Betel Nut Chewing Research Articles

The role of microbiota in esophageal squamous cell carcinoma: A review of the literature.

Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF-κB and IL-6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug-resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.

Study of Oral Squamous Cell Carcinoma with and without Oral Submucous Fibrosis.

Oral submucous fibrosis (OSMF) is a precancerous condition associated with areca nut chewing. Arecoline which isa component of areca nut is considered a carcinogen. The OSMF in patients with oral squamous cell carcinoma (OSCC) indicatesareca nut-induced carcinogenesis. The molecular pathway for oral carcinogenesis caused by areca nut is discrete and considereda different clinicopathological entity. Thus the present study aims to study and compare the demographics, risk factors, and clinicalcharacteristics of OSCC patients with and without OSMF. It was a retrospective study done by medical record review. About 40OSCC cases were selected, of which 20 were with OSMF, and 20 were without OSMF. Demographic data, risk factors includinghistory of habits such as areca nut chewing, tobacco, etc., and clinical characteristics such as anatomical location, extent, tumorsize, and lymph node metastasis were noted, and data were analyzed. The mean age of OSCC cases with OSMF was younger thanthose without OSMF. The study groups did not observe a significant difference in habit type and duration. Most OSCC patientswith OSMF were younger than those OSCC without OSMF. The buccal mucosa was the most common anatomical locationinvolved with ulcers- proliferative growth in both study groups. The incidence of multiple sites and lymph node enlargementinvolvement is higher in OSCC without OSMF compared to those with OSMF. There was no significant difference concerninghistopathological changes between OSCC with and without the OSMF group.

The impact of chewing betel nuts on human dentition in Indonesia: A literature review

Background: Human behavior can significantly alter dental conditions. One such behavior is the habit of chewing betel nuts. Known as nginang, this tradition holds social significance in many cultures across Indonesia. Societal beliefs include the idea that chewing betel nuts offers a sensation similar to smoking cigarettes, provides a pastime, reduces bad breath, and even enhances dental health. However, evidence shows that it can cause severe damage to teeth. Purpose: This research aims to analyze the literature regarding the impact of chewing betel nuts on dental conditions and to recommend actions to address the problems caused by it. Reviews: While this habit can have positive aspects, it may also cause tooth damage when practiced with a certain frequency and intensity and using specific compositions. Issues such as calculus, periodontitis, attrition, and antemortem tooth loss may occur due to this habit. However, inconsistencies have been found concerning this habit’s relation to caries. Conclusion: A pathological chain reaction triggered by betel nut chewing confirms its detrimental effect on dental health. Further investigations are required to explain the inconsistencies found in this review. The researchers recommend promoting tooth brushing to enable society to maintain its tradition without risking further teeth damage.

The Betel Nut Intervention Trial (BENIT)-A Randomized Clinical Trial for Areca Nut and Betel Quid Cessation: Primary Outcomes.

Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials-NCT02942745) is the first known randomized trial designed for ANBQ chewers. We compared the intensive behavioral treatment intervention condition (IC) with the control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English-literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n = 88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n = 88) received only the brochure. Participants were assessed at baseline and on day 22 of follow-up. Self-reported chewing status at day 22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p = 0.0058, which met the Stage 3 criteria for significance, and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Robust self-reported intervention effects at day 22 suggest that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

Trends of smokeless tobacco in India- Narrative review

South Asia, primarily India, is the major producer and exporter of various forms of tobacco products worldwide. All forms of tobacco (smoke and smokeless/chewable/inhaled) such as cigarettes, pipes, cigars, beedis, paan and snuff have been implicated in the development of oral cancer. Almost 13% of the population of India chews tobacco in the form of pan or gutkha. People in India consume various forms of tobacco such as khaini, mishri, zarda, gutkha, mawa and naas. Areca nut chewing is also widely practised in India. Males have been found more likely to develop oral or esophageal cancer because of tobacco consumption. Children, teenagers and pregnant women are also found using products for pleasure, stress relieving, in social situations etc. Epidemiological studies also suggest tobacco consumption is more prevalent in lower socioeconomic strata. Oral cancer also called squamous cell carcinoma, oral submucous fibrosis (OSMF), leukoplakia, erosive lichen planus, asthma, chronic obstructive pulmonary disease (COPD) and hypertension are a few major manifestations of tobacco consumption. Smokeless tobacco users studies show mortality of 1.2–1.96 (men) and 1.3 (women). Educational intervention, mass media intervention in the form of television ads, public posters, newspaper articles, folk dramas and the most recent cessation camps have been implied to spread awareness about the misbeliefs of consuming tobacco and demonstrating health hazards associated with it.

Resveratrol inhibits arecoline-induced fibrotic properties of buccal mucosal fibroblasts via miR-200a activation

Background/purposeOral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methodsThe cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. ResultsCurrent results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. ConclusionIn a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

The association of severely worn dentition resulting from betel nut chewing with temporomandibular disorders: a cross-sectional study

BackgroundMost 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.MethodsA 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.ResultsAfter 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.ConclusionBetel nut chewing related severely worn dentition was associated with intra-articular TMD.

Statin use and its association with decreased risk of esophageal squamous cell carcinoma in betel nut chewers.

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. 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. 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. Statin use was revealed to be associated with a reduced risk of ESCC in betel nut chewers.

Prevalence of Oral Potentially Malignant Disorders among Fishermen Population in and around Pondicherry, South India - A Cross Sectional Study.

In India fishing is a traditional occupation second only to agriculture. Fishermen are a marginalized group with high levels of occupational stress predisposing them to develop addictions to tobacco, alcohol, and areca nut chewing. These habits are well-established causes of developing oral potentially malignant disorders and oral cancer. To determine the prevalence of oral potentially malignant disorders among the fishermen population in and around Pondicherry. Cross-sectional study. A descriptive cross-sectional study was conducted using a pre-designed and pre-tested questionnaire to assess the prevalence of oral potentially malignant disorders among the fishermen population in and around Pondicherry. Descriptive statistics were used with Pearson's correlation. The study showed 24.8% of fishermen consumed tobacco, and 7.3% consumed both tobacco and alcohol. Oral potentially malignant disorders were seen in 16.79% of the population. The fishermen had a higher rate of addictions to tobacco, alcohol, and areca nut chewing and a higher prevalence of oral potentially malignant disorders.

Prevalence of Oral Submucous Fibrosis, Its Correlation of Clinical Grading to Various Habit Factors among Patients of Bihar: A Cross Sectional Study.

To find out the prevalence of OSMF and its Co-relation of clinical grading to various habit factors (time span of habit practiced in years, repetition of habit practiced per day, time of habit practiced in minutes per use). This descriptive, cross-sectional survey was carried out and close ended questionnaire was used for data collection. Demographic details like gender & age and different tissue exploiting habits like, chewing gutkha, chewing areca nut, chewing panmasala with or without tobacco, plain tobacco, mawa, smoking, alcohol was recorded. Also, duration of habit in years, repetition of habit per day, time of habit per use & site of involvement was recorded. Among 5297 patients examined at OPD, 120 were diagnosed with OSMF. The present study found no statistical relation between age, gender & OSMF. The present study concluded that majority 83 (69.17%) of the OSMF patients are guthka user and buccal mucosa was most affected site. OSMF was more prevalent in patients who practiced the habit for more than 15 years. Among the OSMF patients, guthka was most commonly practiced & buccal mucosa was most commonly involved. Duration and frequency of consumption were significantly associated with severity of OSMF.

Serological estimation of values for urea, uric acid, and creatinine as a prognostic marker in oral submucous fibrosis patients: An institutional clinic-biochemical study

ABSTRACT Background: The changes observed in the hematological/serological values and histopathological findings in oral submucous fibrosis (OSMF) patients may help in providing insight into the pathogenesis of this premalignant condition. Aims: The aim of this study is to estimate serum urea, uric acid, and creatinine in OSMF patients and compare them with habitual areca nut chewers and healthy controls and evaluate its potential as a prognostic marker in OSMF. Materials and Methods: A total of 150 patients were selected for the study and further categorized into Category I – included those subjects having OSMF, Category II – those subjects who had the habit of chewing betel nuts but had no features of OSMF, and Category III - comprised healthy controls with no habit history of chewing betel nut/tobacco. All variables from this study were analyzed by applying the analysis of variance (ANOVA) test and Chi-square test. Results: The results obtained from the present study showed statistically significant differences in serum urea, serum uric acid, and serum creatinine with various stages of OSMF. Conclusion: The serological estimation of urea, uric acid, and creatinine levels shows promise as a prognostic marker in OSMF patients. In the present study, elevated levels of these markers were associated with advanced disease stages and correlated positively with disease progression.

Assessment of the Influence of Risk Factors on the Incidence of Oral Squamous Cell Carcinoma (OSCC) in the Northern Pakistani Population

Background: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for over 94 percent of all cases, with substantial disparities in occurrence among South Asian countries. In Pakistan its occurrence rate rises from last two decade. A combination of risk factor habit, duration and intensity doubles the rate of incidence. Methods: Fully informed consent was taken. Both genders having age 18-55 years and cases confirmed by biopsy reports were included in the study. A thorough history of the disease and risk factors were taken and labelled (smoking, alcohol consumption, and betel nut chewing) accordingly. Data was analysed using SPSS 20. Gender base stratification was done using chi-square test and significance was defined as a P value of ? 0.05. Results: In present study 110 (73.3%) male and 40 (26.7%) female patients. Mean ±SD of age of OSCC patients was 47.00± 9.170 years. Among the participants 9 (6.0%) smokers, 39 (26.0%) consumed alcohol, use betel and 24 (16.0%) areca nut pan. Association of smoking with gender was statistically significant (p=0.013). Similarly, betel nut chewing also showed statistically significant correlation with gender (p=0.044). Both alcohol and snuff did not show any statistically significant correlation with gender. Conclusion: The public should be aware of the association of the risk factors and development of oral cancer. Public health measures should be taken to prevent smoking and chewing tobacco.

Review of Chemical, Biological, and Epistemological Elements: Mamaq Tradition

Mamaq by the ancestors of the Sasak people was an activity of chewing betel nut, lime, betel leaf, and tobacco, and ending with shrinkage. Betel leaves contain glycosides, steroids, triterpenoids, flavonoids, tannins, and anthraquinones. These compounds contain antimicrobial activity that can fight Staphylococcus aureus, Escherichia coli, and Candida albicans fungi. Meanwhile, whiting is a strong base because it has a pH of 11-12.5. This is because in the mouth there is saliva which can maintain a pH of around 6.8. Saliva contains phosphate buffer solutions H2PO4- and HPO42-. And gambir contains a component in the form of catechins which function as antioxidants and antibacterials. The purpose of this research is to study philosophical values, especially epistemology, which investigates the origin, and composition of methods and knowledge related to mamaq philosophy and natural science concepts, especially chemistry, and compounds, and what reactions occur in the mamaq process that has not been revealed. The study uses the library method. From the results of thestudy, it was concluded that in addition to the philosophy in the ingredients for mamaq it can also be described the chemical compounds contained in the ingredients for mamaq, starting from whiting, green betel leaf, gambier, and areca nut.

The Smell of Opium in Minangkabau: Tradition of Betel Chewing and Smoking Tobacco in the 19th Century

One of the historical themes of the Padri movement in Minangkabau in the 19th century was about eradicating the habit of smoking madat that occurred in Minangkabau society. The habit of smoking opium cannot be read at face value without investigating how opium-derived opium is used in the daily habits of the Minangkabau people. For example, in the habit of chewing betel nut and smoking tobacco. Therefore, using a social history approach, this paper will describe how opium is involved in the habit of chewing betel nut and smoking tobacco in the Minangkabau community. Thus, this paper will help explain how to understand the social context of the Padri in eradicating habits that they consider to be behavior that is not in accordance with Islamic teachings.

Fibroblast activating protein promotes the proliferation, migration, and activation of fibroblasts in oral submucous fibrosis.

