The influence of different radiotherapy doses on the mechanical properties and microstructure of the enamel and dentin of human premolar teeth.

OBJECTIVE: Radiation therapy is applied in the treatment of head and neck cancer patients. However, oral-health-related side effects like hyposalivation and a higher prevalence of caries have been shown. This study aims to assess the influence of different radiotherapy doses on the mechanical properties, roughness, superficial microstructure, and crystallinity of the enamel and dentin of human premolar teeth. METHODS: Specimens (n = 25) were categorized into five groups based on the radiation dose received (0, 10, 30, 50, and 70 Gy). The enamel and dentin of these specimens were subjected to a microhardness tester, profilometer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and X­ray diffraction (XRD) before and after different irradiation doses and compared to hydroxylapatite in each group. The data were analyzed using repeated-measures analysis of variance (ANOVA). RESULTS: Therapeutic radiation doses of 30, 50, and 70 Gy led to a decrease in the microhardness and an increase in the average roughness of the enamel, and rougher surfaces were observed in the mixed three-dimensional images. Moreover, in the dentin, a similar outcome could be observed for more than 10 Gy. The main crystalline phase structure remained hydroxylapatite, but the crystallinity decreased and the crystalline size increased above 10 Gy. The superficial micromorphology revealed granulation, fissures, and cracks in a dose-dependent manner. Radiation below 70 Gy had little effect on the hydroxylapatite concentration during the whole experiment. CONCLUSION: Above a radiation dose of 30 Gy, the micromorphology of the tooth enamel changed. This occurred for dentin above 10 Gy, which indicates that dentin is more sensitive to radiotherapy than enamel. The radiation dose had an effect on the micromorphology of the hard tissues of the teeth. These results illustrate the possible mechanism of radiation-related caries and have guiding significance for clinical radiotherapy.

Low-level laser therapy alleviates periodontal age-related inflammation in diabetic mice via the GLUT1/mTOR pathway.

Diabetes mellitus (DM) is a chronic age-related disease that was recently found as a secondary aging pattern regulated by the senescence associated secretory phenotype (SASP). The purpose of this study is to detect the potential efficacy and the specific mechanisms of low-level laser therapy (LLLT) healing of age-related inflammation (known as inflammaging) in diabetic periodontitis. Diabetic periodontitis (DP) mice were established by intraperitoneal streptozotocin (STZ) injection and oral P. gingivalis inoculation. Low-level laser irradiation (810 nm, 0.1 W, 398 mW/cm2, 4 J/cm2, 10 s) was applied locally around the periodontal lesions every 3 days for 2 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) stain was analyzed for periodontal soft tissue and alveolar bone. Western blots, immunohistochemistry, and immunofluorescence staining were used to evaluate the protein expression changes on SASP and GLUT1/mTOR pathway. The expression of aging-related factors and SASP including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 were reduced in periodontal tissue of diabetic mice. The inhibitory effect of LLLT on GLUT1/mTOR pathway was observed by detecting the related factors mTOR, p-mTOR, GLUT1, and PKM2. COX, an intracytoplasmic photoreceptor, is a key component of the anti-inflammatory effects of LLLT. After LLLT treatment a significant increase in COX was observed in macrophages in the periodontal lesion. Our findings suggest that LLLT may regulate chronic low-grade inflammation by modulating the GLUT1/mTOR senescence-related pathway, thereby offering a potential treatment for diabetic periodontal diseases.

Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

Material resource decoupling dilemma: Convergence and traps of in-use stock productivity in national economy development.

Various studies have suggested decoupling material stock from economic output as an important measure for promoting sustainable development. Here, we develop three theoretical hypotheses to describe the evolution features and economic effects of material stock intensity, and predict in theory that (1) Countries with higher material stock intensity are more likely to decouple economic growth from material stock. (2) Material stock intensity follows convergence trends. (3) Higher material stock intensity leads to higher long-run economic growth rates. To examine the adaptability of these hypotheses, we choose steel in-use stock as the proxy for the material capital stock and use panel data in 85 countries from 1950 to 2018 to conduct empirical analysis. Our empirical results in most countries support the theoretical predictions of the hypotheses. In particular, a 0.1t/k$ increase in steel stock intensity leads to a 2.12% increase in the probability of decoupling between steel stock and economic output next year and a 0.34% increase in the long-run GDP per capita growth rate annually. Moreover, steel stock intensity converges to approximately 0.25t/k$ to 0.35t/k$ at mature development stages. We predict that, except China, which is expected to follow decoupling trends, other large developing economies will couple economic output with steel stock. However, the shape of intensity curves is still uncertain for highly developed countries in the future.

