The Influence of Neurotrophins on the Brain–Lung Axis: Conception, Pregnancy, and Neonatal Period

Round 1

Reviewer 1 Report

This review by D’Amico et al. nicely covered a broad range of information on neurotrophins role in lung development. I have a few suggestions on the writing:

1) Page 2, line 49. The expression ‘preproprotein precursors’ is improper. It is either ‘preproprotein’ or ‘protein precursor’.

2) Page 2, line 57. ‘Genomic and non-genomic mechanism’ is not common expression. The authors may consider to elaborate it by adding explanations such as that genomic involves  transcription, receptors are located in the nucleus, and thus is slow; whereas non-genomic means direct response in the cytoplasm thus is fast.

3) Page 3, line 110-114 seems not enough to be separated as a paragraph. It is talking about one NT and similar to the previous paragraph, about its role in prenatal development. The authors may consider combine it to previous paragraph.

4) Page 4, line 153-163 talked about that airway epithelium may not be a major receiver of NTs, then the next paragraph talked about confirmation of receptors expressed in airway epithelium and their response to NTs. The authors may need to add a few transition sentences to make the flow easier to follow.

5) Page 5, line 211. ‘may be produced by nerves’. Line 234, ‘vasculature and determine a vascular remodeling process’.

6) Page 7, line 300-303. Again, the authors may consider combine this paragraph to previous one. It can serve as examples to the information of previous paragraph.

7) Page 8, line 332-334. It’s an example serving previous paragraph. The authors may consider combine this paragraph to previous one.

8) Page 9, line 393. ‘promoted by the KFN in the post-natal period’.

9) Page 10, line 461. The authors may consider add some introductory sentences before directly talking about specific studies.

Needs proofreading.

Author Response

REVIEWER 1

Point 1: “Page 2, line 49. The expression ‘preproprotein precursors’ is improper. It is either ‘preproprotein’ or ‘protein precursor’.”

Response: We are grateful to the Reviewer for the constructive comments to our manuscript. We modified the expression in “preproproteins” (page 2, line 51).

Point 2: “Page 2, line 57. ‘Genomic and non-genomic mechanism’ is not common expression. The authors may consider to elaborate it by adding explanations such as that genomic involves transcription, receptors are located in the nucleus, and thus is slow; whereas non-genomic means direct response in the cytoplasm thus is fast.”

Response: We modified the sentence (page 2, lines 59-62) as follows: “NTs’ function involves two types of mechanisms: a genomic one, consisting in a slow pathway regulating cell growth and survival, and typically inducing nuclear transcription processes and gene expression; and a non-genomic mechanism, which is faster and occurring in cytoplasm as a consequence of activation of rapid signaling”. Moreover, other information on the non-genomic pathway is reported in page 2, lines 80-83.

Point 3: “Page 3, line 110-114 seems not enough to be separated as a paragraph. It is talking about one NT and similar to the previous paragraph, about its role in prenatal development. The authors may consider combine it to previous paragraph.”

Response: We combined the lines 112-113 on page 3, to maintain the continuity of the topic on the prenatal development.

Point 4: “Page 4, line 153-163 talked about that airway epithelium may not be a major receiver of NTs, then the next paragraph talked about confirmation of receptors expressed in airway epithelium and their response to NTs. The authors may need to add a few transition sentences to make the flow easier to follow.”

Response: We added transition sentences on page 4, lines 159-168.

Point 5: “Page 5, line 211. ‘may be produced by nerves’. Line 234, ‘vasculature and determine a vascular remodeling process’.”

Response: We corrected the marked sentences.

Point 6: “Page 7, line 300-303. Again, the authors may consider combine this paragraph to previous one. It can serve as examples to the information of previous paragraph.”

Response: Page 7, we combined the lines 302-303.

Point 7: “Page 8, line 332-334. It’s an example serving previous paragraph. The authors may consider combine this paragraph to previous one.”

Response: Page 8, we combined the lines 333-334.

Point 8: “Page 9, line 393. ‘promoted by the KFN in the post-natal period’.”

Response: We corrected the marked sentence.

Point 9: “Page 10, line 461. The authors may consider add some introductory sentences before directly talking about specific studies.”

Response: We added an introductory sentence on page 10, lines 463-464 (“Human studies also supported the correlation between some NTs’ concentration at birth and the development of BPD”).

Reviewer 2 Report

The manuscript titled "The Role of Neurotrophins in the Development of the Brain-Lung Axis: from Conception to Birth" by D’Amico et al. provides a thorough examination of the involvement of neurotrophins (NTs) in various physiological and pathological processes related to lung development, respiratory regulation, and neonatal lung diseases. Below are my comments regarding the manuscript:

• The manuscript effectively outlines the main focus and objectives, providing readers with a clear understanding of the topic.
  
  
• The manuscript demonstrates a comprehensive exploration of NTs' roles, presenting well-researched insights into complex scientific concepts. Clearer transitions between subsections could improve readability and flow, facilitating a smoother progression of ideas throughout the manuscript.
• Providing additional context on the clinical relevance of NT-mediated mechanisms in neonatal lung diseases would enhance the practical utility of the article for healthcare professionals.
  
  
• Comparison with Previous Work: This is my major concern about the article. The manuscript shares similarities with a previously published article by Sara Manti in the 'International Journal of Molecular Sciences,' titled "Neurotrophins: Expression of Brain-Lung Axis Development." While both articles delve into the influence of NTs on respiratory and neurological processes, the reviewed manuscript focuses more on the context of pregnancy. It's essential to clearly distinguish the contributions of the reviewed manuscript from the previous work, emphasizing how it adds new insights to the existing literature while acknowledging any overlap in content.

Recommendations for Revision:

1. Consider restructuring sections and enhancing transitions to improve the manuscript's organization and readability.
   
   
2. Providing clinical case examples or discussing implications for patient care could add depth to the discussion of the clinical relevance of NT-mediated mechanisms.
   
   
3. The authors should revise the title to better reflect the unique contributions of the manuscript and briefly acknowledge their previous article, highlighting how the current manuscript builds upon or complements their earlier work.
   
   
4. If possible include a figure in the manuscript summarizing the idea of review.

Author Response

REVIEWER 2

Point 1: “Consider restructuring sections and enhancing transitions to improve the manuscript's organization and readability.”

Response: We are grateful to the Reviewer for the constructive comments to our manuscript. We restructured sections adding some transition sentences or combining lines (page 4, lines 159-163; page 7, lines 302-303; page 8, lines 333-334; page 10, lines 463-464).

Point 2: “Providing clinical case examples or discussing implications for patient care could add depth to the discussion of the clinical relevance of NT-mediated mechanisms.”

Response: We have already discussed in our original article the implications for patients’ care (used of specific drugs) on page 10-11, lines 476-484. We added other specific sentences on page 11, lines 498-499, and on page 12, lines 518-519.

Point 3: “The authors should revise the title to better reflect the unique contributions of the manuscript and briefly acknowledge their previous article, highlighting how the current manuscript builds upon or complements their earlier work.”

Response: We revised the title in “The Influence of Neurotrophins on the Brain-Lung Axis: conception, pregnancy, and neonatal period. (page 1, lines 1-3)”. Moreover, we briefly acknowledge the previous article on page 1, lines 42-45.

Point 4: “If possible include a figure in the manuscript summarizing the idea of review.”

Response: We are grateful to the Reviewer for the suggestion. We added Figure 1 on page 11, lines 486-487.

Round 2

Reviewer 2 Report

The authors have addressed most of my comments; however, there are still numerous grammatical issues, and some sentences require rephrasing.

Errors such as "we focalized the attention" and "In this this review" should be corrected. I would suggest having the manuscript evaluated by an expert in English language editing to identify and rectify all grammatical errors.

The manuscript is generally well written; however, there are some grammatical errors that need to be corrected.

Author Response

We are grateful to the Reviewer for the constructive comments to our manuscript. We modified the sentences on page 1, lines 42-43, as requested. All mistakes have been corrected and some sentences have been rephrased in all sections of the manuscript as required by the Reviewer.