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Background: Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses anti-cancer properties. It has been shown to inhibit arecoline-induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline-induced oral cancer., Methods: Data mining identified common targets and hub targets of resveratrol in arecoline-induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments., Results: Sixty-one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial-mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down-regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis., Conclusion: Resveratrol inhibits the arecoline-induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objective: Consumption of areca nut and tobacco, often initiated in adolescence, are important causes of oral cancers in India. Areca nut prevention, often subsumed into school tobacco prevention programs, assumes that users are similar. However, differences in gender or age of users could necessitate unique approaches. The study aimed to find if adolescent areca nut-only users are different from tobacco-only users and users of both areca and tobacco., Methods: A cross-sectional survey with school-students attending grades 7, 8, 9 was used to compare differences in age, gender, knowledge, and attitudes among areca nut only users, tobacco-only, users of both, and non-users., Results: Of 1909 respondents, 464 (24.3%) used only areca nut, 25 (1.3%) used only tobacco, 177 (9.3%) used both, and 1243 (65.1%) were never-users. Females, overwhelmingly, consumed only areca nut. Users of both substances, in greater proportions, were male, older in age, and more than half believed that tobacco-users had more friends. A third of tobacco-only and users of both substances found it hard to turn down a friend's request to use compared to a fifth of areca-only and non-users., Conclusions: Differences in gender, age, and behavioral determinants such as subjective norms and perceived behavioral control between the different types of users underlines the need for prevention and cessation programs and policies that are specific to and tailored to their unique profiles and needs.

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck cancer and is associated with high mortality, particularly in Southeast Asian countries. Areca nut usage, smoking, and alcohol consumption are the most common risk factors for OSCC. Areca nut chewing is highly prevalent in Pakistan and has been attributed to an increase in OSCC cases. This study aimed to determine the association between areca nut usage and various clinicopathological features of OSCC and further evaluate the association of clinicopathological parameters of OSCC with tumor recurrence., Materials and Methods: The study was conducted using the data of 228 patients with OSCC resected at Liaquat National Hospital, Karachi, Pakistan, over 5 years between 2018 and 2022. Clinicopathological data were collected from hospital archives, and associations between various risk factors and clinicopathological parameters were determined., Results: Males were more commonly affected (77.2%), and the most common age group was <50 years (54.4%). Areca nut usage was reported in 59.6% of cases, and the buccal mucosa was the most common site (62.7%). Areca nut usage was significantly associated with male gender, greater tumor size, greater depth of invasion (DOI), higher tumor stage, nodal stage, presence of perineural invasion (PNI), and recurrence. In addition, multivariate analysis revealed that OSCC recurrence was significantly associated with older age, larger tumor size and DOI, nodal metastasis, and areca nut usage., Conclusion: Areca nut-related OSCCs were associated with poor prognosis and recurrence in our study population. Furthermore, OSCC recurrence was associated with various clinicopathological parameters, such as larger tumor size, a higher DOI, and nodal metastasis., Competing Interests: The authors declare that they have no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Atif Ali Hashmi et al.)

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 ( p = 0.0194), 4 ( p = 0.0078), 6 ( p = 0.0277), and 8 ( p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 ( p = 0.0313), 4 ( p = 0.0134), 6 ( p = 0.0061), and 8 ( p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score ( p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.

Background: Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive., Methods: Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE., Results: We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters., Conclusion: Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells., (© 2024. The Author(s).)

Background: The principal objective of this study is to ascertain the connections between well-known risk factors of oral cancer, including smoking (cigarette and tobacco), alcohol consumption, betel quid chewing, irritations in the oral cavity, history of head and neck cancer, and history of working outdoor more than 4 days/week, and the presence of OPMDs within the Thai population., Method: 349,318 subjects were recruited for initial screening, then 1,483 subjects who had at least 1 risk factor and a suspicious lesion underwent comprehensive oral examinations followed by a clinical diagnosis and then received initial treatment from either oral surgeons or oral medicine specialists. Among these subjects, individuals with at least 1 risk factor and with a clinical diagnosis of OPMDs were classified as cases, while those with at least 1 risk factor but without OPMDs were categorized as controls. The case group comprised a total of 487 subjects, whereas the control group consisted of 996 subjects. Exclusion criteria were known cases of currently having oral cancer or OPMDs., Results: The outcomes of the multivariate analysis revealed that among the variables assessed, betel quid (adjusted OR 5.12 [3.93-6.68], p < 0.001) and smoking (adjusted OR 1.46 [1.08-1.97], p = 0.013), there were an association with the presence of OPMDs. Conversely, alcohol drinking, having irritations in the oral cavity, a history of head and neck cancer, and a history of working outdoors more than 4 days/week were not associated with the presence of OPMDs. Furthermore, we also study the synergistic effect of alcohol drinking, irritations in the oral cavity, history of head and neck cancer, and history of working outdoors more than 4 days/week using subgroup analysis. The analysis showed that alcohol consumption combined with smoking or betel quid chewing expressed a significantly increased risk of OPMDs, from 1.46 to 2.03 (OR 2.03 [1.16-3.56], p = 0.014) and from 5.12 to 7.20 (OR 7.20 [3.96-13.09], p < 0.001)., Conclusion: Smoking and exposure to betel quid were a significant risk factors for the presence of OPMDs. The combination of alcohol with smoking or betel quid chewing was also found to increase the risk of OPMDs in this Thai northeastern population., (© 2024. The Author(s).)