Treatment and genetic analysis of multiple supernumerary and impacted teeth in an adolescent patient.

BACKGROUND: Multiple supernumerary teeth, combined with numerous impacted teeth, can lead to various malocclusions, posing significant treatment challenges. While certain genes associated with syndromic cases of multiple supernumerary and impacted teeth have been identified, the etiologies of non-syndromic cases still largely remain elusive. CASE PRESENTATION: Here, we report a treatment of a 12-year-old boy who presented with 10 supernumerary teeth and 6 impacted teeth, accompanied by a genetic analysis to explore the underlying etiology. During the treatment, fifteen teeth were extracted, and various skilled techniques, including the closed-eruption technique and the application of by-pass arches, were utilized. Post-treatment, traction was successful for all the impacted teeth, without any tooth mobility or reduction in gingival height. Space closure, well-aligned teeth, and excellent functional occlusion were achieved. Furthermore, comprehensive genetic analysis was conducted through whole-exome sequencing on the patient and his parents, which revealed a potential link between the patient's numerous supernumerary teeth and abnormal mineralization. Notably, the p.Ser496Pro variant in the TCF7L2 gene was identified as a potential candidate variant in this patient. CONCLUSIONS: Overall, our findings not only report the treatment of a rare case involving multiple supernumerary and impacted teeth but also offer valuable insights into the molecular basis of supernumerary teeth.

A cascading learning method with SegFormer for radiographic measurement of periodontal bone loss.

OBJECTIVE: Marginal alveolar bone loss is one of the key features of periodontitis and can be observed via panoramic radiographs. This study aimed to establish a cascading learning method with deep learning (DL) for precise radiographic bone loss (RBL) measurements at specific tooth positions. MATERIALS AND METHODS: Through the design of two tasks for tooth position recognition and tooth semantic segmentation using the SegFormer model, specific tooth's crown, intrabony portion, and suprabony portion of the roots were obtained. The RBL was subsequently measured by length through these three areas using the principal component analysis (PCA) principal axis. RESULTS: The average intersection over union (IoU) for the tooth position recognition task was 0.8906, with an F1-score of 0.9338. The average IoU for the tooth semantic segmentation task was 0.8465, with an F1-score of 0.9138. When the two tasks were combined, the average IoU was 0.7889, with an F1-score of 0.8674. The correlation coefficient between the RBL prediction results based on the PCA principal axis and the clinicians' measurements exceeded 0.85. Compared to those of the other two methods, the average precision of the predicted RBL was 0.7722, the average sensitivity was 0.7416, and the average F1-score was 0.7444. CONCLUSIONS: The method for predicting RBL using DL and PCA produced promising results, offering rapid and reliable auxiliary information for future periodontal disease diagnosis. CLINICAL RELEVANCE: Precise RBL measurements are important for periodontal diagnosis. The proposed RBL-SF can measure RBL at specific tooth positions and assign the bone loss stage. The ability of the RBL-SF to measure RBL at specific tooth positions can guide clinicians to a certain extent in the accurate diagnosis of periodontitis.

Circular RNA hsa_circ_0084054 promotes the progression of periodontitis with diabetes via the miR-508-3p/PTEN axis.