Fibroblast activating protein (FAP) is associated with various organ fibrosis. However, the expression and molecular function of FAP in oral submucous fibrosis (OSF) is still unclear. The high-performance liquid chromatography was used to detect the presence of alkaloids in areca nut extract (ANE). Real-time qPCR, Western blot, and Immunohistochemistry assay were used to analyze the expression of FAP mRNA or protein in OSF and normal oral tissue. A chi-squared test analyzed the relationship between FAP protein expression and clinicopathological data of OSF patients. CCK-8, Wound-healing, and Transwell migration assay were employed to assess the effect of the proliferation and migration ability of hOMF cells with FAP overexpression or knockdown. The expression level of a-SMA, FSP1, and P13K-Akt signaling pathways-related protein in hOMF cells transfected with FAP overexpression or knockdown plasmid was verified by western blot assay. The four specific areca alkaloids (Arecoline, Guvacine, Arecaidine, and Guvacoline) were successfully detected in the ANE. The viability of hOMF cells was significantly improved in the 50 μg/mL ANE group and was inhibited in the 5 and 50 mg/mL ANE groups. The expression of FAP was upregulated in OSF tissues, and hOMF cells treated with 50 μg/mL ANE and was related to pathology grade, clinical stage, and history of chewing betel nut. Additionally, FAP may promote the proliferation, migration, and activation of hOMF cells through the P13K-Akt signaling pathway. This study found that ANE had a bidirectional effect on the viability of hOMF cells, and the FAP gene was a potential therapeutic target in OSF.

Preventable burden of head and neck cancer attributable to tobacco and alcohol between 1990 and 2039 in China.

Tobacco use and heavy alcohol consumption are risk factors for head and neck cancer (HNC), including oral, pharynx, and larynx cancer. No study has investigated the preventable burden of HNC attributable to tobacco and alcohol in China. We extracted data from 1990 to 2019 from the Global Burden of Disease. The preventable burden attributable to tobacco and alcohol was estimated by subtracting the overlapping fraction derived from a literature search. Descriptive analyses were performed initially, followed by joinpoint regression and age-period-cohort (APC) analysis. The future burden was forecasted using a Bayesian APC model. The crude burden increased significantly, while the age-standardized rates showed a downward trend from 1990 to 2019 in China. Both all-age and age-standardized population attributable fractions rose significantly, potentially due to the poor prognosis of tobacco- and alcohol-associated HNC. The absolute burden would continue to climb in the next 20 years from 2019, largely due to population aging. For site-specific burden, compared with total, pharynx, and larynx cancer burden, the substantial upward trend of oral cancer burden indicated a strong interaction with risk factors such as genetic susceptibility, betel nut chewing, oral microbiota, and human papillomavirus. The burden of oral cancer attributable to tobacco and alcohol is a major concern and is anticipated to become more severe than cancer in other anatomic sites. Altogether, our study provides useful information to rethink the current restrictions on tobacco and alcohol, lean healthcare resources, and develop effective HNC prevention and control strategies.

Comparison Between Clinical Outcome of Intralesional Human Placental Extract Alone and Topical Application of Placental Extract Gel After Fibrotomy in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSMF) is a premalignant condition prevalent in our country. Juxtaepithelial inflammation with progressive hyalinization of the lamina propria results in stiffness and fibrosis of the oral mucosa, characterised by trismus, ankyloglossia, and a burning sensation. Various methods of treatment have been tried in these cases, which include placental extract injections and the cutting of fibrous bands. In this study, we aim to compare the outcome of intra-lesional placental extract injection with fibrotomy and placental extract gel application in OSMF. This prospective interventional study included 58 patients clinically diagnosed with OSMF grades II and III at a rural tertiary care hospital between January 2021 and August 2022. The patients were randomised into two groups: group I received 1 ml of intra-lesional human placental extract injection in the submucosal plane of the buccal mucosa and retro-molar trigone (RMT) once a week for five consecutive weeks, and group II was subjected to a transverse division of fibrotic bands in the submucosal plane under general anaesthesia. The surgical wound was left open, and swabs soaked in human-purified placental extract gel were placed in the wound for two hours twice daily until the surgical wound was epithelialized and healed. The patients in both groups I and II were advised to do jaw opening exercises, and weekly follow-up was done. Findings with regard to maximum mouth opening, colour of mucosa, and burning sensation in the oral cavity based on a Likert scale were documented. At the end of five months, the pre-treatment and post-treatment results documented were compared. All patients were between 20 and 60 years of age and were addicted to chewing areca nuts with tobacco. Bilateral involvement was present in all patients, with extension into the RMTand soft palate seen in 31%. Improvement in mouth opening was between 4 mm and 6 mm in group II, and relief of burning sensation and mucosal colour was better in group I. Intra-lesional placental extract injections help in the improvement of the mucosa and relief from the burning sensation. Fibrotomy with placental extract gel application is better at relieving trismus in OSMF. Aggressive mouth-opening exercises may improve mouth opening following the above procedures.

