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Authors have addressed all of the reviewers' comments and manuscript is ready for publication.
[# PeerJ Staff Note - this decision was reviewed and approved by Sonia Oliveira, a PeerJ Section Editor covering this Section #]
Please revise your manuscript as suggested by Reviewer 3.
Clear and unambiguous, professional English used throughout.
Literature references, sufficient field background/context provided.
Professional article structure, figures, tables. Raw data shared.
the review of broad and cross-disciplinary interests and within the journal's scope
The introduction adequately introduces the subject and clarifies who the audience is/what the motivation is?
The content of the article is within the aims and scope of the journal and the type of article.
The content of the article is according to high technical and ethical standards.
The methods are explained in detail and sufficient information is provided to be repeated.
The survey methodology is consistent with a comprehensive and unbiased coverage of the topic.
Sources are adequately cited and have been quoted and paraphrased as appropriate.
The review is logically organized into coherent paragraphs/subsections
The article is well-grounded and has multiple benefits that are relevant to many disciplines
The conclusions are well-formulated, relate to the original research question, and are limited to supporting findings.
The objectives stated in the introduction have been achieved
The conclusion identifies unresolved questions/gaps/future directions
no comment
No comment
No comment
No comment
The authors have responded comprehensively to my comments.
The authors have adequately responded to most of the comments, but there are still a few points that need to be revised.
Line 122: Insert space and capitalize the first letter. “...in vivo model.the gene directly...” should be “...in vivo model. The gene directly...”.
Line 184-186: This sentence would not have been revised. This reads uDKK3 independently predicted CKD progression and so on. However, “Peschard, V.G., et al., Association of Urinary Dickkopf-3 Levels with Cardiovascular Events and Kidney Disease Progression in Systolic Blood Pressure Intervention Trial. Kidney360, 2024.” says “after further adjustment for eGFR and albuminuria, uDKK3 was no longer associated with risks for composite CVD (hazard ratio, 1.07; 95% confidence interval, 0.92 to 1.23), ESKD (0.80; 0.62 to 1.02), AKI (1.01; 0.85 to 1.21), eGFR decline ≥30% (0.88; 0.79 to 0.99), or mortality (1.02; 0.87 to 1.20).” and the conclusion that “Among individuals with hypertension and nondiabetic CKD, higher uDKK3 appeared to have associations with a greater risk of CVD events, incident ESKD, incident AKI, eGFR decline ≥30%, and mortality but these associations were not independent of eGFR and albuminuria.”. Please check it again.
Line 204: Correction would be incomplete. “e(de Wilde et al. 2010)” should be “gastrocnemius and soleus. (de Wilde et al. 2010)”.
no comment
no comment
This manuscript needs a detailed revision before its publication in PeerJ. Please address comments of all reviewers and provide responses in a point wise manner.
[# PeerJ Staff Note: PeerJ can provide language editing services if you wish - please contact us at [email protected] for pricing (be sure to provide your manuscript number and title). Your revision deadline is always extended while you undergo language editing. #]
Topic The review topic is a good, new and somewhat innovative idea because it focused on an important variable DKK3 and highlighted pivotal points by using it to diagnose diseases. It is also a promising target for the field of many diseases that the review is looking forward to, such as cardiovascular, respiratory, renal, and muscular systems.
Specialization: It also gives it scientific importance in many medical specialties
General structure
The general structure of the review is organized and arranged, and the information was presented in an easy, smooth and scientific manner.
Language: The language of the review is somewhat good and systematic
The title is good and concise, but the description of non-malignant diseases gives an idea to the mind directly, unlike malignant diseases such as tumors and cancer, which is somewhat far from the real description of the review. Here I call on the authors to reconsider the title.
The abstract does not explain the definition and importance of DKK3 and how it relates to non-malignant diseases.
I expect the sentence in line 41, page 6, needs clarification (Future studies will explore the specific mechanisms of DKK3 in disease pathogenesis and its viability as a therapeutic target for novel interventions).
