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.

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.

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.

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.

A bibliometric analysis of top 100 most-cited articles in dentistry with author(s) affiliated with Taiwan institutes.

BACKGROUND: Citation analysis can provide a historical perspective in the advancement of research, evolution, and areas of research. Taiwan exhibits rigorous academic and scientific activities in dentistry; however, based on its empirical contribution in research, there is no report in the literature analyzing the top-cited articles published by authors affiliated with Taiwan institutes. The purpose of this study was to analyze the citation characteristics of the top 100 most-cited articles published in dentistry with author(s) affiliated with Taiwan institutes. METHODS: The Scopus database was used to search the qualified articles with authors from Taiwan published in journals. The bibliometric parameters, including year of publication, study design, research fields, citation half-life, self-citation, institute of origin, and international collaboration were analyzed. Multivariable linear regression in generalized linear model was used to find associate factors related to trends of citation counts. RESULTS: The top 100 most-cited articles were determined by analyzing 7667 articles from the Scopus database. The steadily increasing trends were observed in the number and percentage of articles of author(s) affiliated with Taiwan institutes to the world. The most common study design was the in vitro research (55 %). The majority citation half-life is 3-5 and 6-8 years, and self-citation counts were between one to five times (n = 26). The percentage of international collaboration of these most-cited articles was 32%, and the main collaboration country was the United States. By using multivariable linear regression in the generalized linear model, the associated factors, study design, and self-citation were significantly associated with the escalating trends of citation counts. CONCLUSION: This is the first study that provides valuable information in the dentistry regarding the academic activity, and empirical contribution of author(s) affiliated with Taiwan institutes in the world. The trends of citation characteristics were significantly correlated with study design and self-citation of these articles.

Effects of lung protective ventilation on postoperative pulmonary outcomes for prolonged oral cancer combined with free flap surgery.

The intraoperative lung protective ventilation with low tidal volume, positive end expiratory pressure (PEEP) and intermittent lungs recruitment was found to decrease postoperative pulmonary complications. In this retrospective medical records study, we investigated the effects of lung protective ventilation on postoperative pulmonary outcomes among the patients received prolonged oral cancer combined with free flap surgery.We collected the medical records of the patients received oral cancer surgery with the operation time more than 12 hours from January 2011 to December 2015. We recordedFifty nine cases were included. Thirty cases received the lung protective ventilation and 29 cases received conventional ventilation. Compared to the patients received conventional ventilation, the patients received intraoperative lung protective ventilation showedIn conclusion, for the prolonged oral cancer combined with free flap surgery, the intraoperative lung protective ventilation improves postoperative pulmonary outcomes and decreases the duration of ICU stay.