confident that these changes have enhanced the readability of the manuscript and better communicated the key points of our review.
• We conducted a thorough review of the manuscript and corrected all minor writing errors. Regarding the spacing issue on line 72, we corrected it by making it superscript as it should be.
• We have restructured Sections 2 and 3 by dividing them into several subsections, which better align with the manuscript's flow. This reorganization has improved the logical progression and readability of the content.
• We have formatted the title on line 129 to ensure consistency with the writing style throughout the manuscript. The changes have been made to align with the manuscript's overall format.
• We have restructured Section 3 as suggested to improve the logical progression and readability of the content.
• We recognized the excessive use of paragraphs in the original manuscript. We have streamlined the text by merging and reorganizing paragraphs where appropriate, resulting in a more concise and cohesive narrative.