Sodium fluoride-induced autophagy of ameloblast-like cells via the p-ULk1/ATG13/LC3B pathway in vitro.

OBJECTIVE: To investigate the effects of sodium fluoride on the ameloblast and reveal the mechanism of dental fluorosis. MATERIALS AND METHODS: Mouse ameloblast-like cell line (ALC) cells were treated with various concentrations of NaF, and subjected to Incucyte, fluorescence immunoassay, transmission electron microscopy, reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot for autophagy examination, alkaline phosphatase and alizarin red staining for mineralization after osteogenic induction. RESULTS: NaF exerts a dose-dependent inhibitory effect on ALC cell growth. TEM and fluorescence immunoassay showed that 1.5 mM or higher concentrations of NaF could induce a fusion of lysosome and mitochondria, finally increasing the number of autophagosome. RT-qPCR and western blot showed that the upregulation of autophagy related gene 13 (ATG13), downregulation of phosphorylated Unc-51-like kinase 1 (p-ULK1) were found in NaF-induced autophagy of ALC cells. The knockdown of ATG13 could rescue it as well as the expression of p-ULK1 and LC3B. Besides, alizarin red staining showed that fluoride under these concentrations could promote the mineralization of ALC. CONCLUSIONS: The data show that fluoride in higher concentration can induce autophagy via the p-ULk1/ATG13/LC3B pathway of ALCs than lower ones promote mineralization in vitro, which provides insight into the function of NaF in the autophagy and mineralization of ameloblast.

Effect of artesunate on cardiovascular complications in periodontitis in a type I diabetes rat model and related mechanisms.

PURPOSE: Both cardiovascular disease and periodontitis are complications of diabetes that have a great impact on human life and health. Our previous research found that artesunate can effectively improve cardiovascular disease in diabetes and has an inhibitory effect on periodontal disease. Therefore, the present study aimed to explore the potential therapeutic possibility of artesunate in the protection against cardiovascular complications in periodontitis with type I diabetes rats and to elucidate the possible underlying mechanisms. METHODS: Sprague‒Dawley rats were randomly divided into the healthy, diabetic, periodontitis, diabetic with periodontitis, and artesunate treatment groups (10, 30, and 60 mg/kg, i.g.). After artesunate treatment, oral swabs were collected and used to determine changes in the oral flora. Micro-CT was performed to observe changes in alveolar bone. Blood samples were processed to measure various parameters, while cardiovascular tissues were evaluated by haematoxylin-eosin, Masson, Sirius red, and TUNEL staining to observe fibrosis and apoptosis. The protein and mRNA expression levels in the alveolar bone and cardiovascular tissues were detected using immunohistochemistry and RT‒PCR. RESULTS: Diabetic rats with periodontitis and cardiovascular complications maintained heart and body weight but exhibited reduced blood glucose levels, and they were able to regulate blood lipid indicators at normal levels after artesunate treatment. The staining assays suggested that treatment with 60 mg/kg artesunate has a significant therapeutic effect on myocardial apoptotic fibrosis. The high expression of NF-κB, TLR4, VEGF, ICAM-1, p38 MAPK, TGF-ß, Smad2, and MMP9 in the alveolar bone and cardiovascular tissue in the type I diabetes and type I diabetes with periodontitis rat models was reduced after treatment with artesunate in a concentration-dependent manner. Micro-CT showed that treatment with 60 mg/kg artesunate effectively alleviated alveolar bone resorption and density reduction. The sequencing results suggested that each model group of rats had vascular and oral flora dysbiosis, but artesunate treatment could correct the dysbacteriosis. CONCLUSIONS: Periodontitis-related pathogenic bacteria cause dysbiosis of the oral and intravascular flora in type I diabetes and aggravate cardiovascular complications. The mechanism by which periodontitis aggravates cardiovascular complications involves the NF-κB pathway, which induces myocardial apoptosis, fibrosis, and vascular inflammation.

Patient and Physician Satisfaction with Telehealth During the COVID-19 Pandemic: Sports Medicine Perspective.