BACKGROUND AND OBJECTIVE: Diabetes is an important risk factor for periodontitis, and circular RNA (circRNA) may play an important role in aggravating inflammation and accelerating disease progression by regulating miRNA/mRNA. This study aimed to investigate the role and mechanism of the hsa_circ_0084054/miR-508-3p/PTEN axis in the progression of periodontitis with diabetes. METHODS: First, circRNA sequencing was used to screen the differentially expressed circRNAs of periodontal ligament cells (PDLCs) treated with high glucose and/or Porphyromonas gingivalis lipopolysaccharide (LPS) in vitro, and the overtly differentially expressed hsa_circ_0084054 was selected and was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Then, its ring structure was tested by Sanger sequencing, RNase R, and actinomycin D assays. The bioinformatics analysis, dual luciferase reporter assay, and RIP assay were used to explore the interaction of hsa_circ_0084054/miR-508-3p/PTEN axis, whose effects on inflammation, oxidative stress, and apoptosis of PDLCs were evaluated through the measurement of inflammatory factors, reactive oxygen species (ROS), total superoxide dismutase (SOD), malondialdehyde (MDA), and Annexin V/PI assay. RESULTS: By high-throughput sequencing, it was found that hsa_circ_0084054 was significantly increased in HG + LPS group compared with control group and LPS group, which was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Silencing hsa_circ_0084054 in PDLCs decreased the expression of inflammatory factors (IL-1ß, IL-6, TNF-α), the levels of ROS and MDA, and the proportion of apoptotic cells; conversely, SOD activity was enhanced. In addition, we found that hsa_circ_0084054 could up-regulate the expression of PTEN through sponge miR-508-3p to inhibit AKT phosphorylation, finally trigger the aggravation of oxidative stress and inflammation in periodontitis patients with diabetes. CONCLUSION: hsa_circ_0084054 can aggravate inflammation and promote the progression of periodontitis with diabetes by regulating miR-508-3p/PTEN signaling axis, which may serve as a new target for the intervention of periodontitis with diabetes.

Soy isoflavones alleviate periodontal destruction in ovariectomized rats.

OBJECTIVE: The purpose of this study was to investigate whether soy isoflavone supplementation is effective in preventing periodontal destruction exacerbated by estrogen deficiency (ED) and its potential mechanism. BACKGROUND: The progression of periodontitis is affected by host factors, such as smoking, diabetes mellitus, and steroid use. Bone loss in periodontitis can be aggravated by ED. METHODS: A rat model of experimental periodontitis (EP) with ED was established by silk ligature and inoculation with Porphyromonas gingivalis, and some EP rats were subjected to bilateral ovariectomy (OVX). The treatment groups received an intravenous injection of 17-ß-estradiol (E2 B) or soy isoflavones (SI) by gavage. The rats were euthanized, and the maxillary jaws, gingiva, and serum were harvested. Tight junction protein and interleukin (IL)-17 expression, reactive oxygen species (ROS) level, and periodontal destruction were assessed. In addition, we determined whether grainyhead-like 2 (GRHL2) is required for enhancing the epithelial barrier by SI in an in vitro P. gingivalis infection model. RESULTS: Estrogen deficiency impaired the expression of genes encoding tight junction proteins in the gingiva, increased IL-17 level, and accelerated alveolar bone resorption. SI treatment alleviated tight junction protein expression, decreased IL-17 and ROS levels, and prevented the absorption of alveolar bone. Furthermore, GRHL2 expression was significantly induced by SI in human oral keratinocytes-1 (HOK-1) cells; GRHL2 knockdown impaired the expression of OCLN and ZO-1 induced by SI treatment. CONCLUSION: Soy isoflavones alleviates periodontitis in OVX rats, as observed by the increased expression of tight junction proteins, and reduced IL-17 level and alveolar bone loss. The in vitro studies suggested that the enhancement of oral epithelial barrier by SI treatment was partially dependent on GRHL2.

Adjunctive Er:YAG laser in non-surgical periodontal therapy of patients with inadequately controlled type 2 diabetes mellitus: A split-mouth randomized controlled study.

BACKGROUND AND OBJECTIVE: Limited studies are available comparing the outcomes of non-surgical periodontal therapy (NSPT) with or without adjunctive Er:YAG laser (ERL) in patients with type 2 diabetes mellitus (T2DM). This study evaluated the effects of ERL adjunctive NSPT on single-rooted teeth of inadequately controlled T2DM patients with periodontitis. METHODS: Twenty-two inadequately controlled T2DM participants with periodontitis were recruited. Adopting a double-blinded split-mouth design and under block randomization, we investigated the effects of ERL in calculus removal then degranulation mode, or a sham treatment, adjunct NSPT, which included two visits of full-mouth root surface debridement delivered within 4-10 days, to test or control single-rooted teeth (Wuxi Stomatology Hospital, trial 2017-016). We followed periodontal parameters (plaque %, bleeding on probing [BOP] %, probing pocket depth [PPD], probing attachment level [PAL]) and selected systemic parameters (fasting plasma glucose [FPG], glycosylated hemoglobin [HbA1c%], high sensitivity C-reactive protein) at baseline, one, three, and six months after periodontal treatment. RESULTS: The study was completed as planned. Periodontal parameters, FPG and HbA1c% of the 22 participants appeared significantly improved at six months (p < 0.001). The 44 ERL treated, compared to 44 sham treated single-rooted teeth exhibited significant improvement in BOP, mean PPD, and mean PAL at various postoperative follow-up time points (effect size ≥0.44; p < 0.001). No adverse event was reported. CONCLUSION: Periodontal treatment outcomes in the T2DM patients with inadequate glycemic control were better in the single-rooted teeth received ERL adjunct NSPT. Further studies are warranted to confirm the observations reported in this short-term clinical study.

Oxygen-Tolerant RAFT Polymerization Catalyzed by a Recyclable Biomimetic Mineralization Enhanced Biological Cascade System.

An enzyme cascade system including glucose oxidase (GOx) and iron porphyrin (DhHP-6) is encapsulated in a metal-organic framework called zeolitic imidazolate framework-8 (ZIF-8) through one-step facile synthesis. The composite (GOx&DhHP-6@ZIF-8) is then used to initiate oxygen-tolerant reversible addition-fragmentation chain-transfer polymerization for different methacrylate monomers, such as 2-diethylaminoethyl methacrylate, 2-hydroxyethyl methacrylate, and poly(ethylene glycol) methyl ether methacrylate (Mn = 500 g mol-1 ). The composite shows the robustness toward solvent and temperatures, all polymerizations using above monomers and catalyzing by GOx&DhHP-6@ZIF-8 exhibits high monomer conversion (>85%) and narrow molar mass dispersity (<1.3). Besides, acrylic and acrylamide monomers such as 2-hydroxyethyl acrylate and N,N-dimethylacrylamide are also carried to demonstrate the broad applicability. Proton nuclear magnetic resonance characterization and chain extension experiments confirm the retaining end groups of the resultant polymers, which is a significant feature of living polymerization. More importantly, the process of recycling the composite through a centrifuge is simplistic, and the composite still maintains similar activity compared to the original composites after five times. This low-cost and easily separated composite catalyst represents a versatile strategy to synthesize well-defined functional polymers suitable for industrial-scale production.

Hyperglycemia accelerates inflammaging in the gingival epithelium through inflammasomes activation.

BACKGROUND AND OBJECTIVE: Diabetes accelerates inflammaging in various tissue with an increase in senescent cell burden and senescence-associated secretory phenotype (SASP) secretion, which is a significant cause of tissue dysfunction and contributes to the diabetic complications. Recently, inflammasomes are thought to contribute to inflammaging. Here, utilizing diabetic models in vivo and in vitro, we investigated the potential association between hyperglycemia-induced inflammaging and gingival tissue dysfunction and the mechanism underlying inflammasome-associated inflammaging. MATERIALS AND METHODS: Gingival epithelium and serum were collected from control and diabetic patients and mice. The expression of p16, p21, and inflammasomes in the gingival epithelium, SASP factors in serum, and the molecular factors associated with gingival epithelial barrier function were assessed. Human oral keratinocyte (HOK) was stimulated with normal and high glucose, and pre-treated with Z-YVAD-FMK (Caspase-1 inhibitor) prior to evaluating cellular senescence, SASP secretion, and inflammasome activation. RESULTS: In vivo, hyperglycemia significantly elevated the local burden of senescent cells in the gingival epithelium and SASP factors in the serum and simultaneously reduced the expression levels of Claudin-1, E-cadherin, and Connexin 43 in the gingival epithelium. Interestingly, the inflammasomes were activated in the gingival epithelium. In vitro, high glucose-induced the inflammaging in HOK, and blocking inflammasome activation through inhibiting Caspase-1 and glucose-induced inflammaging. CONCLUSIONS: Hyperglycemia accelerated inflammaging in the gingival epithelium through inflammasomes activation, which is potentially affiliated with a decline in the gingival epithelial barrier function in diabetes. Inflammasomes-related inflammaging may be the crucial mechanism underlying diabetic periodontitis and represents significant opportunities for advancing prevention and treatment options.

