Crosstalk Between the Spleen and Other Organs/Systems: Downstream Signaling Events

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

In this review, the authors first address general anatomical and physiological characteristics of the spleen, its general role in inflammation and in the immune system. Also, the functions of the red and white pulp and splenomegaly, which is the most common pathology of this organ, are explained. Subsequently, the authors mention the importance of the interactions between the spleen and other organs, which are called spleen-organ axes, and detail the most important axes: gut-spleen (lactic acid, n-butyric acid and short chain fatty acids as important topics), liver-spleen (and its relationship with nonalcoholic fatty liver disease, parasitosis and heavy metals), gut-spleen-skin (and its relationship with psoriasis), brain-spleen (and its relationship with white adipose tissue and psychological stress), and heart-kidney-spleen (and its relationship with heart failure and cardiac remodeling). Then, the authors explain the involvement of the spleen with hormones, endocrine system disruptors (microplastics, bisphenols), aging and environmental factors. Finally, the authors make a special appeal to physicians not to underestimate the spleen in the clinical field/practice.

The relevance of this review is based on the authors' work in compiling the different interactions and influences of the spleen with other organs/systems and diseases, mainly those associated with inflammation and the immune system. There are no similar reviews that investigate and analyze the spleen with the various organs and systems that are raised in this work.

Since more than 60% of the literature cited in this review was published from 2019 to date (2024), it is possible to affirm that the authors have taken care to use up-to-date references on the subject.

 

2019: 12 cites

2020: 17 cites

2021: 17 cites

2022: 33 cites

2023: 24 cites

2024: 13 cites

 

Total updated cites (2019-2024): 116 of 186 cites (62%)

 

Finally, I encourage the authors to review the document with the assistance of a native English speaker/teacher to correct grammatical details. Some suggestions and corrections to improve English grammar and general content:

·      In line 13, “…leading to various the spleen-organ axes”.

·      In line 16, “And what is more, these observations…” or “Furthermore, these observations…”

·      In line 17, “…identification of novel therapeutical therapeutic strategies targeted targeting several current diseases”.

·      In line 19, “Anyway, much work needs remains to be done to…”.

·      In line 31, “In this regards…”

·      In line 102, “Noteworthy, authors when compared comparing the reliability of the old acronym versus the new one, the authors found that 99% of patients with NAFLD met MASLD criteria”, or “Noteworthy, when the reliability of the old acronym was compared with the new one, the authors found that 99% of patients with NAFLD met MASLD criteria”.

·      In line 113, “Bacteroides uniforms” → “Bacteroides uniformis”

·      Check for “in vitro”, “in vivo” words and scientific names in italics throughout the document.

·      In line 186, “In adequate amounts, heavy metals are essential nutrients…” (Subject should not be skipped in new sentences).

·      In line 311, “These data, on the one hand, present…” (do not forget commas between linkers).

·      In line 361, “Psychological pressure stress” (optional)

·      In line 410-411, “positive (suppression of inflammation in myocardial tissue environment) and negative one…”

·      Figure 1 title is missing.

·      In line 437, “, it is without doubts clearly seen that the…” or “, undoubtedly, the spleen…”

·      In line 466, BPA has not been defined previously.

·      In line 593, “were switched off, suggestive of suggesting oxidative stress in the spleen”

·      In line 695, “being the role…”

·      In line 702, “it is high time that for physicians to thought think of the spleen…”

·      Finally, it seems that section “Future Directions” is a bit long. Perhaps it would be a good idea to create an additional subtitle. Optional.

Comments on the Quality of English Language

 

 Some suggestions and corrections to improve English grammar and general content:

·      In line 13, “…leading to various the spleen-organ axes”.

·      In line 16, “And what is more, these observations…” or “Furthermore, these observations…”

·      In line 17, “…identification of novel therapeutical therapeutic strategies targeted targeting several current diseases”.

·      In line 19, “Anyway, much work needs remains to be done to…”.

·      In line 31, “In this regards…”

·      In line 102, “Noteworthy, authors when compared comparing the reliability of the old acronym versus the new one, the authors found that 99% of patients with NAFLD met MASLD criteria”, or “Noteworthy, when the reliability of the old acronym was compared with the new one, the authors found that 99% of patients with NAFLD met MASLD criteria”.

·      In line 113, “Bacteroides uniforms” → “Bacteroides uniformis”

·      Check for “in vitro”, “in vivo” words and scientific names in italics throughout the document.

·      In line 186, “In adequate amounts, heavy metals are essential nutrients…” (Subject should not be skipped in new sentences).

·      In line 311, “These data, on the one hand, present…” (do not forget commas between linkers).