Oral Submucous Fibrosis (OSMF) is a chronic precancerous disorder of the oral mucosa caused by chewing of areca nut and its other variants. Chewing of areca nuts leads to dysregulated expression of specific genes, leading to various premalignant or malignant disorders. This study aimed to determine the differential expression of the diagnostic genes (MYH6, TNNT3, MYL1, and TPM2) in healthy controls and OSMF patients using saliva and tissue samples, determining the histopathological grade of the clinical samples. A total of 20 patients were included in the study and were divided into two groups: Group I consisted of 10 healthy patients (control group) and Group II consisted of 10 OSMF patients. Unstimulated whole saliva samples were collected from both groups, and the tissue samples were divided into two parts: one for RT-qPCR analysis and the other for histopathological assay. The expression profile of genes concerning OSMF saliva and tissue samples was significantly upregulated compared to the healthy control, and all the clinical samples of the study were categorized into histopathological grade 1. The findings of this study concluded that these genes can be referred to as diagnostic genes for OSMF in early and very early clinical samples, and saliva can be used as a promising diagnostic tool for early OSMF studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Betel quid chewing, prevalent in Southeast Asia and South Asia, involves components such as betel leaf, areca nut, slaked lime, and sometimes tobacco. This study aims to assess buccal mucosa changes in betel quid chewers, develop a clinical tool for assessing exposure, and investigate its usability in predicting dysplasia., Methods: After obtaining ethical approval and informed consent, patients were recruited from the Out-Patient Department of Government Medical College, Omandurar, Government Estate, India. A target sample size of 200 was calculated. The data included the history of betel quid chewing, buccal mucosa cells obtained by oral cytology, and the severity of dysplasia of the slides assessed by pathologists. We utilized principal component analysis (PCA) and confirmatory factor analysis (CFA) to validate a new outcome variable reflecting nuclear morphometric parameters (NMPs). Multiplicative regression models were developed for betel years based on betel exposure and additives. Spearman correlation and Kruskal-Wallis test was used to check the association between betel years and dysplasia., Results: Significant differences in NMPs were observed among different betel chewing groups. We derived multiplicative regression models for betel years. In the logarithmic transformation approach, betel year = 0.05×betel-exposure×0.09×slaked-lime use×0.11×tobacco-use. In the original variable approach, betel year = 5.05×betel-exposure^0.00048×slaked-lime-use^0.18133×tobacco-use^1.47513. Spearman correlation and Kruskal-Wallis tests confirmed associations with dysplasia., Conclusion: Betel year is a pioneering tool for assessing lifetime betel quid exposure, similar to pack years for smoking. It could aid in risk stratification, targeted interventions and shaping public health policies. Despite limitations, betel year holds promise for revolutionizing oral health risk assessment, and future research can expand its scope globally, considering diverse betel quid compositions., (© 2024. The Author(s).)

Background: Chewing betel quid (BQ) - a preparation commonly containing areca nut and slaked lime wrapped in betel leaf - is entrenched in South Asia. Although BQ consumption during pregnancy has been linked to adverse birth outcomes, its effect on postnatal growth remains largely unexplored., Objective: We examined the associations of BQ use during pregnancy with children's height-for-age and body mass index-for-age z-scores (HAZ and BAZ, respectively) and fat and fat-free mass along with sex-based differences in association in rural Bangladesh., Methods: With a prospective cohort design, we assessed BQ use among mothers enrolled in the Preterm and Stillbirth Study, Matlab ( n  = 3140) with a structured questionnaire around early third trimester. Children born to a subset of 614 women (including 134 daily users) were invited to follow-up between October 2021 and January 2022. HAZ and BAZ were calculated from anthropometric assessment, and fat and fat-free mass were estimated using bioelectric impedance. Overall and sex-specific multiple linear regression models were fitted., Results: Growth data were available for 501 children (mean age 4.9 years): 43.3% of them were born to non-users, 35.3% to those using prior to or less-than-daily during the survey, and 21.3% to daily users. No statistically significant associations were observed after adjusting for sex, parity, maternal height and education, and household wealth., Conclusions: There was no effect of BQ use during pregnancy on postnatal growth in this study. Longitudinal studies following up those born to heavy users beyond childhood are warranted for capturing long-term implications of prenatal BQ exposure.

Background: This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy's development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF., Methods: In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping., Results: The study's patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development., Conclusions: Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes., (© 2024. The Author(s).)

Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF., (© 2024. The Author(s).)

Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture., (© 2024. The Author(s).)

Backgrounds: Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the association remains unclear in physically fit military personnel. This study aimed to investigate the combination of these substances use and their associations with new-onset MetS in the military., Methods: A total of 2,890 military men and women, aged 18-39 years, without MetS were obtained from the cardiorespiratory fitness and health in eastern armed forces study (CHIEF) in Taiwan and followed for incident MetS from baseline (2014) through the end of 2020. Incident MetS event was defined by the International Diabetes Federation guideline and confirmed in the annual health examinations. A self-report was used to assess the alcohol, tobacco and betel nut use status (active vs. former/never). Multivariable Cox regression model was performed to determine the association with adjustments for sex, age, body mass index and physical activity at baseline., Results: At baseline, there were 279 active betel nut chewers (9.7%), 991 active smokers (34.3%) and 1,159 active alcohol consumers (40.1%). During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were observed. As compared to no substance users, only one substance, and two and three substances users had a greater risk of incident MetS [hazard ratios (HRs) and 95% confidence intervals: 1.27 (1.06-1.54), 1.38 (1.12-1.69) and 1.78 (1.37-2.32), respectively]. In subgroup analyses, the risk of incident MetS in two and three substances users was significantly greater in those free of baseline low high-density lipoprotein [HRs: 1.54 (1.21-1.95) and 2.57 (1.92-3.46), respectively], as compared to their counterparts (both p for interactions <0.05)., Conclusion: A dose-response association of more substances use for new-onset MetS was noted in military personnel. This finding suggests that the combined alcohol, tobacco and betel nut use may play a role in the development of MetS. Further study is required to establish causation and to investigate the potential benefits of substance use cessation in reducing the risk of MetS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Hsu, Lin, Tsai, Chang, Liu and Lin.)

Introduction: Habitual betel quid chewing, a tobacco product, is a leading cause of oral cancer in Asia-Pacific countries where this practice is most prevalent. However, it is not well understood whether betel quid chewing is also a cause of adverse cardiovascular outcomes. To address this gap, we conducted a systematic literature review of peer-reviewed published studies evaluating the association between habitual betel quid use on the risk of adverse cardiovascular outcomes., Methods: We searched PubMed for studies assessing the correlation between betel quid chewing and cardiovascular health. We included studies if (i) they included human subjects; (ii) were peer-reviewed articles in indexed journals; and (iii) were in English. We extracted data from eligible studies and stratified them by geographical location, study designs and cardiovascular outcomes. Finally, we did a narrative synthesis of the data to identify adverse cardiovascular outcomes associated with chronic betel quid use., Findings: We reviewed data from 19 studies that met the inclusion criteria. Habitual betel quid chewing was associated with hypertension, atherosclerosis, inflammation and ischaemic heart disease. In addition, betel quid use was a risk factor for arrhythmias. Interestingly, betel quid use was an independent risk factor for cardiovascular disease in women. Long-term betel quid consumption was associated with higher risks for all-cause mortality and increased overall cardiovascular risk., Conclusions: Habitual betel quid chewing is an important cardiovascular risk factor in populations where the practice is prevalent., (© 2024 John Wiley & Sons Ltd.)

