{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:09:33Z","timestamp":1769576973453,"version":"3.49.0"},"update-to":[{"DOI":"10.12688\/f1000research.125784.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000}},{"DOI":"10.12688\/f1000research.125784.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000}},{"DOI":"10.12688\/f1000research.125784.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000}}],"reference-count":43,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015767","name":"Universitas Syiah Kuala","doi-asserted-by":"publisher","award":["143\/UN1I\/SPK\/PNBP\/2022"],"award-info":[{"award-number":["143\/UN1I\/SPK\/PNBP\/2022"]}],"id":[{"id":"10.13039\/501100015767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background Oral squamous cell carcinoma (OSCC) is one of the most common oral cancers with a high mortality rate. The biodiversity source in Indonesia makes areca nut a potential antioxidant in treating disease. Objective The study aimed to evaluate the effect of areca nut extract on 4-nitroquinoline-1-oxide (NQO)-tumor-induced rats. Methods Twenty-eight male Sprague-Dawley rats were divided into four groups. Group 1 served as the control group, group 2 was 4NQO-induced rats without treatment, and groups 3 and 4 were given 4NQO-tumor inducer with 500 and 1000 mg\/kg BW of areca nut extract, respectively. The rats in groups 2,3, and 4 received 30 ppm of 4NQO tumor inducer in drinking water for 12 weeks. In the end, all rats were euthanized, and the tongue was removed. The body, liver, kidney, heart, and lung weights were measured. Tongue tumor volume and dysplasia lesions were analyzed. The tumor-infiltrating lymphocytes (TILs) in the tumor and stromal areas were scored semi-quantitatively associating the infiltrate grade (0-3) and analyzed histologically. Results There were significant differences in body weight loss between the initial and final phases in groups 1 and 2 (p&lt;0.05). The areca nut at 500 and 1000 mg\/kg BW significantly reduced the tumor size compared with groups 1 and 2 (p&lt;0.05). The incidence of OSCC in rats with 500 and 1000 mg\/kg BW of areca nut extract after 22 weeks was 0%, but the dysplasia lesions were observed at 28.57% and 85.71%, respectively. The highest mean of stromal TILs was in group 3 and there were significant differences in stromal TILs between groups 2 and 3 (p&lt;0.05). Conclusion Areca nut extract induced infiltrating lymphocytes in the stromal tumor area on the OSCC lesion of the tongue in 4NQO-induced rats.<\/ns3:p>","DOI":"10.12688\/f1000research.125784.4","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T14:50:09Z","timestamp":1750431009000},"page":"1571","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Areca nut extract increased stromal tumor-infiltrating lymphocytes in 4-nitroquinoline-1-oxide-tumor-induced Sprague-Dawley rats"],"prefix":"10.12688","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5038-9913","authenticated-orcid":false,"given":"Liza Meutia","family":"Sari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cut Fera","family":"Novita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poppy","family":"Andriany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-5304","authenticated-orcid":false,"given":"Dina Keumala","family":"Sari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.18332\/tid\/105844","article-title":"Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways.","volume":"17","author":"X Jiang","year":"2019","journal-title":"Tob. 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I apologize for the delay in making revisions because I am in the process of obtaining a functional position at the university so some journals are recommended to be postponed to publish completely until the process is complete.&nbsp;I hope this delay is understandable  \n<b>Review<\/b>: Forty-three references, only 14 from the last 5 years. \n<i><b>Revision:<\/b> We have replaced 15 references to old journals with the latest journals that were published less than the last 5 years.<\/i>  \n<b>Review<\/b>: Please, check and correct reference number 13. \n<i><b>Revision:<\/b> Thank you, We have corrected the mistake by changing the journal with the latest journal<\/i>  \n<b>Review<\/b>: The reviewer suggests the title revision without &quot;the chemotherapeutic activity.&quot; The authors could only show the areca nut extract action in the present tense. \n<i><b>Revision<\/b>: We have deleted the \u201cChemotherapeutic activity\u201d in the title and draft manuscript.<\/i>  \n<b>Review<\/b>: The reviewer suggests beginning with the general data about OSCC and updating this section with the newest National Cancer Institute information regarding oral cancer therapy. Moreover, the authors could enumerate more causal factors of OSCC. After, they can link with herbal therapy and continue with the areca nut presentation.&nbsp; The authors are encouraged to support their statements with more than 1 reference and to organize the data from this section better. \n<i><b>Revision: <\/b>The changes have been made as instructed<b>.&nbsp;<\/b>We have added the data from the National Cancer Institute, the International Agency for Research on Cancer GLOBOCAN 2020, and Cancer Stat Facts<\/i>  \n<b>Review:<\/b> The Plant material subsection could be changed in Plant extract, showing the areca nut extract preparation at the same time.&nbsp; The administered doses of areca nut extract could be shown lately in the experimental procedure. At Statistical Analysis, the authors should indicate the year and provider of the software version. \n<i><b>Revision<\/b>: We have revised the subsection title and the software provider.<\/i>  \n<b>Review:&nbsp;<\/b>The table footer should contain each group's signification to understand the data from tables better.&nbsp;The same indication is available for the figures, with all abbreviations explained.&nbsp;In the tables, the compared data should be better highlighted. \n<i><b>Revision:<\/b> We have made all the revisions in the results section.<\/i> &nbsp; \n<b>Review<\/b>:&nbsp;More recently published references are requested for Discussion.&nbsp; \n<b>Revisions:<\/b>&nbsp;The addition of several journals","URL":"https:\/\/f1000research.com\/articles\/11-1571\/v4#referee-comment-10888","order":2,"name":"referee-comment-10888","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.161333.r257814, Jiaxuan Qiu, Nanchang University, Nanchang, Jiangxi, 11 Apr 2024, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/11-1571\/v3#referee-response-257814","order":3,"name":"referee-response-257814","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was supported by the Research Institute of Universitas Syiah Kuala, Banda Aceh, Indonesia, through Research Grant (Contract Number: 82\/UN11.2.1\/PT.01.03\/PNBP\/2022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}