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.

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.

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.

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.

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.

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.

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.

Association between the presence of distolingual root in mandibular first molars and the presence of C-shaped mandibular second molars: a CBCT study in a Taiwanese population.

OBJECTIVES: The purpose of this study was to assess the prevalence of C-shaped canals in permanent mandibular second molars (SMs) and to determine whether its appearance was associated with the presence of distolingual root (DLR) in permanent mandibular first molars (FMs). METHOD AND MATERIALS: Three hundred and eighty patients were qualified for evaluation of their FMs and SMs using cone beam computed tomography. The prevalence, distribution pattern, external root morphology, and the internal root canal anatomy of the examined molars were recorded and analyzed. Furthermore, the association between the root canal configurations of SMs and the appearance of DLR in FMs was also assessed. RESULTS: The prevalence of SMs with C-shaped root canals was 44.7%. The most common root canal configuration type of the one-rooted SMs with C-shaped anatomy was C3 (45.6%), followed by C2 and C1. The frequency of C-shaped canals in SMs was 45.4% in Non-DLR group, 52.8% in unilateral DLR group, and 33.9% in bilateral DLR group, respectively. Moreover, the prevalence of C-shaped root canals in SMs with the presence of bilateral DLRs in FMs was significantly lowered. CONCLUSION: The association between the presence of DLR in FMs and C-shaped canal configurations in neighboring SMs was surveyed, and the prevalence of C-shaped root canals in SMs with the presence of bilateral DLRs in FMs was found to be significantly lowered.

Citation Characteristics of H-Classics Articles in Implant Dentistry: A Citation Analysis Using H-Classics Method.

PURPOSE: Citation-based metrics, such as the H-classics method, have been used as an indicator to assess academic performance in the scientific community. However, information addressing issues regarding self-citation, citation half-life, and subject area of origin in implant dentistry is lacking. The purpose of this study was to investigate the citation characteristics of H-classics articles in implant dentistry throughout different time periods. MATERIALS AND METHODS: H-classics implant dentistry articles were searched and selected by applying the H-classics method from the Scopus database. Bibliometric analysis was conducted to evaluate the citation characteristics, including institutional and journal self-citation, citation half-life, and subject area of origin of identified H-classics articles. RESULTS: The International Journal of Oral & Maxillofacial Implants and Clinical Oral Implants Research are the leading journals contributing the majority of citations to the retrieved H-classics articles. Articles published in the United States cited the most H-classics articles. Journal self-citation was 12.41% on average, while institutional self-citation was approximately 7.81%. Citation half-life decreased significantly across time periods, with an average decreasing ratio of 43.95%. Research on Scope III, bioengineering interventions, had the most prominent distribution citation frequency in the subject area "Others." CONCLUSION: This study provides insightful views regarding citation characteristics of H-classics articles in implant dentistry (eg, interdisciplinary publications on bioengineering interventions) during the investigation periods, which may foster the translation of preclinical research into clinical applications in the future.

Increasing prominence of implantology research: a chronological trend analysis of 100 top-cited articles in periodontal journals.

PURPOSE: To identify 100 top-cited articles published in periodontal journals and analyse the research trends by using citation analysis. MATERIALS AND METHODS: 100 top-cited articles published in periodontal journals were retrieved by searching the database of the ISI Web of Science and Journal Citation reports. For each article, the following principal bibliometric parameters: authorship, geographic and institute origin, manuscript type, study design, scope of study, and citation count of each time period were analysed from 1965 to 2015. RESULTS: The identified 100 top-cited articles were retrieved from five periodontal journals and citation counts were recorded between 262 and 1,693 times. For the institute of origin, the most productive institute, in terms of the number of 100 top-cited articles published, was the University of Gothenburg (Sweden) (n = 19), followed by the Forsyth Dental Center (USA) (n = 15). Most manuscripts were original research (n = 74), and the inflammatory periodontal disease (n = 59) was the most frequent topic studied. Interestingly, the trend of increase average citation reached significance for implantology (ß = 26.75, P = 0.003) and systemic interactions (ß = 29.83, P = 0.005), but not for inflammatory disease (ß = -10.30, P = 0.248) and tissue regeneration (ß = 9.04, P = 0.081). By using multivariable linear regression in a generalised linear model, suitable published journal (Journal of Clinical Periodontology), geographic regions (Europe), more intense international collaboration, adequate manuscript type (review article) and study design (systematic review) could be attributed to escalating average citation counts in implantology (all P < 0.05). However, for systemic interactions, only geographic region and study design were significantly associated with the increasing citation trend. CONCLUSIONS: These principal bibliometric characteristics revealed escalated trends in average citation count in implantology throughout time.

The Presence of Distolingual Root in Mandibular First Molars Is Correlated with Complicated Root Canal Morphology of Mandibular Central Incisors: A Cone-beam Computed Tomographic Study in a Taiwanese Population.

