Review for 10.1186/s12876-022-02208-x (2022)

Reviewer’s report
Title: 
RIP3 knockdown inhibits necroptosis of human intestinal epithelial cells
via TLR4/MyD88/NF-κB signaling and ameliorates murine colitis
Version: 
0 
Date: 
12 Jan 2022
Reviewer's report:
In general, it is an interesting study that identified a novel potential treatments
for UC and the mechanisms, below are my comments for the authors.
1. In line357, the author found that RIP3 was the most expressed in human small
intestine. But why did the author focus on colon instead of small intestine in this
study? 
2. Figure 2A was to prove the successful knockout of RIP3 gene, and it will be
more persuasive if author increases the relative expression of RIP3 of the control
group without virus transfection.
3. In this study, the author used GSK872 and nec-1 as inhibitors of RIP3 in
different experiments, i
I recommend using one inhibitor in the two experiments to increase the
consistency of experimental results in the paper.
4. In Fig4D, the bar in WT group seems to be different from other groups. The
author should improve the figure.
5. The reasons for the establishment of SASP group should be briefly explained
in the discussion part.
6. The merged image in the immunofluorescence staining diagram of Fig5A
should be show.
7. It is recommended to show the flow cytometry image in Fig5E, not just the
statistical data.
8. In Fig6A, why CD68 was chosen as the indicator reflecting the ROS degree?
The results will be more informative if have more indicators.
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes