MyD88 exacerbates inflammation-induced bone loss by modulating dynamic equilibrium between Th17/Treg cells and subgingival microbiota dysbiosis.

BACKGROUND: This study aimed to investigate the contribution of myeloid differentiation primary-response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis-induced experimental periodontitis. METHODS: Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate-resistant acid phosphatase (TRAP), the receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age- and sex-matched homozygous littermates (wild-type [WT, Myd88+/+] and Myd88-/- on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed. RESULTS: P. gingivalis-infected Myd88-/- mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88-/- CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL-10 and IL-17a expressions in gingival tissue at D14-D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88-/- mice. The Myd88-/- mice exhibited characteristic increases in gram-positive species and species having probiotic properties, while gram-negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88-/- mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection. CONCLUSIONS: MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis-induced experimental periodontitis.

Obesity Phenotypes and Dental Calculus in Young Adults: CHIEF Oral Health Study.

AIM: The study aimed to examine the association of obesity phenotypes with dental calculus. BACKGROUND: Obesity has been recognized as a risk factor for kidney and gallbladder stones formation and periodontitis. OBJECTIVE: We have investigated the association between obesity, metabolic risk factors, and dental calculus, which is a sequela following periodontitis. METHODS: This study included 5,281 military members, aged 19-45 years, without antihypertensive medications in Taiwan. Obesity was defined as body mass index ≥27.5 kg/m2, and metabolic syndrome (MetS) was defined according to the modified ATP III criteria. Supragingival calculus in any teeth, except for impacted teeth and the third molar, was the outcome of interest. Multiple linear regression analysis with adjustments for age, sex, toxic substance use, brushing teeth frequency, and blood leukocyte counts, was used to determine the association of obesity with dental calculus numbers. Multiple logistic regression analysis was used to assess the association between obesity with or without MetS and the presence of any dental calculus. RESULTS: BMI was positively correlated to dental calculus numbers [ß and confidence intervals (CI) = 0.023 (0.014, 0.032)]. Compared to the obesity(-)/MetS(-) group, there were dosedependent associations for the obesity(-)/MetS(+), obesity(+)/MetS(-), and obesity(+)/MetS(+) groups with the presence of any dental calculus [odds ratios (ORs): 1.08 (0.76, 1.53), 1.31 (1.08, 1.58), and 1.51 (1.20, 1.90), respectively]. Of the metabolic risk factors, abdominal obesity and hypertension were independently associated with dental calculus [ORs: 1.33 (1.13, 1.55) and 1.30 (1.11, 1.52), respectively]. CONCLUSION: This study suggests general obesity as an independent risk factor for dental calculus formation, and MetS, particularly the components of abdominal obesity, and hypertension may also increase the prevalence of dental calculus. Diet control and regular exercise might be preventive measures for the development of both obesity and dental calculus.

Mapping out the bibliometric characteristics of classic articles published in a Taiwanese academic journal in dentistry: A scopus-based analysis.

Background/purpose: Since its inception, the Journal of Dental Sciences (JDS) has aimed to publish quality articles relevant to all fields in dentistry. The purpose of this study was to analyze the bibliometric characteristics and dissected associated factors correlated with citation counts of classic articles published in the JDS. Materials and method: Scopus® database was used to search the qualified articles published in JDS from 2009 to 2021. The bibliometric parameters, including journal impact factor (JIF), self-citation, study design, research field, geographic, country and institute of origin, inter-institute, inter-nation collaboration, keywords hotness and associated factors correlated with citation counts of classic articles were analyzed. Results: One hundred and eight articles from Scopus® database were eligible for analysis. The citation counts of classic articles ranged from 12 to 192, the average citation was 22.02. The most common study design was the in vitro/in vivo, followed by the cross-sectional study, and the major research field were Dental Materials. The most productive country and institute is Taiwan, and Chung Shan Medical University, respectively. The trend of inter-institute (71.03%) and inter-nation (11.22%) collaboration steadily increased since 2009. By using the multivariable linear regression model, Preventive and Community Dentistry in the research field significantly increased the citation counts. Conclusion: Despite its limitations, the escalating trends in JIFs, and JIFs without self-citations, and inter-nation and inter-institute collaboration of classic articles were noticed. Of all the dissected associated factors, Preventive and Community Dentistry in the research field significantly increased the citation counts of classic article.

Complement components C3b and C4b as potential reliable site-specific diagnostic biomarkers for periodontitis.

OBJECTIVE: This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site-specific complementary diagnostic markers for periodontitis. BACKGROUND: A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce. METHODS: The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut-off point, area under the ROC curve, sensitivity, and specificity were analyzed. RESULTS: The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b + C4b in the GT can significantly differentiate the disease status at the tissue level (p < .0001). Similarly, the expression levels of C3b + C4b in GCF can statistically distinguish periodontitis sites from healthy ones (p < .0001). CONCLUSIONS: Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site-specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.

The referral pattern and treatment modality for peri-implant disease between periodontists and non-periodontist dentists.

OBJECTIVES: This study is to investigate the referral pattern and treatment modality of dentists in the management of peri-implant diseases between periodontists and non-periodontist dentists (NPDs). MATERIALS AND METHODS: A total of 167 validated questionnaires were obtained from periodontists and NPDs, who had experience of placing implants for at least one year. Question I to IV asked how the dentist would respond if a patient came for treatment of their peri-implant diseases with four different scenarios according to resource of patient and disease severity. For each Scenario, dentists also replied which treatment procedures they would use if they decide to treat the patient. RESULTS: Periodontal training, resource of patient, and disease severity were shown to significantly influence the referral pattern and treatment modality in the management of peri-implant disease (p < 0.05). Periodontists were more likely to use variable treatment procedures, including occlusal adjustment (OR = 2.283, p < 0.01), oral hygiene instruction (OR = 3.751, p < 0.001), topical antiseptic agent (OR = 2.491, p < 0.005), non-surgical mechanical therapy (OR = 2.689, p < 0.001), surgical therapy (OR = 2.009, p < 0.01), and remove implant (OR = 3.486, p < 0.001) to treat peri-implant diseases, compared to NPDs. CONCLUSION: The periodontal specialty training, resource of patient, and disease severity significantly influenced the referral pattern and treatment modality of dentist treating an implant diagnosed with peri-implant disease. This study also highlighted the importance of educating basic periodontal and peri-implant disease-related knowledge to all dentists regularly performing dental implant treatments. CLINICAL RELEVANCE: Peri-implant diseases are highly prevalent among patients with dental implants. Periodontal specialty training could enhance using variable treatment procedures to treat peri-implant diseases for dentists.

A bispecific antibody AP203 targeting PD-L1 and CD137 exerts potent antitumor activity without toxicity.

BACKGROUND: Bispecific antibody has garnered considerable attention in the recent years due to its impressive preliminary efficacy in hematological malignancies. For solid tumors, however, the main hindrance is the suppressive tumor microenvironment, which effectively impedes the activation of infiltrating T cells. Herein, we designed a bispecific antibody AP203 with high binding affinity to PD-L1 and CD137 and assessed its safety and anti-tumor efficacy, as well as explored the mechanism of action. METHODS: The optimal antibody binders against PD-L1 and CD137 were screened from the OmniMab phagemid library. The binding affinity of the constructed AP203 were evaluated using enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry (BLI). T-cell stimulatory capacity was assessed using the allogeneic mixed lymphocyte reaction (MLR), antigen-specific recall response, and coculture with PD-L1-expressing cells. In vivo antitumor efficacy was evaluated using two models of tumor-xenografted humanized mice with profiling of tumor infiltrating lymphocytes (TILs). The possible toxicity of AP203 was examined using in vitro cytokine release assay by human PBMCs. RESULTS: AP203, which simultaneously targeted PD-L1 and costimulatory CD137, elicit superior agonistic effects over parental antibodies alone or in combination in terms of T cell activation, enhanced memory recall responses, and overcoming Treg-mediated immunosuppression (P < 0.05). The agonistic activity of AP203 was further demonstrated PD-L1-dependent by coculturing T cells with PD-L1-expressing cells. In vivo animal studies using immunodeficient or immunocompetent mice both showed a dose-related antitumor efficacy superior to parental antibodies in combination (P < 0.05). Correspondingly, AP203 significantly increased tumor infiltrating CD8 + T cells, while decreased CD4 + T cells, as well as Treg cells (P < 0.05), resulting in a dose-dependent increase in the CD8 + /CD4 + ratio. Moreover, either soluble or immobilized AP203 did not induce the production of inflammatory cytokines by human PBMCs. CONCLUSIONS: AP203 exerts potent antitumor activity not only by blocking PD-1/PD-L1 inhibitory signaling, but also by activating CD137 costimulatory signaling in effector T cells that consequently counteracts Treg-mediated immunosuppression. Based on promising preclinical results, AP203 should be a suitable candidate for clinical treatment of solid tumors.

The impact of smoking on peri-implant microbiota: A systematic review.

OBJECTIVES: Peri-implantitis is associated with bacterial plaque biofilms and with patients who have a history of periodontitis. Smoking is a risk factor for periodontitis, but the relationship between smoking and peri­implantitis is unclear. The aim of this systematic review was to assess evidence ascertaining the relationship between smoking and peri­implant microbiota. DATA SOURCES: An electronic search was conducted in the MEDLINE/PubMed, Embase and Scopus® databases in duplicate up to January 2023 without language restrictions. Studies were considered eligible for inclusion if they involved evaluation of the peri­implant microbiota of smokers and nonsmokers. Methodological quality was assessed with the adapted Newcastle-Ottawa scale. STUDY SELECTION: Fourteen studies were identified for inclusion in the present study, and 85.7% of the studies were defined as medium to high methodological quality. Overall, the evidence presented in this review was limited to medium to high methodological quality. The data indicates that significantly higher frequencies of anaerobic pathogens are detectable in healthy peri­implant tissues of smokers. A lower diversity of microbiota was observed in healthy peri­implant sites of smokers. In the transition from clinically healthy to a diseased status, smoking shaped a reduced peri­implant microbiota by depleting commensal and enriching pathogenic species. CONCLUSIONS: The composition of peri­implant microbiota may be influenced by smoking. More studies are needed to determine the impact of smoking on peri­implant microbiota. CLINICAL SIGNIFICANCE: In the transition from clinically healthy to a diseased status, smoking shaped a reduced peri­implant microbiota by depleting commensal and enriching pathogenic species. The composition of peri­implant microbiota may be influenced by smoking.

Chlorhexidine gel topical application ameliorates inflammatory bone loss in experimental periodontitis.

OBJECTIVES: This study aimed to evaluate the impact of chlorhexidine (CHX) gel on inflammation-induced periodontal tissue destruction, osteoclastogenesis, subgingival microbiota, and on the modulation of the RANKL/OPG as well as inflammatory mediators during bone remodeling in vivo. MATERIALS AND METHODS: Ligation- and LPS injection-induced experimental periodontitis were created to investigate the effect of topical application of CHX gel in vivo. Alveolar bone loss, osteoclast number and gingival inflammation was evaluated by micro-CT, histological, immunohistochemistry and biochemical analysis. The composition of the subgingival microbiota was characterized by 16S rRNA gene sequencing. RESULTS: Data shows significant decreases in the alveolar bone destruction in rats from ligation-plus-CHX gel group compared to ligation group. In addition, significant decreases in the number of osteoclasts on bone surface and the protein level of receptor activator of nuclear factor κB ligand (RANKL) in gingival tissue were observed in rats from ligation-plus-CHX gel group. Moreover, data shows significantly decreased inflammatory cell infiltration and decreased expression of cyclooxygenase (COX-2) and inducible NO synthase (iNOS) in gingival tissue from ligation-plus-CHX gel group versus ligation group. Assessment of the subgingival microbiota revealed changes in rats with CHX gel application treatment. CONCLUSION: HX gel presents protective effect on gingival tissue inflammation, osteoclastogenesis, RANKL/OPG expression, inflammatory mediators, and alveolar bone loss in vivo, which may have a translational impact on the adjunctive use in the management of inflammation-induced alveolar bone loss.

Targeting therapeutic agent against C3b/C4b, SB002, on the inflammation-induced bone loss in experimental periodontitis.

AIMS: To use experimental periodontitis models in rats to investigate the correlation between local expression of the complement components C3b and C4b in periodontal tissues and disease severity, and to assess the therapeutic effects of targeting C3b/C4b on inflammatory bone loss. MATERIALS AND METHODS: The gingival expression of C3, C3b, and C4b in animal experimental periodontitis models were analysed immunohistochemically. The therapeutic effects of the C3b/C4b inhibitor (SB002) on ligation-induced experimental periodontitis was examined using biochemical, histological, and immunohistochemical analyses. RESULTS: The gingival expression levels of C3, C3b, and C4b were positively correlated with the severity of periodontitis. Moreover, both single and multiple injections of the C3b/C4b inhibitor had preventive and therapeutic effects on alveolar bone loss in ligation-induced experimental periodontitis with no associated adverse consequences. CONCLUSIONS: The association between C3b/C4b and periodontitis may provide a basis for the development of novel therapeutic strategies for periodontitis and other inflammatory diseases.

Silibinin alleviates inflammation-induced bone loss by modulating biological interaction between human gingival fibroblasts and monocytes.

BACKGROUND: Silibinin has shown various pharmacological effects that could be attributed to its antioxidant, anti-inflammatory, and immunoregulatory properties. However, the therapeutic potential of silibinin for periodontitis has not been investigated. METHODS: The therapeutic effects of silibinin in ligation-induced experimental periodontitis were investigated using biochemical, histological, and immunohistochemical methods. The effects of silibinin on the osteoclastogenesis of RAW264.7 cells were investigated using TRAP staining, quantitative polymerase chain reaction (qPCR), pit formation, and immunoblotting. Moreover, its effects on inflammatory cytokine production, RANKL expression, and oxidative stress in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) were evaluated using qPCR and flow cytometry. A coculture system was established to elucidate the effects of silibinin on the crosstalk between LPS-stimulated HGFs and undifferentiated monocytes. RESULTS: Silibinin significantly reduced the alveolar bone loss, decreased the gingival inflammation and RANKL expression, and decreased the RANKL/osteoprotegerin ratio in gingival tissues in experimental periodontitis. The in vitro results showed that silibinin inhibited RANKL-induced osteoclast differentiation and function of RAW264.7 cells and suppressed RANKL-induced nuclear factor of activated T cells 1 (NFATc1) induction and translocation through the nuclear factor-κB and mitogen-activated protein kinase signaling pathways. Silibinin decreased the inflammatory cytokine level and oxidative stress production in LPS-stimulated HGFs; significantly suppressed membrane-bound RANKL expression on LPS-stimulated HGFs; and significantly disrupted TRAP+ cell differentiation in the coculture system. CONCLUSIONS: Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators. Collectively, targeting the inflamed HGF resolution that mediates osteogenesis may use silibinin as a potential drug-repurposing candidate for modulating alveolar bone destruction in periodontitis. SUMMARY: Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators.

Association Between Dental Calculus and Hypertension Phenotypes in Highly Fit Adults: CHIEF Oral Health Study.

BACKGROUND: Poor oral health evaluated by presence of dental calculus has been associated with hypertension (HTN) among middle- and old-aged adults. However, it is unclear for the association of HTN phenotypes with dental calculus in young adults. METHODS: This study examined the association between dental calculus and HTN in 5,345 military personnel, aged 19-45 years, without antihypertensive medications therapy in Taiwan from 2018 to 2021. Dental calculus was defined as presence of supragingival calculus in any teeth, except impacted teeth, and third molar. Combined HTN (CHTN) was diagnosed as systolic blood pressure (SBP) ≥130 mm Hg and diastolic blood pressure (DBP) ≥80 mm Hg. Isolated systolic and diastolic HTN were, respectively, defined as SBP ≥130 mm Hg only (ISHTN) and DBP ≥80 mm Hg only (IDHTN). Multiple logistic regression with adjustments for sex, age, toxic substance use, anthropometrics, lipid profiles, fasting glucose, and blood leukocyte counts were used to determine the association between dental calculus and HTN phenotypes in young adults. RESULTS: The prevalence of those with dental calculus, CHTN, ISHTN, and IDHTN was 20.8%, 10.8%, 10.2%, and 7.0%, respectively. The dental calculus was associated a greater possibility with CHTN [odds ratio (OR) and 95% confidence interval: 1.60 (1.31-1.95)]. However, the associations of dental calculus with ISHTN and IDHTN were null [OR: 1.05 (0.81-1.27) and 1.12 (0.86-1.46), respectively]. CONCLUSIONS: Our findings suggest that among young adults, poor oral health manifested by presence of dental calculus was associated with a greater possibility of CHTN, while not for ISHTN and IDHTN.

