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The authors have addressed all of the reviewers' comments. Therefore, this manuscript is now ready for publication.
[# PeerJ Staff Note - this decision was reviewed and approved by Gwyn Gould, a PeerJ Section Editor covering this Section #]
All suggestions were promptly and effectively addressed by the authors.
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The author has addressed the reviewers’ comments in a comprehensive and satisfactory manner. The revised manuscript is now fully compliant with the formatting guidelines and template required by PeerJ.
The author has also elaborated more clearly on the methodology employed to obtain the research findings, thereby improving the clearly of the study design and facilitating a better understanding for the readers.
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**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
Thank you for inviting me to review the manuscript entitled "Role of pyroptosis in pregnancy-related diseases" by Dr. Li et al., submitted for possible publication in PeerJ Life & Environment. In this study, the authors provide valuable insights into the role of pyroptosis in pregnancy-related diseases, an area of growing interest in obstetrics and gynecology.
a) The article meets the standards of scientific writing in English. I noticed a few typical language errors throughout the text. Please consider correcting the title to "Role of pyroptosis in pregnancy-related diseases" for better grammatical accuracy; in addition, there are a variety of acronyms used without first mentioning their full name and functions.
b) The study presents an objective introduction that provides a context for the study. To improve its structure, I suggest that an objective sentence be removed from lines 36-37 and kept only in the last paragraph to maintain coherence and ensure that the introduction flows logically.
c) Regarding the structure of the article, it covers the basic topics required. I have some concerns regarding the figures presented. Figure 1 is not necessary, since it does not summarize the authors' findings and is not informative; Figure 2, in turn, addresses the canonical and non-canonical mechanisms related to pyroptosis, which are not the direct focus of the review; Figure 3 presents a pyroptosis signaling pathway in GDM, however, this pathway is not explained in the text. Furthermore, why only GDM? I suggest that the authors focus their efforts on a figure that summarizes the main findings of the roles of pyroptosis in the reported diseases, showing how the factors involved are positively or negatively regulated in maternal-fetal tissues/targets; the program that created the figures should be cited.
d) Regarding the originality of the review, I am concerned because this field was recently reviewed very well by Li et al., (2024) and Yu and Li, (2021); it is not clear in the contextualization of the study what the limitations in the area still are and which topics are still not well understood. For example, the authors only briefly mention thyroid dysfunctions and their relationship with pyroptosis at the end of the review. This would be a differential topic that has not been reviewed previously.
e) In lines 42-43, the authors mention only patients with the diseases studied as the target audience of this review. In fact, it is a topic that interests many other spheres of the scientific community, such as health professionals and researchers seeking new treatment tools.
a) The topic of this review is within the scope of the journal.
b) The paper presents a clear methodology, with the databases and the period of data collection. However, in lines 51-52, the authors need to indicate whether the studies involved only humans or other models, such as rodents or in vitro studies; also, in lines 52-53, the authors write "Only full-text literature was included". This is not clear whether the authors refer to open-access articles or are excluding published abstracts.
c) I noticed some small mistakes in the article citations:
- Lines 70: I recommend carefully verifying all cytokine references to ensure accuracy, as IL-10 may have been cited erroneously instead of IL-1β in lines 70 and 72;
- Lines 89-90: The cited study does not mention an increase in serum NLRP3. But there is an increase in placental homogenate. Other interesting data from the immunohistochemistry and PCR study could be shown.
- Lines 90-92: Which studies do the authors refer to here?
- Line 93: Avoid using "studies" in the plural and cite only one.
- Lines 108-112: a reference should be added here;
- Line 119: What did this study show? It was not clear here.
- Line 124: Lipoprotein or Lipoxin?
- Lines 157-159: IL-1 exposure in a clinical or experimental context? I always recommend specifying the model.
- Line 228: Why are p-values cited here? What are the functions of miR-106-5p and miR-210-3p in the context of diabetes and pyroptosis? These connections need to be made!
- Lines 229-230: What main roles are listed?
