Reviewer ’s report  
Title: Geranylgeranylacetone attenuates fibrogenic activity an d induces apoptosis in cultured 
human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride -treated mice  
 
Version: 0 Date: 03 Oct 2017  
 
Reviewer: Christian Fingas  
 
Reviewer's report:  
Overall, this is a well written manuscript with a current topic.  
However, some minor aspects should be adressed to strenghten the study.  
 
1. Materials and methods: Source of Image J should be listed.  
2. Materials and methods: Did they use the anova+ post hoc for all the results? This should be 
clarified, because author only state multiple comparison methods whereas there also seems 
to be a comparison between two values.  
3. Materials and methods: What did they do with blood samples  of mice?  
4. Results: GGA induced ER stress, but inhibition of CHOP is not sufficient to block apoptosis 
in HSCs. What is the possible signaling contributing to apoptosis?  
5. Discussion: In the discussion, they argue that appearance of HSC did not change , thus did 
not put them into quiescence pattern. However, the difference between active and 
quiescence depends also on whether they produce pro -fibrotic substances, such as alpha -
SMA. Since they observed a decrease of SMA, it is impossible to claim that th ese cells did 
not go into quiescence state. This section has to be rephrased.  
6.  Discussion: Their finding that GGA did not induce HSP70 is contradictory to  previous 
reports. What is the reason of These different results? Overall, discussion should be 
deepened and improved.  
7.  Figure legends: Number of n for experiments should b e clarified  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions  drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statis tical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaratio n of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose f inancial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
3. Do  you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
5. Do you have any other financial competing interests?  
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I ag ree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential c omments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
Title: Geranylgeranylacetone attenuates fibrogenic activity an d induces apoptosis in cultured 
human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride -treated mice  
 
Version: 0 Date: 03 Oct 2017  
 
Reviewer: Christian Fingas  
 
Reviewer's report:  
Overall, this is a well written manuscript with a current topic.  
However, some minor aspects should be adressed to strenghten the study.  
 
1. Materials and methods: Source of Image J should be listed.  
2. Materials and methods: Did they use the anova+ post hoc for all the results? This should be 
clarified, because author only state multiple comparison methods whereas there also seems 
to be a comparison between two values.  
3. Materials and methods: What did they do with blood samples  of mice?  
4. Results: GGA induced ER stress, but inhibition of CHOP is not sufficient to block apoptosis 
in HSCs. What is the possible signaling contributing to apoptosis?  
5. Discussion: In the discussion, they argue that appearance of HSC did not change , thus did 
not put them into quiescence pattern. However, the difference between active and 
quiescence depends also on whether they produce pro -fibrotic substances, such as alpha -
SMA. Since they observed a decrease of SMA, it is impossible to claim that th ese cells did 
not go into quiescence state. This section has to be rephrased.  
6.  Discussion: Their finding that GGA did not induce HSP70 is contradictory to  previous 
reports. What is the reason of These different results? Overall, discussion should be 
deepened and improved.  
7.  Figure legends: Number of n for experiments should b e clarified  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions  drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statis tical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaratio n of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose f inancial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
3. Do  you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
5. Do you have any other financial competing interests?  
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I ag ree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential c omments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
Title: Geranylgeranylacetone attenuates fibrogenic activity an d induces apoptosis in cultured 
human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride -treated mice  
 
Version: 0 Date: 03 Oct 2017  
 
Reviewer: Christian Fingas  
 
Reviewer's report:  
Overall, this is a well written manuscript with a current topic.  
However, some minor aspects should be adressed to strenghten the study.  
 
1. Materials and methods: Source of Image J should be listed.  
2. Materials and methods: Did they use the anova+ post hoc for all the results? This should be 
clarified, because author only state multiple comparison methods whereas there also seems 
to be a comparison between two values.  
3. Materials and methods: What did they do with blood samples  of mice?  
4. Results: GGA induced ER stress, but inhibition of CHOP is not sufficient to block apoptosis 
in HSCs. What is the possible signaling contributing to apoptosis?  
5. Discussion: In the discussion, they argue that appearance of HSC did not change , thus did 
not put them into quiescence pattern. However, the difference between active and 
quiescence depends also on whether they produce pro -fibrotic substances, such as alpha -
SMA. Since they observed a decrease of SMA, it is impossible to claim that th ese cells did 
not go into quiescence state. This section has to be rephrased.  
6.  Discussion: Their finding that GGA did not induce HSP70 is contradictory to  previous 
reports. What is the reason of These different results? Overall, discussion should be 
deepened and improved.  
7.  Figure legends: Number of n for experiments should b e clarified  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions  drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statis tical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaratio n of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose f inancial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
3. Do  you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
5. Do you have any other financial competing interests?  
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I ag ree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential c omments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant