Background/purpose: Oral 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 methods: The 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. Results: Current 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. Conclusion: In 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.
BACKGROUND/PURPOSE: The diagnosis of peri-implantitis using periapical radiographs is crucial. Recently, artificial intelligence may apply in radiographic image analysis effectively. The aim of this study was to differentiate the degree of marginal bone loss of an implant, and also to classify the severity of peri-implantitis using a deep learning model. MATERIALS AND METHODS: A dataset of 800 periapical radiographic images were divided into training (n = 600), validation (n = 100), and test (n = 100) datasets with implants used for deep learning. An object detection algorithm (YOLOv7) was used to identify peri-implantitis. The classification performance of this model was evaluated using metrics, including the specificity, precision, recall, and F1 score. RESULTS: Considering the classification performance, the specificity was 100%, precision was 100%, recall was 94.44%, and F1 score was 97.10%. CONCLUSION: Results of this study suggested that implants can be identified from periapical radiographic images using deep learning-based object detection. This identification system could help dentists and patients suffering from implant problems. However, more images of other implant systems are needed to increase the learning performance to apply this system in clinical practice.
BACKGROUND Percutaneous coronary intervention (PCI) with angiography guidance is a common procedure. Optical coherence tomography (OCT) is a non-invasive imaging method that uses light waves. This study from a single center aimed to compare 1-year outcomes in 75 patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent OCT-guided primary PCI, with 163 patients with acute STEMI who underwent PCI without OCT guidance from February 2019 to July 2021. MATERIAL AND METHODS Patients with acute STEMI were enrolled from February 2019 to July 2021. Seventy-five patients underwent OCT-guided PCI (OCT group), while 163 underwent PCI without OCT (control group). Baseline characteristics, in-hospital mortality, target lesion revascularization, post-MI heart failure, and 1-year all-cause mortality were compared between groups. RESULTS The OCT group had lower diabetes mellitus and hyperlipidemia prevalence. Additionally, they experienced longer procedures (OCT: 50.45±21.75 min; control: 33.80±14.44 min; P<0.001). After PCI, the control group had lower left ventricular ejection fractions (OCT: 53.4%±10.5%; control: 47.8%±12.4%; P<0.001) and higher post-MI heart failure rates (OCT: 2.7%; control: 11.0%; P=0.030). Notably, the 1-year all-cause mortality rate was significantly lower in the OCT group (OCT: 1.3%; control: 8.0%; P=0.043). CONCLUSIONS During the 1-year follow-up, patients who received OCT-guided primary PCI experienced a notably lower rate of post-MI heart failure than did those who underwent primary PCI without OCT guidance. Importantly, the application of OCT in primary PCI procedures did not result in a higher incidence of distal embolism, even in cases with a significant thrombus burden.
Heart Failure , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/surgery , Tomography, Optical Coherence , Arrhythmias, Cardiac , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/therapy
Background/purpose: Oral 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 methods: Healthy 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. Results: We 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. Conclusion: We demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.
Background/purpose: The RNA-binding protein human antigen R (HuR) recognizes AU-rich elements in the 3'-untranslated regions of mRNA. The expression of cytoplasmic HuR is related to the malignancy of many carcinomas. The aim of this study is investigation of effect of HuR knockdown for invasive activity of oral carcinoma. Materials and methods: Proliferation, invasion, real-time PCR, and reporter gene assays were performed to confirm that the knockdown of HuR downregulates the invasive activity of cancer cells. Immunohistochemical staining was performed for high invasive carcinoma, squamous cell carcinoma (SCC) and low invasive carcinoma, verrucous carcinoma (VC), to determine if the localization of cytoplasmic HuR is related to matrix metalloproteinase-1 (MMP-1) expression. Results: Invasive activity was significantly lower in HuR knockdown cancer cells than in control cells. A luciferase assay revealed that HuR knockdown inactivated the promoter activity of the MMP-1 gene. The mRNA levels of the transcription factors required for MMP-1 expression, including c-fos and c-jun, were decreased in HuR knockdown cancer cells. Immunohistochemical analysis revealed the level of cytoplasmic HuR and MMP-1 in invasive carcinoma to be higher than in low invasive cancer. HuR induced MMP-1 expression in the invasive front of most SCC cases. Conclusion: HuR knockdown attenuated the invasive activity of cancer cells by decreasing the expression of the MMP-1, at least partially. HuR localization may help determine the invasive phenotype of cancer cells and inhibit cancer cell invasion. Furthermore, in oral SCC, HuR may be related to invasive activity through the expression of MMP-1.
Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.
Abstract: Background/purpose: Overlay restorations can be used clinically as a treatment option to preserve natural dentine. However, whether the residual enamel thickness and overlay thickness affect the adhesion between the restoration and tooth is still unknown. This study was to investigate effects of the overlay thickness and residual enamel thickness on bonding strength. Materials and methods: Overlays of different thicknesses were prepared with natural teeth which had 2, 4, and 6 mm of occlusal reduction (n = 10). Specimens were subjected to 10,000 cycles in water at 5-55 °C, and finally compressive strength tests were used to evaluate the bonding strength. Results: All groups showed good bond strength (P > 0.05). The overlay restorations of different thicknesses reduced the preparation amount by 30.3%-7.2% and significantly preserved more of the tooth structure (P < 0.005). Compared to the control group, the overlay restoration increased the marginal fitness by about 0.67-0.88 times. The thermal cycling indicated that the decrease in the maximum bearing stress was due to the aging of the ceramic itself. Therefore, the thickness of the overlay had a greater influence on the compressive strength than the bond strength. Conclusion: Based on the above this study recommends an overlay thickness of at least 2 mm in clinical practice. The aging test confirmed that adhesion between the overlay and teeth was quite firm and stable. This shows that a stable adhesive effect of the overlay can be used as a treatment option for preserving a greater amount of a tooth's structure.
Background/purpose: Tongue squamous cell carcinoma (SCC) has a poor prognosis due to a high rate of cervical lymph node metastasis (CLNM). We aimed to determine clinicopathological features related to the prediction of CLNM in tongue carcinomas (Stage â /â ¡). Materials and methods: Data from 89 patients with tongue SCC (Stage I/II) were analyzed retrospectively. Patients were treated only with partial glossectomy and not with chemotherapy or radiotherapy until CLNM was observed. No cervical lymph node metastasis survival (NCLNMS) was estimated using the Kaplan-Meier method. The difference in NCLNMS between the groups with and without CLNM was compared using the log-rank test. The Cox regression model was used to estimate hazard ratios and the associated 95% confidence interval. Results: Clinical T2, clinical and pathological depth of invasion (cDOI and pDOI, respectively) > 5 mm, Yamamoto-Kohama (YK)-4c, tumor budding ≥5, worst pattern of invasion -4/5, muscle invasion, perineural invasion, and grade of differentiation 3 were found to be significant CLNM risk factors. Conclusion: CLNM was observed in 25.8% of early-stage tongue carcinomas (Stage I/II). YK-4c and pDOI >5 mm were the most important CLNM risk factors identified. Close follow-up is needed after partial glossectomy when patients with tongue SCC have other risk factors, particularly YK-4c and pDOI >5 mm.
The market for orthopedic implant alloys has seen significant growth in recent years, and efforts to reduce the carbon footprint of medical treatment (i.e., green medicine) have prompted extensive research on biodegradable magnesium-based alloys. Magnesium alloys provide the mechanical strength and biocompatibility required of medical implants; however, they are highly prone to corrosion. In this study, Mg-9Li alloy was immersed in cell culture medium to simulate degradation in the human body, while monitoring the corresponding effects of the reaction products on cells. Variations in pH revealed the generation of hydroxyl groups, which led to cell death. At day-5 of the reaction, a coating of MgCO3 (H2O)3, HA, and α -TCP appeared on sample surfaces. The coating presented three-dimensional surface structures (at nanometer to submicron scales), anti-corrosion effects, and an altered surface micro-environment conducive to the adhesion of osteoblasts. This analysis based on bio-simulation immersion has important implications for the clinical use of Mg alloys to secure regenerated periodontal tissue.
AIM: A high risk of bleeding is observed in East Asian patients with acute coronary syndrome (ACS). Therefore, the choice between two antiplatelet therapy drugs, ticagrelor and clopidogrel, remains controversial in this population with ACS. This study aimed to use a large cohort database to assess the clinical outcomes of ticagrelor and clopidogrel therapy, including major bleeding, recurrent ACS, and mortality, in this population. METHODS: Between January 2009 and December 2019, 43,696 patients were diagnosed with ACS based on the medical history (International Classification of Diseases [ICD] code) of the Chang Gung Research Database. After excluding patients without percutaneous coronary intervention, with concurrent medical problems, and on non-standard dual antiplatelet therapy (DAPT) or a single antiplatelet agent, 18,046 patients were recruited for analysis. Ticagrelor- and clopidogrel-based DAPT were administered to 3666 patients and 14,380 patients, respectively. Baseline characteristics and clinical outcomes were compared between the two groups. A total of 4225 patients were defined as a high-bleeding-risk subgroup according to Academic Research Consortium for High Bleeding Risk (ARC-HBR) score (met one major or two minor criteria), of which 466 and 3759 patients received ticagrelor- and clopidogrel-based DAPT, respectively. RESULTS: Before propensity score matching (PSM), younger age, higher prevalence of male sex, and higher body mass index were noted in the ticagrelor-based DAPT group in the whole cohort and high-bleeding-risk subgroup. After PSM, no difference in baseline characteristics and comorbidities between ticagrelor-based and clopidogrel-based DAPT groups in the whole cohort and high-bleeding-risk subgroup was noted. The Kaplan-Meier curves of recurrent ACS and major bleeding were significantly lower in the ticagrelor-based DAPT group than in the clopidogrel-based DAPT group, and that of cardiovascular (CV) and all-cause mortality showed no significant differences. After PSM, in the high-bleeding-risk subgroup, the Kaplan-Meier curve of recurrent ACS was significantly lower in the ticagrelor-based DAPT group than in the clopidogrel-based DAPT group, and that of major bleeding, CV, and all-cause mortality showed no significant differences. CONCLUSION: In this large cohort study, patients receiving ticagrelor-based DAPT were at lower risk of recurrent ACS compared to those receiving clopidogrel-based DAPT, especially in the patients with myocardial infarction. Ticagrelor-based DAPT did not result in a higher risk of major bleeding in the whole ACS population and high-bleeding-risk subgroup. The rate of CV and all-cause mortality were similar between both the groups.
Acute Coronary Syndrome , Humans , Male , Female , Clopidogrel/adverse effects , Acute Coronary Syndrome/drug therapy , Ticagrelor/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Cohort Studies
Background/purpose: The mandible is an independent and protruding bone structure in the lower third portion of the human facial skeleton. Because of its prominent and unprotected position, the mandible is a primary site of facial trauma. Previous studies have not comprehensively discussed the association between the mandibular fractures and concomitant fractures of facial bones, the trunk, or limbs. This study analyzed the epidemiology of mandibular fractures and their correlation with concomitant fractures. Materials and methods: The present study enrolled 118 patients with a total of 202 mandibular fracture sites during at any time from January 1, 2012, to December 31, 2021, in northern Taiwan. Results: According to the study results, the patients between 21 and 30 years of age had the highest occurrence of trauma, and road traffic accidents (RTAs) constituted the primary cause of mandibular fractures. Fall-related injuries were significant in patients >30 years of age. By the analysis of Pearson's contingency coefficient, the number of mandibular fractures was not significantly associated with concomitant fractures of the extremities or the trunk. However, accompanying maxillary fractures can be regarded as an indication of concomitant extremity or trunk fractures in patients with mandibular fractures. Conclusion: Three-site mandibular fractures are not necessarily accompanied by extremity and trunk fractures; however, clinicians should implement multidisciplinary examination and management in patients with mandibular fractures accompanied by maxillary fractures. Maxillary fractures can be regarded as an indication of concomitant fractures of other facial bones, the extremities, or the trunk.
The effects of clinically relevant concentrations of lidocaine on epithelial-mesenchymal transition (EMT) and associated lung cancer behaviors have rarely been investigated. The aim of the present study was to assess the impact of lidocaine on EMT and its related phenomena, including chemoresistance. Lung cancer cell lines (A549 and LLC.LG) were incubated with various concentrations of lidocaine, 5-fluorouracil (5-FU) or both to test their effects on cell viability. Subsequently, the effects of lidocaine on various cell behaviors were assessed in vitro and in vivo using Transwell migration, colony-formation and anoikis-resistant cell aggregation assays, and human tumor cell metastasis in a chorioallantoic membrane (CAM) model quantitated by PCR analysis. Prototypical EMT markers and their molecular switch were analyzed using western blotting. In addition, a conditioned metastasis pathway was generated through Ingenuity Pathway Analysis. Based on these measured proteins (slug, vimentin and E-cadherin), the molecules involved and the alteration of genes associated with metastasis were predicted. Of note, clinically relevant concentrations of lidocaine did not affect lung cancer cell viability or alter the effects of 5-FU on cell survival; however, at this dose range, lidocaine attenuated the 5-FU-induced inhibitory effect on cell migration and promoted EMT. The expression levels of vimentin and Slug were upregulated, whereas the expression of E-cadherin was downregulated. EMT-associated anoikis resistance was also induced by lidocaine administration. In addition, portions of the lower CAM with a dense distribution of blood vessels exhibited markedly increased Alu expression 24 h following the inoculation of lidocaine-treated A549 cells on the upper CAM. Thus, at clinically relevant concentrations, lidocaine has the potential to aggravate cancer behaviors in non-small cell lung cancer cells. The phenomena accompanying lidocaine-aggravated migration and metastasis included altered prototypical EMT markers, anoikis-resistant cell aggregation and attenuation of the 5-FU-induced inhibitory effect on cell migration.
Background/purpose: Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. Materials and methods: First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-ß signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial-mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. Results: We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-ß secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. Conclusion: We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-ß/Smad signaling pathway in OSF.
Background/purpose: Emerging evidence has shown that various failures in cancer therapy, such as drug resistance, metastasis, and cancer relapse are attributed to cancer stem cells (CSCs). Also, growing attention has been paid to the regulation of non-coding RNAs in cancer stemness. Here, we aimed to investigate the contribution of LINC01296 in the modulation of oral CSCs. Materials and methods: The phenotypic assays including migration, invasion, and colony-forming abilities were carried out in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of LINC01296. In addition, the percentage of cells expressing stemness marker, ALDH1, and drug resistance marker, ABCG2, was examined as well as the self-renewal capacity after silencing of LINC01296. Moreover, a luciferase reporter was used to validate the direct interaction between LINC01296 and miR-143. Results: Our results showed that LINC01296 was significantly overexpressed in oral cancer tissues and positively correlated with stemness markers. The phenotypic and flow cytometry assays demonstrated that suppression of LINC01296 reduced the aggressiveness, cancer stemness features, and colony-forming and self-renewal abilities in oral CSCs. Furthermore, we demonstrated that LINC01296 may enhance cancer stemness features through suppression of the effect of miR-143. Conclusion: Silencing of LINC01296 may be a promising direction for oral cancer therapy by reducing cancer stemness via regulation of miR-143.
Patients undergoing cardiac catheterization are at high risk of post-procedure acute kidney injury (AKI) and may experience persistent renal damage after an initial insult, a state known as acute kidney disease (AKD). However, the association between AKD and urinary renal biomarkers has not yet been evaluated in this population. We enrolled 94 patients who underwent elective cardiac catheterization to investigate patterns of urinary renal biomarkers and their associations with post-procedure AKD. Serial urinary renal biomarker levels were measured during pre-procedure, early post-procedure (12-24 h), and late post-procedure (7-10 days) periods. In our investigation, 42.55% of the enrolled patients developed AKD during the late post-procedure period. While the liver-type free-fatty-acid-binding protein level increased sharply during the early post-procedure period, it returned to baseline during the late post-procedure period. In contrast, interleukin-18 (IL-18) levels increased steadily during the post-procedure period. Early post-procedure ratios of IL-18 and gelsolin (GSN) were independently associated with subsequent AKD (odds ratio (95% confidence interval), 4.742 (1.523-14.759) for IL-18 ratio, p = 0.007; 1.812 (1.027-3.198) for GSN ratio, p = 0.040). In conclusion, post-procedure AKD is common and associated with early changes in urinary IL-18 and GSN in patients undergoing cardiac catheterization.
Acute Kidney Injury , Interleukin-18 , Humans , Interleukin-18/urine , Gelsolin , Kidney , Acute Kidney Injury/etiology , Acute Kidney Injury/urine , Biomarkers/urine
Aortic stenosis (AS) is the most prevalent valvular disease in the elderly population and the prevalence of atrial fibrillation (AF) increases in the elderly population. Transcatheter aortic valve replacement (TAVR) becomes an important treatment for patients with AS at high surgical risk. This metanalysis aimed to compare the efficacy and safety of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) in patients with AF undergoing TAVR. We searched the different databases for articles published before January 31, 2022. In total, 7 studies including 25,255 patients were analyzed. Data on demographics, comorbidities, CHA2DS2-VASc score, Society of Thoracic Surgeons (STS) score, and incidences of all-cause mortality, major bleeding, intracranial hemorrhage (ICH), stroke, and thromboembolic events were obtained and analyzed. The VKA group had a lower CHA2DS2-VASc score (3.2 ± 1.2 vs 3.3 ± 1.2; P < .001) and a higher STS score (6.6 ± 3.2 vs 6.1 ± 2.9; P < .001) than the DOAC group. The risks of all-cause mortality (odds ratio [OR]: 0.88; 95% confidence interval [CI], 0.67-1.16), ischemic stroke (OR: 1.06; 95% CI, 0.90-1.24), and thromboembolism (OR: 1.24; 95% CI, 0.63-2.47) in the DOAC group were comparable to the VKA group. The risks of major bleeding (OR: 0.77; 95% CI, 0.71-0.84) and ICH (OR: 0.62; 95% CI, 0.42-0.90) were lower in the DOAC group compared to the VKA group. DOACs were associated with lower risks of major bleeding and ICH, and comparable risks of all-cause mortality, ischemic stroke, and thromboembolism in patients with AF undergoing TAVR compared to VKAs.
Aortic Valve Stenosis , Atrial Fibrillation , Ischemic Stroke , Stroke , Thromboembolism , Transcatheter Aortic Valve Replacement , Humans , Aged , Atrial Fibrillation/drug therapy , Transcatheter Aortic Valve Replacement/adverse effects , Anticoagulants/therapeutic use , Stroke/etiology , Hemorrhage/drug therapy , Thromboembolism/etiology , Aortic Valve Stenosis/surgery , Intracranial Hemorrhages/drug therapy , Ischemic Stroke/drug therapy , Vitamin K , Administration, Oral , Treatment Outcome
