Development and validation of betel-year: a clinical tool for quantifying exposure to betel quid chewing, utilizing nuclear morphometric analysis and validated by cytomorphological analysis.

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.

A study of risk factors associated with the presence of oral potentially malignant disorders: a community-based study from Northeastern Thailand.

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.

Maternal betel quid use during pregnancy and child growth: a cohort study from rural Bangladesh.

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.

Main findings: In this cohort study, no association was observed between maternal betel quid use during pregnancy and children's growth around five years of age.Added knowledge: Although catch-up growth among those born to heavy users may have attenuated any negative impact of prenatal exposure to betel quid on postnatal growth, such catch-up growth often involves greater acquisition and a more centralized distribution of body fat and insulin resistance later in life; leading to a potential heightening of cardiometabolic risk.Global health impact for policy and action: Given that betel quid consumption during pregnancy remains socially acceptable across south and south-east Asia, this study highlights the need for following up those born to betel quid users beyond childhood for capturing long-term health implications of prenatal betel quid exposure.

Treatment outcomes of oral leukoplakia on the irradiated or nonirradiated mucosa among survivors of head and neck cancer in the papulation where practice of betel nut chewing and cigarette smoking are widespread.

BACKGROUND: Radiotherapy (RT) has numerous effects on the oral mucosa, primarily genetic alterations and changes in the microenvironment. The characteristics of oral leukoplakia (OL) may differ between patients who have received previous head and neck cancer (HNC) treatment with radiation therapy and those who have not. Due to a lack of data on this scenario, we aimed to investigate the surgical outcomes of OL by comparing these two patient groups. METHODS: This retrospective cohort study enrolled a total of 224 OL lesions in 124 patients who underwent carbon dioxide laser (CO2 laser) surgery from July 2002 to Aug 2021. All patients had received previous treatments for HNC, with 59 patients undergoing only surgical approach, 65 patients undergoing RT, and 46 patients undergoing concurrent chemotherapy during RT. The analysis was performed on a per-lesion basis, not a per-capita basis. We investigated the associations of clinicopathological characteristics and treatment outcomes of OL lesions that developed from irradiated or nonirradiated oral mucosa. RESULTS: The median follow-up time was 5.87 years. Postoperative recurrence of OL occurred in 30 patients. Malignant transformation occurred in 17 patients with the incidence rate 4.19% annually and 13.7% cumulatively. The average time for OL transforming into squamous cell carcinoma was 3.27 ± 3.26 years (median 1.82, range 0.11 - 11.90). In univariate analysis, non-homogeneous morphology (P = 0.042), moderate to high-grade dysplasia (P = 0.041), and nonirradiated oral mucosa (P = 0.0047) were predictors for malignant transformation. However, in the Cox proportional hazard model, only nonirradiated oral mucosa remained an independent prognostic factor related to postoperative malignant transformation of OL (P = 0.031, HR 5.08, CI95 1.16 - 22.25). CONCLUSION: In the population whose OL is strongly aetiologically linked to environmental carcinogens such as betel nut and tobacco, OL lesions that develop on previously irradiated oral mucosa have a lower risk for postoperative malignant transformation compared to those that develop on nonirradiated mucosa. This finding highlights the potential impacts of radiation on OL. Further research is needed to confirm this observation and elucidate the underlying mechanism.

TUSC3, p53 and p21 genetic association with development of oral submucous fibrosis and oral squamous cell carcinoma among addictive tobacco chewers of Pakistan.

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.

Substance use and incidence of metabolic syndrome before midlife among military adults: the CHIEF cohort study.

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.

Oropharyngeal stenosis in patient with oral submucous fibrosis: a case report with 8-year follow-up.

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.

[Oral submucosal fibrosis induced by active components in areca nut: a network pharmacology-based analysis and validation of the mechanism].

OBJECTIVE: To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis (OSF) and the possible mechanism. METHODS: The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software. The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia (2015), PubChem, Chemical book, and SciFinder databases. The potential active components, core targets, biological functions and signaling pathways affecting OSF were analyzed by network pharmacology. The targets of OSF were obtained by integrating Genecards and KEGG databases. The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine (TCMSP), and the target-compound, compound-TCM, target-compound-TCM network was constructed. Molecular docking was used to analyze the component-target binding. Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF. RESULTS: The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways. In the clinical samples, the expressions of PI3K protein decreased and the expressions p-PI3K, AKT1 and PAkt all increased significantly in OSF tissue, where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected. The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals. CONCLUSION: The main active ingredients including arecoline, arecaine, and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia, thus leading to the occurrence of oral submucosal fibrosis.

Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis.

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-ß receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-ß 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-ß fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Expression profile of diagnostic genes in oral submucous fibrosis.

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.

Detection and identification of Bogia coconut syndrome phytoplasma from seed-associated tissues and seedlings of coconut (Cocos nucifera) and betel nut (Areca catechu).

Evidence for seed transmission of phytoplasmas has grown in several pathosystems including coconut (Cocos nucifera). Bogia coconut syndrome (BCS) is a disease associated with the lethal yellowing syndrome associated with the presence of 'Candidatus Phytoplasma noviguineense' that affects coconut, betel nut (Areca catechu) and bananas (Musa spp.) in Papua New Guinea. Coconut and betel nut drupes were sampled from BCS-infected areas in Papua New Guinea, dissected, the extracted nucleic acid was used in polymerase chain reaction (PCR), and loop mediated isothermal amplification (LAMP) used to check for presence of phytoplasma DNA. In a second study, drupes of both plant species were collected from multiple field sites and grown in insect-proof cages. Leaf samples taken at 6 months were also tested with PCR and LAMP. The studies of dissected coconut drupes detected phytoplasma DNA in several tissues including the embryo. Drupes from betel nut tested negative. Among the seedlings, evidence of possible seed transmission was found in both plant species. The results demonstrate the presence of 'Ca. P. noviguineense' in coconut drupes and seedlings, and in seedlings of betel nut; factors that need to be considered in ongoing management and containment efforts.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study.

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged -7.09-11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

Association between habitual betel quid chewing and risk of adverse cardiovascular outcomes: A systematic review.

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.

Bioactive Components of Areca Nut: An Overview of Their Positive Impacts Targeting Different Organs.

Areca catechu L. is a widely cultivated tropical crop in Southeast Asia, and its fruit, areca nut, has been consumed as a traditional Chinese medicinal material for more than 10,000 years, although it has recently attracted widespread attention due to potential hazards. Areca nut holds a significant position in traditional medicine in many areas and ranks first among the four southern medicines in China. Numerous bioactive compounds have been identified in areca nuts, including alkaloids, polyphenols, polysaccharides, and fatty acids, which exhibit diverse bioactive functions, such as anti-bacterial, deworming, anti-viral, anti-oxidant, anti-inflammatory, and anti-tumor effects. Furthermore, they also display beneficial impacts targeting the nervous, digestive, and endocrine systems. This review summarizes the pharmacological functions and underlying mechanisms of the bioactive ingredients in areca nut. This helps to ascertain the beneficial components of areca nut, discover its medicinal potential, and guide the utilization of the areca nut.

Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study.

This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

Ameliorative Effect of Areca Nut Polyphenols on Adverse Effects Induced by Lipopolysaccharides in RAW264.7 Cells.

In Asian regions, areca nuts are tropical fruits that are extensively consumed. The areca nut contains a lot of polyphenols and its safety is unknown. In this research, we investigated the effects of lipopolysaccharides (LPS) and areca nut polyphenols (ANP) on normal RAW264.7 cells. The results showed that LPS stimulated adverse effects in normal cells by affecting cytokine production. The GO analysis results mainly affected DNA repair, cell division, and enzyme activities. In the KEGG analysis results, the NOD-like receptor signaling pathway, which is related to NF-κB, MAPK, and the pro-inflammatory cytokines, is the most significant. In the protein-protein interaction network (PPI) results, significant sub-networks in all three groups were shown to be related to cytokine-cytokine receptor interaction. Collectively, our findings showed a comprehensive understanding of LPS-induced toxicity and the protective effects of ANP by RNA sequencing.

A Patient With Oral Discomfort and Reduced Oral Aperture.

A patient had burning and pain in the mouth, reduced oral aperture, white-tan plaques on the oral mucosa, and thickened buccal mucosae bilaterally; biopsy of the lower labial mucosa showed subepithelial fibrosis. She had no history of cigarette smoking or use of chewing tobacco but had current and past history of chewing areca nuts. What is the diagnosis and what would you do next?

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.