- Line 236: "trophoblast" should be used in the singular;
- Lines 217-219: "Inflammasomes in the adipose tissue, such as IL-1β induced by caspase-1, could be used as evidence of insulin resistance in women with GDM". IL-1β is not an inflammasome, but rather a pro-inflammatory mediator released after inflammasome activation. Review this;
d) As for the organization of the structure, I have no concerns about the larger topics. However, I suggest that the information within the paragraphs in all topics be better connected.
a) Lines 270-271: Although it is true that "Pyroptosis not only plays a role in the physiology of pregnancy, but the excessively activated inflammasomes are closely related to the onset of various pregnancy-related diseases", this study did not address the physiological roles of pyroptosis and inflammasome.
a) Pyroptosis in preeclampsia
- Line 85: It is very poor to characterize preeclampsia only as "a complication of pregnancy." What factors indicate a state of preeclampsia?
- Many other studies involving the inflammasome pathway and preeclampsia were not cited here. How often is NLRP3 increased in women with preeclampsia? What are the clinical implications of this? What therapeutic approaches have been discussed to attenuate inflammasome activation in preeclampsia models? Are there ongoing or completed clinical studies investigating the relationship between pyroptosis and preeclampsia in specific populations? I did not see any mention of other study models, such as rodents or in vitro, that address relevant molecular details on the topic; how does pyroptosis contribute to maternal-fetal complications associated with preeclampsia, such as intrauterine growth restriction, placental abruption, or severe vascular alterations? Is there evidence of non-canonical mechanisms of pyroptosis related to preeclampsia? Addressing these questions could significantly enhance the discussion of pyroptosis in preeclampsia.
b) Recurrent spontaneous abortion (RSA) and pyroptosis
- The discussion on RSA lacks clarity in the sequence of ideas, and important questions remain unanswered: What are the pyroptosis-mediated pathways involved in RSA? How does NLRP3 activation contribute to implantation failure? What molecular alterations occur in maternal-fetal tissues during RSA? Providing a cohesive narrative with these details would strengthen this section.
c) Neonatal developmental dysplasia
- Similarly to the previous item, the topic structure presents relevant information, but the connection between them is not clear; I recommend organizing the paragraphs by separating the topics by clinical context: first addressing FGR, then BPD, and finally the neurodevelopmental effects.
- Regarding BPD, the role of Nrf2 in regulating pyroptosis seems well explained, but the interaction between the activation of the NLRP3 inflammasome and the development of damage in lung and brain tissues could be elaborated.
d) Pyroptosis with preterm birth
- This topic is more organized in the sequence of ideas than the previous ones, but still lacks more details: how do inflammasomes, such as NLRP3, lead to preterm labor? Explaining the downstream signaling pathways would be beneficial.
e) Gestational diabetes mellitus (GDM) and pyroptosis
- The text goes from metabolic alterations in GDM directly to the relationship between inflammasomes and insulin resistance, and then to biomarkers and therapies, without a clear link between the topics.
- Despite discussing potential therapies such as procyanidins and SPOCD1, the excerpt does not clearly connect the mechanisms described above with these interventions. Explaining how these therapies interfere with inflammasome-associated signaling pathways would be essential for a more robust reasoning.
f) Pyroptosis in other pregnancy-related diseases
- The text in the “Pyroptosis in other pregnancy-related diseases” section would benefit from better organization and logical transitions between ideas, rather than listing diseases sequentially without connections. For example, the authors begin by discussing maternal hypothyroidism, then shift abruptly to viral diseases, and later return to thyroid dysfunction in the final paragraph. Additionally, the mention of smoking is presented in the same paragraph as thyroid dysfunction, which disrupts the logical flow of the narrative. I recommend restructuring this section to group related diseases by themes or mechanisms, using transitional phrases to connect them. This approach would improve coherence and provide a more comprehensive understanding of the topic."
Very well represented. I consider that this review meets the criteria to be published.
Yes, the review was made in good quality.
I appreciate the impact of results in the literature field.
I consider that this paper deserves to be published.
The literature cited is both relevant and up to date, providing sufficient background and contextualization to demonstrate the significance and relevance of the study within its field. Figures and tables are appropriate and contribute meaningfully to the presentation of the findings. However, some minor formatting revisions may be necessary to ensure full alignment with the target journal’s specific guidelines.
The methodology section still needs to be completed by including the steps of the Systematic Literature Review (SLR) and the possible applications that could be used for data collection in this article.
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See the PDF file.
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