Background:Owing to the COVID-19 pandemic, there has been a large shift in health care toward virtual platforms. This study analyzed patient and physician satisfaction with telehealth during the height of the pandemic within the division of sports medicine.Methods:All sports medicine patients who completed a telemedicine visit from March 30, 2020, through April 30, 2020, were sent a 14-question Likert scale (1-5/5) survey. Sports medicine physicians who used telemedicine were sent a separate 14-question Likert scale (1-5/5) survey at the end of the study period. Factors influencing patient satisfaction were determined using a multivariate linear regression model.Results:A total of 143 patients and 9 sports medicine attendings completed the surveys. Most patients were "satisfied" (4/5) or "very satisfied" (5/5) (88.8%). A multivariate linear regression determined that patients who believed they had a greater ability to adopt new technology and were more effective at communicating questions/concerns to their physicians had greater satisfaction (p = 0.009 and p = 0.015, respectively). Most physicians were either "satisfied" (4/5) or "very satisfied" (5/5) (75.0%). On average, physicians felt that physical examinations conducted through telemedicine were "moderately effective" (2.75/5.00 ± 1.3), that they were "fairly confident" (3.86/5.00 ± 0.83) in their diagnoses, and that most sports medicine attendings plan to use telemedicine in the future (87.5%).Conclusion:Telehealth emerged as a valuable tool for the delivery of health care to sports medicine patients during the COVID-19 pandemic. Patients and physicians reported high levels of satisfactions with its use, and this study further identifies areas that can improve the patient and physician experience.

Antibacterial activity of viable and heat-killed probiotic strains against oral pathogens.

Probiotics can stabilize gut flora, regulate intestinal immunity and protect the host from enteric diseases; however, their roles in oral health have received little attention compared to their roles in gut health. Nowadays, the prevalence of sugar-sweetened foods and abuse of antibiotics contribute towards dysbiosis of oral microbiota and drug resistance development in oral pathogens, resulting in various intractable oral diseases. We screened the antibacterial activities of viable and heat-killed probiotic strains against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. The probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 displayed strong antipathogenic activities, whereas heat-killed AP-32, CT-53 and ET-66 displayed high levels of pathogen inhibition. The antibacterial activities of these probiotics were not associated with their H2 O2 production; L. acidophilus TYCA02 produced high levels of H2 O2 but merely exhibited moderate antibacterial activities. Oral tablets containing probiotics showed positive inhibitory effects against oral pathogens, particularly those containing viable probiotics. Our results indicate that probiotics prevent the growth of oral pathogens and improve oral health, providing insights into the antipathogenic efficacy of different probiotic species and their potential role in functional foods that improve oral health. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study provides insights into the antipathogenic efficacy of different probiotic species and their potential roles in developing functional foods to improve oral health. We showed that the probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 have great potential for use in the development of functional foods to improve oral health. Since active probiotics may provide strong and long-term protection, the development of functional food products should favour the use of viable bacteria.

The antibiofilm and collagen-stabilizing effects of proanthocyanidin as an auxiliary endodontic irrigant.

AIM: To evaluate the antibiofilm effect of proanthocyanidin (PA) solution as an irrigant against Enterococcus faecalis (E. faecalis) and its influence on the mechanical properties and biodegradation resistance of demineralized root dentine. METHODOLOGY: Enterococcus faecalis were introduced into human root dentine tubules by a serial centrifugation method and grown for 1 week. Dentine blocks infected with 1-week-old E. faecalis biofilms were treated with the following irrigants: sterile water (control), 2% chlorhexidine (CHX), 2% PA, 5% PA and 10% PA. After treatment, the live and dead bacteria proportions within E. faecalis biofilms were analysed using confocal laser scanning microscopy. To evaluate the biostability of fully demineralized dentine treated by the aforementioned irrigants, the elastic modulus and hydroxyproline release of human dentine incubated in collagenase solution were tested at baseline, after irrigant treatment and after biodegradation, respectively. Furthermore, the surface chemical bond of demineralized dentine collagen treated by various irrigants was characterized by X-ray photoelectron spectroscopy (XPS). Statistical analysis was performed using one-way anova and Tukey's post hoc multiple comparisons with the significance level at 5%. RESULTS: The proportion of dead E. faecalis volume was significantly higher in the PA and CHX groups than that in the control group (P < 0.05). PA irrigation significantly increased the mechanical properties of demineralized dentine (P < 0.05), and the effect was enhanced with increasing PA concentration. CHX and PA groups had significantly less elasticity loss and hydroxyproline release (P < 0.05). The biomodification of dentine collagen by PA was verified by increased C-O/C-N peak percentage under C1s and C-O peak percentage under O1s narrow-scan XPS spectra. CONCLUSIONS: Proanthocyanidin killed E. faecalis within biofilms and enhanced the biostability of the collagen matrix of demineralized root dentine. It might be used as an auxiliary endodontic irrigant with antibiofilm and collagen-stabilizing effects.

Production of prebiotic xylooligosaccharide from aqueous ammonia-pretreated rice straw by ß-xylosidase of Weissella cibaria.

AIMS: This study focuses on the development of a new strategy xylooligosaccharide (XOS) production from aqueous ammonia-pretreated rice straw (A-PRS), followed by ß-xylosidase hydrolysis produced by the newly identified strain Weissella cibaria FB069. METHODS AND RESULTS: We report a higher efficiency of A-PRS, including the removal of lignin and increase in cellulose and xylan content, compared to that of the alkali and stream explosion methods. Using the ammonia pretreatment method, rice straw was used to obtain 32·4% xylan. The crude xylanase from W. cibaria was used to hydrolyse A-PRS over different hydrolysis times. The highest XOS yield (131 mg XOS per gram rice straw) was observed after 10 h. XOS produced from the PRS was tested on stimulation effect on Bifidobacterium and Lactobacillus. CONCLUSION: The possibility of XOS production from PRS using ß-xylosidase with strong prebiotic properties. SIGNIFICANCE AND IMPACT OF THE STUDY: We investigated the new strain for signification production of XOS. The two-stage process here described could help to further explore the optimization conditions for prebiotic production. Additionally, the stimulation effect of XOS from alternative source has a promising prospect in functional food.

[Analysis of edge morphology of partial veneers made by different processing techniques and materials].

OBJECTIVE: To compare the edge morphology of partial veneers made of different materials by slurry molding, heat-pressed and computer aided design/computer aided manufacturing (CAD/CAM) techniques. METHODS: Thirty premolars with smooth surface and intact enamel were selected and randomly divided into five groups, 6 specimens for each group. Group A were made from feldspathic porcelain (Noritake®) by slurry molding, while Group B were made from lithium disilicate glass ceramic (IPS E.max® Press) by heat-pressed. Group C/D/E were respectively made from feldspar porcelain block (VITA Mark II®), zirconia-reinforced glass ceramic (VITA Suprinity®) and hybrid ceramic with a ceramic-polymer network (VITA Enamic®) by CAD/CAM techniques. All the partial veneers luted with light-cured composite resin. Then the partial veneers were trimmed and polished to achieve the smooth finishing margin, clinical polishing sets were used according to the product descriptions. Scanning electron microscope (SEM) was used to observe the edge morphology of prostheses and the exposure of resin cements. RESULTS: The smooth surface and knife-like edge of the partial veneers could be obtained after bonding, trimming and polishing. The edges of Group A were slightly rough and the width of the exposed adhesive was (106.00±9.17) µm. In Group B, the edges were smoother than Group A, and the exposed wide adhesive strip was visible, which was (138.33±20.59) µm. In Group E, the edges were smooth too, and the width of exposed adhesive strip was (186.00±5.66) µm. The edges of Group C and Group D were rough and uneven, and the adhesive was rarely exposed, they were (50.67±7.51) µm and (65.67±17.90) µm. There were all significant differences between two groups, except Group C and Group D. CONCLUSION: After trimming and polishing in accordance with clinical procedures, the expected knife-like edge can be obtained in all groups. The width of the exposed resin adhesive of each group is different, the order: Mark II/Suprinity < Noritake < E.max Press < Enamic. The edge morphology of partial veneers in different processing technic and materials are different.

Periodontitis and dental scaling associated with pyogenic liver abscess: A population-based case-control study.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the relationship between periodontitis, dental scaling (DS) and pyogenic liver abscesses (PLAs). MATERIAL AND METHODS: A nationwide population-based case-control study was applied using data from the National Health Insurance Research Database in Taiwan. We identified and enrolled 691 PLA patients, who were individually matched by age and sex to 2764 controls. RESULTS: Conditional logistic regression was applied to estimate adjusted odds ratios (aORs) in patients with exposure to periodontitis and DS before PLA. After adjusting for other confounding factors, periodontitis remained a risk factor for PLA among patients aged 20-40 years, with an aOR of 2.31 (95% confidence interval [CI] = 1.37-3.90, P = .0018). In addition, the average aOR for PLA was significantly lower among patients with one DS (aOR = 0.76, 95% CI = 0.59-0.96) and more than one DS (aOR = 0.61, 95% CI = 0.39-0.95) within 1 year before the index date. CONCLUSION: According to these results, we concluded that adult patients with periodontitis aged <50 years old are more at risk for PLA than controls, particularly when they have no DS. Moreover, from 20 years of age, non-periodontal patients subjected to at least 2 DS per year are less at risk for PLA than controls.

In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy.

Post-operative epidural fibrosis is a biological response after laminectomy that may lead to clinical symptoms, such as radicular pain. An ideal material for prevention of epidural fibrosis should be able to inhibit fibroblast adhesions and reduce formation of scar tissue. An injectable hydrogel would be the material of choice for this purpose, since it could fill an irregular surgical defect completely, gelate in situ and be delivered in a minimally-invasive manner. The objective of this study was to evaluate, in vitro and in vivo, the cytocompatibility and anti-adhesive effect of an oxidised hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) hydrogel. Different cell types present in the spine were used to test the cytocompatibility of the hydrogel. The hydrogel extraction medium had no deleterious effects on neural cells (PC-12), but reduced fibroblasts viability (NIH/3T3). Although the hydrogel did not change the release of lactate dehydrogenase from myoblasts (C2C12) and Schwann cells (RSC96), the extraction medium concentration slightly affected the mitochondrial activity of these two cell types. qPCR showed that the hydrogel down-regulated S100a and P4hb expression in NIH/3T3 cells, supporting the hypothesis that the hydrogel might inhibit fibroblast activity. The animal study showed a reduction of scar tissue formation as well as severity of adhesion between scar tissue and the dura mater in a rat laminectomy model. Superficially, the peel-off test showed significantly decreased tenacity. In conclusion, the oxi-HA/ADH hydrogel is a promising injectable and thermosensitive material for prevention of post-operative epidural fibrosis.

Biodegradation of kraft lignin by a newly isolated anaerobic bacterial strain, Acetoanaerobium sp. WJDL-Y2.

UNLABELLED: An anaerobic kraft lignin (KL)-degrading bacterial strain was isolated from sludge of a pulp and paper mill. It was characterized as Acetoanaerobium sp. WJDL-Y2 by 16S rRNA gene sequencing. The maximum KL degradation capability of strain Y2 was determined to be 24·9% on a COD basis under an optimal condition with temperature of 31·5°C, initial pH of 6·8 and KL to nitrogen (as NH4 Cl) ratio of 6·5 by mass. Growth kinetic studies showed that the KL tolerance of strain Y2 was relatively high (Ki  = 8120·45 mg l(-1) ). Analysing KL degradation products by GC-MS revealed the formation of low-molecular-weight aromatic compounds (LMWACs), including benzene-propanoic acid, syringic acid and ferulic acid. This indicates that strain Y2 can oxidize lignin structure's p-hydroxyphenyl (H) units, guaiacyl (G) units and syringyl (S). In addition, the inoculated sample also contained low-molecular acid compounds, such as hexanoic acid, adipic acid and 2-hydroxybutyric acid, further validating strain Y2's ability to degrade KL. SIGNIFICANCE AND IMPACT OF THE STUDY: Kraft lignin containing effluents discharged from pulp and paper industries causes serious environmental pollution in developing countries. Due to the immense environmental adaptability and biochemical versatility, bacterial ligninolytic potential deserve to be studied for application in effluent treatment of pulp and paper industry. In this study, an anaerobic lignin-degrading bacterium, Acetoanaerobium sp. WJDL-Y2 (accession no. KF176997),was isolated from the sludge of a pulp and paper mill. Strain Y2 can play an important role in treating pulp and paper wastewater, as well as breaking down materials for biofuel and chemical production.

