Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans
Round 1
Reviewer 1 Report
The manuscript entitled “Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans” by Xingyu Li et al al focuses on twelve cannabinoids selected as active compounds through text mining and drug-like properties screening and used for initial protein-target prediction.
The manuscript is well written and is very detailed. However, I have one comment:
- Table 1. report beneficial effects from the use of cannabis treating various diseases, such as cancers, inflammation. The authors could add in the table a brief sentence to explain what has been specifically found.
Author Response
Dear Reviewer,
Thank you for your hard work and kind comments to my manuscript.
We have modified our manuscript, and the details following:
Comments and Suggestions for Authors
The manuscript entitled “Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans” by Xingyu Li et al al focuses on twelve cannabinoids selected as active compounds through text mining and drug-like properties screening and used for initial protein-target prediction.
The manuscript is well written and is very detailed. However, I have one comment:
- Table 1. report beneficial effects from the use of cannabis treating various diseases, such as cancers, inflammation. The authors could add in the table a brief sentence to explain what has been specifically found.
Response to the reviewer: We thank you for your kind comments. Table 1 was the summary of the literature review. Due to the limitation of space and tables, as well as the complexity found in each disease, it prevents us to provide “a brief sentence” to explain what has been specifically found. Since there were many research and review articles available, we did provide the relevant references to each disease indicated and hope this is acceptable to the reviewer and editor.
Best regards,
Xingyu Li
Reviewer 2 Report
In this article by Li et al, the authors attempt to analyze the network-based pharmacology study to reveal protein targets for determining beneficial and harmful effects of cannabinoids in humans. This article is interesting however, there are some suggestions to improve the purpose of this article. For instance
- The significance of this study is missing in the abstract. The authors should clearly state the importance of this study in the abstract.
- The authors should explain elaborately the harmful effects of cannabis on human health and associated mechanism.
- In table 1, beneficial use and adverse effects of cannabis should be separated in different column or row. Author can make two separate tables to make it clearer and more understandable.
- In table 1, mechanism should be included by which cannabis induce beneficial or adverse effects.
- List of abbreviation is missing in the article. Authors should carefully abbreviate the terms in text as well.
- Authors should carefully check and correct the spelling and spacing error in the manuscript.
- Throughout the manuscript (page 3,4,5,6) authors have mentioned references as ‘Available at …..’. Authors should include these references in ‘References’ list and in the text as numbered.
- Authors should mention limitation (s) of this study in the conclusion.
Comments for author File: 
Comments.docx
Author Response
Dear Reviewer,
Thank you for your hard work and kind comments on my manuscript.
We have modified our manuscript, and the details following:
In this article by Li et al, the authors attempt to analyze the network-based pharmacology study to reveal protein targets for determining beneficial and harmful effects of cannabinoids in humans. This article is interesting however, there are some suggestions to improve the purpose of this article. For instance
- The significance of this study is missing in the abstract. The authors should clearly state the importance of this study in the abstract.
Response to the reviewer: Thank you for your kind comments. We have clarified the purpose of this article by adding the following in the abstract “which provides an important foundation for further deployment of preclinical and clinical studies of cannabis.”
- The authors should explain elaborately the harmful effects of cannabis on human health and associated mechanism.
Response to the reviewer: We did elaborate on the harmful effects of cannabinoids on human health and associated mechanism in Section 3.7, Figure 7, and Table S5.
- In table 1, beneficial use and adverse effects of cannabis should be separated in different column or row. Author can make two separate tables to make it clearer and more understandable.
Response to the reviewer: Table 1 has been divided into two, Table 1A for the beneficial use and Table 1B for the adverse effects.
- In table 1, mechanism should be included by which cannabis induce beneficial or adverse effects.
Response to the reviewer: Table 1 was the summary of the literature review. Since many of the beneficial and adverse effects were based on clinical observations or empirical uses of cannabis, the detailed mechanisms of cannabis were not clear or uncertain. Therefore, it leads to our current research to elucidate the mechanisms of cannabinoids through the network pharmacology approach.
- List of abbreviation is missing in the article. Authors should carefully abbreviate the terms in text as well.
Response to the reviewer: The list of abbreviations was provided at the end of the text, before the references.
- Authors should carefully check and correct the spelling and spacing error in the manuscript.
Response to the reviewer: We have corrected the spelling in the manuscript, which is shown in the article with track changes. The spacing in the manuscript is predetermined by the Journal template.
- Throughout the manuscript (page 3,4,5,6) authors have mentioned references as ‘Available at …...’. Authors should include these references in ‘References’ list and in the text as numbered.
Response to the reviewer: "Available at..." were the online databases, online software, and online tool websites, such as STRING, GeneCards, KEGG, etc. They were research tools, not references; therefore, they were not listed in references.
- Authors should mention limitation (s) of this study in the conclusion.
Response to the reviewer: The findings of this research were based on data/literature mining, network construction and analysis, biological function and pathway enrichments, and molecular docking simulation. The findings of this work await validation by preclinical and clinical studies. "The findings of this study need to be verified by preclinical and clinical studies" is described at the end of the conclusion paragraph of section 4.
Best regards,
Xingyu Li
Reviewer 3 Report
The manuscript named „Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans” deals with a highly important topic – potential targets and related effects of cannabinoids in human health.
The study reveals many important points. The manuscript is designed and written well. However, there are some text parts written in other colors (f. e. abstract, name of table 1A etc.), and in other parts, it seems like somebody corrected the mistakes there and the authors left it like this (f. e. green color in the pages 3, 5, 6, 8, 10 or 15).
The manuscript brings really new and important insight into the topic and is of high relevance
After minor revisions, I would recommend the manuscript to be accepted.
Author Response
Response to the reviewer: We thank you for your kind comments. Those colored words are the modification marks according to the requirements of the Applied Sciences Editorial Office，which is that any revisions made to the manuscript should be marked up using the “Track Changes” function if you are using MS Word/LaTeX, such that changes can be easily viewed by the editors and reviewers.
Reviewer 4 Report
I have carefully studied the submission titled “Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans”. Interesting and very well performed experiment, with useful and practical outcomes. Appropriate tools are used to process the obtained results and data. The some suggestions can be considered in PDF file.
Comments for author File: 
Comments.pdf
Author Response
The family name should not be italic. And the first part of the scientific name is the genus, and it is always capitalized, Correct the whole text.
Response to the reviewer: We thank you for your kind comments. I have revised it according to your suggestion.
When the same name is used more than once in a paper, the first letter of the genus (still capitalized) may be used as an abbreviation in the second and subsequent uses of the name, but the rest of the name is not abbreviated
I have revised it according to your suggestion.
In addition to hemp, a number of other plants also contain cannabinoid compounds; Why focus only on cannabis?
Yes, other plants have also been found to synthesize cannabinoid compounds, but this paper focuses on the effect of cannabis application on human body, because cannabis is widely cultivated and used.