·      In line 361, “Psychological pressure stress” (optional)

·      In line 410-411, “positive (suppression of inflammation in myocardial tissue environment) and negative one…”

·      Figure 1 title is missing.

·      In line 437, “, it is without doubts clearly seen that the…” or “, undoubtedly, the spleen…”

·      In line 466, BPA has not been defined previously.

·      In line 593, “were switched off, suggestive of suggesting oxidative stress in the spleen”

·      In line 695, “being the role…”

·      In line 702, “it is high time that for physicians to thought think of the spleen…”

·      Finally, it seems that section “Future Directions” is a bit long. Perhaps it would be a good idea to create an additional subtitle. Optional.

Author Response

Reply to Reviewer number 1

 

In this review, the authors first address general anatomical and physiological characteristics of the spleen, its general role in inflammation and in the immune system. Also, the functions of the red and white pulp and splenomegaly, which is the most common pathology of this organ, are explained. Subsequently, the authors mention the importance of the interactions between the spleen and other organs, which are called spleen-organ axes, and detail the most important axes: gut-spleen (lactic acid, n-butyric acid and short chain fatty acids as important topics), liver-spleen (and its relationship with nonalcoholic fatty liver disease, parasitosis and heavy metals), gut-spleen-skin (and its relationship with psoriasis), brain-spleen (and its relationship with white adipose tissue and psychological stress), and heart-kidney-spleen (and its relationship with heart failure and cardiac remodeling). Then, the authors explain the involvement of the spleen with hormones, endocrine system disruptors (microplastics, bisphenols), aging and environmental factors. Finally, the authors make a special appeal to physicians not to underestimate the spleen in the clinical field/practice.

The relevance of this review is based on the authors' work in compiling the different interactions and influences of the spleen with other organs/systems and diseases, mainly those associated with inflammation and the immune system. There are no similar reviews that investigate and analyze the spleen with the various organs and systems that are raised in this work.

Since more than 60% of the literature cited in this review was published from 2019 to date (2024), it is possible to affirm that the authors have taken care to use up-to-date references on the subject.

 

On behalf of my co-author, I would like to express my gratitude for his/her appreciation and for the time spent  and efforts made in reviewing our paper.

 

 

Comment  (C) 

Answer (A)

 

C: Finally, I encourage the authors to review the document with the assistance of a native English speaker/teacher to correct grammatical details. Some suggestions and corrections to improve English grammar and general content:

·      In line 13, “…leading to various the spleen-organ axes”.

·      In line 16, “And what is more, these observations…” or “Furthermore, these observations…”

·      In line 17, “…identification of novel therapeutical therapeutic strategies targeted targeting several current diseases”.

·      In line 19, “Anyway, much work needs remains to be done to…”.

·      In line 31, “In this regards…”

·      In line 102, “Noteworthy, authors when compared comparing the reliability of the old acronym versus the new one, the authors found that 99% of patients with NAFLD met MASLD criteria”, or “Noteworthy, when the reliability of the old acronym was compared with the new one, the authors found that 99% of patients with NAFLD met MASLD criteria”.

·      In line 113, “Bacteroides uniforms” → “Bacteroides uniformis”

·      Check for “in vitro”, “in vivo” words and scientific names in italics throughout the document.

·      In line 186, “In adequate amounts, heavy metals are essential nutrients…” (Subject should not be skipped in new sentences).

·      In line 311, “These data, on the one hand, present…” (do not forget commas between linkers).

·      In line 361, “Psychological pressure stress” (optional)

·      In line 410-411, “positive (suppression of inflammation in myocardial tissue environment) and negative one…”

·      Figure 1 title is missing.

·      In line 437, “, it is without doubts clearly seen that the…” or “, undoubtedly, the spleen…”

·      In line 466, BPA has not been defined previously.

·      In line 593, “were switched off, suggestive of suggesting oxidative stress in the spleen”

·      In line 695, “being the role…”

·      In line 702, “it is high time that for physicians to thought think of the spleen…”

·      Finally, it seems that section “Future Directions” is a bit long. Perhaps it would be a good idea to create an additional subtitle. Optional.

 

A: We authors thank the reviewer for his/her suggestions concerning grammar and general content, as well as adding a subtitle to Future Directions, which were totally accepted. The modifications were highlights in yellow and 

 

Comments on the Quality of English Language

 

C: Some suggestions and corrections to improve English grammar and general content.

A: Ditto. Furthermore, a deep revision of the text was made substituting various  words present in many periods according to the attached report to avoid gross similarities in terminology, and when realizable rephrasing the text, without giving modified or ill-interpreted messages. It should be emphasized that every concept/finding/sentence was constantly and opportunely referenced, without appropriating of nobody of them, how easy it is to check. That said,  concerning the scientific terms and passages  which represent the most part of the review, it was impossible to change the text without worsening the significance  and the understanding of the content of the review, which is in perfect agreement with the exposition of data by each author or group of research. Finally, I wish that the modifications, made according to the request with a collaborative spirit, did not worsen the fluency.

 

 

 

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

The authors decided to explore the function of the spleen in the context of other organs, emphasizing its role in the human organism. This review is up-to-date and based on the current literature. However, it requires a few improvements:

 

1. Please, include in the Abstract a general aim of your review.

2. The first  sentence of the introduction does not have to be separated from the rest of this section and written in the first line. For now it does not look like the title or something highlighted. Thus I would just normally start the introduction with this sentence.

3. Capital letters should be removed from several sentences, e.g Lines: 43, 45, 46, 59, 60, 61.

4. Please, replace expressions from the informal language (e. g. fresh studies - line 200) with more scientific synonyms.

5. I would suggest including additional references: 10.1007/s10741-024-10418-6 (Interplay of the heart, spleen, and bone marrow in heart failure: the role of splenic extramedullary hematopoiesis), 10.3389/fnmol.2024.1400808 (Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk), 10.1080/07853890.2024.2362871 (Research progress of megakaryocytes and platelets in lung injury), 10.1186/s13244-024-01727-3 (The impact of hepatic and splenic volumetric assessment in imaging for chronic liver disease: a narrative review) and discussing them with the manuscript

6. I miss in the conclusions one or two sentences indicating further explorations that could be performed in order to understand even better the role of spleen and to use already known axes in clinical life.

Comments on the Quality of English Language

Grammar mistakes need to be corrected.

Author Response

Reply to Reviewer 2

 

Comment  (C) 

Answer (A)

 

 

On behalf of my co-author, I would like to express my gratitude for the  suggestions, for the time spent and efforts made in reviewing our paper.

 

The authors decided to explore the function of the spleen in the context of other organs, emphasizing its role in the human organism. This review is up-to-date and based on the current literature. However, it requires a few improvements:

 

C: Please, include in the Abstract a general aim of your review.

           A: A general sentence was added concerning the aim of the review

        

C: The first  sentence of the introduction does not have to be separated from the rest of this section and written in the first line. For now it does not look like the title or something highlighted. Thus I would just normally start the introduction with this sentence.

           A: The capital letters were removed.

 

C: Capital letters should be removed from several sentences, e.g Lines: 43, 45, 46, 59, 60, 61.

           A: The capital letters were removed.

 

C: Please, replace expressions from the informal language (e. g. fresh studies - line 200) with more scientific synonyms.

           A: The term fresh was substituted with more formal words in the whole text.

 

C: I would suggest including additional references: 

 

10.1007/s10741-024-10418-6 (Interplay of the heart, spleen, and bone marrow in heart failure: the role of splenic extramedullary hematopoiesis), 

10.3389/fnmol.2024.1400808 (Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk), 

10.1080/07853890.2024.2362871 (Research progress of megakaryocytes and platelets in lung injury), 

10.1186/s13244-024-01727-3 (The impact of hepatic and splenic volumetric assessment in imaging for chronic liver disease: a narrative review) and discussing them with the manuscript.

       

          A: We wish to thank the reviewer for his /her suggestions concerning these very innovative topics that were added in the subtopic captivating trends. The content of these articles was reported in the subtopic and the related references were added into the References list.

 

C: I miss in the conclusions one or two sentences indicating further explorations that could be performed in order to understand even better the role of spleen and to use already known axes in clinical life.

          A: A sentence concerning the new trends was added in the Conclusion section 

 

C: Comments on the Quality of English Language

Grammar mistakes need to be corrected.

          A: According with this suggestion, typos, mistakes and grammatical error were amended. Furthermore, a deep revision of the text was made substituting various  words present in many periods according to the attached report to avoid gross similarities in terminology, and when realizable rephrasing the text, without giving modified or ill-interpreted messages. It should be emphasized that every concept/finding/sentence was constantly and opportunely referenced, without appropriating of nobody of them, how easy it is to check. That said,  concerning the scientific terms and passages  which represent the most part of the review, it was impossible to change the text without worsening the significance  and the understanding of the content of the review, which is in perfect agreement with the exposition of data by each author or group of research. Finally, I wish that the modifications, made according to the request with a collaborative spirit, did not worsen the fluency.

Author Response File: Author Response.pdf