Review for 10.1186/s12876-020-01453-2 (2020)

Reviewer’ s report
Title: ROLE OF SEX HORMONES AND THEIR RECEPTORS ON GASTRIC NRF2 AND
NEURONAL NITRIC OXIDE SYNTHASE FUNCTION IN AN EXPERIMENTAL HYPER-GLYCEMIA MODEL
Version: 1Date: 27 Jan 2020
Reviewer: Wenxie Xu
Reviewer's report:
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attachment. Please only upload as attachments annotated versions of manuscripts, graphs,supporting materials or other aspects of your report which cannot be included in a text format.Please overwrite this text when adding your comments to the authors.The manuscript is designedto investigate whether sex hormones/their receptors can attenuate altered Nuclear factor(erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression andnitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Theresults were demonstrated that the expressions of ER, Nrf2, and nNOS in gastric specimens weresignificantly reduced in HG group compared to NG; In addition, in-vitro treatment with sexhormones and/or their agonists significantly restored the expressions of Nrf2, nNOSα and total
nitrite production; Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSαexpression and nitrergic relaxation. The authors suggested that ER's can regulate nitrergic functionby improving Nrf2/nNOS expression in experimental hyperglycemia. This study is interesting, butsome questions need to be answered in the present state.
Comments:
1.Gastric receptive relaxation induced by nitrergic nerve is very important for gastric fundusaccommodation. The authors suggested that ER's can regulate nitrergic function by improvingNrf2/nNOS expression in experimental hyperglycemia. Do animals of different sex have differenttolerance to diseases, especially diabetic gastroparesis, i.e. are female mice more resistant todiabetic gastroparesis?2.In present study the neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxationwere checked in gastric neuromuscular tissues exposed for 48h to in-vitro hyperglycemia (HG) .However, general diabetes-induced damage of gastric nitrergic nerve was showed after diabetes 4-8 weeks, do the authors think the two methods have the same mechanism to damage the nitrergicnerve?
Are the methods appropriate and well described?
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Yes
Does the work include the necessary controls?
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YesAre the conclusions drawn adequately supported by the data shown?
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Yes
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Not relevant to this manuscriptQuality of written English
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AcceptableDeclaration of competing interests
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