Paneth Cells and Lgr5+ Intestinal Stem Cells in Radiation Enteritis
Round 1
Reviewer 1 Report
The manuscript is written nicely. The authors need to address the following comments before proceeding further.
1. Authors need to improve the English of the manuscript.
2. Abstract may be made more attractive.
3. Role of microbiota in cancer need to be elaborated. Effect of radiation therapy on microbiota should also be elaborated.
4. The authors need to conclude the manscript in more effective way.
Some new ref must be added like
Singh V, Ahlawat S, Mohan H, Gill SS, Sharma KK. Balancing reactive oxygen species generation by rebooting gut microbiota. J Appl Microbiol. 2022 Jun;132(6):4112-4129. doi: 10.1111/jam.15504. Epub 2022 Mar 6. PMID: 35199405
Author Response
Please see attached.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript is well written. I have only few comments:
1) In the introduction (lines 75-78), I suggest to improve the section regarding the aim of this review.
2) Please insert the citations in Table 1
3)Recommendations and Future Perspectives: I suggest to merge these parts in the conclusion.
Author Response
Please see attached.
Author Response File: Author Response.pdf
Reviewer 3 Report
“Paneth cells and Lgr5 intestinal stem cells in radiation enteritis”
Reviewer’s comments:
The manuscript titled “Paneth cells and Lgr5 intestinal stem cells in radiation enteritis” by Emmanuel et al. reviews an important area of radiation therapy in patients with gut and pelvic cancers. Authors have covered and touched all the relevant and current information in the area. I am sure this review will benefit the readers. However, before it can be published it has to be significantly improved by adding few more information, by improvising grammer and english writing. My observations are given below.
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There are two Section 3 in the manuscript “3. Regulation of Lgr5 ISCs” and “3. Radiation enteritis”
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The 3rd point, Regulation of Lgr5 ISCs can be elaborated further. For example how these each factors regulate the proliferation of Lgr5 ISCs.
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Include references also in the Table 1.
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The manuscript should benefit from including the role of dietary supplements and type of diet on the repairment of gut health and its impact on ISCs.
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Please look into the grammer throughout the manuscript.
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Some sentences apears to be incomplete or not framed properly, like:
Line 42-43: The crypt-based ISCs are known as the leucine-rich re- 42 peat-containing G-protein coupled receptor 5 ISCs (Lgr5 ISCs) [10-14]
Line 57: immunity of the in the gut
Line 67: The other complications of chronic radiation are enteritis internal fistulae, dysbiosis and malabsorption syndromes.
Line 83: preventative, wrong spelling
Line 86-88 “Solutions to the persistent challenges related to reducing the risk, prevention and management of radiation are likely to be achieved if treatment modalities which enhance the interactive functions of all key role players in gut homeostasis.” is a non-concluding open-ended statement.
Correct the statement in line 100-101 “M-cells are specialized enterocytes which are found only in regions where they are lymphoid follicles.”
Line 108: of nutrients they like all the other progenies, incomplete confusing sentence.
Line 109 “The area of the small intestine is nutritious” what is meant by the statement? Please elaborate in the manuscript.
Line 118: sample the luminal in the, lumnal what?
Line 128-129: Replacement of Lgr5 stem cells is happen sequentially, Grammatical error.
Line 155 “The set-up in the lumen of the small intestine is nutritious but hostile with in certain areas up to 104/ml bacteria.” The authors need to clarify this statement.
Line 309 “Management of radiation starts with measures to prevent its occurrence by ensuring the patients is fit for radiotherapy.” Highlight some of the factors that influence the selection criteria for radiotherapy.
Line 271: the group of cells and ....?.... which influences
line 275: ionizing irradiation, it should be ionizing radiation.
Line 275-276: at higher dose can affect stable and permanent cells, it can affect.
Line 299-300: abdominal pain, nausea, vomiting and abdominal pains, abdominal pain written twice.
Line 309: Management of radiation ....?..... starts
Line 310: the patients is fit, gramatical error.
These are just few observations, which I could identify while reading the draft. I suggest the authors to read the entire manuscript throghly and correct the english.
Author Response
Please see attached file.
Author Response File: Author Response.pdf
Reviewer 4 Report
The authors performed an overview on the main cell types in intestinal mucosa describing their role in gut homeostasis. But even if it shouldbe of interest I do not see any involvment of these cells in radiation injury and repair. Furthermore no specific cell type is identified as protective from injury.
I consider this paper of interest, but at the moment not ready for publishing.
Specific Comments
In lines 40-50 the description of the layers of cell only by number is difficult to understand. I suggest to add an image that represents this description.
Lines 55-57: rewrite this sentence.
Figure 1: ISCs are not represented in figure as described in the caption.
Figure 2 and 3 represents the same pathway of differentiation. I suggest to delete figure 3.
Also Figure 2 in not complete but I can imagine the meaning of it. I think this is usefull to summarize the cell lineages.
The manuscript must be strongly revised for English and also for redundant and unclear sentences.
Author Response
Please see attached file.
Author Response File: Author Response.pdf
Round 2
Reviewer 4 Report
THE AUTHORS STRONGLY REVISED THE MANUSCRIPT AND I THAT NOW IT CAN BE ACCEPTED.
FIGURE 3 LACK HALF OF RIGHT PART.PLEASE PROVIDE A COMPLETE FIGURE
Author Response
Please attachment for the response to Reviewer 4 Second Round.
Author Response File: Author Response.pdf
