Demethoxymurrapanine, an indole-naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells.

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 µg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.

Third-generation sequencing-selected Scardovia wiggsiae promotes periodontitis progression in mice.

BACKGROUNDS: Periodontitis is an oral-bacteria-directed disease that occurs worldwide. Currently, periodontal pathogens are mostly determined using traditional culture techniques, next-generation sequencing, and microbiological screening system. In addition to the well-known and cultivatable periodontal bacteria, we aimed to discover a novel periodontal pathogen by using DNA sequencing and investigate its role in the progression of periodontitis. OBJECTIVE: This study identified pathogens from subgingival dental plaque in patients with periodontitis by using the Oxford Nanopore Technology (ONT) third-generation sequencing system and validated the impact of selected pathogen in periodontitis progression by ligature-implanted mice. METHODS: Twenty-five patients with periodontitis and 25 healthy controls were recruited in this study. Subgingival plaque samples were collected for metagenomic analysis. The ONT third-generation sequencing system was used to confirm the dominant bacteria. A mouse model with ligature implantation and bacterial injection verified the pathogenesis of periodontitis. Neutrophil infiltration and osteoclast activity were evaluated using immunohistochemistry and tartrate-resistant acid phosphatase assays in periodontal tissue. Gingival inflammation was evaluated using pro-inflammatory cytokines in gingival crevicular fluids. Alveolar bone destruction in the mice was evaluated using micro-computed tomography and hematoxylin and eosin staining. RESULTS: Scardovia wiggsiae (S. wiggsiae) was dominant in the subgingival plaque of the patients with periodontitis. S. wiggsiae significantly deteriorated ligature-induced neutrophil infiltration, osteoclast activation, alveolar bone destruction, and the secretion of interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α in the mouse model. CONCLUSION: Our metagenome results suggested that S. wiggsiae is a dominant flora in patients with periodontitis. In mice, the induction of neutrophil infiltration, proinflammatory cytokine secretion, osteoclast activation, and alveolar bone destruction further verified the pathogenic role of S. wiggsiae in the progress of periodontitis. Future studies investigating the metabolic interactions between S. wiggsiae and other periodontopathic bacteria are warranted.

Stimulation phosphatidylinositol 3-kinase/protein kinase B signaling by Porphyromonas gingivalis lipopolysacch aride mediates interleukin-6 and interleukin-8 mRNA/protein expression in pulpal inflammation.

BACKGROUND/PURPOSE: The signaling mechanisms for Porphyromonas gingivalis lipopolysaccharide (PgLPS)-induced inflammation in human dental pulp cells are not fully clarified. This in vitro study aimed to evaluate the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in PgLPS-induced pulpal inflammation. METHODS: Human dental pulp cells (HDPCs) were challenged with PgLPS with or without pretreatment and coincubation with a PI3K/Akt inhibitor (LY294002). The gene or protein levels of PI3K, Akt, interleukin (IL)-6, IL-8, alkaline phosphatase (ALP), osteocalcin and osteonectin were analyzed by reverse transcription polymerase chain reaction (PCR), real-time PCR, western blotting, and immunofluorescent staining. In addition, an enzyme-linked immunosorbent assay was used to analyze IL-6 and IL-8 levels in culture medium. RESULTS: In response to 5 µg/ml PgLPS, IL-6, IL-8, and PI3K, but not Akt mRNA expression of HDPCs, was upregulated. IL-6, IL-8, PI3K, and p-Akt protein levels were stimulated by 10-50 µg/ml of PgLPS in HDPCs. PgLPS also induced IL-6 and IL-8 secretion at concentrations higher than 5 µg/ml. Pretreatment and co-incubation by LY294002 attenuated PgLPS-induced IL-6 and IL-8 mRNA expression in HDPCs. The mRNA expression of ALP, but not osteocalcin and osteonectin, was inhibited by higher concentrations of PgLPS in HDPCs. CONCLUSION: P. gingivalis contributes to pulpal inflammation in HDPCs by dysregulating PI3K/Akt signaling pathway to stimulate IL-6 and IL-8 mRNA/protein expression and secretion. These results are useful for understanding the pulpal inflammation and possible biomarkers of inflamed pulp diagnosis and treatment.

Oxidative-Stress-Mediated ER Stress Is Involved in Regulating Manoalide-Induced Antiproliferation in Oral Cancer Cells.

Manoalide provides preferential antiproliferation of oral cancer but is non-cytotoxic to normal cells by modulating reactive oxygen species (ROS) and apoptosis. Although ROS interplays with endoplasmic reticulum (ER) stress and apoptosis, the influence of ER stress on manoalide-triggered apoptosis has not been reported. The role of ER stress in manoalide-induced preferential antiproliferation and apoptosis was assessed in this study. Manoalide induces a higher ER expansion and aggresome accumulation of oral cancer than normal cells. Generally, manoalide differentially influences higher mRNA and protein expressions of ER-stress-associated genes (PERK, IRE1α, ATF6, and BIP) in oral cancer cells than in normal cells. Subsequently, the contribution of ER stress on manoalide-treated oral cancer cells was further examined. ER stress inducer, thapsigargin, enhances the manoalide-induced antiproliferation, caspase 3/7 activation, and autophagy of oral cancer cells rather than normal cells. Moreover, N-acetylcysteine, an ROS inhibitor, reverses the responses of ER stress, aggresome formation, and the antiproliferation of oral cancer cells. Consequently, the preferential ER stress of manoalide-treated oral cancer cells is crucial for its antiproliferative effect.

Does a high-sugar diet alter the bacterial diversity of the oral cavity?

DATA SOURCES: The electronic databases PubMed, Scopus, and Science Direct from 2010 onwards were searched to identify the eligible studies to determine the effect of sugar intake on oral microbiota diversity. STUDY SELECTION: Clinical trials, cohort studies, and case-control studies in English and Spanish language were selected by four reviewers independently. DATA EXTRACTION AND SYNTHESIS: Data extraction (which comprised authors and year of publication, type of study, patients, origin, selection criteria, method of determining sugar consumption, amplified region, relevant results, and bacteria identified in patients with high sugar intake) was performed by three reviewers. Quality assessment of included studies was done by two reviewers using the Newcastle-Ottawa scale. RESULTS: 374 papers were identified through three databases searched, out of which eight studies were finally selected. These included two interventional studies, two case-control studies, and four cohort studies. All except one study reported that the richness and diversity of oral microbes in the saliva, dental biofilm, and oral swab sample were significantly lower in participants with higher sugar consumption. There was a decrease in the population of certain bacteria but an enhancement of specific bacterial genera, such as Streptococcus, Scardovia, Veillonella, Rothia, Actinomyces, and Lactobacillus. Additionally, communities associated with high sugar intake showed enrichment of sucrose and starch metabolism pathways. All eight included studies had a low risk of bias. CONCLUSIONS: Within the limitations of the included studies, the authors concluded that consuming a sugar-rich diet leads to dysbiosis of the oral ecosystem, thereby increasing carbohydrate metabolism and the overall metabolic activity of oral microorganisms.

Does periodontal treatment improve glycaemic control in periodontitis patients with diabetes mellitus?

DATA SOURCES: The electronic databases Cochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, CINAHL EBSCO, LILACS BIREME Virtual Health Library from inception to September 2021, along with trial registers and journals (hand searching) were searched to identify the randomized controlled trials (RCTs). STUDY SELECTION: Two reviewers independently identified and selected RCTs of at least three months' duration, comparing the effectiveness of subgingival instrumentation relative to no active intervention or usual care (oral hygiene instruction, education, or supportive interventions, and/or supragingival scaling) in the reduction of glycated haemoglobin (HbA1c) in periodontitis patients with type 1 or 2 diabetes mellitus. DATA EXTRACTION AND SYNTHESIS: Data extraction and risk of bias assessment were performed by two reviewers independently. Data were synthesized quantitatively with meta-analyses using a random-effects model, and pooled outcomes were expressed as mean differences with 95% confidence intervals. In addition, subgroup analysis, heterogeneity assessment, sensitivity analyses, summary of findings, and assessment of the certainty of the evidence were performed. RESULTS: Out of 3109 identified records, 35 RCTs were included for qualitative synthesis, and amongst them, 33 studies were included for meta-analysis. Meta-analyses showed that periodontal treatment with subgingival instrumentation, compared to usual care or no treatment, led to a mean absolute reduction of 0.43% in HbA1c at 3 to 4 months, 0.30% at six months, and 0.50% at 12 months. The certainty of the evidence was assessed to be moderate. CONCLUSIONS: The authors concluded that periodontitis treatment by subgingival instrumentation improves glycaemic control in diabetic patients. However, there is insufficient evidence about the effect of periodontal treatment on quality of life or diabetic complications.

Effect of butyrate, a bacterial by-product, on the viability and ICAM-1 expression/production of human vascular endothelial cells: Role in infectious pulpal/periapical diseases.

AIM: To investigate the effects of butyric acid (BA), a metabolic product generated by pulp and root canal pathogens, on the viability and intercellular adhesion molecule-1 (ICAM-1) production of endothelial cells, which are crucial to angiogenesis and pulpal/periapical wound healing. METHODOLOGY: Endothelial cells were exposed to butyrate with/without inhibitors. Cell viability, apoptosis and reactive oxygen species (ROS) were evaluated using an MTT assay, PI/annexin V and DCF fluorescence flow cytometry respectively. RNA and protein expression was determined using a polymerase chain reaction assay and Western blotting or immunofluorescent staining. Soluble ICAM-1 (sICAM-1) was measured using an enzyme-linked immunosorbent assay. The quantitative results were expressed as mean ± standard error (SE) of the mean. The data were analysed using a paired Student's t-test where necessary. A p-value ≤0.05 was considered to indicate a statistically significant difference between groups. RESULTS: Butyrate (>4 mM) inhibited cell viability and induced cellular apoptosis and necrosis. It inhibited cyclin B1 but stimulated p21 and p27 expression. Butyrate stimulated ROS production and hemeoxygenase-1 (HO-1) expression as well as activated the Ac-H3, p-ATM, p-ATR, p-Chk1, p-Chk2, p-p38 and p-Akt expression of endothelial cells. Butyrate stimulated ICAM-1 mRNA/protein expression and significant sICAM-1 production (p < .05). Superoxide dismutase, 5z-7oxozeaenol, SB203580 and compound C (p <  .05), but not ZnPP, CGK733, AZD7762 or LY294002, attenuated butyrate cytotoxicity to endothelial cells. Notably, little effect on butyrate-stimulated sICAM-1 secretion was found. Valproic acid, phenylbutyrate and trichostatin (three histone deacetylase inhibitors) significantly induced sICAM-1 production (p < .05). CONCLUSION: Butyric acid inhibited proliferation, induced apoptosis, stimulated ROS and HO-1 production and increased ICAM-1 mRNA expression and protein synthesis in endothelial cells. Cell viability affected by BA was diminished by some inhibitors; however, the increased sICAM-1 secretion by BA was not affected by any of the tested inhibitors. These results facilitate understanding of the pathogenesis, prevention and treatment of pulpal/periapical diseases.

Horizontal root fracture in posterior teeth without dental trauma: A diseased condition with special characteristics.

Horizontal root fractures (HRF) were observed mostly in the anterior teeth of young adults due to dental injury. However, HRFs in posterior teeth (PHRF) without dental trauma cannot be neglected. The etiology and risk factors of PHRF were unclear. Lower premolars and palatal root of maxillary molars were particularly affected, indicating the specificity of this diseased entity. PHRF were mainly reported in Asian population, suggesting possible racial difference. Whereas most PHRF teeth showed symptoms mimicking endodontic and periodontal lesions, some affected teeth were asymptomatic. Periodontal pocket, soft tissue swelling, chronic pain or discomfort during mastication were commonly noted. Diagnosis of PHRF depended on thorough clinical examination, radiographic images or exploratory surgery. Intracanal bleeding and electronic apex locator confirmation during endodontic treatment were also useful for diagnosis. Flexible splinting, endodontic/periodontal treatment or root amputation were treatment strategies to preserve the fractured teeth. The aim of this narrative review is to summarize the demography, tooth and root distribution, diagnostic methods, etiology and possible related factors, clinical features, radiographic characteristics, and the treatment schemes of PHRF without dental trauma. A better understanding and identification of this particular root fracture could be achieved. The diagnostic tools and practical management are useful for clinical guides.

Biological properties of human periodontal ligament cell spheroids cultivated on chitosan and polyvinyl alcohol membranes.

BACKGROUND/PURPOSE: Multicellular spheroid cultures have attracted increasing attention in the field of periodontal regeneration. However, very few studies have reported the periodontal ligament (PDL) cell spheroid formation via biomaterials-induced processes. This study investigated the biological characteristics of human PDL cell spheroids formed on two hydrophilic polymer-based biomaterials, namely chitosan and polyvinyl alcohol. METHODS: The expressions of periostin, paxillin, hypoxia-inducible factor 1-α (HIF-1α), and vascular endothelial growth factor (VEGF) were analyzed. Cell migration ability was assessed using a scratch assay. Furthermore, PDL cell spheroids were cultured in 3D-printed polylactic acid scaffolds to evaluate mineralizing capability. RESULTS: Western blot analysis revealed increased expressions of periostin, HIF-1α, and VEGF in the 3D spheroids. After the spheroids were reseeded, the cells gradually migrated outward from the spheroids and time-dependent distribution of paxillin was observed. The cells migrating outward from the 3D spheroids demonstrated greater migration ability than that of 2D monolayer cells. Compared to the dissociated cells from a monolayer culture, the cell spheroids formed on the chitosan membrane exhibited elevated alkaline phosphatase activity and an increase in mineralized matrix deposition. CONCLUSION: The biomaterial-induced formation of PDL cell spheroids suggests a novel strategy for cell delivery in research and clinical applications of periodontal regeneration.

Cracked teeth: Distribution and survival at 6 months, 1 year and 2 years after treatment.

BACKGROUND/PURPOSE: The unpredictable condition of cracked teeth warrants further investigation and clinical experiences. The purpose of this study was to collect and record data on demographics, clinical characteristics, different treatment modalities and survival of cracked teeth at 6-month, 1-year and 2-year recalls. METHODS: 77 cracked teeth from 65 patients were included. Data on demographics, clinical parameters, treatment modalities and recall were collected. Binomial, multinomial and chi square tests were used for statistical analysis. RESULTS: Most cracked teeth occurred in patients greater than 40 years old (p < 0.01). Cracked teeth themselves were most often molars (79.22%; p < 0.01), a non-terminal tooth in the arch (62.34%; p < 0.05) and nonendodontically-treated teeth (94.81%; p < 0.01). Cracked teeth exhibited pain to percussion (63.64%, p < 0.05) or biting (74.03%; p < 0.01), and no or only positive mobility (76.62%; p < 0.01). Cracks were most often oriented in the mesiodistal direction (68.83%; p < 0.01). Higher survival rates were noted in cracked teeth lacking pre-operative pain to palpation or spontaneous pain, and with no or only positive mobility at 6-month and 1-year recalls. In vital cracked teeth, higher survival rates were noted in teeth lacking pre-operative pain to palpation and with no or only positive mobility at 2-year recalls. CONCLUSION: The absence of pre-operative palpation discomfort, spontaneous pain and minimal mobility, as well as the presence of pulp vitality were associated with higher survival rates of cracked teeth at all recall times. Results are useful for diagnosis and outcomes-based treatment planning of cracked teeth.

Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation.

The selective antiproliferation to oral cancer cells of Physalis peruviana-derived physapruin A (PHA) is rarely reported. Either drug-induced apoptosis and DNA damage or DNA repair suppression may effectively inhibit cancer cell proliferation. This study examined the selective antiproliferation ability of PHA and explored detailed mechanisms of apoptosis, DNA damage, and repair. During an ATP assay, PHA provided high cytotoxicity to two oral cancer cell lines (CAL 27 and Ca9-22) but no cytotoxicity to two non-malignant oral cells (HGF-1 and SG). This selective antiproliferation of PHA was associated with the selective generation of reactive oxygen species (ROS) in oral cancer cells rather than in non-malignant oral cells, as detected by flow cytometry. Moreover, PHA induced other oxidative stresses in oral cancer cells, such as mitochondrial superoxide generation and mitochondrial membrane potential depletion. PHA also demonstrated selective apoptosis in oral cancer cells rather than non-malignant cells in annexin V/7-aminoactinmycin D and caspase 3/7 activity assays. In flow cytometry and immunofluorescence assays, PHA induced γH2AX expressions and increased the γH2AX foci number of DNA damages in oral cancer cells. In contrast, the mRNA expressions for DNA repair signaling, including homologous recombination (HR) and non-homologous end joining (NHEJ)-associated genes, were inhibited by PHA in oral cancer cells. Moreover, the PHA-induced changes were alleviated by the oxidative stress inhibitor N-acetylcysteine. Therefore, PHA generates selective antiproliferation, oxidative stress, and apoptosis associated with DNA damage induction and DNA repair suppression in oral cancer cells.

Are partially edentulous patients with a history of severe periodontitis more prone to develop peri-implantitis over the long term?

Aim This study aimed to compare the long-term outcome of implant therapy in partially edentulous patients with severe periodontitis compared to those with no history of periodontitis.Design Retrospective cohort study.Cohort selection Eighty-eight patients (34 men and 54 women; age ranging from 28 to 45 years) with severe periodontitis (47 patients with 108 implants) and no history of periodontitis (41 patients with 78 implants) were included in this institutional study. All these cohorts had received implants 6-8 years previously.Data analysis Probing pocket depth, radiographic marginal bone level and peri-implantitis were the primary outcomes, while bleeding on probing was the secondary outcome. The effect of variables was measured by odds ratio with 95% confidence interval. Both patient-level and implant-level analyses were used to evaluate the association between peri-implantitis and potential risk factors. In addition, the association between probing pocket depth and radiographic marginal bone level with potential risk factors was assessed at implant-level analyses. In contrast, for patient-level data, a positive relationship was assessed with the Chi-square test.Results Patients with a history of severe periodontitis (OR = 11.13; p = 0.045), implants with a lack (<2 mm) of peri-implant keratinised mucosa (OR = 14.94; p <0.001) and implants placed in bone-grafted sites (OR = 4.93; p = 0.047) were associated with greater risk of peri-implantitis, at 6-8 years post-implant placement. The risk of developing radiographic marginal bone level ≥3 mm was significantly greater (OR = 1.20; p <0.001) in patients with higher full-mouth bleeding scores. The chance of peri-implant bleeding on probing was independently and especially higher in patients who brushed their teeth at most once per day (OR = 3.20; p = 0.04), with higher full-mouth bleeding score values (OR = 1.16; p <0.001) and irregular recall visits (OR = 15.34; p = 0.001).Conclusion This retrospective cohort study concluded that partially edentulous patients with a history of severe periodontitis were more prone to develop peri-implantitis at 6-8 years post-implant placement.

Analysis of root canal system of maxillary first and second molars and their correlations by cone beam computed tomography.

BACKGROUND/PURPOSE: Understanding the root canal systems of molars and the association of root canal system in adjacent or contralateral molars is important for dental practice. This study aimed to use cone-beam computed tomography (CBCT) to analyze the morphology similarity of root canal systems in the maxillary first and second molars. METHODS: CBCT images of 1741 maxillary molars in a total of 519 patients were blindly examined to analyze the correlation of root canal systems between maxillary first and second molars as well as the bilateral first and second molars. RESULTS: The most common type in maxillary first molars is 3R4C (3 roots/4 canals), whereas in maxillary second molars is 3R3C.The symmetry in type of root canals in bilateral maxillary first and second molars were 87.36% and 79.85%, respectively. The similarities of root canal system in adjacent maxillary first and second molars were 53.07% (right side) and 52.58% (left side). The concurrence of MB2 canal in bilateral maxillary first molars is 77.8%, and 35.97% in maxillary second molars. In the 110 patients with MB2 canal in bilateral maxillary second molars, the chance of bilateral MB2 canals in their maxillary first molar is almost 100%. CONCLUSION: Maxillary first molars have higher prevalence of 3R4C than second molars. The symmetry in bilateral maxillary molars is higher than the similarity in adjacent maxillary first and second molars. Application of CBCT analysis of root canal system can improve endodontic treatment outcomes. The correlation of root canal system between teeth is useful for genetic linkage.

Effect of bFGF on the growth and matrix turnover of stem cells from human apical papilla: Role of MEK/ERK signaling.

BACKGROUND/PURPOSE: Basic fibroblast growth factor (bFGF) exhibits multiple biological functions in various tissues. Stem cells from apical papilla (SCAP) can be isolated from human apical papilla tissues in developmental teeth of children. The purposes of this study were to investigate the expression of FGF receptors (FGFRs) and the effects of bFGF on SCAP and related MEK/ERK signaling. METHODS: SCAP cells were treated under different concentrations of bFGF with or without U0126 (an inhibitor of MEK/ERK). Expression of FGFR1 and FGFR2 in SCAP was analyzed by RT-PCR. Cell proliferation was measured by MTT assay. The expressions of type I collagen, cdc 2, cyclin B1, TIMP-1 and p-ERK proteins were examined by Western blot. RESULTS: SCAP cells expressed FGFR1 and FGFR2. Exposure of SCAP to bFGF enhanced cell proliferation, and the expression cyclinB1, cdc 2, and TIMP-1, but not type I collagen. U0126 pretreatment and co-incubation attenuated the bFGF-induced proliferation, cdc2, cyclin B1 and TIMP-1 proteins' expression, but not type I collagen in SCAP. CONCLUSION: SCAP cells express FGFRs. bFGF may stimulate proliferation and affect the matrix turnover of SCAP cells, possibly via stimulation of FGFRs and MEK/ERK signaling pathway. These results are useful for clinical therapies for apexogenesis and regeneration of pulpo-dentin complex.

Genetic Susceptibility and Protein Expression of Extracellular Matrix Turnover-Related Genes in Oral Submucous Fibrosis.

Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-ß1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment.

Antiplatelet, antioxidative, and anti-inflammatory effects of hydroquinone.

Platelets play crucial roles in thrombosis and hemostasis through platelet activation and aggregation that are crucial in cardiovascular diseases. Hydroquinone (HQ) and its derivatives are present in many dermatological creams, paints, motor fuels, air, microorganisms, and plant products like wheat bread, fruit, coffee, and red wine. The effect of HQ on humans is not clear. In this study, we found that HQ (>25 µM) inhibited arachidonic acid (AA)-induced platelet aggregation. HQ suppressed AA-induced thromboxane B2 production of platelets. HQ (>10 µM) also attenuated ex vivo platelet-rich plasma aggregation. HQ prevented the interleukin (IL)-1ß-induced 8-isoprostane, and PGE2 production, but not IL-8 production of pulp cells. These results indicate that HQ may have an antiplatelet effect via inhibition of thromboxane production. HQ has antioxidative and anti-inflammatory effects, and possible inhibition of COX. Exposure and consumption of HQ-containing products, food or drugs may have antiplatelet, antioxidative, and anti-inflammatory effects.

Outcome assessment of apical surgery: A study of 234 teeth.

BACKGROUND/PURPOSE: Apical surgery is an option for management of endodontically-treated tooth with persistent periapical lesions or symptom and sign. The objective of this study was to investigate the correlation between the demography, preoperative, postoperative factors and healed rate of apical surgery. METHODS: Subjects were retrospectively collected from patients who received apical surgery/apicoectomy at the Endodontic Department, National Taiwan University Hospital from January 2013 to June 2015. The standard apical surgery procedures were performed. The demography, preoperative clinical and radiographic examination data as well as postoperative variables were collected. The outcome assessment was carried out after surgery. Statistical analysis was performed by chi square test to evaluate the potential outcome predictors. RESULTS: Total 187 patients and 234 teeth receiving apical surgery were included. 53 male and 134 female patients were collected. The age was ranged between 17 and 89 years old and the mean age was 43.64 years old. Better healed rate with significant differences were observed in female patient (p < 0.05), age ≤60 years old (p < 0.01), preoperative root canal filling material >2 mm short of apex (p < 0.01), lesion size from ≤2 mm to ≤12 mm (p < 0.05) and follow-up period â‰§12 months (p < 0.01) groups. CONCLUSION: Gender, age, preoperative root canal filling material extent, lesion size and follow-up period may affect the outcome of apical surgery. Tooth type, post, prosthesis, and lesion area showed no marked effect on apical healing. These results provide more detailed information for the clinical practitioners to make treatment plans and are important for clinical endodontic practices.

IL-1ß-induced ICAM-1 and IL-8 expression/secretion of dental pulp cells is differentially regulated by IRAK and p38.

BACKGROUND/PURPOSE: Interleukin 1 beta (IL-1ß) is a pro-inflammatory cytokine involved in the acute and chronic inflammatory processes of dental pulp. Intercellular adhesion molecule-1 (ICAM-1) and IL-8 are two major inflammatory mediators. However, the role of interleukin-1 receptor-associated kinases (IRAKs) signaling pathways in responsible for the inflammatory effects of IL-1ß on dental pulp cells is not clear. METHODS: Cultured human dental pulp cells were exposed to IL-1ß with/without pretreatment and co-incubation with IRAK1/4 inhibitor or SB203580 (p38 inhibitor). IRAK-1 phosphorylation was evaluated by immunno fluorescent staining. The protein expression of ICAM-1 and IL-8 were tested by western blotting. The secretion of soluble ICAM-1 (sICAM-1) and IL-8 was measured by enzyme-linked immunosorbant assay (ELISA). RESULTS: IL-1ß stimulated IRAK-1 phosphorylation of pulp cells within 120 min of exposure. IRAK1/4 inhibitor attenuated the IL-1ß-induced ICAM-1, but not IL-8 protein expression. IRAK1/4 inhibitor also prevented the IL-1ß-induced sICAM-1, but not IL-8 secretion. SB203580 showed little effect on IL-1ß-induced sICAM-1 secretion, but effectively inhibited its induction of IL-8 secretion in pulp cells. CONCLUSION: The Results reveal the important role of IL-1ß in pulpal inflammatory responses via stimulation of IL-8 and ICAM-1 expression and secretion. Moreover, IL-1ß-induced effects on IL-8 and ICAM-1 are differentially regulated by IRAK1/4 and p38 signaling in dental pulp cells. Blocking of IRAKs and p38 signaling may have potential to control inflammation of dental pulp in the future.

Periostin inhibits mechanical stretch-induced apoptosis in osteoblast-like MG-63 cells.

BACKGROUND/PURPOSE: Appropriate mechanical stress plays an important role in regulating the proliferation and differentiation of osteoblasts, whereas high-level mechanical stress may be harmful and compromise cell survival. Periostin, a matricellular protein, is essential in maintaining functional integrity of bone and collagen-rich connective tissue in response to mechanical stress. This study investigated whether or not high-level mechanical stretch induces cell apoptosis and the regulatory role of periostin in mechanical stretch-induced apoptosis in osteoblastic cells. METHODS: Osteoblast-like MG-63 cells were seeded onto Bio-Flex I culture plates and subjected to cyclic mechanical stretching (15% elongation, 0.1 Hz) in a Flexercell tension plus system-5000. The same process was applied to cells pre-treated with exogenous human recombinant periostin before mechanical stretching. We used a chromatin condensation and membrane permeability dead cell apoptosis kit to evaluate the stretch-induced cell responses. Expression of caspase-3 and cPARP was examined by immunofluorescent stain and flow cytometry. RESULTS: The expression of periostin in MG-63 cells is involved in the TGF-ß signaling pathway. High-level cyclic mechanical stretch induced apoptotic responses in MG-63 osteoblastic cells. The percentages of apoptotic cells and cells expressing cPARP protein increased in the groups of cells subjected to mechanical stretch, but these responses were absent in the presence of exogenous periostin. CONCLUSION: Our study revealed that high-level mechanical stretch induces apoptotic cell death, and that periostin plays a protective role against mechanical stretch-induced apoptosis in osteoblastic cells.

Cemental tear: To know what we have neglected in dental practice.

Cemental tear is a special kind of root surface fracture, contributing to periodontal and periapical breakdown. However, it is a challenge for doctors to diagnose, resulting in delayed or improper treatment. We reviewed the predisposing factors, location, radiographic/clinical characteristics, diagnosis and treatments of cemental tears. From the literature, patients with cemental tear were mainly males, over 60 year-old. Possible predisposing factors include gender, age, tooth type, traumatic occlusal force and vital teeth. Cemental tears were common in upper and lower anterior teeth, single or multiple, and can be present in cervical, middle and apical third of roots. Morphology of cemental tears can be either piece-shaped or U-shaped. Clinically, cemental tear shows a unitary periodontal pocket and signs/symptoms mimicking localized periodontitis, apical periodontitis and vertical root fractures. Treatment of cemental tears include scaling, root planning, root canal treatment, periodontal/periapical surgery, guided tissue regeneration, bone grafting, and intentional replantation. Recurrence of cemental tear is possible especially when the fracture involves root apex. Extraction is recommended for teeth with poor prognosis. In conclusion, cemental tears can involve both periodontal and periapical area. Dentists should understand the predisposing factors and clinical features of cemental tears for early diagnosis/treatment to prevent bone loss/tooth extraction.