Localized periodontitis and kidney function for the risk of proteinuria in young adults in the CHIEF oral health study.

This study aimed to investigate the association of localized periodontitis with proteinuria in 1281 military young adults in Taiwan. Localized periodontitis was classified as Healthy/Stage I (N = 928) or Stage II/III (N = 353). Stage 2 chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) of 60-89 mL/min/1.73 m2. Proteinuria was defined as protein levels of 2+ or 3+ on the dipstick test. Multiple logistic regression analysis with adjustments for age, sex, body mass index, remaining teeth number and other potential covariates were used to determine the association between localized Stage II/III periodontitis and dipstick proteinuria in patients with and without CKD. Localized stage II/III periodontitis was associated with a higher risk of dipstick proteinuria [odds ratio (OR) and 95% confidence interval: 1.89 (1.04-3.42)], but not with stage 2 CKD. However, the association between localized stage II/III periodontitis and dipstick proteinuria was observed only in patients with stage 2 CKD [OR: 3.80 (1.56-9.27)], while the association was null in participants without stage 2 CKD [OR: 1.02 (0.42-2.45)]. Our findings suggest that among young adults, especially those with a mildly impaired eGFR, localized periodontitis might contribute to acute or chronic kidney injury, which manifests as proteinuria.

Corrigendum: RvE1 Impacts the Gingival Inflammatory Infiltrate by Inhibiting the T Cell Response in Experimental Periodontitis.

[This corrects the article DOI: 10.3389/fimmu.2021.664756.].

Associations of decayed and filled teeth with localized stage II/III periodontitis in young adults: The CHIEF oral health study.

Background/purpose: To investigate the associations between treated and untreated dental caries and periodontitis in young adults. Materials and methods: The study enrolled 1289 participants aged 18-45 years in Taiwan. Localized periodontitis was categorized into healthy and stage II/III (n = 936 and n = 353, respectively) based on the 2017 criteria of the World Workshop. Multivariable logistic regression analysis with adjustments for sex, age, tobacco smoking status, betel nut consumption status, metabolic syndrome, and total white blood cell count was used to determine the associations. Results: Decayed tooth numbers were positively associated with localized stage II/III periodontitis [odds ratio (OR): 1.15 (95% confidence intervals (CI): 1.06-2.25)], while filled tooth numbers were inversely associated with localized stage II/III periodontitis in young adults [OR: 0.96 (95% CI: 0.92-0.99)]. Conclusion: Our study confirms the relationship between dental caries and periodontitis by direct evidence that the more decayed teeth there are, the higher the risk of periodontitis and by indirect evidence that the more treated decayed teeth there are, the lower the risk of periodontitis in young adults.

Periodontitis, Helicobacter pylori infection, and gastrointestinal tract cancer mortality.

AIM: Periodontitis has been proposed to lead to Helicobacter pylori infection, which could cause many gastrointestinal tract cancers. This study aimed to determine the association or otherwise between periodontitis and survival outcomes in individuals with respect to H. pylori infection. MATERIALS AND METHODS: The study population comprised 4955 subjects aged 20-90 who had received both periodontal examination and H. pylori serum test in the Third National Health and Nutrition Examination Survey (NHANES III) database. Logistic regression models were used to analyse the association between periodontitis and H. pylori seropositivity (H. pylori infection). Survival analysis was performed using the NHANES III linked to mortality data. Cox proportional hazard regression was carried out to investigate the association between periodontitis and gastrointestinal tract cancer mortality in individuals with/without H. pylori infection. RESULTS: Compared to periodontal health, periodontitis was significantly associated with increased odds of H. pylori infection (OR = 1.271, 95% CI = 1.177-1.372). Periodontitis significantly increased the mortality risk from all causes (HR = 1.574, 95% CI = 1.327-1.866) and all cancers (HR = 1.948, 95% CI = 1.701-2.232), including gastrointestinal (GI) tract cancer (HR = 4.140, 95% CI = 3.656-4.687), gastric cancer (HR = 4.288, 95% CI = 3.969-4.632), and colorectal cancer (HR = 4.814, 95% CI = 3.849-6.020) in subjects with H. pylori infection after adjusting for health-related factors. Periodontitis was significantly related to the decreased survival time in subjects with GI tract (p = .001) or colorectal cancer (p = .002) and H. pylori infection. CONCLUSION: Our study demonstrated that periodontitis was significantly associated with higher mortality risk of GI tract, gastric, and colorectal cancer in subjects with H. pylori infection. Owing to an interactive effect between periodontitis and H. pylori infection on cancer mortality, H. pylori infection has a significant moderating effect in regulating the association between periodontitis and mortality due to all cancers, including GI tract cancer and colorectal cancer.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Associations between metabolic biomarkers and localized stage II/III periodontitis in young adults: The CHIEF Oral Health study.

AIM: To investigate the associations between metabolic risk factors and periodontitis in young adults. MATERIALS AND METHODS: The study included 1123 participants, aged 19-40 years, in Taiwan. Metabolic syndrome components were defined by the International Diabetes Federation criteria. Localized periodontitis was graded to healthy (n = 828) and stage II/III (n = 295) according to the 2017 criteria of the World Workshop. Multiple logistic regression analysis with adjustment for sex, age, betel nut consumption, and smoking were used to determine the associations. RESULTS: Greater waist circumference, serum triglycerides, and serum uric acid were associated with higher localized stage II/III periodontitis risk [odds ratio (OR) and 95% confidence interval (CI): 1.04 (1.02-1.05), 1.004 (1.002-1.006), and 1.10 (1.00-1.21), respectively]. There were no associations for total cholesterol, high-density lipoprotein, and blood pressure. There was a non-linear association between fasting glucose and localized stage II/III periodontitis, where the turning point was 105 mg/dl [OR: 0.97 (0.95-0.99) and 1.06 (1.00-1.13) when the levels were <105 and ≥105 mg/dl, respectively]. CONCLUSIONS: The risks of localized stage II/III periodontitis vary with metabolic components, in which waist circumference, serum triglycerides, and serum uric acid are the risk factors, whereas plasma glucose shows a non-linear relationship in young adults.

Risk assessment of labial bone perforation in the anterior mandibular region: a virtual immediate implant placement study.

BACKGROUND: This study investigated the prevalence of labial bone perforation (LBP) related to the associated anatomic factors in anterior mandibular region using a virtual immediate implant placement procedure. METHODS: Series qualified CBCT images of 149 participants (894 teeth) were selected to analyze the assigned anatomical parameters, including concavity depth, concavity angle, torque, and deep bone thickness. Four classes of crestal and radicular dentoalveolar bone phenotypes (CRDAPs) of mandibular anterior teeth were categorized according to the thickness of dentoalveolar bone at both crestal and radicular zones. Data were adjusted for categorical (gender and CRDAP) and continuous (age, cavity angle, cavity depth, and deep bone thickness) variables using a multivariable logistic regression analysis with generalized estimating equation method. RESULTS: The overall probability of LBP after virtual implant placement was 21.6%. There is statistically significant higher prevalence of LBP at canine (28.5%) and CRDAP class II (29.2%) regions (p < 0.001). After adjusting confounding variables, CRDAP class II and class IV regions are more likely to have LBP when compared with CRDAP class I (control) regions (p < 0.01). The risk of LBP at canine site is 6.31 times more likely than at the central incisor (control) (p < 0.01). CONCLUSIONS: Using a virtual immediate implant placement technique, the prevalence of LBP is significantly higher at the mandibular canine site and thin radicular dentoalveolar phenotype in the anterior mandibular region.

Recommendations for treating stage I-III periodontitis in the Taiwanese population: A consensus report from the Taiwan Academy of Periodontology.

BACKGROUND/PURPOSE: Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population. METHODS: The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions. RESULTS: The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population. CONCLUSION: The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered.