Reviewer's report
Title:High mobility group B1 impairs hepatocyte regeneration in acetaminophen
hepatotoxicity
Version: 2Date:12 February 2012
Reviewer: Vincent Zimmer
Reviewer's report:
This is an important preclinical study examining the efficacy of anti-HMGB1 in
attenuating liver injury in a mouse model of acetaminophen (APAP)
hepatotoxicity. The Authors show that blocking HMGB1 after APAP exposure
results in attenuation of liver injury most pronounced so after 48 h (relative to the
first time point 24 h) suggesting a role for HMGB1 as a progression factor in this
injury model.
Improvements in hepatocyte regeneration by the anti-HMGB1 strategy is
supported by up-regulation of NF-kB DNA binding capacity and the cell-cycle
regulator cyclin D1.
However, there remain some minor concerns to be addressed:
1. The exclusive use of Western blots has to be critically discussed - for HMGB1
serum measurements complementary use of e.g. reliable commercial ELISAs or
in case of e.g. cyclin D1 complementary use of immunohistochemistries might
have strengthened the validity of experimental data. These limitations, if not
eliminated in the first place, should at least be stated and discussed appropriately
in the manuscript.
2. The legend for Figure 2 is not readily comprehensible and should be
rephrased - it is motivated to first introduce the general experimental protocol and
then to individually state what the corresponding pictures show.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
Nothing to declare
Reviewer's report
Title:High mobility group B1 impairs hepatocyte regeneration in acetaminophen
hepatotoxicity
Version: 2Date:12 February 2012
Reviewer: Vincent Zimmer
Reviewer's report:
This is an important preclinical study examining the efficacy of anti-HMGB1 in
attenuating liver injury in a mouse model of acetaminophen (APAP)
hepatotoxicity. The Authors show that blocking HMGB1 after APAP exposure
results in attenuation of liver injury most pronounced so after 48 h (relative to the
first time point 24 h) suggesting a role for HMGB1 as a progression factor in this
injury model.
Improvements in hepatocyte regeneration by the anti-HMGB1 strategy is
supported by up-regulation of NF-kB DNA binding capacity and the cell-cycle
regulator cyclin D1.
However, there remain some minor concerns to be addressed:
1. The exclusive use of Western blots has to be critically discussed - for HMGB1
serum measurements complementary use of e.g. reliable commercial ELISAs or
in case of e.g. cyclin D1 complementary use of immunohistochemistries might
have strengthened the validity of experimental data. These limitations, if not
eliminated in the first place, should at least be stated and discussed appropriately
in the manuscript.
2. The legend for Figure 2 is not readily comprehensible and should be
rephrased - it is motivated to first introduce the general experimental protocol and
then to individually state what the corresponding pictures show.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
Nothing to declare
Please review this paper.
user
Reviewer's report
Title:High mobility group B1 impairs hepatocyte regeneration in acetaminophen
hepatotoxicity
Version: 2Date:12 February 2012
Reviewer: Vincent Zimmer
Reviewer's report:
This is an important preclinical study examining the efficacy of anti-HMGB1 in
attenuating liver injury in a mouse model of acetaminophen (APAP)
hepatotoxicity. The Authors show that blocking HMGB1 after APAP exposure
results in attenuation of liver injury most pronounced so after 48 h (relative to the
first time point 24 h) suggesting a role for HMGB1 as a progression factor in this
injury model.
Improvements in hepatocyte regeneration by the anti-HMGB1 strategy is
supported by up-regulation of NF-kB DNA binding capacity and the cell-cycle
regulator cyclin D1.
However, there remain some minor concerns to be addressed:
1. The exclusive use of Western blots has to be critically discussed - for HMGB1
serum measurements complementary use of e.g. reliable commercial ELISAs or
in case of e.g. cyclin D1 complementary use of immunohistochemistries might
have strengthened the validity of experimental data. These limitations, if not
eliminated in the first place, should at least be stated and discussed appropriately
in the manuscript.
2. The legend for Figure 2 is not readily comprehensible and should be
rephrased - it is motivated to first introduce the general experimental protocol and
then to individually state what the corresponding pictures show.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
Nothing to declare
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