Peer Review History
Original SubmissionMay 12, 2023 |
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PONE-D-23-13279Immunomodulatory effects of bibenzyls from Dendrobium species on diverse human immune cell types under inflammatory conditionsPLOS ONE Dear Dr. Böttcher, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Sep 24 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:
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Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Additional Editor Comments: We appreciate your manuscript and the valuable insights it presents. However, prior to final acceptance, we kindly request that you address some key revisions to enhance the manuscript's quality and validity. Specifically, we recommend focusing on improving graph clarity, correcting inaccuracies related to compound effects, practicing caution in interpreting results, and ensuring missing values are included. Additionally, consider making minor adjustments, such as refining the abstract's focus, offering clarifications on prior studies, providing full forms for abbreviations, incorporating a schematic for compound purification, optimizing graph scaling and font size, rectifying legend inconsistencies, and accurately setting graph gaps. These revisions will undoubtedly contribute to elevating the manuscript's overall quality, aligning it more closely with our standards, and ensuring its readiness for final acceptance. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Partly ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: No ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Comments to the authors: The manuscript entitled “Immunomodulatory effects of bibenzyls from Dendrobium species on diverse human immune cell types under inflammatory conditions” is interesting as it explores the potential of natural compounds in immunomodulation under inflammatory conditions. The authors have put in good effort in the study, but the manuscript is not well written and there are many grammatical mistakes. Also, the flow and explanation of findings are not up to the mark. There are multiple queries that are needed to be addressed: 1. In the abstract “Our study demonstrated board immunomodulatory effects…” correct broad. Also change the sentence to: Our study demonstrated broad immunomodulatory effects of Dendrobium compounds on multiple immune cell types including CD14+ monocytes. 2. In the abstract “This broad spectrum of activity on immune responses of Dendrobium compounds may lead to effectively therapeutic potential of these compounds in complex disease conditions including inflammation.” Replace effectively with effective. Also, this sentence is an exaggeration of the findings and hence can simply be written as “The broad spectrum of activity on immune responses of Dendrobium compounds may have promising therapeutic potential in various diseases including inflammation”. 3. The above 2 points are just an example of the grammatical errors and mistakes cited only from the abstract. The authors are recommended to get the whole manuscript checked by a writing expert. 4. Lines 48-51 can be put in the discussion section. 5. There are many sentences in the introduction section which have grammatical mistakes and thus change the context and meaning. 6. Line 86-87 says that LPS treatment is decreasing the TNF expression while from the results LPS is increasing the expression and the treatment with bibenzyls are reducing the expression of TNF. 7. What’s the rationale for taking 4 different Dendrobium species for isolating bibenzyls? 8. There is no information about the blood donor's age, gender, and health conditions from which PBMCs were isolated. 9. From Figure 3, it can be observed that treatment with compound 2 decreases the TNF in CD14+ monocytes even at 1µM concentration and is dose-dependent as well till 10 µM condition. Why didn’t the authors consider this compound for further studies when less concentration is showing significant results? 10. In Figure Legend 3, the authors should clearly state the treatment conditions. The current statement is confusing and misleading. 11. What’s the rationale for taking CD45+ cells for the cytotoxicity experiment? Why not the CD14+ monocytes taken for the study when the previous experiment shows the effect on these cells? 12. For deep immune profiling experiments, authors should consider PBMCs from more healthy donors. It is observed that the basal level of active immune cells of one of the donors is high without any stimulation. 13. Authors should consider isolating PBMCs from individuals with inflammatory conditions and then treating them with these compounds to substantiate their findings with more results. Reviewer #2: Kongkatitham et. al., focuses on the immunomodulatory effects of seven bibenzyl compounds derived from Dendrobium plants. To do so the author’s mainly focuses on the effect of these compounds on various human peripheral blood mononuclear cells (PBMCs). They used flow cytometry and single-cell mass cytometry (CyTOF) to evaluate the impact of these compound on the cell population of several PBMCs. Moreover, they checked the phosphorylation status of multiple phosphor-proteins within the selected PBMCs types. The results clearly shows that LPS stimulation increases TNF expression primarily in CD14+ monocytes. Treatment of these cells with bibenzyl compounds exhibits inhibition of TNF expression in LPS-stimulated PBMCs. Among the seven compounds tested, author chose two bibenzyls, moscatilin and crepidatin, for further studies. Overall, this study provides a good preliminary assessment of the broad immunomodulatory effects of Dendrobium compounds on various immune cell types but fall short in addressing few key issues. Major Comments 1. In Figure 3 – A graph showing a comparison of TNF expression in monocytes upon compound treatment—will help in better understating the data. Currently, it is challenging to make accurate assessments. Could authors clarify the control condition? Furthermore, authors should elaborate on what occurs within the cells or with TNF expression in unstimulated cells upon compound treatment? 2. As authors stated “only two compounds (i.e., moscatilin (3) and crepidatin (4)) exhibited inhibitory effects in a dose-dependent manner and decreased LPS-induced TNF expression significantly at the concentration of 5, 10 and 20 μM (Fig. 3)”— however, based on the data in Fig. 3, this statement is not entirely accurate. For instance, in the presence of Aloifol (7), a marked and significant decrease in TNF expression can be observed at 5 μM compared to the LPS positive control. This also holds true for compounds 6, 5, and 2. 3. “Decreased abundance of CD56+CD16+Tbet+ effector NK cells (cluster 4, Fig.5D), CD14-CD16+CD11c+CXCR4+ non-classical monocytes (cluster 7, Fig. 5E) and CD14+CD16 low monocytes expressing co-stimulatory molecule CD86 (cluster 19, Fig. 5F) have been detected in LPS treated PBMCs after the treatment with crepidatin (4), compared to LPS-treated PBMCs”— appears overly assertive based on the available data. When examining the data for cluster 7, it's notable that donor 2 demonstrates no significant difference. Moreover, the blood from donor 3 does not adhere to the observed trend whatsoever. In the case of cluster 4 and 7, no noticeable difference is observed in their frequencies. Additionally, contrary to the authors' assertion, an increase in the frequency of cluster 19 is observed, rather than a decrease. Considering the data, I would recommend that the authors incorporate additional donor data, accompanied by corresponding p-values, to elucidate the significance. 4. In Figure 5G, expression value without compound (control) is missing. Minor comments 1. The authors should avoid the mentioning of number of biological replicates, and the concentration of the compounds used in the study in the abstract. The abstract should maintain a general focus, emphasizing the study's background, key questions addressed, the methodology employed for validation, and the ultimate outcomes. 2. In line 62-64 authors stated “However, these studies were mostly performed in cell lines or animal models, and very few studies were performed using primary human cell culture”. Does it mean that the prior studies were performed using cell line from animal models? Do specify. Additionally, provide references to support your statement. 3. In line 67-68: The full form of “TNF and IL-6” should be provided. 4. A schematic diagram of how these seven compounds were purified from the Dendrobium plants would be nice. It will help in to easily follow the steps used during purification. 5. Figure 2 and 3, Increase the graph scale and axis title font size. It is hard to read. 6. In Figure 2, the histograms represent all cell populations from G-5 to G-9, but the legends state otherwise. Please correct this discrepancy. 7. In Figure 5C, the selected gap for the bar graph is incorrect. The chosen gap value results in the omission of the error bar for group 7. Kindly redraw this bar graph with the appropriate gap. In heat map, scale correlating color with frequency is missing. ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. 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Revision 1 |
Diverse modulatory effects of bibenzyl from Dendrobium species on human immune cell responses under inflammatory conditions PONE-D-23-13279R1 Dear Dr. Böttcher, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Syed M. Faisal, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: |
Formally Accepted |
PONE-D-23-13279R1 Diverse modulatory effects of bibenzyls from Dendrobium species on human immune cell responses under inflammatory conditions Dear Dr. Böttcher: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Syed M. Faisal Academic Editor PLOS ONE |
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