Smokeless Tobacco: A Comprehensive Review of Molecular Effects, Societal Perception, and Cessation Strategies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank You for a pleasure to read Your work.

I have several comments and offer to improve Your work.

 

Firstly, please, check English.

 

Title

Please, change it for better understanding.

For example, replace all parts after phrase ‘comprehensive review’ before it (with ‘smokeless tobacco).

 

Abstract 

Please, check the rules of journal because usually it must be not less 200 words at least.

 

Introduction

Please, add in the end of section, the aim of review

 

Section 2.1

Please, make an accent exactly on precancer/cancer development

 

Please, before table 1 list all groups of cancerogenic compounds for better understanding. If it was written in some articles, please, leave references for this classification.

 

Section 2.2

Please, make the accent on the cancer as it

is the aim of Your study. 

The atherosclerosis is important disease but it is absent in the aim of Your study.

 

You wrote ‘others have reported..’ and have only one references, please, change more links.

 

Section 3.1

Is this section exactly for smokeless tobacco or common for all nicotine substances?

Please, explain in this section.

Figure 1. Please, write in the legend if it is Your own or You got from some source (with reference). The same is for figure 2.

Part about macrophages characteristics is not obligate, please, leave only information according to topic of Your study. 

 

Section 4.1

It is mostly about the outcomes of surgery in patients with cancer of head and neck. Please, leave information only directly connected with ST.

 

Section 4.2.2

You wrote ‘numerous systematic reviews…’ and had only 2 references. Please, add more or change word “numerous’.

 

Conclusion

Please, write it according to the aim of Your article and results of analysis.

 

Sincerely, Reviewer

 

 

 

 

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The paper entitled "Smokeless Tobacco: A Comprehensive Review of Molecular Effects, Societal Perception, and Cessation Strategies" assesses the molecular mechanisms associated with smokeless tobacco (ST) components, its role in speech impairment and cancer progression, and examines the effectiveness of tobacco cessation strategies while reviewing the perceptions held by ST consumers.

The paper is interesting and written with moderate scientific rigor. However, several issues need to be addressed.

 The authors should use a template appropriate for this journal.

  Abstract:

Add  search strategy, results and conclusion

  

Keywords: should be in alphabetical order, KEYWORDS should not contain the same words that are within the title of the text. Thus these should be changed appropriately.

 

Add citations to the following statements:

 

-          “Others have reported a strong correlation between ST-induced oxidative stress and poor cardiovascular outcomes and risk of atherosclerosis.”

-          “Increased plasma nitric oxide levels have been observed in ST users compared to non-users. ST users also have significant elevation of plasma peroxynitrite levels, which causes protein nitration and increases atherosclerosis risk. Peroxynitrite, a reactive nitrogen species, has multiple harmful effects such as DNA damage and lipid peroxidation. ST users have elevated plasma levels of malondialdehyde, a marker of lipid peroxidation. Increased levels of total phospholipids, protein carbonyls, and creatinine, along with decreased uric acid levels and renal dysfunction are also associated with ST use. The oxidative stress induced by ST products initiates a cascade of metabolic pathways involving TSNAs. Although salivary SOD has been assessed in the saliva of smokers, few studies have included participants exposed to ST products. Salivary SOD, malondialdehyde, or plasma nitric oxide may be effective biomarkers for oxidative stress in ST users to aid in the early detection of precancerous conditions. These biomarkers are essential to develop targeted preventive and treatment approaches for ST-associated lesions.”

-          “Nicotine and nicotine derive nitrosamines (NDN) function as agonists on nAChRs, particularly α4β2nAChR and α7nAChR. By activating these receptors, nicotine and NDN promotes dopamine release in the nucleus accumbens and prefrontal cortex of the brain to enhance cravings. The addiction or reward circuitry within the brain is primarily regulated by dopaminergic neurons.”

-          Alterations in metastasis-related markers have been reported in ST users, including overexpression of EGFR and c-Met, activation of the HGF/c-Met pathway, and upregulation of the SDF1α/CXCR4 axis. The HGF/c-Met-stimulated SDF1α/CXCR4 axis promotes lymph node metastasis among chewing tobacco users with oral squamous cell carcinoma and may therefore be a useful prognostic and stratification biomarker for cancer aggressiveness [63]. Further translational studies are necessary to explore the diagnostic and therapeutic implications of these findings in clinical settings. Another study explored the effect of nicotine on healthy oral epithelial cells, revealing its potential to induce proliferation through PI3K and MAPK pathways.

-          However, existing literature primarily focuses on patients who smoke tobacco rather than on those who use ST. Studies have also demonstrated the importance of involving family members in tobacco cessation efforts, as patients may be influenced by regularly observing continued tobacco use.

-          A recent study introduced an innovative framework utilizing artificial intelligence to develop a conversational agent (CA) designed to prevent relapses in tobacco cessation. The study used peer interaction data and social media discourse to evaluate sequential patterns of behavior change techniques and speech acts embedded in online conversations.

-          The study showed that data-driven, theory-linked approaches may be applied to develop effective behavior change CAs that emphasize engagement, sustainability, and acceptance in relapse prevention efforts.

-          This statement should be changed and a reference should be added: One company has also used data from tobacco users to evaluate the potential population-level impact of authorizing modified risk claims for moist ST products.

-          Longitudinal studies have linked marketing to increased initiation of ST use, especially among young adults.

-          Unlike FDA-approved smoking cessation treatments, oral tobacco products lack thorough testing for smoking cessation efficacy.

 

The conclusion should be rewritten with direct statements that clearly summarize the results of the study.

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank You for Your corrections but there are yet small corrections need.

Firstly, You attached the answer which is not for my Review. 
Secondary, please, write in legends for figures who is owner (You or other author with link), Make a conclusion shorter as it is too big.

Sincerely, Reviewer

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The paper was corrected in accordance with my remarks. I suggest accept the paper in its current form.

Author Response

Reply: Thank you very much for your valuable feedback. The paper has been corrected in accordance with your remarks, and we appreciate your suggestion to accept it in its current form.