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: 08 Mar 2017 
 
Reviewer:  Ulrich  Peitz  
 
Reviewer’s report:  
 
The authors have choosen an interesting subject and performed an elaborated animal experiment. 
They used sophisticated molecular determinations to provide evidence that induction of Heme 
Oxygenase -1 might be protective in severe acute pancrea titis.  
 
I have some concerns.  
 
 
Major  
 
Abstract  
 
It should be mentioned in the abstract which species of animals were used.  
 
 
Methods  
 
Effects of hemin and ZnPP on rats without induction of acute pancretitis were not tested as 
control. This should be commented on.  
 
 
Results  
 
The authors refer to "hemin pretreatment", but hemin was administered 30 minutes after 
induction of pancreatitis.  
 
 
Availability of data and material  
 
"The work described was original research that has not been published previously, and not under 
consideration for publication elsewhere, in whole or in part. All the authors listed have approved 
the manuscript that is encl osed."  
 
 
Figures  
 
Figures 1 and 3 are blurred.  
 
English may deserve an overhaul  
 
 
Minor  
 
No numeration of pages  
 
 
Abstract  
 
cells through the mechanism of anti -oxidation, maintaining microcirculation and anti -
inflammatory ???  
 
sentence is incomplete  
 
 
Background  
 
It is clear that such a common disease associated with mortality up to 30% in severe cases  
 
Sentence is incomplete  
 
If this inflammation is marked, it would lead to inappropriate activation of immune system 
demonstrating as systemic inflammatory response s yndrome(SIRS) and eventually result in 
multiple organs dysfunction syndrome(MODS) [3].  
 
Grammar:  it will lead  
 
In this procession, the therapy targeting…  
 
Wording: In this process  
 
are highly conserved  
 
are a highly conserved  
 
these proteins perform a variety of cells  
 
Is this what you mean? these proteins induce a variety of cells  
 
catalyzea  
 
catalyzes  
 
Methods  
 
was retrograde injected  
 
Grammar: was retrogradely injected  
 
Promrga A3500, Madison, WI  
 
Spelling: Promega A3500, Madison , WI 
 
 
Results  
 
increased significantly  
 
were significantly increased  
 
decreased significantly  
 
were significantly decreased  
 
The pathological scores is significantly  
 
The pathological scores were significantly  
 
 
Discussion  
 
was associated with a marked increase HO -1 gene expression in  
 
was associated with a marked increase of HO -1 gene expression in  
 
it can inhibit the synthetize  
 
it can inhibit the synthesis  
 
have demonstrated a major anti -inflammatory effect  
 
have demonstrated  a major of anti -inflammatory effect  
 
HO-1 is the stress -inducible from which is known to…  
 
Is this what you mean? HO -1 is the stress -inducible isoform of heme oxygenase which is known 
to… 
 
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.  
 
No 
 
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 recommend additional statistical review  
 
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 competing 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: 08 Mar 2017 
 
Reviewer:  Ulrich  Peitz  
 
Reviewer’s report:  
 
The authors have choosen an interesting subject and performed an elaborated animal experiment. 
They used sophisticated molecular determinations to provide evidence that induction of Heme 
Oxygenase -1 might be protective in severe acute pancrea titis.  
 
I have some concerns.  
 
 
Major  
 
Abstract  
 
It should be mentioned in the abstract which species of animals were used.  
 
 
Methods  
 
Effects of hemin and ZnPP on rats without induction of acute pancretitis were not tested as 
control. This should be commented on.  
 
 
Results  
 
The authors refer to "hemin pretreatment", but hemin was administered 30 minutes after 
induction of pancreatitis.  
 
 
Availability of data and material  
 
"The work described was original research that has not been published previously, and not under 
consideration for publication elsewhere, in whole or in part. All the authors listed have approved 
the manuscript that is encl osed."  
 
 
Figures  
 
Figures 1 and 3 are blurred.  
 
English may deserve an overhaul  
 
 
Minor  
 
No numeration of pages  
 
 
Abstract  
 
cells through the mechanism of anti -oxidation, maintaining microcirculation and anti -
inflammatory ???  
 
sentence is incomplete  
 
 
Background  
 
It is clear that such a common disease associated with mortality up to 30% in severe cases  
 
Sentence is incomplete  
 
If this inflammation is marked, it would lead to inappropriate activation of immune system 
demonstrating as systemic inflammatory response s yndrome(SIRS) and eventually result in 
multiple organs dysfunction syndrome(MODS) [3].  
 