Effect of adjunctive diode laser in the non-surgical periodontal treatment in patients with diabetes mellitus: a systematic review and meta-analysis.

This study aimed to systematically review and analyze the present randomized clinical trials (RCTs) regarding the clinical efficacy of a diode laser (DL) adjuvant to scaling and root planning (SRP) in patients with chronic periodontitis (CP) who have diabetes mellitus (DM). Five databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trails, Web of Science, and Chinese BioMedical Literature Databases) were searched. A meta-analysis was implemented to evaluate periodontal parameters including probing depth (PD) and clinical attachment level (CAL) as primary outcomes. Hemoglobin A1c (HbA1c), plaque index (PI), and the gingival index (GI) were also observed as secondary outcomes. Independent scanning of 239 papers resulted in 9 RCTs. Moderate evidence demonstrated that the test groups showed significant benefits for PD reduction, CAL gain, and HbA1c reduction after 3 and 6 months. Significant differences in PI and GI reduction were not found except for GI reduction within 1 month. The collective evidence suggested that the DL with SRP had significant improvements in clinical results compared to SRP alone. Based on our results, the DL could be a recommended therapy for patients with CP who have DM.

Clinical Efficacy of Chlorhexidine as an Adjunct to Mechanical Therapy of Peri-Implant Disease: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to determine the efficacy of chlorhexidine (CHX) as an adjunctive therapy to mechanical debridement in the treatment of peri-implant diseases. Five databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trails, Web of Science, and ClinicalTrials.gov) were searched. Randomized controlled trials (RCTs) comparing mechanical debridement combined with CHX to mechanical debridement alone for patients with peri-implant disease were identified. The trial investigators evaluated factors indicating inflammatory levels, including bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL). Six RCTs with 207 patients were ultimately included in this review. Low- to moderate-quality evidence demonstrated that the adjunctive CHX therapy had no significant effect on BOP reduction within 1 month (mean difference [MD], 0.10; 95% confidence interval [CI], -0.06 to 0.25), 3-4 months (MD, 0.06; 95% CI, -0.03 to 0.15), and 6-8 months (MD, 0.06; 95% CI, -0.03 to 0.14) of follow-up. Significant differences in PD reduction and CAL gain were also not found. Although 1 subgroup analysis revealed a significant result (MD, 009; 95% CI, 0.01-0.18) for the use of CHX solution, this could be interpreted as clinically slight. Based on available evidence, adding CHX to mechanical debridement, compared with mechanical debridement alone, did not significantly enhance the clinical results. Therefore, clinicians should consider the negligible effect of adjunctive CHX.

Hyaline fibromatosis syndrome: a case presenting with gingival enlargement as the only clinical manifestation and a report of two new mutations in the ANTXR2 gene.

BACKGROUND: Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive disorder caused by mutations in the gene for anthrax toxin receptor-2 (ANTXR2). The clinical features of HFS include skin thickening with nodules, papules and plaques, gingival enlargement, joint stiffness and contractures, and systemic manifestations. Notably, in all patients with HFS reported in the literature, gingival enlargement has never occurred alone. CASE PRESENTATION: A case of a child with gingival enlargement as the only clinical manifestation, who was later diagnosed with HFS, is described. In this case, the absence of skin and joint lesions and other characteristic clinical presentations gave rise to a diagnostic problem. This uncommon condition was clinically indistinguishable from other diseases or conditions that presented with diffuse gingival enlargement. A definitive diagnosis of HFS was reached through genetic analysis. Trio whole exome sequencing revealed compound heterozygous mutations of ANTXR2 in this patient and two new mutations were reported. CONCLUSIONS: The findings of this case serve as an important reminder to clinicians. When dental practitioners encounter gingival manifestations of HFS without accompanied skin or joint involvement, there is a need to pay attention to the differential diagnosis and increase awareness of HFS.

