Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells.

Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.

LncRNA DANCR sponges miR-216a to inhibit odontoblast differentiation through upregulating c-Cbl.

Enhanced odontoblast differentiation of human dental pulp cells (hDPCs) is considered a keystone in dentin-pulp complex formation. We have revealed lncRNA DANCR was implicated in this differentiation program, however, its mechanism in odontoblast differentiation of hDPCs remains further explored. In this study, by employing loss-of-function approach, we identified downregulation of DANCR drived odontoblast differentiaion of hDPCs. Bioinformatics analysis was utilized to show that DANCR contained binding site for miR-216a and an inverse correlation between DANCR and miR-216a was obtained. Dual luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) were applied to further confirm that DANCR conferred its functions by directly binding to miR-216a. Notably, miR-216a was able to bind to the 3'-UTR of c-Cbl and repressed its expression. In addition, the protein level of c-CBL was significantly downregulated during hDPCs differentiation, while c-Cbl overexpression inhibited odontoblast differentiation of hDPCs. Moreover, downregulation of miR-216a efficiently reversed the suppression of c-Cbl level and odontoblast differentiation induced by knockdown of DANCR. Taken together, these analyses indicated that DANCR positively regulated the expression of c-Cbl, through sponging miR-216a, and inhibited odontoblast differentiation of hDPCs. Our results will extend the field of clinical application for cell-based therapy in regenerative medicine.

Functional Dental Pulp Regeneration: Basic Research and Clinical Translation.

Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.

The antibacterial, cytotoxic, and flexural properties of a composite resin containing a quaternary ammonium monomer.

STATEMENT OF PROBLEM: The use of composite resin to restore teeth has increased substantially during the last decades. However, secondary caries and the fracture of restorations are the leading reasons for clinical restoration failure. Mechanically strong composite resins with caries-inhibition capabilities are needed. Although antibacterial dimethacrylate quaternary ammonium monomers have been synthesized, composite resin containing dimethacrylate quaternary ammonium monomers and glass fillers has rarely been reported. PURPOSE: The purpose of this in vitro study was to evaluate the possibility of the clinical use of an experimental composite resin containing urethane dimethacrylate quaternary ammonium compound (UDMQA-12) by investigating its antibacterial activity, cytotoxicity, flexural strength, and flexural modulus. MATERIAL AND METHODS: Antibacterial activity against Streptococcus mutans was investigated by means of direct contact test. The antibacterial activity of specimens after water immersion and saliva treatment was also tested. These were compared with a commercially available composite resin, Z250, and a glass ionomer cement, Fuji VII. Effects of the eluent from the experimental composite resin on the metabolic activity of human dental pulp cells were quantified. Disks of 1 mm in thickness and 15 mm in diameter were used in the antibacterial and cytotoxic tests. Flexural strength and flexural modulus were measured with a 3-point bend test with bars of 2×2×25 mm. Three commercially available composite resins (Filtek Z250, G-aenial Anterior, and G-aenial Posterior) were used as controls in the flexural test. RESULTS: Bacterial growth was inhibited on the experimental composite resin. After water immersion or saliva treatment, the experimental composite resin showed significant antibacterial effect compared with the conventional composite resin (P<.05). No significant difference was found in cytotoxicity between the experimental composite resin and the conventional composite resin (P＞.05), and a significantly higher cytotoxicity was shown by glass ionomer cement compared with the experimental composite resin and the conventional composite resin (P<.05). The conventional composite resin had the highest flexural strength and flexural modulus (P<.05), followed by the experimental composite resin, then G-ænial Posterior and G-ænial Anterior. CONCLUSIONS: The antibacterial experimental composite resin was biocompatible and had mechanical properties similar to those of some commercially available composite resins. It might, therefore, be useful in preventing the occurrence of secondary caries.

A study of the coupling relationship between concrete surface temperature and concrete surface emissivity in natural conditions.

Land surface emissivity (LSE) has already been recognized as a crucial parameter for the determination of land surface temperature (LST). There is an ill-posed problem for the retrieval of LST and LSE. And laboratory-based emissivity is measured in natural constant conditions, which is limited in the application in thermal remote sensing. To solve the above problems, the coupling of LST and LSE is explored to eliminate temperature effects and improve the accuracy of LES. And then, the estimation accuracy of LST from passive remote sensing images will be improved. For different land surface materials, the coupling of land surface emissivity and land surface temperature is various. This paper focuses on studying concrete surface that is one of the typical man-made materials in urban. First the experiments of measuring concrete surface emissivity and concrete surface temperature in natural conditions are arranged reasonably and the suitable data are selected under ideal atmosphere conductions. Then to improve the determination accuracy of concrete surface emissivity, the algorithm worked on the computer of Fourier Transform Infrared Spectroradiometer (FTIR) has been improved by the most adapted temperature and emissivity separation algorithm. Finally the coupling of concrete surface temperature and concrete surface emissivity is analyzed and the coupling model of concrete surface temperature and concrete surface emissivity is established. The results show that there is a highest correlation coefficient between the second derivative of emissivity spectra and concrete surface temperature, and the correlation coefficient is -0.925 1. The best coupling model is the stepwise regression model, whose determination coefficient (R2) is 0.886. The determination coefficient (R2) is 0.905 and the root mean squares error (RMSE) is 0.292 1 in the validation of the model. The coupling model of concrete surface temperature and concrete surface emissivity under natural conditions provides a new approach for improving the estimation accuracy of LST from passive remote sensing images.

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure.

The consumption of a high-fat diet (HFD) has been linked to osteoporosis and an increased risk of fragility fractures. However, the specific mechanisms of HFD-induced osteoporosis are not fully understood. Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells (BMSCs), diminishing their proliferation and osteogenic capability, and thereby contributes to osteoporosis. Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor (VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice, suggesting that VDR is a key regulator of BMSC senescence. Notably, the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis, bone mass, and other bone parameters. Mechanistically, VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species (ROS) levels and preserving mitochondrial function. Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2 (SOD2)-ROS axis.

Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration.

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. STATEMENT OF SIGNIFICANCE: Functional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.

9-Hydroxy-8-oxypalmatine, a novel liver-mediated oxymetabolite of palmatine, alleviates hyperuricemia and kidney inflammation in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Palmatine is a main bioactive alkaloid of Cortex Phellodendri, which has been commonly prescribed for the treatment of hyperuricemia (HUA) in China. The metabolites of palmatine were crucial to its prominent biological activity. 9-Hydroxy-8-oxypalmatine (9-OPAL) is a novel liver-mediated secondary oxymetabolite of palmatine. AIM OF THE STUDY: The current study was to assess the efficacy of 9-OPAL, a novel liver-mediated secondary oxymetabolite of palmatine derived from Cortex Phellodendri, in experimental HUA mouse model and further explore its underlying mechanism. MATERIALS AND METHODS: An in vitro metabolic experiment with oxypalmatine was carried out using liver samples. We separated and identified a novel liver metabolite, and investigated its anti-HUA effect in mice. HUA mice were induced by potassium oxonate and hypoxanthine daily for one week. After 1 h of modeling, mice were orally administered with different doses of 9-OPAL (5, 10 and 20 mg/kg). The pathological changes of the kidneys were evaluated using hematoxylin-eosin staining (H&E). The acute toxicity of 9-OPAL was assessed. The effects of 9-OPAL on serum levels of uric acid (UA), adenosine deaminase (ADA), xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN) and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) or biochemical method. Furthermore, Western blot, quantitative real-time PCR (qRT-PCR) and molecular docking were used to investigate the effect of 9-OPAL on the expression of renal urate transporters and NLRP3 signaling pathway in HUA mice. RESULTS: 9-OPAL had been discovered to be a novel liver-mediated oxymetabolite of palmatine for the first time. Treatment with 9-OPAL significantly reduced the UA, CRE as well as BUN levels, and also effectively attenuated abnormal renal histopathological deterioration with favorable safety profile. Besides, 9-OPAL significantly decreased the serum and hepatic activities of XOD and ADA, dramatically inhibited the up-regulation of UA transporter protein 1 (URAT1) and glucose transporter protein 9 (GLUT9), and reversed the down-regulation of organic anion transporter protein 1 (OAT1). Additionally, 9-OPAL effectively mitigated the renal inflammatory markers (TNF-α, IL-1ß, IL-6 and IL-18), and downregulated the transcriptional and translational expressions of renal Nod-like receptor family pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like (ASC) and IL-1ß in HUA mice. Molecular docking results revealed 9-OPAL bound firmly with XOD, OAT1, GLUT9, URAT1, NLRP3, caspase-1, ASC and IL-1ß. CONCLUSIONS: 9-OPAL was found to be a novel liver-mediated secondary metabolite of palmatine with favorable safety profile. 9-OPAL had eminent anti-hyperuricemic and renal-protective effects, and the mechanisms might be intimately associated with repressing XOD activities, modulating renal urate transporter expression and suppressing the NLRP3 inflammasome activation. Our investigation might also provide further experimental evidence for the traditional application of Cortex Phellodendri in the treatment of HUA.