Key words :It is preferable to add other words
Introduction : It adequately introduces the subject and makes it clear
Compatibility with the scope of the journal : within the scope of the journal
The methods section is generally well-structured and provides sufficient detail for understanding the study design and replicating the experiments.
Including some explanation of potential limitations regarding residual confounding would be beneficial
Relationship between DKK3 and many diseases: the review presented in this study offers a mix of good and insightful findings as well as areas where additional clarity or exploration may be beneficial. This outcome merits more detailed investigation and cautious interpretation.
Literature references: The citations were logical and specialized, and they were from reliable sources related to the topic.
Good, but needs to add additional information about diagnosis and treatment for DKK3, the sentence in line 284, page 18
It is preferable to provide deeper and more precise details about how the study makes a meaningful contribution to the broader context of DKK3 research, especially in terms of advocating for treatment strategies.
The review appears well structured and the studies reported represent recent literature.
The review appears well structured.
The studies reported represent recent literature.
The "Conclusion and Prospective" section appears not very incisive. In my opinion, the authors should include personal considerations and/or any experimental studies that hypothesize or evaluate the activity of molecules capable of enhancing the activity of DKK3.
This review on DKK3 by Sun and colleagues provides a valuable summary of the multifaceted roles of DKK3, offering significant insights for researchers interested in the gene's involvement in various pathological conditions. This is particularly important given the limited availability of reviews focusing on DKK3 in non-cancer diseases.
However, I found several points requiring revision regarding the accuracy of information derived from the cited references, as detailed below.
no comment
1. Line 88, 89: According to Ref. 10, SPPB score is negatively associated with plasma DKK3 level. I recommend clarifying the association of SPPB and DKK3 is negative.
2. Line 94, 95: Ref. 13 reported the effects of curcumin from turmeric, not chrysin and not from Aspergillus. Please check the original paper.
3. Line 95, 96: As described in Ref. 14, the gene directly associated with AMD is HTRA1. Since DKK3 is its substrate, it can be utilized as a biomarker. I recommend clarifying this point.
4. Line 97: For non-specialist researchers, it would be better to add an explanation of the “Bruneck prospective study”.
5. Line 126: 127. Ref. 26 is the paper for the study of adrenal gland, not kidney. Please check the original paper.
6. Line 127, 128: There would be no description of “T-cell response” in Ref. 27. Please check the original paper.
7. Line138: It would be better to include the full term “estimated glomerular filtration rate” for “eGFR”.
8. Line 147: According to Ref. 40, associations of uDKK3 were not independent of eGFR and albuminuria. Please check the original paper.
9. Line 159: It would be better to add the gene name “of Baf60c” after “myofiber-specific ablation”
10. Line 163, 164: “muscular dystrophy” appears to be a mistake and should likely be “muscle atrophy”. Please check Ref. 45.
11. Line 165, 166: “gastrointestinal tract and flounder” would be a mistake and should likely be “gastrocnemius and soleus”. Please check Ref. 46.
12. Line 193, 194: According to Ref. 54, the effect of DKK3 on differentiation of pluripotent stem cells into mdDA neurons is discussed in the context of PD modeling, drug screening, and cell-replacement therapies. The endogenous DKK3 protein, which may serve as a therapeutic target, acts on mdDA progenitor cell population, not on pluripotent stem cells. These points should be addressed separately. Please check the original paper.
13. Line 197-200: This sentence is difficult for me to understand. It should be properly described that the patients in the third quintile of serum Dkk-3 had the lowest cumulative incidence rate of primary outcome compared to those in the other four quintiles of serum Dkk-3, based on Ref. 56. Additionally, log-rank p value would not be 0.0001. Please check the original paper.
14. Line 204, 205: In the case of Ref. 59, inhibition of Dkk3 and the contextual activation of the Wnt/β-catenin pathway are neuroprotective. I think it would be better to mention and discuss that this has the opposite to the protective effect of Dkk3 stated in the previous sentences.
15. Line 217-220: In Ref. 63, EAE is induced by injecting MOG33–55 peptide. The ablation or neutralization of Dkk3 exacerbates it, not directly induce EAE by itself. Please check the original paper.
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