Background: Oral submucous fibrosis (OSF) is a pathological condition characterized by excessive tissue healing resulting from physical, chemical, or mechanical trauma. Notably, areca nut consumption significantly contributes to the development of oral fibrosis. The current definition of OSF, recognizing its potential for malignant transformation, necessitates a more comprehensive understanding of its pathophysiology and etiology., Highlights: Areca nut induces fibrotic pathways by upregulating inflammatory cytokines such as TGF-β and expressing additional cytokines. Moreover, it triggers the conversion of fibroblasts to myofibroblasts, characterized by α-SMA and γSMA expression, resulting in accelerated collagen production. Arecoline, a component of areca nut, has been shown to elevate levels of reactive oxygen species, upregulate the expression of various cytokines, and activate specific signaling pathways (MEK, COX2, PI3K), all contributing to fibrosis. Therefore, we propose redefining OSF as "Areca nut-induced oral fibrosis" (AIOF) to align with current epistemology, emphasizing its distinctive association with areca nut consumption. The refined definition enhances our ability to develop targeted interventions, thus contributing to more effective prevention and treatment strategies for oral submucous fibrosis worldwide., Conclusion: Arecoline plays a crucial role as a mediator in fibrosis development, contributing to extracellular matrix accumulation in OSF. The re-evaluation of OSF as AIOF offers a more accurate representation of the condition. This nuanced perspective is essential for distinguishing AIOF from other forms of oral fibrosis and advancing our understanding of the disease's pathophysiology., Competing Interests: Declaration of competing interest All the authors of the manuscript now state that there is no financial implication or personal relationship with other people or organizations that could inappropriately influence the outcome of this work., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Objectives: This study investigated the association of alcohol consumption, betel nut chewing, and cigarette smoking (ABC) with mortality in patients with head and neck cancer (HNC). This nationwide population-based cohort study determined whether ABC habits were associated with overall or cancer-specific mortality in patients with HNC in Taiwan., Methods: Data from the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database were used to identify patients with HNC from 2011 to 2017. All the identified patients were monitored until the date of death or the end of 2017. Poisson regression models were employed to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) associated with the effect of ABC habits on mortality., Results: A total of 31,246 patients with HNC were analyzed in this study. The results revealed that betel nut chewing alone exhibited the strongest effect, significantly increasing the risk of overall mortality (adjusted IRR = 1.44, 95% CI = 1.27-1.63). Additionally, betel nut chewing alone was significantly associated with cancer-specific mortality (adjusted IRR = 1.51, 95% CI = 1.30-1.44). Stratified analyses by sex and tumor location indicated that the effect of betel nut chewing alone on overall or cancer-specific mortality remained significant across both sexes, and among patients with oral cancer and patients with oropharyngeal cancer., Conclusions: ABC habits, particularly betel nut chewing, are significantly associated with diminished survival rates in patients with HNC. Accordingly, the implementation of an integrated campaign targeting the prevention of betel nut chewing would be one of the effective public health strategies for improving outcomes for HNC patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Chewing betel nuts can increase the risk of periodontal disease severity and potentially become malignant in the oral cavity., Objective: This study aimed to investigate the effect of the duration and frequency of betel quid chewing behaviour on periodontitis severity and the life quality of people in Tanini Village, Kupang Regency, Indonesia., Methods: The type of this study was an analytic observational study with a cross-sectional design. We used a questionnaire to obtain sociodemographic data. Oral Health Survey Basic Methods were used to measure debris index, plaque index, bleeding on probing, loss of attachment, and pocket depth. Behaviour and quality of life were measured by questionnaire and WHOQOL-BREF method as well., Results: The largest number of respondents were male. Duration of chewing had a significant relationship with the frequency of chewing and periodontal status. Periodontitis was higher compared to all categories. The lifestyle of the community greatly influenced their behaviour in betel nut chewing and also affected the severity of their periodontitis and OHIs significantly., Conclusion: The lifestyle of betel nut chewing of the people in Tanini Village, greatly influences their behaviour. Prolonged and excessive use of betel nut induced significant adverse effects on human health. The longer and more often chew betel or areca nut, the higher the incidence of periodontitis, which significantly affects the quality of life as there is a possibility of the development of carcinogenesis, particularly in the oral cavity., (© 2023 The Authors. International Journal of Dental Hygiene published by John Wiley & Sons Ltd.)

Hepatitis C virus (HCV) infection may cause chronic liver disease, liver cirrhosis, and liver cancer. It has been reported to associate with habits including alcohol, betel nut and cigarette use. We aimed to investigate the association between alcohol, betel nut, and cigarette use with HCV infection in Taiwan and to explore their effects. A total of 121,421 participants were enrolled from the Taiwan Biobank. They were stratified into two groups according to whether they had (n = 2750; 2.3%) or did not have (n = 118,671; 97.7%) HCV infection. All participants were also classified into four groups according to the number of habits, including a history of alcohol drinking, betel nut chewing, and cigarette smoking. There were 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits) participants in the four groups, respectively. Multivariable analysis showed that the participants who had an alcohol drinking history (odds ratio [OR] 1.568; 95% confidence interval [CI] 1.388-1.773; p < 0.001), betel nut chewing history (OR 1.664; 95% CI 1.445-1.917; p < 0.001), cigarette smoking history (OR 1.387; 95% CI 1.254-1.535; p < 0.001), were significantly associated with HCV infection. Furthermore, the participants were classified into four groups according to the number of habits as follows: 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits). The HCV infection rates in these four groups were 2.11%, 2.14%, 3.23%, and 4.78%, respectively. Compared to the participants with no or one habit, those with two habits had a higher HCV infection rate (all p < 0.001). In addition, compared to the participants who had no, one or two habits, those who had three habits also had higher HCV infection rates (all p < 0.001). The participants who had three habits had the highest prevalence of HCV infection. In an era when most HCV can be cured, understanding the epidemiology link between habits and HCV may help the case finding., (© 2024. The Author(s).)

Oral submucous fibrosis (OSF) is a chronic, progressive and potentially malignant oral mucosal disease. Patients often have a habit of chewing betel nuts. Areca catechu has been listed as a Class 1 carcinogen by the International Agency for Research on Cancer (IARC), and its main active component, arecoline, is classified as a Group 2B carcinogen by the IARC. The World Health Organization (WHO) categorises OSF as an oral potentially malignant disorder (OPMD). The present guideline describes the risk factors, clinical symptoms and clinical signs of OSF. Clinical staging, auxiliary examination methods, basis for diagnosis and differential diagnosis and the need to improve bad lifestyle habits are proposed and addressed, and local treatment drugs, therapies, dosage and course of treatment, possible adverse reactions, and oral treatment drugs, dosage and course of treatment are proposed. The guideline also addresses the indications for surgical treatment, alternative non-drug treatment methods, selection of treatment plans for different clinical stages, criteria for efficacy evaluation, and preventive measures.

