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Article
Peer-Review Record

A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity

Int. J. Mol. Sci. 2022, 23(3), 1762; https://doi.org/10.3390/ijms23031762
by Yujia Liu 1,2,3,†, Takumi Myojin 3,†, Kexin Li 2,3, Ayuki Kurita 3, Masayuki Seto 3, Ayano Motoyama 3, Xiaoyang Liu 2,3, Ayano Satoh 4, Shintaro Munemasa 3, Yoshiyuki Murata 3, Toshiyuki Nakamura 3 and Yoshimasa Nakamura 3,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Int. J. Mol. Sci. 2022, 23(3), 1762; https://doi.org/10.3390/ijms23031762
Submission received: 24 January 2022 / Revised: 31 January 2022 / Accepted: 1 February 2022 / Published: 3 February 2022
(This article belongs to the Special Issue Nutrition and Metabolism in Health and Disease: From Gene to Organism)

Round 1

Reviewer 1 Report

The presented manuscript describes a major intestinal catabolite of quercetin glycosides, 3-hydroxyphenylacetic acid can enhancer of aldehyde dehydrogenase activity. The presented work is authentic, and the study is scientifically sound and well designed. The conclusion is supported with the results and the discussion is appropriate. Few modifications can improve the manuscript.

  1. The title of the manuscript doesn’t reflect the contents of this study. Please modify the title.
  2. In the “Abstract”, the author should better illuminate innovations, the important results and innovative conclusions of the study. So, please modify the abstract.
  3. The design idea of the paper was not illuminated, so, the author should better illuminate particularly after the introduction.

     4. In introduction, the paragraph 2 and 5 should be state together.

     5. “1. Results” should be changed to “2. Results”. Others should be similarly modified.

    6. Fig 1 and Fig 2 should be redrawn and stated in manuscript.

   7. The introduction needs English language revision.

   8. Please check and modify the format of references in line with journal requires.

Author Response

The presented manuscript describes a major intestinal catabolite of quercetin glycosides, 3-hydroxyphenylacetic acid can enhancer of aldehyde dehydrogenase activity. The presented work is authentic, and the study is scientifically sound and well designed. The conclusion is supported with the results and the discussion is appropriate. Few modifications can improve the manuscript.

Response: Thank you very much for the reviewer for his/her careful reading of the manuscript and constructive suggestions. We have revised the manuscript according to each suggestion of the reviewers. Revised portions have been highlighted on the revised manuscript. We believe that the paper is significantly improved and hope that the corrections made together with the attached reply satisfy the concerns raised.

  1. The title of the manuscript doesn’t reflect the contents of this study. Please modify the title.

Response: According to the suggestion, the title has been replaced by “A major intestinal catabolite of quercetin glycosides, 3-hydroxyphenylacetic acid, protects the hepatocytes from the acetaldehyde-induced cytotoxicity through the enhancement of the total aldehyde dehydrogenase activity”.

  1. In the “Abstract”, the author should better illuminate innovations, the important results and innovative conclusions of the study. So, please modify the abstract.

Response: We appreciate your valuable comments and suggestions for helping us to improve the manuscript. As suggested, we have considerably revised the abstract, such as insertion of the innovative conclusion and rearrangement of the results to make the need for this manuscript clearer.

  1. The design idea of the paper was not illuminated, so, the author should better illuminate particularly after the introduction.

Response: As suggested, at the end of the introduction, we have more clearly mentioned the motivation and model of this study. 

  1. In introduction, the paragraph 2 and 5 should be state together.

Response: According to this advice, we have rearranged the paragraphs of the introduction to state the topics of quercetin glycosides and their metabolites together.

  1. “1. Results” should be changed to “2. Results”. Others should be similarly modified.

Response: As suggested, the styles of the chapter titles have been revised.

  1. Fig 1 and Fig 2 should be redrawn and stated in manuscript.

Response: According to this suggestion, we have redrawn Fig. 1 to combine all the data of the former Fig. 1 and Fig. 2, and revised the corresponding sentences in the result section of the revised manuscript.

  1. The introduction needs English language revision.

Response: We apologize for the spelling and grammatical errors. We have carefully studied and corrected the errors.

  1. Please check and modify the format of references in line with journal requires.

Response: As suggested, the styles of the references have totally been revised.

Reviewer 2 Report

I’ve read with attention the paper of Liu et al. that is potentially of interest. The background and aim of the study have been clearly defined. The methodology applied is overall correct, the results are reliable and adequately discussed. I’ve only some minor comments:

  • The statistical analysis should be improved, in particular since the authors should demonstrate the normal distributio of the tested parameters before to apply the t-test to all comparisons.
  • In the discussion, the authors should mention if data are available on the bioavailability of OPAC, since it could really affects its potential usefulness in practice
  • Alwyas in the discussion, the authors should shortly list and discuss the pontential limitation of their research approach and suggest the next steps of their research in this field
  •  

Author Response

I’ve read with attention the paper of Liu et al. that is potentially of interest. The background and aim of the study have been clearly defined. The methodology applied is overall correct, the results are reliable and adequately discussed. I’ve only some minor  

Response: Thank you very much for the reviewer for his/her careful reading of the manuscript and constructive suggestions. We have revised the manuscript according to each suggestion of the reviewers. Revised portions have been highlighted on the revised manuscript. We believe that the paper is significantly improved and hope that the corrections made together with the attached reply satisfy the concerns raised.

* The statistical analysis should be improved, in particular since the authors should demonstrate the normal distribution of the tested parameters before to apply the t-test to all comparisons.

Response: Thank you very much for the reviewer’s thoughtful comment. We believe that the current method of statistical analysis (Student's paired two-tailed t-test) is acceptable. The reasons are as follows: 1) All the data are expressed as values relative to the control; 2) The value of the control is always 1; 3) The F-test cannot be applied, because there is no variance; 4) The data of each single experiment is paired, because the data of the treatment group is always compared with the control for each experiment. As for multiple comparison, we performed one-way analysis of variance (ANOVA) before Tukey's honestly significant difference (HSD) test. Thus, we have added this information in the method section.

* In the discussion, the authors should mention if data are available on the bioavailability of OPAC, since it could really affects its potential usefulness in practice. 

Response: We entirely agree with the reviewer’s idea that the bioavailability data of OPAC is very important for the readers. Therefore, we have added the sentence “In addition, the OPAC concentrations required for enhancement of the ALDH activity (~10 μM) might be supraphysiological, since a previous intervention study revealed that OPAC concentration in the plasma was achieved to approximately 100~400 nM after the consumption of berries (160 g/day) [34].” in the discussion.

* Always in the discussion, the authors should shortly list and discuss the pontential limitation of their research approach and suggest the next steps of their research in this field.

Response: According to this suggestion, we have added the list of the potential limitation of this study and the future efforts to solve these issues in the discussion section of the revised manuscript.

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