Ren-Yeong Huang

Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function

Dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity. Thus, DCs have been regarded as a major target of immunosuppressants for the control of harmful immune responses. In this study, we examined the effect of quercetin, a natural flavonoid found in many vegetables and fruits, on the activation and function of mouse DCs. Quercetin effectively inhibited LPS-induced DC activation by reducing the production of proinflammatory cytokines/chemokines and the expression levels of MHC class II and costimulatory molecules. In addition, quercetin uniquely blocked endocytosis by DCs and the LPS-induced DC migration was diminished by quercetin treatment. Furthermore, quercetin abrogated the ability of LPS-stimulated DCs to induce Ag-specific T cell activation, both in vitro and in vivo. Remarkably, coadministration of quercetin with 2,4-dinitro-1-fluorobenzene prevented 2,4-dinitro-1-fluorobenzene–induced contact hypersensitivity, indicating the potential of quercetin for treating delayed-type hypersensitive diseases. Blockage of LPS-induced ERK, JNK, Akt, and NF-κB activation contributed to the inhibitory effect of quercetin on DCs. These results strongly suggest that quercetin may be a potent immunosuppressive agent and could be used in the prevention and therapy of chronic inflammation, autoimmunity, and transplantation via the abolishment of DC activation and function.

Three‐dimensional analysis of the root morphology of mandibular first molars with distolingual roots

AIM To determine the prevalence of distolingual roots in mandibular first molar teeth in Taiwanese Han Chinese, and its impact on root morphology. METHODOLOGY The presence of distolingual roots in 375 subjects (521 molars) were assessed from 624 patients attending the dental clinics of medical centres around Taiwan island from August 2004 to April 2007 using computed tomography. The following observations were made: (i) numbers of roots and canals, (ii) mesial and distal root types and (iii) levels of furca in the molars presence or absence of distolingual root. RESULTS The mean age of the subject was 45; 43% were women. Among all the examined molars, 56%, 27% and 18% were two-, three- and four-rooted, respectively. Two per cent, 72% and 26% of molars had two, three and four canals, respectively. All of the four-rooted molars had four canals, but all of the molars with four canals varied in the number of roots. All molars with distolingual roots had two mesial canals. Bilateral consistency in terms of distolingual root, root canal number, root number and root type was observed in subjects with bilateral molars. In molars with distolingual roots, a higher prevalence of two mesial roots and a shorter mesial root trunk were observed than in teeth without distolingual roots. CONCLUSIONS A distolingual root was found in 22% of molars and in 24% of the subjects examined. Most subjects with a distolingual root had them bilaterally. The presence of a distolingual root was associated with variation in the root morphology, including the furcation level, the root type and the number of roots and canals.

Ameliorative effect of quercetin on the destruction caused by experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE The purpose of this study was to evaluate the effect of quercetin, a flavonol that exhibits anti-inflammatory properties, on experimental periodontal destruction in rats. MATERIAL AND METHODS Osteoclast formation on maxillary palatal alveolus was induced with daily lipopolysaccharide (LPS) injections (0, 1 or 5 mg/mL) for 3 d. Five days later, the osteoclasts on bony surfaces were counted after histochemical staining for tartrate-resistant acid phosphatase. The effect of intragastric quercetin on the osteoclast formation was evaluated in the following three groups: quercetin (75 mg/kg/d by oral feeding); LPS (5 mg/mL); and quercetin plus LPS. Moreover, the effect of quercetin on the ligature-induced periodontitis around maxillary second and mandibular first molars was further evaluated by microcomputerized tomography (on days 0, 4, 8 and 12) and by histometry (on day 8). RESULTS A dose-dependent increase in osteoclasts occurred after LPS injections. However, quercetin (75 mg/kg) reduced the 5 mg/mL LPS-induced osteoclasts. Using microcomputerized tomography, the bone crest levels at ligation sites were found to be significantly more apical than at the control sites on days 8 and 12; however, the apically located bone crests rebounded in rats from the quercetin-plus-ligation group. Histometry demonstrated significantly more coronal alveolar crest bone levels, less inflammatory cell-infiltrated connective tissue areas and less connective tissue attachments in the ligation-plus-quercetin group compared with those in the ligation group. CONCLUSION As the quercetin could reduce the LPS-induced osteoclast formation and the ligature-enhanced periodontal inflammation and bone loss, we suggest that it may have an ameliorative effect on periodontal destruction.

Magnolol Ameliorates Ligature-Induced Periodontitis in Rats and Osteoclastogenesis: In Vivo and In Vitro Study

Periodontal disease characterized by alveolar bone resorption and bacterial pathogen-evoked inflammatory response has been believed to have an important impact on human oral health. The aim of this study was to evaluate whether magnolol, a main constituent of Magnolia officinalis, could inhibit the pathological features in ligature-induced periodontitis in rats and osteoclastogenesis. The sterile, 3–0 (diameter; 0.2 mm) black braided silk thread, was placed around the cervix of the upper second molars bilaterally and knotted medially to induce periodontitis. The morphological changes around the ligated molars and alveolar bone were examined by micro-CT. The distances between the amelocemental junction and the alveolar crest of the upper second molars bilaterally were measured to evaluate the alveolar bone loss. Administration of magnolol (100 mg/kg, p.o.) significantly inhibited alveolar bone resorption, the number of osteoclasts on bony surface, and protein expression of receptor activator of nuclear factor-κB ligand (RANKL), a key mediator promoting osteoclast differentiation, in ligated rats. Moreover, the ligature-induced neutrophil infiltration, expression of inducible nitric oxide synthase, cyclooxygenase-2, matrix metalloproteinase (MMP)-1 and MMP-9, superoxide formation, and nuclear factor-κB activation in inflamed gingival tissues were all attenuated by magnolol. In the in vitro study, magnolol also inhibited the growth of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans that are key pathogens initiating periodontal disease. Furthermore, magnolol dose dependently reduced RANKL-induced osteoclast differentiation from RAW264.7 macrophages, tartrate-resistant acid phosphatase (TRAP) activity of differentiated cells accompanied by a significant attenuation of resorption pit area caused by osteoclasts. Collectively, we demonstrated for the first time that magnolol significantly ameliorates the alveolar bone loss in ligature-induced experimental periodontitis by suppressing periodontopathic microorganism accumulation, NF-κB-mediated inflammatory mediator synthesis, RANKL formation, and osteoclastogenesis. These activities support that magnolol is a potential agent to treat periodontal disease.

Risk assessment of inferior alveolar nerve injury for immediate implant placement in the posterior mandible: A virtual implant placement study

OBJECTIVES To investigate the prevalence and morphological parameters of lingual concavity, and whether these factors are related to a higher risk of inferior alveolar nerve (IAN) injury when performing an immediate implant surgery in posterior mandible region. METHODS The CBCT images from 237 subjects (1008 teeth) were analysed the shape of the mandibles (C, P, U type), dimensional parameters of lingual concavity (angle, height, depth), and its relation to inferior alveolar canal (IAC) (A, B, C zone), RAC (distance from root apex to IAC) and probability of IAN injury. Multiple logistic regression modelling to determine the odds ratio of variables that made an important contribution to the probability of IAN injury and to adjust for confounding variables. RESULTS The U type ridge (46.7%) and the most concave point located at C zone (48.8%) are most prevalent in this region. The mandibular second molar presents highest risk for IAN injury than other tooth type (p<0.001), which were 3.82 times to occur IAN injury than the mandibular second premolar. The concave point located at A zone and B zone were 7.82 and 3.52 times than C zone to have IAN damage, respectively. The probability of IAN injury will reduce 26% for every 1mm increase in RAC (p<0.001). CONCLUSIONS The tooth type, morphological features of lingual concavities, and RAC are associated with risks of IAN injury during immediate implant placement. CLINICAL SIGNIFICANCE Pre-surgical mapping of the IAC and identification of its proximity relative to the lingual concavity in the posterior mandible regions may avoid unpleasant complications, specifically when performing immediate implant procedures.

Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma

BACKGROUND This study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). METHODS Condition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects on macrophage (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-κB were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues. RESULTS THP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-κB diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues. CONCLUSION Axl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-κB pathway.

Are Chronic periodontitis and gingivitis associated with dementia? A nationwide, retrospective, matched-cohort study in Taiwan

Background: Chronic periodontitis and gingivitis are associated with various diseases; however, their impact on dementia is yet to be elucidated. This study is aimed at investigating the association between chronic periodontitis and gingivitis, and the risk of developing dementia. Methods: A total of 2,207 patients, with newly diagnosed chronic periodontitis and gingivitis between January 1, 2000 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 6,621 controls matched for sex and age. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing dementia during the 10-year follow-up period. Results: Of the study subjects, 25 (1.13%) developed dementia compared to 61 (0.92%) in the control group. Cox proportional hazards regression analysis revealed that the study subjects were more likely to develop dementia (hazard ratio (HR) 2.085, 95% CI 1.552-4.156, p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for dementia was 2.54 (95% CI 1.297-3.352, p = 0.002). Conclusions: Patients with chronic periodontitis and gingivitis have a higher risk of developing dementia. However, further studies on other large or national data sets are required to support the current findings.