Competing Interests: The authors declare that they have no conflict of interest.

Betel quid (BQ) is commonly used in the Asia-Pacific region. Disulfiram is prescribed for people with alcohol use disorders (PwAUDs) after the completion of detoxification as an alternative to rehabilitation. This prospective observational study reported the aversive reactions and common symptoms of disulfiram and BQ in PwAUDs. Participants included PwAUDs admitted to the psychiatric ward at the Jigme Dorji Wangchuck National Referral Hospital for detoxification, who were on Disulfiram and using BQ at the same time. Aversive reactions between disulfiram and BQ were observed for 100 patients over a year. Twenty participants showed aversive reactions between BQ and disulfiram. Common symptoms included sweating, diarrhea, dizziness, tremors, palpitations, shortness of breath, nausea and vomiting, and headache. Since PwAUDs in Bhutan are inducted on disulfiram after detoxification, and most use BQ simultaneously, this study will help inform health care providers to educate people about the aversive reactions of disulfiram and BQ., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Betel nut chewing involves the chewing of areca nuts or betel quid (areca nuts wrapped in betel leaves), which is associated with an increased risk of esophageal squamous cell carcinoma (ESCC). Statins have anticancer properties. We investigated the association between statin use and ESCC risk in betel nut chewers., Methods: The study included 105 387 betel nut chewers matched statin users and nonusers. Statin use was defined as the use of ≥28 cumulative defined daily doses (cDDDs) of statin. The primary outcome was incidence of ESCC., Results: The incidence rate of ESCC was significantly lower in statin users than in nonusers (2.03 vs. 3.02 per 100 000 person-years). Statin users had a lower incidence rate ratio of 0.66 for ESCC (95% confidence interval [CI]: 0.43-0.85) relative to nonusers. After potential confounders were adjusted for, statin use was determined to be associated with a reduced risk of ESCC (adjusted hazard ratio [aHR], 0.68; 95% CI: 0.51-0.91). A dose-response relationship was observed between statin use and ESCC risk; the aHRs for statin use at 28-182 cDDDs, 183-488 cDDDs, 489-1043 cDDDs, and > 1043 cDDDs were 0.92, 0.89, 0.66, and 0.64, respectively., Conclusion: Statin use was revealed to be associated with a reduced risk of ESCC in betel nut chewers., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Certain evidence indicated high prevalence of Candida in oral potentially malignant disorders (OPMDs) and oral cancer (OC). This study was aimed to investigate the presence of Candida and its associated factors in participants who attended the oral cancer screening program in the lower northeastern districts of Thailand., Methods: Convenient participants residing in the lower northeastern districts of Thailand who attended the oral cancer screening were enrolled. A questionnaire retrieving demographic characteristics, risk factors of oral cancer, and risk of having Candida was completed. Oral examination was performed by oral medicine specialists or oral surgeons. The participants were categorized into 4 groups according to their clinical diagnosis, namely normal oral mucosa (NOM), OPMDs/OC, non-OPMDs/OC and clinically suspected oral candidiasis (CSOC). Stimulated saliva flow rate was measured. Dip-slide test was performed in each participant to evaluate the presence of Candida. The levels of Candida were categorized into high and low levels according to the score received from the dip-slide test. Factors associated with high levels of Candida were identified using multivariate logistic regression analysis., Results: A total of 577 participants were recruited. High levels of Candida were found in 31.3%, 24.7%, 25.9% and 18.1% in the OPMDs/OC, the non-OPMDs/OC, the CSOC and the NOM groups, respectively. According to multivariate logistic regression analysis, age above 60 years, female gender, betel quid chewing habit, use of denture, hyposalivation, and being in the CSOC group were found to be significantly associated with high levels of Candida., Conclusion: Higher number of participants in the OPMDs/OC group was found to have high levels of Candida. Increasing age, female gender, betel quid chewing habit, use of denture, hyposalivation and having CSOC lesions were associated with high levels of Candida., (© 2023. The Author(s).)

Background: There has been a noticeable trend of younger people being diagnosed with oral cancer, particularly among those from low socio-economic backgrounds. Poor knowledge on risk factors toward oral cancer and the growing fashion of using tobacco also identified among younger generation. Present study aimed to assess the effectiveness of a health promotion intervention to improve the knowledge and encourage positive practices associated with oral cancer among a group of vulnerable youth in Sri Lanka., Methods: The study was a community based quasi experimental study, conducted in urban slums in the district of Colombo, Sri Lanka. Sample size for one group was 120 youth participants aged between 15 and 24 years. Health promotion intervention was implemented to the intervention group and follow up period was 6 months. The control group did not receive the intervention. Awareness of oral cancer and oral potentially malignant disorders, tobacco chewing practice (betel quid chewing and commercially prepared tobacco and areca nut packet (CPTAP) chewing) and self-mouth examination practice were assessed at the beginning and after 6 months in both groups using an interviewer administered questionnaire. Changes in the knowledge, self-mouth examination practice, quit rate and fresh up take rate were computed to determine the effectiveness., Results: There was no loss to follow up. No significant difference was observed between the groups in pre intervention assessment regarding the knowledge, tobacco chewing and self-mouth examination practices. Knowledge score was significantly differed between the groups P = 0.000 in the post intervention assessment as well as among females P = 0.001. Quit rate of the tobacco chewing practice, betel chewing practice and CPTAP chewing practice among intervention group was 33%, 70%, and 13% respectively while control group did not have any quitters, P = 0.001. Fresh up take rate of tobacco chewing in the intervention group was 6.7% compared to the 37.5% in the control group, P = 0.001. Practicing self-mouth examination was significantly higher in intervention group in post intervention assessment, P = 0.000., Conclusion: Multicomponent health promotion intervention (Advocacy, Interactive discussions, IEC materials and Community mobilization) was significantly effective in enhancing the knowledge, increasing self-mouth examination practice, and reducing tobacco chewing practice among a vulnerable group of youth in Sri Lanka., (© 2023. The Author(s).)

Background: Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD., Methods: A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used., Results: After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271-2.244), P = 0.001] in a betel nut chewing dose-dependent manner., Conclusion: Betel nut chewing related severely worn dentition was associated with intra-articular TMD., (© 2023. The Author(s).)