INTRODUCTION: The aim of this study was to assess the prevalence of complicated root canals in permanent mandibular central incisors (PMCIs) and its correlation with the presence of a distolingual root (DLR) in permanent mandibular first molars (PMFMs) using cone-beam computed tomographic imaging in a Taiwanese population. METHODS: A total of 400 patients (800 pairs of PMCIs and PMFMs) were qualified for further analysis. The prevalence of DLRs in PMFMs along with root canal configurations of PMCIs were assessed at subject and tooth levels. Multivariable logistic regression analysis was used to evaluate the correlation between the root canal configurations of PMCIs with the existence of DLRs in PMFMs. RESULTS: The prevalence of PMFMs with DLRs and complicated root canal configurations in PMCIs was 23.0% and 15.6%, respectively. A significant difference in age (<50 years vs ≥50 years) was found for complicated root canal configurations in PMCIs. The most prevalent root canal system in PMCIs was Vertucci type I (84.4%) followed by type III (13.5%). A positive correlation between the presence of DLRs in PMFMs and complicated root canal configurations in PMCIs was noted. After adjusting for categoric variables including sex, age, and side, the odds ratios for the occurrence of complicated root canal configurations of PMCIs in the unilateral DLR group and the bilateral DLR group compared with the non-DLR group were 2.13 and 2.53, respectively. CONCLUSIONS: The concurrent appearance of DLRs in PMFMs and complicated root canal morphology in PMCIs is prominent in Taiwanese individuals.

Relationship of the Incidence of C-shaped Root Canal Configurations of Mandibular First Premolars with Distolingual Roots in Mandibular First Molars in a Taiwanese Population: A Cone-beam Computed Tomographic Study.

INTRODUCTION: The aim of this study was to determine the prevalence of C-shaped canal configurations (CSs) and radicular grooves (RGs) in permanent mandibular first premolars (MPs) and to investigate the relevance of such complexities with the presence of distolingual roots (DLRs) in permanent mandibular first molars (MMs). METHODS: A total of 800 pairs of MPs and MMs were investigated using a cone-beam computed tomographic system (NewTom 5G; QR srl, Verona, Italy). The frequency and symmetry of DLRs in MMs along with the occurrence of RGs and CSs in examined MPs were evaluated. Multivariable logistic regression analysis was applied to examine the correlation between the CSs of MPs with the appearance of DLRs in MMs. RESULTS: In the examined teeth, 23.0% of MMs had a DLR, whereas 16.6% of MPs had RGs and 12.5% of MPs had C-shaped canals. Although the most common canal configuration in MPs is the single canal (74.1%), the other 25.9% still possess complicated root canals. Of these MPs that have different canal configurations, 54.6% had 2 canals, whereas 44.4% had CSs. Specifically, the CS showed a high prevalence of C3 morphologies at 98.9% followed by C1 at 1.1%. A corresponding and increasing frequency was noted in CSs and RGs of MPs and MMs with DLRs (P < .001). After adjusting for related categoric variables, the adjusted odds ratios for CSs of MPs in the bilateral DLR group compared with the non-DLR group was 3.294 (P < .001). CONCLUSIONS: This study showed an increased appearance of CSs in MPs when DLRs were present in MMs in the Taiwanese population.

Complicated Root Canal Morphology of Mandibular Lateral Incisors Is Associated with the Presence of Distolingual Root in Mandibular First Molars: A Cone-beam Computed Tomographic Study in a Taiwanese Population.

INTRODUCTION: The aim of this study was to assess the root canal configurations in permanent mandibular lateral incisors (PMLIs) and the correlation between the root canal configurations of PMLIs with the appearance of a distolingual root (DLR) in permanent mandibular first molars (PMFMs) using cone-beam computed tomographic (CBCT) imaging. METHODS: A total of 1200 CBCT images (300 patients) of PMFMs and PMLIs were investigated. The frequency and distribution of DLRs in PMFMs along with root canal configurations of PMLIs were assessed ipsilaterally and contralaterally. Multivariable logistic regression analysis was used to evaluate the correlation between the root canal configurations of PMLIs with the appearance of a DLR in PMFMs. RESULTS: The prevalence of PMFMs with a DLR was 24.3%, and the incidence of complicated root canal configurations in PMLIs was 25.0%. The most prevalent root canal systems of PMLIs were Vertucci types I (75%) and III (23.0%). The incidence of complicated root canal configurations in PMLIs was 19.5% in the non-DLR group (ie, no DLR was found on either side of the PMFMs), 33.3% in the unilateral DLR (Uni-DLR) group (ie, a DLR was found in 1 of the PMFMs [the left or right side] and a DLR was not found on the other PMFM), and 39.8% in the bilateral DLR (Bil-DLR) group (ie, a DLR was found in both the right and left PMFMs). After adjusting for categoric variables including sex, age, and side, the odds ratios for the frequency of complicated root canal configurations of PMLIs in the Uni-DLR and Bil-DLR groups compared with the non-DLR group were 2.12 (P = .003) and 2.707 (P < .001), respectively. CONCLUSIONS: The simultaneous appearance of DLRs in PMFMs and complicated root canal configurations in PMLIs is prominent in Taiwanese individuals. Clinicians should be aware of the correlation between the anatomic variants of PMFMs and PMLIs, which are important before endodontic treatment.