Association between dental pain and depression in Korean adults using the Korean National Health and Nutrition Examination Survey.

The purpose of this study was to evaluate the relationships between the prevalence of depression and dental pain using a well characterised, nationally representative, population-based study. This study analysed data from the 2012 Korea National Health and Nutrition Examination Survey (n = 4886). Oral health status was assessed using the oral health questionnaire, and oral examination was performed by trained dentists. Depression was defined as the participant having been diagnosed as depression during the previous year. Logistic regression was applied to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI), controlling for a range of covariates. Results demonstrated that participants included in 'root canal treatment is necessary' showed higher prevalence of self-reported dental pain; in particular, participants with depression presented more dental pain than those without depression. After adjusting for sociodemographic factors, self-reported dental pain increased in participants with depression. The AOR (95% CI) for having self-reported dental pain was 1·58 (1·08-2·33) in dentists' diagnosis of no dental pain/depression group, 1·62 (1·32-1·98) in dentists' diagnosis of dental pain/no depression group and 2·84 (1·10-7·37) in dentists' diagnosis of dental pain/depression group. It was concluded that depression was associated with dental pain after adjustment for potential confounders in Korean adults. Thus, dentists should consider the possible presence of psychopathology when treating patients with dental pain.

Transgene silencing of sucrose synthase in alfalfa (Medicago sativa L.) stem vascular tissue suggests a role for invertase in cell wall cellulose synthesis.

BACKGROUND: Alfalfa (Medicago sativa L.) is a widely adapted perennial forage crop that has high biomass production potential. Enhanced cellulose content in alfalfa stems would increase the value of the crop as a bioenergy feedstock. We examined if increased expression of sucrose synthase (SUS; EC 2.4.1.13) would increase cellulose in stem cell walls. RESULTS: Alfalfa plants were transformed with a truncated alfalfa phosphoenolpyruvate carboxylase gene promoter (PEPC7-P4) fused to an alfalfa nodule-enhanced SUS cDNA (MsSUS1) or the ß-glucuronidase (GUS) gene. Strong GUS expression was detected in xylem and phloem indicating that the PEPC7-P4 promoter was active in stem vascular tissue. In contrast to expectations, MsSUS1 transcript accumulation was reduced 75-90 % in alfalfa plants containing the PEPC7-P4::MsSUS1 transgene compared to controls. Enzyme assays indicated that SUS activity in stems of selected down-regulated transformants was reduced by greater than 95 % compared to the controls. Although SUS activity was detected in xylem and phloem of control plants by in situ enzyme assays, plants with the PEPC7-P4::MsSUS1 transgene lacked detectable SUS activity in post-elongation stem (PES) internodes and had very low SUS activity in elongating stem (ES) internodes. Loss of SUS protein in PES internodes of down-regulated lines was confirmed by immunoblots. Down-regulation of SUS expression and activity in stem tissue resulted in no obvious phenotype or significant change in cell wall sugar composition. However, alkaline/neutral (A/N) invertase activity increased in SUS down-regulated lines and high levels of acid invertase activity were observed. In situ enzyme assays of stem tissue showed localization of neutral invertase in vascular tissues of ES and PES internodes. CONCLUSIONS: These results suggest that invertases play a primary role in providing glucose for cellulose biosynthesis or compensate for the loss of SUS1 activity in stem vascular tissue.

Emergence agitation after orthognathic surgery: a randomised controlled comparison between sevoflurane and desflurane.

BACKGROUND: This study aimed to compare emergence agitation following sevoflurane and desflurane anaesthesia in adults undergoing orthognathic surgery. The hypothesis was that there might be a difference in the incidence of emergence agitation following sevoflurane and desflurane anaesthesia considering the difference in blood solubility and speed of recovery between the two. METHODS: In this prospective randomised double-blind study, 144 adults undergoing orthognathic surgery were randomly allocated to either sevoflurane or desflurane anaesthesia. The incidence of emergence agitation and possible causative factors were then compared between the groups. RESULTS: The incidence of emergence agitation was lower in the desflurane group than in the sevoflurane group (24% vs. 71%, P < 0.001). In addition, the time intervals between the discontinuation of anaesthetics and the first response, extubation, and discharge from post-anaesthesia care unit were significantly shorter in the desflurane group (P = 0.002, P < 0.001 and P = 0.003, respectively). The other variables were similar in the two groups. CONCLUSIONS: In adults undergoing orthognathic surgery, desflurane anaesthesia was associated with less emergence agitation than was sevoflurane anaesthesia.