Grammar:  it will lead  
 
In this procession, the therapy targeting…  
 
Wording: In this process  
 
are highly conserved  
 
are a highly conserved  
 
these proteins perform a variety of cells  
 
Is this what you mean? these proteins induce a variety of cells  
 
catalyzea  
 
catalyzes  
 
Methods  
 
was retrograde injected  
 
Grammar: was retrogradely injected  
 
Promrga A3500, Madison, WI  
 
Spelling: Promega A3500, Madison , WI 
 
 
Results  
 
increased significantly  
 
were significantly increased  
 
decreased significantly  
 
were significantly decreased  
 
The pathological scores is significantly  
 
The pathological scores were significantly  
 
 
Discussion  
 
was associated with a marked increase HO -1 gene expression in  
 
was associated with a marked increase of HO -1 gene expression in  
 
it can inhibit the synthetize  
 
it can inhibit the synthesis  
 
have demonstrated a major anti -inflammatory effect  
 
have demonstrated  a major of anti -inflammatory effect  
 
HO-1 is the stress -inducible from which is known to…  
 
Is this what you mean? HO -1 is the stress -inducible isoform of heme oxygenase which is known 
to… 
 
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.  
 
No 
 
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 recommend additional statistical review  
 
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 competing 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: 08 Mar 2017 
 
Reviewer:  Ulrich  Peitz  
 
Reviewer’s report:  
 
The authors have choosen an interesting subject and performed an elaborated animal experiment. 
They used sophisticated molecular determinations to provide evidence that induction of Heme 
Oxygenase -1 might be protective in severe acute pancrea titis.  
 
I have some concerns.  
 
 
Major  
 
Abstract  
 
It should be mentioned in the abstract which species of animals were used.  
 
 
Methods  
 
Effects of hemin and ZnPP on rats without induction of acute pancretitis were not tested as 
control. This should be commented on.  
 
 
Results  
 
The authors refer to "hemin pretreatment", but hemin was administered 30 minutes after 
induction of pancreatitis.  
 
 
Availability of data and material  
 
"The work described was original research that has not been published previously, and not under 
consideration for publication elsewhere, in whole or in part. All the authors listed have approved 
the manuscript that is encl osed."  
 
 
Figures  
 
Figures 1 and 3 are blurred.  
 
English may deserve an overhaul  
 
 
Minor  
 
No numeration of pages  
 
 
Abstract  
 
cells through the mechanism of anti -oxidation, maintaining microcirculation and anti -
inflammatory ???  
 
sentence is incomplete  
 
 
Background  
 
It is clear that such a common disease associated with mortality up to 30% in severe cases  
 
Sentence is incomplete  
 
If this inflammation is marked, it would lead to inappropriate activation of immune system 
demonstrating as systemic inflammatory response s yndrome(SIRS) and eventually result in 
multiple organs dysfunction syndrome(MODS) [3].  
 
Grammar:  it will lead  
 
In this procession, the therapy targeting…  
 
Wording: In this process  
 
are highly conserved  
 
are a highly conserved  
 
these proteins perform a variety of cells  
 
Is this what you mean? these proteins induce a variety of cells  
 
catalyzea  
 
catalyzes  
 
Methods  
 
was retrograde injected  
 
Grammar: was retrogradely injected  
 
Promrga A3500, Madison, WI  
 
Spelling: Promega A3500, Madison , WI 
 
 
Results  
 
increased significantly  
 
were significantly increased  
 
decreased significantly  
 
were significantly decreased  
 
The pathological scores is significantly  
 
The pathological scores were significantly  
 
 
Discussion  
 
was associated with a marked increase HO -1 gene expression in  
 
was associated with a marked increase of HO -1 gene expression in  
 
it can inhibit the synthetize  
 
it can inhibit the synthesis  
 
have demonstrated a major anti -inflammatory effect  
 
have demonstrated  a major of anti -inflammatory effect  
 
HO-1 is the stress -inducible from which is known to…  
 
Is this what you mean? HO -1 is the stress -inducible isoform of heme oxygenase which is known 
to… 
 
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.  
 
No 
 
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 recommend additional statistical review  
 
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 competing 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