Hyperglycemia-induced inflamm-aging accelerates gingival senescence via NLRC4 phosphorylation.

Inflamm-aging was recently affiliated with the progression of diabetic complications. Local cellular senescence together with senescence-associated secretory phenotype (SASP) are the main contributors to inflamm-aging. However, little is known about their involvement in diabetic periodontitis. Gingiva is the first line of host defense in the periodontium, and macrophages are key SASP-carrying cells. Here, we explored the molecular mechanism by which hyperglycemia drives the inflamm-aging in the gingival tissue of diabetic mice and macrophages. We demonstrated that hyperglycemia increased the infiltrated macrophage senescence in gingival tissue of diabetic mice. Simultaneously, hyperglycemia elevated the local burden of senescent cells in gingival tissue and induced the serum secretion of SASP factors in vivo Moreover, in vitro, high glucose induced macrophage senescence and SASP factors secretion through phosphorylation of NLRC4, which further stimulated the NF-κB/Caspase-1 cascade via an IRF8-dependent pathway. Deletion of NLRC4 or IRF8 abolished hyperglycemia-induced cellular senescence and SASP in macrophages. In addition, we found that treatment with metformin inhibited NLRC4 phosphorylation and remarkably decreased cellular senescence and SASP in the context of hyperglycemia. Our data demonstrated that hyperglycemia induces the development of inflamm-aging in gingival tissue and suggested that NLRC4 is a potential target for treatment of diabetes-associated complications.

The combined use of salivary biomarkers and clinical parameters to predict the outcome of scaling and root planing: A cohort study.

AIM: To explore the application of the combined use of baseline salivary biomarkers and clinical parameters in predicting the outcome of scaling and root planing (SRP). MATERIALS AND METHODS: Forty patients with advanced periodontitis were included. Baseline saliva samples were analysed for interleukin-1ß (IL-1ß), matrix metalloproteinase-8 and the loads of Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Tannerella forsythia. After SRP, pocket closure and further attachment loss at 6 months post-treatment were chosen as outcome variables. Models to predict the outcomes were established by generalized estimating equations. RESULTS: The combined use of baseline clinical attachment level (CAL), site location and IL-1ß (area under the curve [AUC] = 0.764) better predicted pocket closure than probing depth (AUC = 0.672), CAL (AUC = 0.679), site location (AUC = 0.654) or IL-1ß (AUC = 0.579) alone. The combination of site location, tooth loss, percentage of deep pockets, detection of A. actinomycetemcomitans and T. forsythia load (AUC = 0.842) better predicted further clinical attachment loss than site location (AUC = 0.715), tooth loss (AUC = 0.530), percentage of deep pockets (AUC = 0.659) or T. forsythia load (AUC = 0.647) alone. CONCLUSION: The combination of baseline salivary biomarkers and clinical parameters better predicted SRP outcomes than each alone. The current study indicates the possible usefulness of salivary biomarkers in addition to tooth-related parameters in predicting SRP outcomes.

Hyperglycemia Induces Osteoclastogenesis and Bone Destruction Through the Activation of Ca2+/Calmodulin-Dependent Protein Kinase II.

Hyperglycemia induces osteoclastogenesis and bone resorption through complicated, undefined mechanisms. Ca2+/calmodulin-dependent protein kinase II (CaMKII) promotes osteoclastogenesis, and could be activated by hyperglycemia. Here, we investigated whether CaMKII is involved in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption. Osteoclast formation, bone resorption, CaMKII expression and phosphorylation were measured under high glucose in vitro and in streptozotocin-induced hyperglycemia rats with or without CaMKII inhibitor KN93. The results showed that 25 mmol/L high glucose in vitro promoted cathepsin K and tartrate-resistant acid phosphatase expression (p < 0.05) and osteoclast formation (p < 0.01) associated with enhancing ß isoform expression (p < 0.05) and CaMKII phosphorylation (p < 0.001). Hyperglycemia promoted the formation of osteoclasts and resorption of trabecular and alveolar bone, and inhibited sizes of femur and mandible associated with enhanced CaMKII phosphorylation (p < 0.001) in rats. All these changes could be alleviated by KN93. These findings imply that CaMKII participates not only in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption, but also in the hyperglycemia-induced developmental inhibition of bone.