Complex relation among Health Belief Model components in TB prevention and care.

OBJECTIVES: This study aims to explore the relationships among components of the Health Belief Model, tuberculosis (TB) preventive behavior, and intention of seeking TB care. STUDY DESIGN: Cross section study. METHODS: Using convenience sampling, 1154 rural-to-urban migrant workers were selected between the ages of 18-50 years in six urban areas of three provinces in China. The survey was conducted by individual, face-to-face interviews with a standardized questionnaire. Lisrel 8.7 was used to conduct path analysis. RESULTS: The knowledge and benefits components of the Health Belief Model predicted preventive behaviors: cover nose/mouth when coughing or sneezing (ß = 0.24, 0.33 respectively), evade others' coughs (ß = 0.13, 0.25) and also predicted seeking TB care (ß = 0.27, 0.19). Susceptibility and severity also predicted seeking TB care (ß = 0.12, 0.16). There were also important relationships among model components. Knowledge of TB predicted both susceptibility (ß = 0.32-0.60) and severity (ß = 0.41-0.45). Further, each of susceptibility (ß = 0.30) and severity (ß = 0.41) predicted perceived benefits of preventive care. CONCLUSION: Thus, a path from knowledge, through severity and susceptibility, and then through benefits predicted prevention and TB care seeking behaviors.

Upregulation of relaxin receptors in the PDL by biophysical force.

OBJECTIVES: We have previously reported that relaxin (Rln) expression from the ovary is upregulated by orthodontic tooth movement. This study was performed to test the hypothesis that Rln family peptides (Rxfps), the G-protein-coupled Rln receptor, is induced in periodontal ligament (PDL) cells to modulate the molecules involved in periodontal tissue remodeling while applying biophysical force. MATERIALS AND METHODS: Rats were implanted with orthodontic appliances to investigate changes to Rxfps in vivo. An in vitro biophysical force analysis was performed to measure the level of Rxfp 1 messenger RNA (mRNA) in primary human PDL cells. RESULTS: The levels of Rxfp 2 transcription and translation increased in a time-dependent manner during tooth movement. Rxfp 2 was localized in the PDL by immunofluorescence. In vitro analyses revealed that the level of Rxfp 1 mRNA in PDL cells increased significantly with both compression and tension force. The levels of matrix metalloproteinase (MMP)-1, MMP-2, interleukin-6, and vascular endothelial growth factor mRNA, which are important for periodontal tissue remodeling, also changed under force application and Rln treatment. CONCLUSIONS: PDL cells responded to Rln to modulate effector molecules for periodontal tissue remodeling by upregulating Rxfps expression under a biophysical force. CLINICAL RELEVANCE: Rln and Rxfps may serve as a PDL turnover molecule complex to control orthodontic tooth movement.

Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of supplementation.

AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis.

Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the intricate involvement of macrophage-mediated inflammation in the pathogenesis of periodontitis under both normal and T2DM conditions. However, the underlying mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein featuring an MHC-I domain, has been implicated in both inflammation and metabolic disorders. In this study, we found that AZGP1 was primarily colocalized with macrophages in periodontitis tissues. AZGP1 was increased in periodontitis compared with controls, which was further elevated when accompanied by T2DM. Adeno-associated virus-mediated overexpression of Azgp1 in the periodontium significantly enhanced periodontal inflammation and alveolar bone loss, accompanied by elevated M1 macrophages and pyroptosis in murine models of periodontitis and T2DM-associated periodontitis, while Azgp1-/- mice exhibited opposite effects. In primary bone marrow-derived macrophages stimulated by lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or knockout of Azgp1 markedly upregulated or suppressed, respectively, the expression of macrophage M1 markers and key components of the NLR Family Pyrin Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium from Azgp1-overexpressed macrophages under LPS or LPS+PA stimulation induced higher inflammatory activation and lower osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization and pyroptosis in macrophages and associated detrimental effects on hPDLSCs induced by Azgp1 overexpression could be rescued by NLRP3 or caspase-1 inhibition. Collectively, our study elucidated that AZGP1 could aggravate periodontitis by promoting macrophage M1 polarization and pyroptosis through the NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. This finding deepens the understanding of AZGP1 in the pathogenesis of periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects of diabetes on periodontal inflammation.

