Reviewer's report
Title:Apolipoprotein E COG 133 mimetic peptide improves
5-fluorouracil-induced intestinal mucositis
Version: 9Date:15 January 2012
Reviewer: Jerzy-Roch Nofer
Reviewer's report:
The revised version of the manuscript entitled „ApoE COG 133 mimetic peptide
improves 5-fluorouracil-induced intestinal mucositis“ by Azevedo and colleagues
contains results of several new experiments. The paper has been significantly
improved and the authors satisfactorily responded to most of my comments.
While no further experimentation is in my view necessary, some points still
deserve authors’ attention:
1. The authors have apparently overlooked to respond to point 4 of my initial
criticism
2. The authors claim (in the reply to reviewer) that COG 133 comprises only
residues of N-terminal domain responsible for binding to LDL-receptor and is not
amphipathic. This is in contradiction to the information available in the web,
according to which COG133 may assume the structure of an amphipathic alpha
helix, which is responsible for its anti-inflammatory activity. At least two results of
the present study reinforce the notion that amphipathicity is critical to the
protective effects of COG 133. First, some effects of COG 133 examined by the
authors were imitated by D-4F, which is also amphipathic, but most likely does
not bind to members of LDL-receptor family. Second, the 5FU-induced injury was
not exacerbated in apoE-KO mice, which argues against the contention that the
protective effects of COG133 are apoE-specific (or - to be more precise -
mediated via one or more of apoE receptors). The authors should include the
information regarding COG133 amphipathicity into the manuscript and discuss
their results in context of potential mechanisms (amphipathicity vs. apoE-receptor
binding) accounting for protection against 5FU injury.
3. I suggest that the figures are put together and better structured. In the present
manuscript panels of the same figure are dispersed and figures are difficult to
follow
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:Apolipoprotein E COG 133 mimetic peptide improves
5-fluorouracil-induced intestinal mucositis
Version: 9Date:15 January 2012
Reviewer: Jerzy-Roch Nofer
Reviewer's report:
The revised version of the manuscript entitled „ApoE COG 133 mimetic peptide
improves 5-fluorouracil-induced intestinal mucositis“ by Azevedo and colleagues
contains results of several new experiments. The paper has been significantly
improved and the authors satisfactorily responded to most of my comments.
While no further experimentation is in my view necessary, some points still
deserve authors’ attention:
1. The authors have apparently overlooked to respond to point 4 of my initial
criticism
2. The authors claim (in the reply to reviewer) that COG 133 comprises only
residues of N-terminal domain responsible for binding to LDL-receptor and is not
amphipathic. This is in contradiction to the information available in the web,
according to which COG133 may assume the structure of an amphipathic alpha
helix, which is responsible for its anti-inflammatory activity. At least two results of
the present study reinforce the notion that amphipathicity is critical to the
protective effects of COG 133. First, some effects of COG 133 examined by the
authors were imitated by D-4F, which is also amphipathic, but most likely does
not bind to members of LDL-receptor family. Second, the 5FU-induced injury was
not exacerbated in apoE-KO mice, which argues against the contention that the
protective effects of COG133 are apoE-specific (or - to be more precise -
mediated via one or more of apoE receptors). The authors should include the
information regarding COG133 amphipathicity into the manuscript and discuss
their results in context of potential mechanisms (amphipathicity vs. apoE-receptor
binding) accounting for protection against 5FU injury.
3. I suggest that the figures are put together and better structured. In the present
manuscript panels of the same figure are dispersed and figures are difficult to
follow
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Apolipoprotein E COG 133 mimetic peptide improves
5-fluorouracil-induced intestinal mucositis
Version: 9Date:15 January 2012
Reviewer: Jerzy-Roch Nofer
Reviewer's report:
The revised version of the manuscript entitled „ApoE COG 133 mimetic peptide
improves 5-fluorouracil-induced intestinal mucositis“ by Azevedo and colleagues
contains results of several new experiments. The paper has been significantly
improved and the authors satisfactorily responded to most of my comments.
While no further experimentation is in my view necessary, some points still
deserve authors’ attention:
1. The authors have apparently overlooked to respond to point 4 of my initial
criticism
2. The authors claim (in the reply to reviewer) that COG 133 comprises only
residues of N-terminal domain responsible for binding to LDL-receptor and is not
amphipathic. This is in contradiction to the information available in the web,
according to which COG133 may assume the structure of an amphipathic alpha
helix, which is responsible for its anti-inflammatory activity. At least two results of
the present study reinforce the notion that amphipathicity is critical to the
protective effects of COG 133. First, some effects of COG 133 examined by the
authors were imitated by D-4F, which is also amphipathic, but most likely does
not bind to members of LDL-receptor family. Second, the 5FU-induced injury was
not exacerbated in apoE-KO mice, which argues against the contention that the
protective effects of COG133 are apoE-specific (or - to be more precise -
mediated via one or more of apoE receptors). The authors should include the
information regarding COG133 amphipathicity into the manuscript and discuss
their results in context of potential mechanisms (amphipathicity vs. apoE-receptor
binding) accounting for protection against 5FU injury.
3. I suggest that the figures are put together and better structured. In the present
manuscript panels of the same figure are dispersed and figures are difficult to
follow
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
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