Profile of Patients with Oral Cavity Cancer Seen at the Department of Ear Nose Throat – Head and Neck Surgery of the Bicol Medical Center

ABSTRACT
 Objective: To determine the profile of patients with oral cavity cancer seen at the Ear, Nose and Throat – Head and Neck Surgery (ENT-HNS) Department of the Bicol Medical Center from January 2018 to December 2020.Methods: Design: Retrospective review of records Setting: Tertiary Government Training Hospital Participants: Medical records of patients with oral cavity lesions with malignant biopsy results seen at the Bicol Medical Center Department of ENT-HNS from January 2018 to December 2020.Results: Records of 42 patients were included, 30 (71%) male; 12 (29%) female with the mean age of 62 ± 10.02 (range 34 to 80 years old). Squamous cell carcinoma was the most common histopathologic diagnosis (38/42; 91%), mostly affecting the anterior tongue (16/42; 38%) and buccal regions (14/42; 33%). Most tumors were in advanced stages: 25/42 (59%) in stage IVA; 7 (17%) in stage IVB. A total of 61% (17) of 28 oral cavity cancer patients with recorded risk factors practiced a combination of two or three high risk habits (betel nut chewing, tobacco smoking, alcoholic beverage intake) and a third practiced all three (10/28; 36%).Conclusion: The profile of oral cavity cancer patients in our study is different from the reported profiles in Asia and European and US counterparts. Our profile patient is a married male farmer in the 7th decade of life with poor dental hygiene and advanced stage IV squamous cell carcinoma of the tongue and buccal region, and combined habits of regular alcoholic beverage drinking, chronic tobacco smoking, and/or betel nut chewing, who lives in coastal or mountainous communities where access to health care may be limited.

Targeting histone deacetylase 9 represses fibrogenic phenotypes in buccal mucosal fibroblasts with arecoline stimulation

Background/purposeOral submucosal fibrosis (OSF) is a premalignant disorder positively associated with betel nut chewing. Recent studies supported the promising benefits of histone deacetylase (HDAC) inhibitors for fibrosis treatment. Here we aim to clarify the pro-fibrogenic role of HDAC9 in regulating OSF. Materials and methodsHealthy and OSF specimens were collected to investigate the clinical significance of HDAC9. Chronic arecoline treatment process was used to induce arecoline-mediated myofibroblasts-related activation of primary buccal mucosa fibroblasts (BMFs). Functional analysis of collagen gel contraction, transwell migration, and wound-healing assays were performed to assess the change in pro-fibrogenic properties of BMFs and fibrotic BMFs (fBMFs). Lentiviral-mediated HDAC9 knockdown was used to verify the role of HDAC9 in the pro-fibrogenic process. ResultsWe found that arecoline significantly increased the mRNA and protein expression of HDAC9 of BMFs in a dose-dependent manner. Knockdown of HDAC9 in BMFs reversed the strengthened effects of arecoline on collagen gel contraction, cell migration, and wound-healing ability. We further demonstrated that knockdown of HDAC9 in fBMFs significantly attenuated its inherent pro-fibrogenic properties. Furthermore, we confirmed a significantly increased expression of HDAC9 mRNA in OSF compared to normal tissues, which suggested a positive correlation between the up-regulation of HDAC9 and OSF. ConclusionWe demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.

Prevalence and predictive modeling of undiagnosed diabetes and impaired fasting glucose in Taiwan: a Taiwan Biobank study

IntroductionWe investigated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) in individuals without known diabetes in Taiwan and developed a risk prediction model for identifying undiagnosed diabetes and...