New Monomer Capable of Dual Chemical Binding with Dentin to Improve Bonding Durability.

The water-rich nature of the dentin bonding microenvironment, coupled with the stresses on the bonding interface, contributes to the hydrolytic degradation of the hybrid layer, resulting in a decline in bonding durability and, ultimately, restoration failure. Currently, the 3-step etch-and-rinse technique remains the gold standard for dentin bonding, and the bonding mechanism mainly involves a physical interaction with little chemical bonding. In this study, we have developed a siloxane-modified polyurethane monomer (SPU) with acrylate and siloxane modifications that chemically binds to both collagen and hydroxyapatite in dentin. Formulated as a bisphenol A-glycidyl methacrylate alternative, the SPU monomer-based adhesive was designed to improve dentin bonding quality and durability. Attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscope, and hydroxyproline release assays were performed on SPU-treated collagen, hydroxyapatite, and acid-etched dentin slices to dentin. The physicochemical properties of the configured SPU adhesives were profiled for polymerization behavior, water contact angle, and tensile strain and strength. The bonding effectiveness was assessed through micro-tensile strength, nano-leakage tests conducted on the bonded samples before and after thermal cycle aging. Finally, we further conducted in vivo and in vitro experiments to assess the biocompatibility of adhesives. The results showed that the siloxane groups of SPU monomer could covalently bind to dentin collagen and hydroxyapatite. The incorporation of SPU in the adhesive led to a significant increase in adhesive polymerization (P < 0.05) and tensile strain at break up to 134.11%. Furthermore, the SPU adhesive significantly improved dentin bond strength (P < 0.05), reduced interfacial nano-leakage (P < 0.05), and displayed good biocompatibility. In conclusion, the application of SPU, which achieves dual chemical bonding with dentin, can improve the quality of the hybrid layer, buffer the interfacial stresses, enhance the interfacial resistance to hydrolysis, and provide a feasible strategy to extend the service life of adhesive restorations.

Lipopolysaccharide-induced indoleamine 2,3-dioxygenase expression in the periodontal ligament.

BACKGROUND AND OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-oxidizing enzyme with immune-inhibitory effects. The aim of this study was to investigate the expression of IDO by lipopolysaccharide (LPS), a component of gram-negative bacteria, in human periodontal ligament (PDL) cells. MATERIAL AND METHODS: Human PDL cells and gingival fibroblasts (GFs) were prepared from explants of human PDLs and from gingival tissues of clinically healthy donors, respectively. Real-time RT-PCR, western blotting and the IDO enzyme assay were performed to determine the expression of IDO following LPS treatment of cells. LPS was injected into mice tail veins to evaluate the effects of LPS in vivo in the maxillary first molar. Immunofluorescence staining and histological analysis were followed to localize IDO in mouse PDL. RESULTS: The level of expression of IDO mRNA in primary human PDL cells after LPS treatment was increased in a dose-dependent manner, reaching a peak 8 h after LPS treatment. The expression and activities of IDO protein were significantly increased in comparison with those of the control. In addition, the increased production of kynurenine in culture medium was observed 72 h after LPS treatment. In the immunofluorescence findings, stronger immunoreactivities were shown in PDL than in gingival tissues in the maxillae. In accordance with the immunofluorescence findings, LPS treatment induced a strong up-regulation of IDO mRNA in human PDL cells, whereas human GFs showed only a weak response to LPS. CONCLUSION: These results clearly show that IDO was induced by LPS in primary human PDL cells, suggesting that PDL might be involved in the regulation of oral inflammatory disease.