Reviewer ’s report  
 
Title:  Protective effects of heme oxygenase -1 against severe acute pancreatitis via inhibition of 
tumor necrosis factor -α and augmentation of inte rleukin -10 
 
Version: 0 Date: 25 Mar 2017 
 
Reviewer:  Jannette  Dufour  
 
Reviewer’s report:  
 
This is a nice study by Zhang et al., testing the effect of heme oxygenase -1 (HO -1) on severe 
acute pancreatitis (SAP). The authors were able to demonstrate a decrease in TNF -alpha and 
increase in IL -10 in serum, pancreas and liver after HO -1 sti mulation compared to the SAP 
group. Likewise, this group showed improved pancreas and liver histology. In opposite, HO -1 
inhibition increased TNF -alpha and decreased IL -10 in serum, pancreas and liver as well as 
showed pancreas and liver tissue damage comp ared to the SAP group. Overall the results are 
very interesting. I have several comments provided below.  
 
 
Specific Comments  
 
1. Grammar should be checked through out the manuscript.  
 
2. Abstract, line 32: do you mean examine or analyze the role of HO -1 on  systemic 
inflammation? The word "improve" does not fit here.  
 
3. Second page of Abstract, line 4: How do you know this is the main mechanism? HO -1 
could also effect other pathways.  
 
4. Background line 20 -22: this sentence (It is clear … in severe cases) is  a little confusing. 
Maybe reword.  
 
5. Background line 43: add "activities to protect" to the sentence. For example, "perform a 
variety of activities to protect cells against stressful"  
 
6. Background lines 49 -56, state HO -1 plays an important role SAP, whi le the next page, 
lines7 -9 indicate the role is unknown. How can it be important and unknown at the same time.  
 
7. Results, line 54, pancreatic histology: should this be the pancreas not the pancreatic duct? 
The duct is not shown in the images or described in the SAP group. Also, this sentence should be 
split into 3 sentences rather than describing all of the treatments in one run on sentence.  
 
8. Figure 3: the treatments are not labeled in the figure or indicated in the figure legend. 
This should be added. Also, the image resolution is too low to confirm the description in the text. 
Higher resolution images should be included.  
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 nec essary 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 manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify 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:  
 
Needs some language corrections before being published  
 
Declaration 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 financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any  stocks or shares in an organisation that 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 competi ng interests.  
 
I agree to th e 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 agree 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 comments 
to the editors, which will not be published.  
\ 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Protective effects of heme oxygenase -1 against severe acute pancreatitis via inhibition of 
tumor necrosis factor -α and augmentation of inte rleukin -10 
 
Version: 0 Date: 25 Mar 2017 
 
Reviewer:  Jannette  Dufour  
 
Reviewer’s report:  
 
This is a nice study by Zhang et al., testing the effect of heme oxygenase -1 (HO -1) on severe 
acute pancreatitis (SAP). The authors were able to demonstrate a decrease in TNF -alpha and 
increase in IL -10 in serum, pancreas and liver after HO -1 sti mulation compared to the SAP 
group. Likewise, this group showed improved pancreas and liver histology. In opposite, HO -1 
inhibition increased TNF -alpha and decreased IL -10 in serum, pancreas and liver as well as 
showed pancreas and liver tissue damage comp ared to the SAP group. Overall the results are 
very interesting. I have several comments provided below.  
 
 
Specific Comments  
 
1. Grammar should be checked through out the manuscript.  
 
2. Abstract, line 32: do you mean examine or analyze the role of HO -1 on  systemic 
inflammation? The word "improve" does not fit here.  
 
3. Second page of Abstract, line 4: How do you know this is the main mechanism? HO -1 
could also effect other pathways.  
 
4. Background line 20 -22: this sentence (It is clear … in severe cases) is  a little confusing. 
Maybe reword.  
 
5. Background line 43: add "activities to protect" to the sentence. For example, "perform a 
variety of activities to protect cells against stressful"  
 
6. Background lines 49 -56, state HO -1 plays an important role SAP, whi le the next page, 
lines7 -9 indicate the role is unknown. How can it be important and unknown at the same time.  
 
7. Results, line 54, pancreatic histology: should this be the pancreas not the pancreatic duct? 
The duct is not shown in the images or described in the SAP group. Also, this sentence should be 
split into 3 sentences rather than describing all of the treatments in one run on sentence.  
 
8. Figure 3: the treatments are not labeled in the figure or indicated in the figure legend. 
This should be added. Also, the image resolution is too low to confirm the description in the text. 
Higher resolution images should be included.  
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 nec essary 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 manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify 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:  
 
Needs some language corrections before being published  
 
Declaration 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 financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any  stocks or shares in an organisation that 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 competi ng interests.  
 
I agree to th e 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 agree 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 comments 
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:  Protective effects of heme oxygenase -1 against severe acute pancreatitis via inhibition of 
tumor necrosis factor -α and augmentation of inte rleukin -10 
 
Version: 0 Date: 25 Mar 2017 
 
Reviewer:  Jannette  Dufour  
 
Reviewer’s report:  
 
This is a nice study by Zhang et al., testing the effect of heme oxygenase -1 (HO -1) on severe 
acute pancreatitis (SAP). The authors were able to demonstrate a decrease in TNF -alpha and 
increase in IL -10 in serum, pancreas and liver after HO -1 sti mulation compared to the SAP 
group. Likewise, this group showed improved pancreas and liver histology. In opposite, HO -1 
inhibition increased TNF -alpha and decreased IL -10 in serum, pancreas and liver as well as 
showed pancreas and liver tissue damage comp ared to the SAP group. Overall the results are 
very interesting. I have several comments provided below.  
 
 
Specific Comments  
 
1. Grammar should be checked through out the manuscript.  
 
2. Abstract, line 32: do you mean examine or analyze the role of HO -1 on  systemic 
inflammation? The word "improve" does not fit here.  
 
3. Second page of Abstract, line 4: How do you know this is the main mechanism? HO -1 
could also effect other pathways.  
 
4. Background line 20 -22: this sentence (It is clear … in severe cases) is  a little confusing. 
Maybe reword.  
 
5. Background line 43: add "activities to protect" to the sentence. For example, "perform a 
variety of activities to protect cells against stressful"  
 
6. Background lines 49 -56, state HO -1 plays an important role SAP, whi le the next page, 
lines7 -9 indicate the role is unknown. How can it be important and unknown at the same time.  
 
7. Results, line 54, pancreatic histology: should this be the pancreas not the pancreatic duct? 
The duct is not shown in the images or described in the SAP group. Also, this sentence should be 
split into 3 sentences rather than describing all of the treatments in one run on sentence.  
 
8. Figure 3: the treatments are not labeled in the figure or indicated in the figure legend. 
This should be added. Also, the image resolution is too low to confirm the description in the text. 
Higher resolution images should be included.  
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 nec essary 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 manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify 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:  
 
Needs some language corrections before being published  
 
Declaration 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 financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any  stocks or shares in an organisation that 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 competi ng interests.  
 
I agree to th e 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 agree 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 comments 
to the editors, which will not be published.  
\ 
I agree to the open peer review policy of the journal  
assistant