Relationship between serum 25-hydroxyvitamin D3 levels and severity of chronic periodontitis in type 2 diabetic patients: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Serum 25-hydroxyvitamin D3 (25(OH)D3 ), a newly emerged immune regulator, is considered to be involved in type 2 diabetic periodontitis (T2DCP). However, the risk factors and genes with altered expression that influence the progression and severity of T2DCP remain unknown. Accordingly, the aim of the present study was to elucidate the relationship between 25(OH)D3 deficiency and severity of T2DCP as well as the potential mechanisms. MATERIAL AND METHODS: A total of 182 subjects were divided into two groups: chronic periodontitis without diabetes (P group, n = 88) and type 2 diabetes mellitus with periodontitis (DM+P group, n = 94). Patients in both groups were further classified according to age as young (Y) and elderly (E) for a total of four groups: P/Y, P/E, DM+P/Y, and DM+P/E. Periodontal status was evaluated based on the probing depth (PD) and clinical attachment loss (CAL). The serum levels of human 25(OH)D3 , interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. Immunohistochemistry was used to measure the expression of protein tyrosine phosphatase non-receptor type 2 (PTPN2), vitamin D receptor (VDR), and JAK/STAT proteins in the gingival tissue. RESULTS: Serum 25(OH)D3 levels were lower in the DM+P group than those in the P group (P < 0.001). When the patients were subgrouped according to age, 25(OH)D3 deficiency was more commonly found in DM+P/E than in DM+P/Y (67% vs 51%), with a significant difference detected in the 25(OH)D3 quartile of 15-20 ng/mL (P = 0.007). The 25(OH)D3 level showed a significant negative correlation with fasting blood glucose (FBG) (r = -0.623), serum IL-1ß (r = -0.392), serum TNF-α (r = -0.218), PD (r = -0.269), and CAL (r = -0.305) in the DM+P group (all P < 0.05), but not with hemoglobin A1c (P = 0.123). Additionally, reduced VDR and PTPN2 expression levels were observed in DM+P patients, whereas JAK1 and p-STAT5 protein levels were increased in this group. CONCLUSIONS: Vitamin D3 deficiency is strongly associated with T2DCP, and age mediates this relationship. Abnormal FBG and IL-1ß levels should be considered as important potential risk factors for the progression and severity of T2DCP. Moreover, 25(OH)D3 deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.

Metal-Folded Single-Chain Nanoparticle: Nanoclusters and Self-Assembled Reduction-Responsive Sub-5-nm Discrete Subdomains.

Easy access to discrete nanoclusters in metal-folded single-chain nanoparticles (metal-SCNPs) and independent ultrafine sudomains in the assemblies via coordination-driven self-assembly of hydrophilic copolymer containing 9% imidazole groups is reported herein. 1 H NMR, dynamic light scattering, and NMR diffusion-ordered spectroscopy results demonstrate self-assembly into metal-SCNPs (>70% imidazole-units folded) by neutralization in the presence of Cu(II) in water to pH 4.6. Further neutralization induces self-assembly of metal-SCNPs (pH 4.6-5.0) and shrinkage (pH 5.0-5.6), with concurrent restraining residual imidazole motifs and hydrophilic segment, which organized into constant nanoparticles over pH 5.6-7.5. Atomic force microscopy results evidence discrete 1.2 nm nanoclusters and sub-5-nm subdomains in metal-SCNP and assembled nanoparticle. Reduction of metal center using sodium ascorbate induces structural rearrangement to one order lower than the precursor. Enzyme mimic catalysis required media-tunable discrete ultrafine interiors in metal-SCNPs and assemblies have hence been achieved.