Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review written by Alobaid A, Al Judeid R and Rai V provides an overview on the role of galectins in diabetes with an aim to focus on current knowledge on diabetic foot ulcer, knowledge gaps and future directions for novel drug targets, which is interesting. Unfortunately as written now there are redundancies that needs to be taken care of to improve readability.

Comments:

1. Diabetes means both type 1 and type 2 and even more subclasses. Are the results presented applicable to all types of diabetes? Clarify this in the review.
2. It is not easy to cover all literature but the reviews by Fryk E et al in Metabolites 2022 and by Thiemann & Baum (PMID 26907217)  should be cited mentioning a potential role of galectin-1  in obesity and type 2 diabetes including the pathophysiology of DFU.
3. The review can be shortened eg by referring to previous reviews and by doing so get rid of information that is repeated and not necessary to cover for describing the translational potential of galectins to treat DFU. 

Author Response

Comments: The review written by Alobaid A, Al Judeid R and Rai V provides an overview on the role of galectins in diabetes with an aim to focus on current knowledge on diabetic foot ulcer, knowledge gaps and future directions for novel drug targets, which is interesting. Unfortunately, as written now there are redundancies that needs to be taken care of to improve readability.

Response: Thank you for your comments and suggestions. We have revised the manuscript to address these concerns.

Concern 1: Diabetes means both type 1 and type 2 and even more subclasses. Are the results presented applicable to all types of diabetes? Clarify this in the review.

Response: Thank you for your comment. We have revised the manuscript and have mentioned that these findings are mainly associated with T2DM, but galectins are involved in type I, type II, and GDM.

Concern 2: It is not easy to cover all literature but the reviews by Fryk E et al in Metabolites 2022 and by Thiemann & Baum (PMID 26907217)  should be cited mentioning a potential role of galectin-1  in obesity and type 2 diabetes including the pathophysiology of DFU.

Response: Thank you for your comments and suggestions. We have included the text from these articles in the revised manuscript.

Concern 3: The review can be shortened eg by referring to previous reviews and by doing so get rid of information that is repeated and not necessary to cover for describing the translational potential of galectins to treat DFU. 

Response: Thank you for your comments and suggestions. We have revised the manuscript to address this issue.

Reviewer 2 Report

Comments and Suggestions for Authors

The review contains lots of data and interesting information about galectins and their implication in diabetic complications. However, it can be ambiguous and unfocused for the reader. Authors should deep into the potential role of galectins in the origin and evolution of diabetic foot ulcers. Therefore, authors must justify why is important to know the role of these factors in this field of diabetic complications.

Then, the role of galectins on diabetes (section 4) must be deleted. Thus, the title should be more precise. The order of galectin appearance must be conserved along the work. At the end, important issues as the potential use as therapeutic targets or diagnostic/prognostic biomarkers should be separated and further documented. Galectin can be secreted or excreted factors? from what tissue under diabetes? Also, at the end of the abstract, methodological details can be avoided. Some acronyms are repeated along the work (must be spelt out only once in the manuscript)

Author Response

Comments: The review contains lots of data and interesting information about galectins and their implication in diabetic complications. However, it can be ambiguous and unfocused for the reader.

Response: Thank you for your comments and suggestions.

 

Concern 1: Authors should deep into the potential role of galectins in the origin and evolution of diabetic foot ulcers. Therefore, authors must justify why is important to know the role of these factors in this field of diabetic complications.

Response: Thank you for your comments and suggestions. We have included Figure 2 in the revised manuscript to reflect the possible role of galectins in DFU pathogenesis.

 

Concern 2: Then, the role of galectins on diabetes (section 4) must be deleted. Thus, the title should be more precise.

Response: Thank you for your comments and suggestions. We agree that deleting the topic on the role of galectins in diabetes will reduce the length and the review will focus on DFU. However, the special issue is about the role of galectins in diabetes and its complication and the other reviewers want us to elaborate more on the underlying mechanisms in diabetes and its complications. In line with this, we have modified the sections and subsections and have removed the title “Galectins in Diabetes”.

 

Concern 3: The order of galectin appearance must be conserved along the work.

Response: Thank you for your comment. We have rearranged the sequence of galectins in each section. Now they in same order in each section.

 

Concern 4: At the end, important issues as the potential use as therapeutic targets or diagnostic/prognostic biomarkers should be separated and further documented.

Response: Thank you for your comments and suggestions. We have revised the manuscript and diagnostic/prognostic biomarkers, and therapeutic aspects have been discussed in separate sections.

 

Concern 5: Galectin can be secreted or excreted factors? from what tissue under diabetes?

Response: Thank you for your comment. We have revised the manuscript to discuss this aspect (section 5).

Concern 6: Also, at the end of the abstract, methodological details can be avoided.

Response: Thank you for your comment. We have revised the abstract.

 

Concern 7: Some acronyms are repeated along the work (must be spelt out only once in the manuscript)

Response: Thank you for your comment. We have checked the manuscript thoroughly to address this issue.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I congratulate the authors for improving the manuscript and I have no more comments.

Author Response

Comments: I congratulate the authors for improving the manuscript and I have no more comments.

Response: Thank you for your comments and suggestions to improve the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

The work has been improved and clarified. The potential role of galectin as biomarkers and therapeutic targets can be suggestive for future readers. So far, gal-3 has been demonstrated as a bona fide biomarker for cardiovascular or renal events after acute coronary syndrome in diabetic patients (doi: 10.3390/jcm14155264; 10.17219/acem/147665). The galectin blockade must be tested in human beings to further confirm this property. These issues should be discussed in the manuscript

 

Author Response

Comments: The work has been improved and clarified. The potential role of galectin as biomarkers and therapeutic targets can be suggestive for future readers. So far, gal-3 has been demonstrated as a bona fide biomarker for cardiovascular or renal events after acute coronary syndrome in diabetic patients (doi: 10.3390/jcm14155264; 10.17219/acem/147665). The galectin blockade must be tested in human beings to further confirm this property. These issues should be discussed in the manuscript.

Response: Thank you for your comments and suggestions to improve the manuscript. We have revised the manuscript to include the text from the studies suggested (doi: 10.3390/jcm14155264; doi: 10.17219/acem/147665).