Diacerein: A potential therapeutic drug for periodontal disease

Periodontal diseases are chronic inflammatory diseases characterized by the destruction of the tooth-supporting structures. They are the most prevalent form of bone pathology in humans and act as a modifying factor of the systemic health of patients. Accumulating evidence has provided insight into mechanisms of periodontal inflammation revealing that oral pathogens induce inflammatory cascades, including a variety of cytokines produced by different cell types, which promotes host-mediated tissue destruction. Cytokine networks established in diseased periodontal tissues are extremely complex, and substances regulating immuno-inflammatory reactions and signaling pathways, in addition to traditional periodontal treatment, could potentially be targeted as an approach for prevention and treatment of periodontal diseases. Diacerein, a purified anthraquinone derivative, was derived originally from plants with profound anti-inflammatory and analgesic activities. Its wide range of biological activities have been applied and discussed for several decades; however, studies of diacerein have mainly concentrated on effects on joint-derived tissues/cells, which suggest a beneficial role in osteoarthritis treatment. Diacerein reduces association of the IL-1 receptor to form heterodimer complexes, repressing IL-1 and its related downstream events and impairing active IL-1 release due to the inhibition of the IL-1-converting enzyme (ICE). To date, there are no reports describing the therapeutic effect of diacerein for treatment of periodontitis. Given the involvement of inflammation and occurrence of tissue destruction in periodontal disease, we propose that diacerein might be a promising biological drug for periodontal disease due to its therapeutic advantages. In addition, we hypothesize that the underlying mechanisms might involve the capacity of diacerein to selectively inhibit signal transduction to affect the cytokine profiles and, consequently, produce the outcome of ameliorating disease breakdown.

Factors Affecting Treatment Decisions and Outcomes of Root-Resected Molars: A Nationwide Study

BACKGROUND Treatment of furcation-involved molars presents a clinical challenge. This study retrospectively investigates the demographic parameters affecting treatment decisions and outcomes of root-resected molars using a nationwide population-based dataset. METHODS De-identified data from 471 eligible patients were obtained from a representative cohort composed of 1 million of Taiwans population. Demographic factors that influence treatment decisions and outcomes of root-resected teeth were examined. Cox regression was performed to statistically analyze the factors. RESULTS The overall survival rate for root-resected molars was 91.1%. The survival times of the extracted and surviving teeth were 303.0 ± 274.6 and 551.8 ± 327.2 days, respectively (P <0.001). The analyzed patient-related factors, such as living district, urbanization level, medical institution, and monthly income, have remarkable influence on treatment decisions; however, there is no statistically significant difference in survival rate between root-resected molars receiving flap surgery and those that do not (P = 0.504). After adjusting for other factors, patients aged >74 years have 3.33 times (hazard ratio = 3.33; 95% CI = 1.04 to 10.66; P = 0.043) higher rates of molar extraction than younger counterparts. CONCLUSIONS The overall survival rate of root-resected molars was satisfactory. Patients with advanced age (>74 years) had a higher risk of extraction occurrence on resected molars. Patient-related factors may influence the treatment decision of whether molars receive flap surgery. These findings suggest that demographic factors should be carefully evaluated before and after performing root-resection procedures because these factors may eventually impact the outcome of root-resected molars.

Concomitant Horner and Harlequin Syndromes after Inferior Alveolar Nerve Block Anesthesia

INTRODUCTION Intraoral anesthesia is probably the most commonly used procedure in dentistry. METHODS Although inferior alveolar nerve block (IANB) anesthesia is one of the safest procedures to anesthetize the mandibular teeth, side effects of IANB anesthesia can still give rise to potential risks for patients. Fortunately, most observed alterations are transient and self-limited. RESULTS The complications of IANB anesthesia are varied in nature and could be specifically categorized into systemic, localized, and distant complications. When the complications occur around the orofacial structures including the temporomandibular joint, middle ear, facial skin, and the eye, which are away from the oral cavity, it can be defined as distant complications. However, to our best knowledge, the concomitant occurrence of neurologic phenomena such as Horner syndrome combined with cutaneous complications in a patient receiving IANB anesthesia has never been discussed. CONCLUSIONS In this exceptional case, the unusual Horner syndrome manifestations related to unilateral ptosis, miosis, and anisocoria were simultaneously developed with skin ischemia, paresthesia, and asymmetric flushing after the administration of IANB anesthesia.