Background: Worldwide millions peoples consume AN who are at risk of OSMF. Prevalence of OSMF is reported between 0.03% and 30% irrespective of AN habit. Further, these estimates are based on sample population comprised of OSMF patients or general population rather AN chewers (ANC). Therefore, available evidence does not reflect the true prevalence of OSMF among ANC., Method: The studies providing the prevalence of OSMF in ANC were identified in PubMed, Scopus, and Web of Science. Pooled prevalence and quality assessment using New-Ottawa Scale were performed., Results: Fifteen studies reported the prevalence of OSMF (929) in ANC (53,213). Most studies were from China (six studies) and India (four studies) correlating with regions having high ANC. The pooled prevalence of OSMF in ANC was 5% (0.05 [95% CI, 0.03, 0.08]). All studies' quality was satisfactory; however, the OSMF diagnosis method, age, gender, and habits need further scrutiny., Conclusion: Available evidence suggested a low prevalence of OSMF in ANC, although further large-scale studies are recommended to validate this finding. Understanding the prevalence and distribution patterns of OSMF might aid intervention healthcare programs and contribute to the reduction of the oral cancer burden related to OSMF., (© 2022 Wiley Periodicals LLC.)

Background: This study examines the relationship between statin use and oral cancer squamous cell carcinoma (OCSCC) risk in a cohort of 47 942 betel nut chewers., Methods: The study used individual 1:1 matching and propensity score matching to compare statin users and nonusers., Results: The incidence rate of OCSCC was significantly lower in statin users compared to nonusers (17.12 vs. 26.75 per 10 000 person-years), yielding an incidence rate ratio of 0.64. After adjusting for confounders, statin use was associated with a reduced risk of OCSCC (adjusted hazard ratio: 0.61; 95% confidence interval: 0.52-0.71). A dose-response relationship was observed, with a significant reduction in OCSCC incidence when the cumulative defined daily dose of statin use was equal to or greater than Q3. The risk of OCSCC was lower among users of both hydrophilic and lipophilic statins., Conclusion: This study provides evidence that statin use is associated with a reduced risk of OCSCC in betel nut chewers., (© 2023 Wiley Periodicals LLC.)

Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was used as early as about A.D. 25-220 as a remedy. Traditionally, AN was applied for several medicinal functions. However, it was also reported to have toxicological effects. In this review article, we updated recent trends of research in addition to acquire new knowledge about AN. First, the history of AN usage from ancient years was described. Then, the chemical components of AN and their biological functions was compared; arecoline is an especially important compound in AN. AN extract has different effects caused by different components. Thus, the dual effects of AN with pharmacological and toxicological effects were summarized. Finally, we described perspectives, trends and challenges of AN. It will provide the insight of removing or modifying the toxic compounds of AN extractions for enhancing their pharmacological activity to treat several diseases in future applications.

Background: This study aimed to establish a simple predictive model for oropharyngeal cancer (OPC) in an area with a relatively low prevalence of human papillomavirus (HPV) and frequent betel nut chewing., Methods: A total of 116 patients with OPC were recruited from the clinical research database of a referral cancer center between 2013 and 2018. Patient characteristics-including age, gender, tumor stage, differentiation, and treatment modality-were extracted from the database. Patients diagnosed after 2018 were staged using the 7th AJCC staging system to explore the impact of extra-nodal tumor extension (ENE) on survival. Immunohistochemical analysis was performed for p16, epidermal growth factor receptor (EGFR), p53, and programmed cell death ligand 1 (PD-L1). ENE status was evaluated by pathological analysis or radiological features. Primary outcome was disease-specific overall survival (OS). Univariate and multivariate Cox regression were used to establish a predictive model., Results: Mean age was 57.3 ± 9.9 years; 103 patients (88.8%) were male. P16 positive OPC was positively associated with higher PD-L1 and a tonsillar sub-site and negatively associated with betel nut chewing and cigarette smoking. In Cox regression, age, p16 status, EGFR, cT4, ENE, and cigarette smoking were significantly associated with OS. In survival tree analysis, cT stage was the most important risk stratification parameter, followed by EGFR expression and p16 status. Patients with cT4 stage or high EGFR were classified as the high-risk group and had poorest OS., Conclusions: Due to the low prevalence of HPV and popularity of betel nut chewing in Asia, the relative importance of prognostic predictors for OPC are not identical to Western countries. Identification of significant prognostic biomarkers may improve treatment. Trial registration This study was registered and approved by the Institutional Review Board (IRB) of Kaohsiung Veterans General Hospital (VGHKS19-CT9-07; date of approval: Aug 9, 2019)., (© 2023. The Author(s).)

Purpose: Oral potentially malignant disorders are associated with a risk of undergoing malignant transformation and a concomitant increase in morbidity and mortality. Moreover, epidemiological studies, especially from rural areas, are important in assessing their prevalence and the identification of determinants of these disorders so that preventive strategies can be employed in tackling them., Methods: Cross-sectional descriptive study was conducted based on guidelines of the World Health Organization's Guide Epidemiology and Diagnosis of Oral Mucosal Disease and Conditions 1995 in rural areas of south India., Results: Prevalence of oral potentially malignant disorders (OPMDs) in the studied population was 13.28%, with oral submucous fibrosis (OSMF) accounting to 6.21% and erythroplakia at 1.3%. Regression analysis revealed, age 40-54 years (odds ratio [OR] = 3.8, confidence interval [CI] at 95%-1.5-4.0, P < 0.05), lower socioeconomic groups (OR = 2.1, CI at 95%-1.4-3.1, P < 0.05), habits (OR = 3.2, CI at 95%-1.9-3.8, P < 0.05), smoke form of tobacco-beedi (OR = 2.5, CI at 95%-1.6-2.8, P < 0.05), smokeless form of tobacco-areca nut lime and leaf and tobacco (OR = 3.1, CI at 95%-1.9-3.4, P < 0.05) to be the possible determinants for OPMDs., Conclusions: The overall prevalence of OPMDs in the studied population was 13.28%. The most common OPMDs were OSMF. Identified determinants were age, socioeconomic group, ethnicity, diet, body mass index, and associated harmful habits.

Background: Several cross-sectional studies have reported risk factors for metabolic syndrome (MetS). However, these studies did not focus on sex differences in middle-aged and senior populations or employ a longitudinal design. These study design differences are important, as there are sex differences in lifestyle habits associated with MetS, and middle-aged and senior individuals have increased MetS susceptibility. Therefore, the purpose of this study was to examine whether sex differences influenced MetS risk over a ten-year follow-up period among middle-aged and senior hospital employees., Methods: This population-based and prospective cohort study enrolled 565 participants who did not have MetS in 2012 for a ten-year repeated-measurement analysis. Data were retrieved from the hospital's Health Management Information System. Analyses included Student's t tests, χ 2 tests and Cox regression. P < 0.05 indicated statistical significance., Results: Male middle-aged and senior hospital employees had an elevated MetS risk (hazard ratio (HR) = 1.936, p < 0.001). Men with more than four family history risk factors had an increased risk of MetS (HR = 1.969, p = 0.010). Women who worked shift duty (HR = 1.326, p = 0.020), had more than two chronic diseases (HR = 1.513, p = 0.012), had three family history risk factors (HR = 1.623, p = 0.010), or chewed betel nuts (HR = 9.710, p = 0.002) had an increased risk of MetS., Conclusions: The longitudinal design of our study improves the understanding of sex differences in MetS risk factors in middle-aged and senior adults. A significantly elevated risk of MetS over the ten-year follow-up period was associated with male sex, shift work, the number of chronic diseases, the number of family history risk factors, and betel nut chewing. Women who chewed betel nuts had an especially increased risk of MetS. Our study indicates that population-specific studies are important for the identification of subgroups susceptible to MetS and for the implementation of hospital-based strategies., (© 2023. The Author(s).)

Background: Areca nut (AN) is a proven human carcinogen and a global public health menace. There is yet no review providing comprehensive information on the determinants and interventions available for cessation of AN. This systematic review was aimed at summarizing the available literature on drivers and interventions for cessation of AN chewing habit and to highlight the research lacunae., Methods: A systematic literature search (from 1990 till March 2021) was conducted for studies on AN cessation. Relevant data were extracted independently by two authors., Results: A total of 16 studies were included, which highlighted the influence of socio-cultural factors, addictive nature of AN and withdrawal symptoms as barriers to quitting. However, the knowledge of ill-effects of AN use on health, absence of concurrent alcohol use or smoking and family pressure were associated with likelihood of AN cessation. The interventions utilized for AN cessation have been behavioural in majority of the studies except for one where antidepressants were used for this purpose., Conclusions: The current review emphasizes the imperative need of appropriate cessation strategies for AN chewing habit including enhancing awareness of the harmful effects and research into additional behavioural and pharmacologic cessation therapies to control this significant public health problem., (© The Author(s) 2022. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The areca nut is a high-risk carcinogen for head and neck cancer (HNC) patients in Southeast Asia. The underlying molecular mechanism of areca nut-induced HNC remains unclear, especially regarding the role of long non-coding RNA (lncRNA). This study employed a systemic strategy to identify lncRNA signatures related to areca nut-induced HNC. In total, 84 cancer-related lncRNAs were identified. Using a PCR array method, 28 lncRNAs were identified as being dysregulated in HNC cells treated with areca nut (17 upregulated and 11 downregulated). Using bioinformatics analysis of The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset, 45 lncRNAs were differentially expressed in tumor tissues from HNC patients (39 over- and 6 under-expressions). The integrated evaluation showed 10 lncRNAs dysregulated by the areca nut and altered expression in patients, suggesting that these panel molecules participate in areca nut-induced HNC. Five oncogenic (LUCAT1, MIR31HG, UCA1, HIF1A-AS2, and SUMO1P3) and tumor-suppressive (LINC00312) lncRNAs were independently validated, and three key molecules were further examined. Pathway prediction revealed that LUCAT1, UCA1, and MIR31HG modulate multiple oncogenic mechanisms, including stress response and cellular motility. Clinical assessment showed that these lncRNAs exhibited biomarker potentials in diagnosis (area under the curve = 0.815 for LUCAT1) and a worse prognosis (both p < 0.05, survival analysis). Cellular studies further demonstrated that MIR31HG facilitates areca nut-induced cancer progression, as silencing this molecule attenuated arecoline-induced invasion ability in HNC cells. This study identified lncRNA signatures that play a role in areca nut-induced HNC. These molecules may be further applied in risk assessment, diagnosis, prognosis, and therapeutics for areca nut-associated malignancies.

Background: Betel quid (BQ) chewing is associated with poor oral hygiene, psychological impairment, and acute and long-term addictive effects, resulting in worse oral-related quality of life (OHRQoL). The purpose of this study was to characterize the factors associated with OHRQoL among BQ users receiving oral mucosal screening., Methods: A cross-sectional study was conducted. Data were collected by random sampling of BQ users who visited outpatient departments receiving oral mucosal screening in a medical center Taiwan. The oral health assessment tool, the state anxiety inventory, the betel quid dependence scale, and the oral health impact profile were used to measure oral health status, anxiety, BQ dependence, and OHRQoL, respectively. Pearson's product-moment coefficient was used to examine the relationship between OHRQoL and the selected independent variables. Independent-samples t-test was used to compare OHRQoL by annual family income, the presence of chronic disease, and BQ dependence. Hierarchical multiple linear regression analysis was used to identify factors associated with OHRQoL., Results: A total of 175 BQ users were surveyed. Factors associated with OHRQoL included oral health status, anxiety, and BQ dependence. BQ users reporting low oral health status, greater anxiety, and more BQ dependence were more likely to have worse OHRQoL., Conclusions: Poor oral health status, anxiety, and BQ dependence negatively impact on OHRQoL among patients with BQ use receiving oral mucosal screening., (© 2023. The Author(s).)

Dental calculus is a potential material that can be used for assessing chronic exposure to trace heavy metals in oral cavity as it is a long-term reservoir. The aim of this study was to investigate the correlation between dental calculus copper levels and risk of oral submucous fibrosis (OSF) due to chewing dried areca-nut quids in Mainland China. This study included 34 OSF (grade 1) sufferers with dried areca-nut quids chewing as the patient group and 23 healthy individuals without areca-nut chewing as the control group. The dental calculus sample was obtained from all 57 participants and evaluated by inductively coupled plasma mass spectrometry (ICP-MS) for dental calculus level of copper. This work revealed that the mean copper level of dental calculus was significantly higher in OSF (grade 1) sufferers with areca-nut chewing than those in healthy individuals without areca-nut chewing (p < 0.001). This work provided an evidence to support that there may be a positive correlation between elevated levels of copper in dental calculus caused by chewing dried areca-nut quids and an increased risk of developing OSF in Mainland China., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study targets to establish a factorial association of oral microbiome alterations (oral dysbiosis) with betel quid chewing habits through a comparison of the oral microbiome of Betel quid chewers and non-chewing individuals. Oral microbiome analysis of 22 adult individuals in the Delhi region of India through the 16S sequencing approach was carried out to observe the differences in taxonomic abundance and diversity. A significant difference in diversity and richness among Betel Quid Chewers (BQC) and Betel Quid Non-Chewers (BQNC) groups was observed. There were significant differences in alpha diversity among the BQC in comparison to BQNC. However, in the age group of 21-30 years old young BQC and BQNC there was no significant difference in alpha diversity. Similar result was obtained while comparing BQC and Smoker-alcoholic BQC. BQ smoker-chewers expressed significant variance in comparison to BQC, based on cluster pattern analysis. The OTU-based Venn Diagram Analysis revealed an altered microbiota, for BQ chewing group with 0-10 years exposure in comparison to those with 10 years and above. The change in the microbial niche in early chewers may be due to abrupt chemical component exposure affecting the oral cavity, and thereafter establishing a unique microenvironment in the long-term BQC. Linear discriminant analysis revealed, 55 significant features among BQC and Alcoholic-Smoker BQC; and 20 significant features among BQC and Smoker BQC respectively. The study shows the abundance of novel bacterial genera in the BQC oral cavity in addition to the commonly found ones. Since the oral microbiome plays a significant role in maintaining local homeostasis, investigating the link between its imbalance in such conditions that are known to have an association with oral diseases including cancers may lead to the identification of specific microbiome-based signatures for its early diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bahuguna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Global estimates indicate that over 600 million individuals worldwide consume the areca (betel) nut in some form. Nonetheless, its consumption is associated with a myriad of oral and systemic ailments, such as precancerous oral lesions, oropharyngeal cancers, liver toxicity and hepatic carcinoma, cardiovascular distress, and addiction. Users commonly chew slivers of areca nut in a complex consumable preparation called betel quid (BQ). Consequently, the user is exposed to a wide array of chemicals with diverse pharmacokinetic behavior in the body. However, a comprehensive understanding of the metabolic pathways significant to BQ chemicals is lacking. Henceforth, we performed a literature search to identify prominent BQ constituents and examine each chemical's interplay with drug disposition proteins. In total, we uncovered over 20 major chemicals (e.g., arecoline, nicotine, menthol, quercetin, tannic acid) present in the BQ mixture that were substrates, inhibitors, and/or inducers of various phase I (e.g., CYP, FMO, hydrolases) and phase II (e.g., GST, UGT, SULT) drug metabolizing enzymes, along with several transporters (e.g., P-gp, BCRP, MRP). Altogether, over 80 potential interactivities were found. Utilizing this new information, we generated theoretical predictions of drug interactions precipitated by BQ consumption. Data suggests that BQ consumers are at risk for drug interactions (and possible adverse effects) when co-ingesting other substances (multiple therapeutic classes) with overlapping elimination mechanisms. Until now, prediction about interactions is not widely known among BQ consumers and their clinicians. Further research is necessary based on our speculations to elucidate the biological ramifications of specific BQ-induced interactions and to take measures that improve the health of BQ consumers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: As the prevalence of metabolic syndrome, obesity and diabetes increase worldwide, the need to identify modifiable lifestyle risk factors also increases, especially those that may be relatively unique to a specific population. To explore a possible association between betel quid chewing and metabolic syndrome, a community-based cross-sectional study was conducted., Methodology: Three hundred ninety-one (391) adults were interviewed and the following parameters were measured: triglycerides, HDL-cholesterol, glucose, waist circumference, body mass index and blood pressure. Multiple logistic regression was used to determine the association between betel quid chewing and metabolic syndrome while controlling for confounders., Results: The prevalence of metabolic syndrome was similar in chewers and non-chewers, 50% and 49%, respectively. After controlling for other factors, development of metabolic syndrome was positively associated with number of betel quids chewed per day, age greater than 40 years, and a positive family history of hypertension and diabetes. Regarding the duration of betel chewing, when analyzed by sex, the risk was doubled in men compared to non-chewers (OR 2.15; 95% CI = 1.21, 3.84). As a result, a man chewing more than 10 pieces (OR 2.49; 95% CI = 1.36, 4.57) of betel quids per day for more than 10 years had a two-fold increased chance of developing the metabolic syndrome., Conclusions: Frequency and duration of betel quid chewing may represent a behavioral lifestyle target for approaches to reduce the incidence of metabolic syndrome., Competing Interests: The authors declared no conflict of interest., (© 2023 Journal of the ASEAN Federation of Endocrine Societies.)

Background: Association with variety of etiological agents is one of the characteristic features of oral squamous cell carcinoma (OSCC). We hypothesized the existence of tobacco consumption habit-based heterogeneity in the immunohistochemical expression of carcinogenesis relevant molecular markers in OSCC. Hence, the present study was conducted to investigate the carcinogenesis relevant three commonly expressed markers (Ki-67, CD105, and α-smooth muscle acting [SMA]) in various forms of tobacco consumption habits in OSCC patients., Materials and Methods: A total of 217 patients of OSCC were included in the study, and based on the habit, they were broadly categorized into tobacco lime (TL), TL and areca nut (TLAN), and areca nut (AN). Further, categorization was done on the basis of absence or presence of additional habit of smoking. Immunohistochemistry (IHC) was performed using Ki-67, CD105, and α-SMA markers on formalin-fixed paraffin-embedded tissues., Results: TLAN (62.21%) was the most common habit noted in OSCC patient followed by TL (20.73%) and AN (15.20%). The additional habit of smoking was observed in 31.11% and 25.92% of TL and TLAN habits of OSCC patients, respectively. All the three markers (Ki-67, CD105, and α-SMA) showed statistically significant differences in the habit group such as TL, TLAN, and AN (P < 0.001). Although the expression of all the three markers was increased in TL as compared with TLAN, differences were not statistically significant. When these markers were compared in with and without smoking category, only TLAN with smoking and TLAN without smoking showed statistically significant differences in the expression of all three markers., Conclusions: Ki-67 CD105 and α-SMA immunohistochemical expression in OSCC corresponds with different forms of tobacco consumption habits. Habit-related unique carcinogenesis events are reflected at IHC level thus providing proof of concept for future studies., Competing Interests: None

Background: Betel quid (BQ) is the fourth most commonly used psychoactive substance and its use is highly prevalent among southeast Asian countries due to the influence of psychosocial, behavioral, and environmental factors. As a result, even young children and women are becoming addicted and find it difficult to achieve long-term abstinence. Systematic research addressing the influence of behavioral and psychosocial factors on BQ chewing is scarce, hence pointing to the need for understanding the interplay of these factors to develop tailored intervention strategies for BQ cessation., Objective: The objective of this systematic review is to assess various behavioral and psychosocial risk factors from pre-existing literature that lead individuals to initiate and/or maintain BQ chewing in developed and developing countries., Materials and Methods: The electronic retrieval systems and databases PUBMED [MEDLINE], EMBASE, SCOPUS, WEB OF SCIENCE, GOOGLE SCHOLAR, and SCIENCE DIRECT were searched independently by two authors for relevant articles from January 2011 to July 2021 using combinations of keywords. Primary studies published in English focusing on the behavioral and psychosocial risk factors for BQ chewing were included., Results: Out of the initial 264 articles searched, 12 articles met the selection criteria. Included studies addressed the influence of behavioral and psychosocial factors toward the initiation and/or maintenance of BQ chewing. Included studies reported that dependent BQ was not able to quit BQ chewing due to habituation, addiction, and withdrawal symptoms. Few social BQ chewers in Southeast Asian countries were not willing to initiate quitting as they considered AN as an important social and cultural identifier and claimed that they could not resist chewing in a peer group, and it has become part of their social life., Conclusion: In the future, studies should take into consideration behavioral and psychosocial risk factors, which are major barriers toward successful quitting. These factors should be integrated into areca nut cessation guidelines, and there is a need to develop more comprehensive culture-specific intervention approaches to achieve long-term abstinence.

Contemporarily, there has been a growing consumption rate of areca nut (AN) products worldwide, despite the fact that both fresh and processed AN contain various hazardous ingredients, including toxic alkaloids and carcinogenetic aflatoxins. However, there is a dearth of toxicity and potential cancer risk information regarding toxic alkaloids and aflatoxins via consuming AN products. The present study conducted a comprehensive assessment of the combined hazardous effects of AN alkaloids and aflatoxins towards human digestive system, by methods of HPLC analysis, cell study and in vitro digestive system study. The results revealed a synergetic effect of arecoline and aflatoxins was on human gingival normal fibroblast cell of HGF-1 and a proliferation effect on human tongue squamous carcinoma cell of CAL-27. Specifically, the residual arecoline was as high as 91.08 μg·ml -1 in oral phase and 72.41 μg·ml -1 in gastric phase, which could be an evidence of oral cancer. More importantly, 25.93 % of AN products were contaminated with aflatoxins and the maximum value was three times the MRLs. Under these circumstances, the cytotoxic and MOE values raised a considerable health concern in terms of malignancy risk for children that consume processed AN product, especially compared to scenarios that involve adults and/or fresh AN samples. This study would give rise to a better understanding of the hazards associated with AN alkaloids and aflatoxins towards digestive system, and thus to predict the potential carcinogenic risk of AN products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Oral cavity cancer is estimated to be the third most common malignancy after cancer of cervix and stomach in developing countries., Objectives: The objective of this study is to investigate the relationship between smoking, alcoholic consumption, betel quid chewing, and OPMD in a prospective manner., Materials and Methods: A descriptive, cross-sectional study was conducted among 35-55-year-old adults of Western Maharashtra, India. Oral cavity examination as recommended by the American Dental Association specification was followed. Data recorded were transferred from precoded survey pro forma to the computer. The prevalence of OPMD was assessed by determining the percentage of the study population affected. Analysis was done to find out the risk of oral premalignant disorders. The Chi-square (x 2 ) test and adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated. The Statistical Package for the Social Sciences (SPSS) software version 21.0 was used for the statistical analysis and significance level was set at P < 0.05., Results: Odds of having OPMD are five times higher for those who smoke (OR = 5.78; 95% CI, [6.18, 7.82]) as compared to those who do not. The odds of suffering from OPMD are about five times higher among those who chew as compared to those who do not (OR = 4.98; 95%CI, [2.91, 7.28]). The mean frequency of tobacco chewing per day and duration in years in participants with OPMDs was significantly higher as compared with normal oral mucosa (P < 0.05 and P < 0.05), respectively, in the use of different tobacco forms., Conclusion: These findings can be used to design case control or cohort studies to further understand the relation between habits and OPMD., Competing Interests: None

Areca nut (AN) is widely consumed all over the world, bringing great harm to human health and economy. Individuals with AN chewing are at high risk of cardiovascular disease and impaired immune system and metabolic system. Despite a growing number of studies having reported on the adverse effects brought by AN chewing, the exact mechanism of it is limited and the need for additional exploration remains. In recent years, the interaction between microorganisms, especially intestinal microorganism and host, has been extensively studied. AN chewing might disrupt the oral and intestinal microbiota communities through direct connect with the microbes it contains, altering PH, oxygen of oral and intestinal microenvironment, and disturbing the immune homeostasis. These mechanisms provide insights into the interplay between areca nut and host microbiota. Emerging studies have proposed that bidirectional interaction between polyphenols and intestinal microbes might play a potential role in the divergence of polyphenol, extracted from AN, among individuals with or without AN-induced cancer development and progression. Although some AN chewers have been aware of the harmful effects brought by AN, they cannot abolish this habit because of the addiction of AN. Increasing studies have tried to revealed that gut microbiota might influence the onset/development of addictive behaviors. Altogether, this review summarizes the possible reasons for the disturbance of host microbiota caused by areca nut chewing and clarifies the complex interaction between human microbiome and major constituents and the addiction and carcinogenicity of AN, tempting to provide novel insights into the development and utilization of it, and to control the adverse consequences caused by AN chewing.

Introduction: TikTok has gained increasing popularity over the past year. The social media may affect awareness and perceptions of betel quid (BQ) and smokeless tobacco (SLT) by utilizing content generated by TikTok users. The purpose of this study is to examine how BQ and SLT are portrayed on TikTok., Methods: The 28 most viewed hashtag-based keywords were used to identify popular BQ and SLT-related videos on TikTok (n=513) from June 2018 to September 2021. Two researchers independently coded the number of likes, shares, views, user category and themes., Results: A final sample of 513 videos containing BQ and SLT that met the study criteria were included. Collectively, these videos were viewed over 725 million times, with a median 'view' count of 17,300 (range 152-155,000,000) and a median 'likes' count of 831 (range 4-2,400,000) and a median 'share' count of 21 (range 0-48,400). Majority of the videos showed BQ and SLT use positively i.e promoting the product (390/513; 76%) and these had more than 686 million times views. Neutral depictions of BQ and SLT use were viewed 15 million times (72/513; 14%) and negative portrayals of BQ and SLT have been viewed 193 million times (105/808; 13%). The video themes included 'life style' (349/513; 68.0%), 'marketing' (62/513; 12.09%), 'comedy' (44/513; 8.6%), 'warning' (25/513; 4.87%), 'awareness' (12/513; 2.3%), 'sports and other' (12/513; 2.3%) and social events or culture (9/513; 1.75%)., Conclusion: Our results demonstrated that video clips related to BQ and SLT on TikTok, a fast-growing, popular video-sharing platform among teens, which is available with no age restrictions has been viewed multiple times. Majority (76%) promoted these two products, that could be detrimental to oral health. Therefore, the age restrictions especially for the videos containing BQ and SLT is mandatory in order to reduce the potential exposure of adolescents/young adults.