Targeting cariogenic pathogens and promoting competitiveness of commensal bacteria with a novel pH-responsive antimicrobial peptide.

Novel ecological antimicrobial approaches to dental caries focus on inhibiting cariogenic pathogens while enhancing the growth of health-associated commensal communities or suppressing cariogenic virulence without affecting the diversity of oral microbiota, which emphasize the crucial role of establishing a healthy microbiome in caries prevention. Considering that the acidified cariogenic microenvironment leads to the dysbiosis of microecology and demineralization of enamel, exploiting the acidic pH as a bioresponsive trigger to help materials and medications target cariogenic pathogens is a promising strategy to develop novel anticaries approaches. In this study, a pH-responsive antimicrobial peptide, LH12, was designed utilizing the pH-sensitivity of histidine, which showed higher cationicity and stronger interactions with bacterial cytomembranes at acidic pH. Streptococcus mutans was used as the in vitro caries model to evaluate the inhibitory effects of LH12 on the cariogenic properties, such as biofilm formation, biofilm morphology, acidurance, acidogenicity, and exopolysaccharides synthesis. The dual-species model of Streptococcus mutans and Streptococcus gordonii was established in vitro to evaluate the regulation effects of LH12 on the mixed species microbial community containing both cariogenic bacteria and commensal bacteria. LH12 suppressed the cariogenic properties and regulated the bacterial composition to a healthier condition through a dual-functional mechanism. Firstly, LH12-targeted cariogenic pathogens in response to the acidified microenvironment and suppressed the cariogenic virulence by inhibiting the expression of multiple virulence genes and two-component signal transduction systems. Additionally, LH12 elevated H2O2 production of the commensal bacteria and subsequently improved the ecological competitiveness of the commensals. The dual-functional mechanism made LH12 a potential bioresponsive approach to caries management.

Injectable decellularized extracellular matrix hydrogel promotes salivary gland regeneration via endogenous stem cell recruitment and suppression of fibrogenesis.

Saliva is key to the maintenance of oral homeostasis. However, several forms of salivary gland (SG) disorders, followed by hyposalivation, often result in dental caries, oral infection, and decreased taste, which dramatically affect the quality of patient's life. Functional biomaterials hold great potential for tissue regeneration in damaged or dysfunctional SGs and maintaining the good health of oral cavity. Herein, we prepared an injectable hydrogel derived from decellularized porcine submandibular glands (pDSG-gel), the material and biological properties of the hydrogel were systematically investigated. First, good biocompatibility and bioactivities of the pDSG-gel were validated in 2D and 3D cultures of primary submandibular gland mesenchymal stem cells (SGMSCs). Especially, the pDSG-gel effectively facilitated SGMSCs migration and recruitment through the activation of PI3K/AKT signaling pathway, suggested by transcriptomic analysis and immunoblotting. Furthermore, proteomic analysis of the pDSG revealed that many extracellular matrix components and secreted factors were preserved, which may contribute to stem cell homing. The recruitment of endogenous SG cells was confirmed in vivo, upon in situ injection of the pDSG-gel into the defective SGs in rats. Acinar and ductal-like structures were evident in the injury sites after pDSG-gel treatment, suggesting the reconstruction of functional SG units. Meanwhile, histological characterizations showed that the administration of the pDSG-gel also significantly suppressed fibrogenesis within the injured SG tissues. Taken together, this tissue-specific hydrogel provides a pro-regenerative microenvironment for endogenous SG regeneration and holds great promise as a powerful and bioactive material for future treatments of SG diseases. STATEMENT OF SIGNIFICANCE: Decellularized extracellular matrix (dECM) has been acknowledged as one of the most promising biomaterials that recapitalizes the microenvironment in native tissues. Hydrogel derived from the dECM allows in situ administration for tissue repair. Herein, a tissue-specific dECM hydrogel derived from porcine salivary glands (pDSG-gel) was successfully prepared and developed for functional reconstruction of defective salivary gland (SG) tissues. The pDSG-gel effectively accelerated endogenous SG stem cells migration and their recruitment for acinar- and ductal-like regeneration, which was attributed to the activation of PI3K/AKT signaling pathway. Additionally, the introduction of the pDSG-gel resulted in highly suppressed fibrogenesis in the defective tissues. These outcomes indicated that the pDSG-gel holds great potential in clinical translation toward SG regeneration through cell-free treatments.

[Characteristics of thermal infrared hyperspectra and prediction of sand content of sandy soil].

To explore the potential of thermal infrared hyperspecra for retrieving sand content in soil, the sandy soil was measured using a 102F Fourier Transform Infrared Spectroradiometer (FTIR), and the characteristics of sandy soil's emissivity spectra were discussed based on correlation analysis and principal component analysis. Moreover, the sand contents were predicted using two modeling methods: Partial least squares regression (PLSR) and principal component regression (PCR). The results show that the Reststrahlen feature (RF) of SiO2 is obvious in the emissivity spectra of sandy soil with two large asymmetrical absorption troughs near 8.13 and 9.17 microm and two small troughs in the region of 12-13 microm. Soil emissivity becomes lower when sand content increases, this trend is more evident especially in the regions of 8-9.5 microm and 9.5-10.4 microm of which correlation coefficients are above 0.65 and 0.5 respectively, and these two regions can account for 84.07% of total emissivity variance. Predictive precision varies significantly when sand content is predicted by different modeling methods or spectral variables. The PLSR model can achieve the highest predictive precision by using first-order derivative spectra, and it's RMSE of modeling and prediction is 0.45 and 0.53 respectively, and the R2, 0.9907 and 0.9836, which means that the thermal hyperspectra has promising potential for retrieving sand content in soil.

Size Dependence of Particulate Calcium Phosphate Fillers in Dental Resin Composites.

Resin composites that consist of polymeric resins and functional fillers are commonly used as restorative materials for dental caries. Various types of calcium phosphates (CaPs) are studied as remineralizing fillers in the formulation of dental resin composites, which are generally inhibitory to demineralization of teeth, but the performance of resin composites has not yet been investigated comprehensively with respect to the size of CaP particles. In this study, the same tricalcium phosphate (TCP) particles within two different size ranges, the as-received TCP particles (TCP) and those resulted from grinding (TCP-G), were tested to determine the size dependence of CaP fillers in dental resin composites. The buffering capability, mechanical properties, ion release, antibacterial performance, and remineralization effect of TCP/TCP-G-containing composites were experimentally characterized and compared against two other commercial dental materials. The integration of micrometer-sized TCP particles resulted in a similar buffering effect and Ca2+/PO4 3- release behaviors compared to the resin composite containing much smaller TCP-G particles. The flexural strength of the TCP-G resin composite was lower than that of the TCP composite after immersion in water for 30 days. However, the TCP-G composite facilitated crystal deposition toward better gap-closing performance at the dentin-composite interface. This study explored detailed insights about the size effect of CaP fillers, which is useful for the development of functional dental resin composites and their clinical translation.

A Decellularized Matrix Hydrogel Derived from Human Dental Pulp Promotes Dental Pulp Stem Cell Proliferation, Migration, and Induced Multidirectional Differentiation In Vitro.

INTRODUCTION: Dental pulp is a major composition in the pulp-dentin complex, which serves as protective system against dental trauma/infection. Functional dental pulp regeneration is highly desirable after pulpitis or pulp necrosis. However, endodontic regeneration has remained challenging for decades because of the deconstructive microenvironment and the lack of functional cells within the root canal system. The present study developed a decellularized matrix hydrogel derived from human dental pulp (hDDPM-G), which might serve as a growth-permissive microenvironment for dental pulp regeneration. METHODS: Human dental pulps extracted from healthy wisdom teeth were decellularized and digested and then underwent sol-gel transition to form hDDPM-G. The protein compositions were identified by proteomic analysis. Human dental pulp stem cells (hDPSCs) were seeded on hDDPM-G-coated surfaces and evaluated by immunofluorescence staining, transwell migration, and Cell Counting Kit-8 (Dojindo, Kumamoto, Japan) assays. Induced hDPSC differentiation was examined in vitro and characterized by immunostaining, Western blotting, and reverse transcription polymerase chain reaction. RESULTS: Complete decellularization was implemented. Protein contents found in the human decellularized dental pulp matrix were identified to contribute in promoting cell proliferation, migration, and regulation of stem cell differentiation. The hDDPM-G-coated surfaces promoted hDPSC adhesion, migration, and proliferation. Furthermore, hDDPM-G coatings facilitated odontoblastlike, neural-like, and angiogenic differentiation of the seeded hDPSCs after being cultured in induction media for 14 days. CONCLUSIONS: This study showed that hDDPM-G effectively contributed in promoting hDPSC proliferation and migration and induced multidirectional differentiation. Considering the injectability and gelation at body temperature, hDDPM-G may hold translational potential for endodontic regeneration.

[Analysis of lead in soil with partial least square regression (PLS) method and field portable X-ray fluorescence(FPXRF) analyzer].

In the present study, soil samples were scanned by NITON XLt920 field portable X-ray fluorescence (FPXRF) analyzer, and the relationship between the X-ray fluorescence spectra and the concentration of Pb in soil was studied. For predicating the Pb concentration in soil, a partial least square regression model (PLS)was established with 6 optimal factors and two closely relevant electron volt ranges: 10.40-10.70 keV and 12.41-12.80 keV. After cross-calibration, the correlation coefficient of value predicted by PLS model against that measured by ICP was 0.9666, and the root mean square error of prediction (RMSEP) was 0.8732. Meanwhile, the univariate linear regression and multivariate linear regression models were also built with the correlation coefficient of 0.6805 and 0.7302, respectively. Obviously, the PLS method was better than the other two methods for predication. Comparing to the conventional approach of atomic absorption spectroscopy (AAS), FPXRF has the advantages of rapidness, non-destruction and relatively low cost with the acceptable accuracy. It would be a powerful tool to decide which sample is needs for further analysis.

AIM2 Inflammasome Is Critical for dsDNA-Induced IL-1ß Secretion in Human Dental Pulp Cells.

The AIM2 inflammasome pathway has been determined to play an important role in cellular immune defense against bacterial and viral infections; however, its function and regulatory mechanism in human dental pulp cells (HDPCs) during pulpitis remains poorly understood. In this study, we explored whether the AIM2 inflammasome pathway was activated in HDPCs in response to dsDNA and defined its role in regulating IL-1ß secretion. We demonstrated that stimulation with IFN-γ and cytoplasmic DNA significantly activated the AIM2 inflammasome and increased IL-1ß secretion in HDPCs. Moreover, AIM2 overexpression significantly up-regulated both cleaved Caspase-1 expression and IL-1ß release in HDPCs, while suppression of ASC and Caspase-1 resulted in down-regulation of cleaved Caspase-1 and IL-1ß secretion. These results suggest that Caspase-1-dependent IL-1ß processing and secretion require the AIM2 inflammasome pathway in HDPCs and that the AIM2 inflammasome pathway is critical for regulation of the dental pulp immune response.

Mechanical and antibacterial properties of benzothiazole-based dental resin materials.

A synthesized benzothiazole containing mono-methacrylate monomer BTTMA was incorporated into Bis-GMA/TEGDMA dental resin system with a series of mass concentration from 5 to 30 wt.% as an antibacterial agent. The influence of BTTMA on physicochemical properties of dental resin system, such as double bond conversion (DC), volumetric shrinkage (VS), flexural strength (FS) and modulus (FM), water sorption (WS) and solubility (SL) were investigated. Direct contact testing and agar diffusion testing were used to evaluate the antibacterial activity of BTTMA containing dental resin. The results showed that BTTMA could endow dental resin with significant antibacterial activity when its concentration reached a certain amount (20 wt.%), and the antibacterial activity of BTTMA containing dental resin was mainly attributed to the immobilized BTTMA instead of the unreacted leachable BTTMA. BTTMA had no negative effect on physicochemical properties of dental resin, and even some BTTMA containing dental resins had advantages like higher DC, lower VS and WS when compared with control resin. Therefore, BTTMA could be considered as a suitable antibacterial agent in dental material, but much more researches concerned about biocompatibility should be done in future to prove whether it could be applied in clinic.

Physicochemical properties of discontinuous S2-glass fiber reinforced resin composite.

The objective of this study was to investigate several physicochemical properties of an experimental discontinuous S2-glass fiber-reinforced resin composite. The experimental composite was prepared by mixing 10 wt% of discontinuous S2-glass fibers with 27.5 wt% of resin matrix and 62.5 wt% of particulate fillers. Flexural strength (FS) and modulus (FM), fracture toughness (FT), work of fracture (WOF), double bond conversion (DC), Vickers hardness, volume shrinkage (VS) and fiber length distribution were determined. These were compared with two commercial resin composites. The experimental composite showed the highest FS, WOF and FT compared with two control composites. The DC of the experimental composite was comparable with controls. No significant difference was observed in VS between the three tested composites. The use of discontinuous glass fiber fillers with polymer matrix and particulate fillers yielded improved physical properties and substantial improvement was associated with the use of S2-glass fiber.

Immunomodulatory Role of Stem Cells from Human Exfoliated Deciduous Teeth on Periodontal Regeneration.

Periodontitis is initiated by the infection of periodontal bacteria and subsequent tissue inflammation due to immunoreaction, eventually leading to periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration. However, the immunomodulatory functions of SHEDs have not been elucidated in the context of periodontitis treatment. In this study, we investigated the potential immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated that multidose delivery of SHEDs led to periodontal tissue regeneration. SHEDs and monocytes/macrophages were cocultured in transwell systems and SHEDs were found to be capable of promoting monocyte/macrophage conversion to CD206+ M2-like phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and distribution of SHEDs after delivery in periodontal tissues in an induced periodontitis model, and BLI revealed that SHEDs survived for ∼7 days in periodontal tissues with little tissue diffusion. Then, multidose SHED delivery was applied to treat periodontitis at 7-day intervals. Results showed that mutidose SHEDs altered the cytokine expression profile in gingival crevicular fluid, reduced gum bleeding, increased new attachment of periodontal ligament, and decreased osteoclast differentiation. Micro-computed tomography analysis showed SHED administration significantly increased periodontal regeneration and alveolar bone volume, and decreased distance of cementoenamel junction to alveolar bone crest. Furthermore, an increase in the number of CD206+ M2 macrophages was observed in periodontal tissues following the delivery of SHEDs, which aligned well with the promoted conversion to CD206+ M2-like cells from monocytes/macrophages in vitro after stimulation by SHEDs. This study demonstrated in a rat periodontitis model that local delivery of SHEDs attributed to the induction of M2 macrophage polarization, reduction of periodontal tissue inflammation, and enhancement of periodontal regeneration.

Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR2-overexpressing MSCs (MSCsCXCR2) for mucositis treatment. Indeed, MSCsCXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSCCXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

Oral multidisciplinary considerations for clinical strategies of endodontic microsurgery / 口腔疾病防治

@#Endodontic microsurgery is a vital treatment modality for teeth with persistent periradicular pathoses that have not responded to nonsurgical retreatment. The principle is to determine the reason for failure, completely eliminate the infection and promote periapical healing. Within recent years, endodontic microsurgery has evolved to become standardized and presents with a high success rate. However, its outcome is still influenced by many factors, including anatomy, periodontal condition, crown-to-root ratio, occlusion, the type of periradicular lesion, and prosthesis. Moreover, endodontists always concentrate on “the apex”, paying little attention to the general preoperative evaluation, accurate diagnosis, and comprehensive treatment plan. This article reviews the latest literature on these issues and the clinical experience of our research group and discusses the correlation between endodontic microsurgery and other oral disciplines, including periodontology, prosthodontics, oral implantology, oral and maxillofacial surgery and orthodontics. The oral interdisciplinary assessment should be made with comprehensive consideration of the root canal system, periradicular lesion, adjacent anatomical relationships, periodontal condition, occlusion, and esthetic rehabilitation. Based on these findings, the continuity of treatment will be optimized, and the best treatment plan will be proposed to provide clinical strategies for the diagnosis and treatment of complex periradicular diseases.